Ueg Week 2020 Poster Presentations

doi:10.1177/2050640620927345

. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345

Ueg Week 2020 Poster Presentations

PMCID: PMC8939488 PMID: 33043826

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.1

P0001 Serum Adipokines As Non-Invasive Biomarkers in Crohn's Disease

Moreno L Ortega ^1,^2,^✉, A Sanz-Garcia ³, MJ Fernandez de la Fuente ⁴, R Arroyo Solera ⁵, S Fernández-Tomé ¹, AC Marin ^1,⁶, I Mora-Gutierrez ¹, P Fernández ⁵, M Baldan-Martin ^1,⁶, M Chaparro Sanchez ^1,^2,⁶, D Bernardo ^1,^6,⁷, J Gisbert ^1,^2,⁶

Introduction

Adipose tissue wrapping the gastrointestinal tract is a risk factor for disease activity in Crohn's disease (CD). Indeed, adipokines associated to lipid metabolism can modulate local immune responses. However, few studies have investigated the possible association between adipokines and CD.

Aims & Methods

Here, we aimed to evaluate the role of serum adipokines as possible biomarkers in CD.

Serum samples were obtained from 18 patients with endoscopically active CD (aCD), 22 patients with endoscopically quiescent CD (qCD) and 36 non-inflamed healthy controls (HC). All serum samples were obtained from CD patients and HC at the moment of colonoscopy in Hospital Universitario La Princesa, Madrid, Spain. The Simple Endoscopic Score for Crohn's Disease (SES-CD) was determined during colonoscopy in all CD patients in order to classify them as aCD (SES-CD ³ 3) or qCD (SES-CD ≤ 2). Demographic variables (i.e. sex, age and BMI) were analysed by chi square test (frequencies) or ANOVA test (means). Serum leptin, ghrelin, resistin and adiponec-tin were analysed by Multiplex (Bio-Rad, Hercules, CA, USA) in a Luminex 200 system technology following manufacturer's instructions. The final concentration value of each adipokine was the result of the mean from the two duplicated measures. Adipokines normality was tested and adipokines were natural log transformed. Spearman correlation was performed for the adipokines. Adipokine means for each group of patients were compared by ANOVA test. Median and interquartile range for each patient group was determined for those skewed adipokines and Kruskal-Wallis test was performed. Receiver Operating Characteristic (ROC) curves and the area under the curve (AUC) were carried on to evaluate the discriminatory capacity of the adipokines levels between study groups. The Youden cut-off index got from the ROC curve was matched with the adipokines concentration. Furthermore, for those adipokines that showed an AUC ≥ 0.7, a binary logistic regression adjusted by possible confounders (i.e sex, age, BMI) was performed in order to test their possible association with CD.

Results

No differences were found in age, sex or BMI among aCD, qCD and HC. There was no correlation among the adipokines analyzed. Means distribution for serum resistin was different among aCD, qCD and HC (p=0.02). However, only comparisons between aCD and HC a groups showed significant differences (p=0.03) in the post hoc test. Serum leptin, ghrelin and adiponectin did not show differences between means. ROC curve for resistin showed an AUC along with its 95% confidence interval of 0.75 (0.61-0.89) when HC and aCD groups were compared. Furthermore, in this case, as sensitivity and specificity for Youden index correspond to the total resistin median concentration (9822pg/ml), this value was selected as a cut-off for the binary logistic regression analysis; thus, odds ratio (OR) along with their 95% confidence interval analysis of high relative resistin levels (values higher than total resistin median) adjusted by age, sex and BMI yielded a value of 5.46 (1.34-22.14) when active patients were compared to HC. Comparisons between qCD and aCD or between qCD and HC showed an AUC < 0.7. ROC curves analysis for leptin, ghrelin and adiponectin did not show enough accuracy to discriminate between groups.

Conclusion

Resistin may modulate the inflammation state in CD and it is probably associated to activity, being this association independent of sex, age or BMI. Resistin may work as a serum biomarker of activity in CD.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.2

P0003 Redefining Patterns of Tumour Response To Chemoradiotherapy in Oesophageal Cancer with The Aid of Ai

Martínez C Graham ^1,^✉, A Al-Kaabi ², T Strausz ¹, JM Bokhorst ³, C Rosman ⁴, PD Siersema ², ID Nagtegaal ¹, C van der Post ¹

Introduction

Tumour response has been categorized in many ways with-in-and-between tumour types. in order for tailored treatment decisions to be made, there is a need for a reproducible, objective and standardized assessment of response which combines histological patterns and down-staging.

Aims & Methods

Our cohort was composed of 100 patients with oesophageal adenocarcinoma (cT2-T3) treated with chemoradiotherapy. Three H&E slides per patient were analysed by a panel of pathologists and run through an algorithm to determine tumour cell percentage (TC%), size and distance between tumour fragments. Clinical data was used to determine correlations to survival and recurrence.

Results

Four histological patterns of regression were distinguished; fragmented (clustered or scattered), shrinkage and no-response. TC% was found to be significantly higher in clustered fragmentation subtype compared to scattered subtype in the mucosa (p=0.04) and tended to be higher in submucosa (p=0.08), muscularis (p=0.15) and subserosa (p=0.32). Preliminary results were obtained with only 70 patients, which we hope to increase to 100.

Conclusion

By using trained algorithms it is possible to accurately determine subtypes of patterns of response in an unbiased approach which might form the basis of predictive biomarker research. Recognition of these patterns of response and correlation with clinical outcome could provide a useful prognostic marker for further treatment. Moreover, our algorithms might be transferable to other cancer types.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.3

P0004 Significance of Estrogen Receptor Expression in Esophageal Adenocarcinoma: Proof of Concept

A Mokrowiecka ^1,^✉, E Malecka-Panas ¹, D Jacenik ²

Introduction

Estrogens play a crucial role in the development and progression of multiple types of cancer. Estrogen signaling through nuclear estrogen receptors (ERs), i.e. ERa and ERβ as well as membrane-bound estrogen receptor, i.e. G protein-coupled estrogen receptor (GPER), participates in the regulation of cancer cell proliferation and migration. However, the importance of estrogen receptors in esophageal adenocarcinoma is elusive.

Aims & Methods

To better assess the significance of estrogen receptors in esophageal adenocarcinoma, bioinformatic analysis was performed using datasets provided by Global Expression Omnibus and The Cancer Genome Atlas Esophageal Carcinoma from The Cancer Genome Atlas. Gene expression correlation was carried out with the Genevestigator co-expression tool. Pathway enrichment was evaluated with The Kyoto Encyclopedia of Genes and Genomes pathway using functional annotation of The Database for Annotation, Visualization and Integrated Discovery. Survival analysis was determined with Kaplan-Meier plotter.

Results

Gene expression profiling of estrogen receptors using dataset from Global Expression Omnibus revealed deregulation of ERa, ERβ and GPER expression in esophageal adenocarcinoma. Pathway enrichment analysis confirmed that estrogen receptors are correlated with genes participated in metabolic pathways, S. aureus infection, complement and coagulation cascades, oxidative phosphorylation, neurodegenerative diseases, spliceosome and ribosome biology as well as RNA transport. The Kaplan-Meier analysis documented poor overall survival in esophageal carcinoma patients with lower expression of ERa. in contrast, lower expression of GPER seems to be associated with better overall survival in esophageal adenocarcinoma patients.

Conclusion

In the present study, we found alterations of estrogen receptors expression and a relationship between the level of estrogen receptors and genes involved in numerous essential processes in the neoplastic transformation of esophagus. Moreover, our analysis highlighted prognostic significance of ERa and GPER expression in esophageal adenocarcinoma patients. These findings point to the need of a better understanding on the role exerted by estrogen receptors in esophageal adenocarcinoma.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.4

P0005 Mitochondria-Targeting Hydrogen Sulfide-Releasing Ap-39 in Prevention of Chemically-Induced Gastric Mucosal Damage

D Bakalarz ^1,^2,^✉, D Wójcik ¹, M Surmiak ³, E Korbut ¹, T Brzozowski ¹, K Magierowska ¹, M Szetela ¹, M Whiteman ⁴, M Magierowski ¹

Introduction

Hydrogen sulfide (H₂S) is an endogenous gaseous mediator produced by L-cysteine metabolism due to the activity of particular enzymatic pathways. This molecule has been shown to affect mitochondrial complexes and in result to modulate anti-oxidative mechanisms. Interestingly, H₂S-releasing pharmacological tools were shown to play a key role within digestive system pathophysiology exerting anti-inflammatory and anti-oxidative activity. Taking into account the experimental data, beneficial effects of H₂S is strictly dose-dependent and the controlled release of this molecule seems to be crucial to avoid cytotoxicity and to obtain desired biological effects. Thus, we aimed to assess the effect of mitochondria-targeting H₂S-releasing compound, AP-39 administered i.g. against the development of aspirin- or ethanol-induced GI damage.

Aims & Methods

Wistar rats were pretreated with vehicle, AP-39 (0.004-2.5 mg/kg i.g.) or NC-AP-39 as structural control to AP-39 without ability to release H₂S. After 30 min, gastropathy was induced by aspirin (125 mg/ kg i.g.) or 75%-ethanol (1.0 ml, i.g.). Gastric lesions area and gastric blood flow (GBF) were determined by planimetry, histology and laser flowmetry, respectively. Gastric mucosal mRNA expressions of COX-1, COX-2, iNOS, annexin-A1 and TGF-β1 as well as serum contents of TGF-β1, TGF-β2, and TGF-β3 were determined by real-time PCR or Luminex platform, respectively. Gastric mucosal PGE₂ content was determined by ELISA.

Results

Pretreatment with AP-39 (0.02 mg/kg i.g.) reduced gastric damage area induced by both, aspirin or ethanol with accompanied increased in GBF level. AP-39 decreased upregulated gastric mucosal mRNA expression for pro-inflammatory iNOS and maintained upregulated mRNA expression for anti-inflammatory annexin-A1 in gastric mucosa exposed to aspirin or ethanol. AP-39 decreased serum concentration of TGF-b1 and TGF-b2 but did not affect PGE₂ content in gastric mucosa administered with aspirin or ethanol. NC-AP-39 did not prevent gastric mucosa in tested experimental models.

Conclusion

We conclude that mitochondria-targeting and H₂S-releasing AP-39 applied i.g. exerts gastroprotective effect dose-dependently affecting gastric microcirculation. This compound seems to be promising for the further studies related to the role of hydrogen sulfide in regulation of mitochondrial complexes activity in pathophysiology of GI tract.

Disclosure

Nothing to disclose

10.1177/2050640620927345

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.5

P0006 Tracking The Somatic Gastric Cancer Tissue Mutations in The Blood: Proportion of The Patients with Detectable Alterations and Association with Oncoproteins

G Streleckiene ^1,^✉, M Forster ², K Balciute ¹, J Kupcinskas ³, L Kupcinskas ^1,⁴, J Skieceviciene ¹

Introduction

Gastric cancer (GC) is one of the most common and lethal oncological diseases of the gastrointestinal tract worldwide (Ferlay et al. 2015). Determination of specific and individual molecular multi-layer “signatures” has been shown to be pivotal for prediction, diagnosis and monitoring of various cancers, with implications for precision medicine (Cohen et al. 2018). Since the discovery of the circulating plasma cell-free DNA (cfDNA) the origin and characteristics of cfDNA were extensively studied. It was shown that cfDNA could harbour genetic aberrations from malignant tissue. However, there is a lack of comprehensive studies conducted in GC.

Aims & Methods

GC tissue and blood were collected from 30 patients who were recruited at the Department of Gastroenterology, Lithuanian University of Health Sciences Hospital. Tumour tissue samples were obtained from the primary lesion of the resected specimen or biopsy and stored at -80 °C as a fresh-frozen sample. Peripheral blood was drawn at admission (before surgery), centrifuged and stored at -80 °C until DNA isolation. Genomic DNA form primary lesion was isolated using Qiagen miRNeasy Mini kit and DNA from white blood cells (WBC) was isolated using salting-out method. Total circulating nucleic acids from plasma were extracted using column based QIAamp Circulating Nucleic Acid isolation kit according to the manufacturers’ protocol. Whole exome sequencing (WES) was performed for GC patients’ tissue and paired WBC samples using IDT xGen Exome Research Panel and pair-end sequenced (2 x 100 bp) on NovaSeq 6000 platform. Targeted NGS using IDT xGen Custom Panel consisting of 38 gastric cancer-associated genes selected according WES results was performed for GC plasma cfDNA only. cfDNA libraries were pair-end sequenced (2 x 150 bp) on NovaSeq 6000 platform. Serum level of oncoproteins (CEA, CA19-9 and CA72-4) was measured with enzyme-linked immunosorbent assay (ELISA) in patients’ serum upon admission to the hospital.

Results

After WES was performed for GC tissue and normal WBC samples, in total for 23 of 30 patients (76.7 %) mutations associated with GC were determined. The most frequently mutated genes in our study were TP53, FAT4, GLI3,APC, KMT2C, SYNE1, EPHB1, PIK3CA, and TRRAP. Matching tissue and cfDNA alterations were detected for 14 of 23 (60.9 %) GC patients. A total of 121 variants in cell-free DNA, 202 variants in tumour samples and 40 matching alterations were detected. Tissue matching alterations in plasma were detected in genes: TP53, ERBB2, FAT1, MLH1, FAT4, SPEN, KMT2C, MUC16, ACVR2A, ERBB4, PREX2, and SYNE1. Matching tumour and plasma alterations were detected significantly more often in samples of the patients with larger tumours (55.6 % and 10.0%, T3-T4 and T1-T2 respectively, p=0.018). Number of detected alterations moderately correlated with age (R=0.38, p=0.048; R=0.47, p=0.012; and R=0.40, p=0.035; respectively number of matching alterations; tissue and plasma alterations). Specific mutations and levels of oncoproteins were analysed for discriminating T and M status. Levels of CEA correlated with total cfDNA yield (R=0.38, p=0.041) and was observed in higher levels for poorly differentiated ad-enocarcinoma cases (p=0.045).

Conclusion

Our results show, that tissue and cfDNA matching mutations were mostly detected for GC patients with larger tumours and in combination with different molecular analytes may enable cfDNA analysis for monitoring of the GC patients’ disease state.

Disclosure

Nothing to disclose

References

1.Ferlay Jacques et al. 2015. “Cancer Incidence and Mortality Worldwide: Sources, Methods and Major Patterns in GLOBOCAN 2012.” International Journal of Cancer 136(5): E359–86. [DOI] [PubMed] [Google Scholar]
2.Cohen Joshua D. et al. 2018. “Detection and Localization of Surgically Resectable Cancers with a Multi-Analyte Blood Test.” Science 359(6378): 926–30. [DOI] [PMC free article] [PubMed] [Google Scholar]

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.6

P0007 Leukaemia Inhibitory Factor Signalling For Targeting Cancer Stem Cells in Gastric Adenocarcinoma

L Seeneevassen ^1,^✉, J Giraud ¹, S Molina-Castro ², E Sifré ¹, C Tiffon ¹, C Beauvois ¹, C Staedel ³, F Megraud ^1,⁴, P Lehours ^1,⁴, O Martin ¹, H Boeuf ⁵, P Dubus ^1,⁴, C Varon ¹

Introduction

Cancer stem cells (CSCs) present intrinsic chemo-resistance mechanisms contributing to tumour maintenance and recurrence, making their targeting of utmost importance in cancer therapy. The Hippo pathway has recently been implicated in gastric CSC properties. and some studies have shown that it can be regulated by Leukaemia Inhibitory Factor Receptor (LIFR) and its ligand LIF. Interestingly, the impact of LIF on gastric CSCs has never been investigated. Consequently, this study aimed to determine the effect of LIF on CSC phenotype and properties in GC cell lines and patient derived xenograft (PDX) cells.

Aims & Methods

RTqPCR, 3D tumoursphere assays as well as immunofluorescence analysis were used to decipher the effect of LIF treatment on gastric CSC markers expression, tumoursphere formation and regulation of the Hippo pathway and LIF/LIFR canonical JAK/STAT pathway were evaluated.

Results

Results indicate that LIF treatment decreased gastric tumorigenic and chemo-resistant CSC population, in both GC cell lines and PDX cells. in addition, LIF increased activation of LATS1/2 Hippo kinases thereby decreasing downstream YAP/TAZ nuclear accumulation, TEAD transcriptional activity and target gene expression. LIF anti-CSC effect was reversed by Hippo kinase inhibition but not by JAKSTAT inhibition, highlighting the opposite effects of these two pathways downstream LIFR.

Conclusion

In conclusion, this study shows for the first time that LIF displays anti-CSC properties in GC and relates this effect to the activation of Hippo kinases LATS1/2. LIF treatment could in fine constitute a new CSCs-targeting strategy to help decrease relapse cases and bad prognosis in GC.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.7

P0008 Can Neutrophil-To-Lymphocyte Ratio (Nlr) Be A Simple Predictive Marker For Gastric Intestinal Metaplasia?

U Kutluana ^1,^✉

Introduction

Gastric intestinal metaplasia (GIM) and gastric atrophy (GA) are pre-neoplastic lesions that can lead to gastric cancer (GC). The diagnosis of GIM and GA usually based on endoscopic and histopathological findings (1). Nowadays, there are no recognized good biomarkers of GIM and GA. The neutrophil-to-lymphocyte ratio (NLR) is an economical, effective, and repetitive indicator of inflammation (2). in this study, we aimed to comparatively evaluate red cell distribution width (RDW) and NLR values in cases with GIM, GA and chronic gastritis, and to show the increased NLR in GIM.

Aims & Methods

88 patients with GIM and 48 patients with GA and 64 patients with non-atrophic non-metaplastic gastritis were included in the study. NLR and RDW levels were measured in patients and controls.

Results

NLR levels were significantly higher in patients with GIM than in controls (p < 0.05). There was no significant difference in NLR levels in patients with GA and controls. There was no significant difference in RDW levels between groups. NLR level was correlated positively with presence of GIM (p < 0.05), H.pylori presence in GIM and GA (p < 0.05), and menopause (p < 0.05). A multiple logistic regression analysis showed the presence of GIM was predictor for elevated NLR (p < 0.05). According to the ROC curve analysis, the best cut-off NLR value to differentiate between patients with GIM from GA and/or controls was ≥2.92 (p < 0.05).

Conclusion

NLR is significantly higher in patients with GIM. NLR can be an independent determinant factor for GIM.

Disclosure

We have no conflict of interest

References

1.Eshmuratov A., Nah J.C., Kim N., Lee H.S., Lee H.E., Lee B.H. et al. The correlation of endoscopic and histological diagnosis of gastric atrophy. Dig Dis Sci 2010; 55: 1364–75. PMID: 19629687 [DOI] [PubMed] [Google Scholar]
2.Sato Y., Gonda K., Harada M., Tanisaka Y., Arai S., Mashimo Y. et al. Increased neutrophil-to-lymphocyte ratio is a novel marker for nutrition, inflammation and chemotherapy outcome in patients with locally advanced and metastatic esophageal squamous cell carcinoma. Biomedical Reports 2017: 7; 79–84. PMID: 28685065 [DOI] [PMC free article] [PubMed] [Google Scholar]

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.8

P0010 An Inflammatory Tumour Microenvironment Is Associated with Poor Response To Neo-Adjuvant Chemoradiotherapy and Poor Prognosis in Oesophageal Adenocarcinoma

W Koemans ^1,^✉, J van Dieren ², J Van den Berg ³, G Meijer ³, P Snaebjornsson ³, M Chalabi ⁴, F Lecot ⁵, R Riedl ⁶, I Hofland ⁷, A Broeks ⁷, F Voncken ⁷, M Sosef ⁹, J van Sandick ¹, L Kodach ¹⁰

Introduction

Oesophageal adenocarcinomas (OAC) are relatively unresponsive to neo-adjuvant chemoradiotherapy (nCRT). The mechanism of a poor response to nCRT is not yet understood. One critical factor in the (non-)responsiveness to nCRT might be an immunosuppressive tumour microenvironment (TME). in this study, TME characteristics associated with a poor response to nCRT in OAC patients were investigated.

Aims & Methods

To study TME characteristics post-nCRT surgical resection specimens from 123 OAC patients and pre-nCRT biopsies from 42 patients were analysed using immunohistochemistry for immune cell subsets. The association between TME parameters and response to nCRT was studied, as well as the association between TME parameters and patient survival. in addition, characteristics in pre-nCRT and post-nCRT samples were compared.

Results

Non-responsive tumours showed a higher immune infiltrate density compared to responsive tumours in post-nCRT tumour samples, with a higher density of CD3+ T-cells (p< 0.001), CD8+ T-cells (p=0.001), FOXP3+T-cells (p=0.02) and CD20+ B-cells (p=0.006) (Table 1). The ratio between the different subsets of immune cells was not different between responders and non-responders. Non-responders showed more frequently PD-L1 expression compared to responders (59% versus 23%, p< 0.001). A high CD8 T-cell infiltration was significantly associated with a worse patient survival compared to a low CD8 T-cell infiltration. The PD-L1 status was discordant between pre- and post-CRT samples in 15 of 40 (38%) patients.

[Table 1]

		Responders n=62		Non-responders n=61		p-value
mean CD3+ count/mm2		1324		2370		<0.001
mean CD4+ count/mm2		442		827		<0.001
mean CD8+ count/mm2		641		1126		0.001
mean FOXP3+ count/mm2		182		261		0.024
mean CD20+ count/mm2		416		717		0.006
CD8+/CD3+ ratio		0.51		0.46		0.93
FOXP3+/CD3+ ratio		0.14		0.13		0.10
PD-L1 expression*	negative	46	77%	25	41%	<0.001
	positive	14	23%	36	59%

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Conclusion

Following results of this study, an ‘immune-inflamed pheno-type’ and an immunosuppressive TME identify OAC patients refractory to nCRT, suggesting that immunotherapy may be a valuable alternative or additional treatment option for this group of patients.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.9

P0011 Anti-Inflammatory Effect of Ev (Extracellular Vesicles) Isolated From Bifidobacterium Breve in Raw264.7 Macrophage

D-H Lee ^1,^✉, JH Kim ², Sung K Ki ², C-M Shin ³, H Yoon ⁴, YS Park ⁴, N Kim ⁴, EJ Lee ⁴, YJ Kim ⁴

Introduction

Bifidobacterium breve (B. breve) secrete extracellular membrane vesicles (EV), which contain DNA, protein, and cell-wall components. EV is involved in microbiota-host cell communications in various biological systems. It was also reported EVs from B. breve can prevent intestinal inflammation through the induction of intestinal IL-10-producing Tr1 cells. in this study, we tested whether EV isolated from B. breve has an anti-inflammatory effect in LPS-induced inflammation.

Aims & Methods

B. breve was isolated from a human fecal sample, and it was cultured over 48 hours at 37°C under anaerobic conditions. After cultivation, the culture medium was centrifuged, subsequently, the supernatant was collected and concentrated. To measure whether the EV affects the viability of the Raw264.7 cell line, WST-1 analysis was used. NO (nitric oxide) concentration involved in immunity and inflammation was investigated in the cell line. ELISA was used to measure the production of inflammatory cytokine.

Results

The anti-inflammatory effect of EV isolated from B. breve was confirmed in Raw264.7 cell line. All experiments about EV treatment were under conditions of LPS-stimulation. When the pre-stimulated macrophages were treated with the EV, the concentration of NO, inflammatory factor, was significantly reduced than control. The EV (1ug/ml) treatment group (59.0±3.46 uM/L, p value vs positive = 0.012) had a 13% lower NO value than the positive control group (67.7±8.58 uM/L). It was also significantly reduced the TNF (tumor necrosis factor) level (40%, p value vs positive = 0.0029) of EV (1ug/ml) treatment group under the same conditions. However, IL-6 (interleukin-6) level (165%, p value vs positive = 0) which acts as both the anti-inflammatory factor and pro-inflammatory factor was increased. in this condition, cell viability was not different between EV treatment group and control group.

Conclusion

EV isolated from B. breve had an anti-inflammatory effect in the macrophage of inflammatory condition induced by LPS. These results suggested the potential that just EV alone without whole live form probi-otics could help suppress the inflammation.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.10

P0012 A Risk-Based Diagnostic Algorithm Optimizes The Management of Caustic Intake

Pardo AM Sánchez ^1,^✉, J Tosca ¹, R Villagrasa ¹, A Sanahuja ¹, B Herreros ², I Pascual-Moreno ¹, MP Mas Mercader ¹, M Minguez Pérez ¹

Introduction

Caustic ingestion is a potentially severe condition and identifying patients with a worse prognosis is essential to guide the treatment. Some authors recently proposed the use of computed tomography (CT) as the first test after every caustic intake, instead of endoscopy (1); however, these studies are based on samples from severe patients and their conclusions may not be completely inferred to the general population. An optimal diagnostic algorithm, based on the analysis of the different prognostic markers, would allow to detect severe cases and reduce the number of diagnostic tests.

Aims & Methods

Aims

1.
To identify risk factors for poor evolution of caustic intake in order to develop a diagnostic algorithm based on these predictive factors.
2.
To evaluate its diagnostic accuracy and to compare this algorithm to a CT-based strategy.

Methods

A prospective cohort study was designed to include all patients older than 15 years attended on Clinical University Hospital of Valencia after a caustic intake, between 1995 and 2020.

The main variable is the adverse outcome, defined as any of these three conditions:

-
Intensive care unit (ICU) admission.
-
Emergency surgery.
-
Death.

The intensity of the association of clinical, analytical, endoscopic and radiological variables with the adverse outcome was evaluated; a logistic regression analysis was therefore performed to identify independent risk factors for poor outcome and to develop a diagnostic algorithm based on the risk of poor evolution. Multiple imputation was used to address the missing data.

The diagnostic performance of this algorithm was assessed and finally, the number of tests required by this algorithm were compared with those of a CT-based strategy (1).

Results

509 cases of caustic ingestion were included during this period. The variables predicting poor outcome were: a high volume intake (>200 ml) or a strong pH substance (OR 3.0, 95%CI 1.6-5.9), oropharyngeal and laryngeal lesions (OR 2.1, 95%CI 1.1-4.1), relative neutrophilia (OR 5.4, 95%CI 3.4-8.6), metabolic acidosis (OR 17.5, 95%CI 10.7-28.5) and the grade of endoscopic injury according to Zargar's grade (OR 5.1, 95%CI 4.0-6.5).

In case of low-volume ingestion of weak caustic (< 200 mL), the risk of adverse outcome, in the absence of oropharyngeal lesions, is 0% in our series. Neutrophilia (≥75%) and acidosis (pH< 7.35) also predict the risk of poor outcome after caustic intake: in their absence, the risk of unfavorable evolution is low (OR 0.0, 95%CI 0.0-0.1), medium if one of them exists (OR 23.3, 95%CI 9.1-59.8) and high if both are present (OR 73.2, 95%CI 28.4-188.6).

The diagnostic algorithm based on these variables has an overall 92.5% sensitivity, 95.4% specificity, 76.5% positive predictive value and 98.8% negative predictive value for any adverse outcome (Table 1).

Table 1.

[Diagnostic accuracy of the algorithm]

	Sensitivity (%)	Specifity (%)	Positive predictive value (%)	Negative predictive value (%)
ICU admission	92.1	94.5	71.6	98.8
Surgery	100	86.1	19.8	100
Death	96.4	88.1	33.3	99.8
Any outcome	92.5	95.4	76.5	98.8

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According to this algorithm, 46.2% of patients would not require any examination, 53.8% would need a blood test, 11.5% a CT scan and 35.7%, an endoscopy; on the other hand, according to a CT-based strategy, CT would be performed in 100% of patients and endoscopy in 23.6%.

Conclusion

A risk-based diagnostic algorithm can reliably predict the outcome of caustic ingestion and reduce the number of tests of a CT-based strategy.

Disclosure

Nothing to disclose

References

1.Lancet 2017; 389: 2041–52. [DOI] [PubMed] [Google Scholar]

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.11

P0013 Cryptogenic Esophageal Strictures: Can The Dermatologists Help Us?

S Oumrani ^1,^2,^✉, V Seta ³, E Abou Ali ^2,⁴, A Belle ⁴, R Coriat ^2,⁵, S Chaussade ^2,⁴, N Dupin ^2,³, M Barret ^2,⁴

Introduction

Esophageal strictures can be associated with cryptogenic esophagitis, sometimes termed esophagitis dissecans or lymphocytic esophagitis. This endoscopic presentation condition is heterogeneous and associated with alcohol and tobacco consumption, and dermatologi-cal conditions, such as lichen planus or auto immune bullous dermatosis. Endoscopic findings include a thickening of the esophageal mucosa, a narrowed esophageal lumen and mucosal sloughing, spontaneously or following a mucosal biopsy. We aimed to assess the prevalence of derma-tological conditions in patients with a cryptogenic esophageal strictures.

Aims & Methods

All patients identified with a cryptogenic esophagitis associated with dysphagia revealing an esophageal stricture were identified from a prospective database. These patients were scheduled for a workup including clinical evaluation with a gastroenterologist and a dermatologist, blood tests, skin biopsies, and upper gastrointestinal endoscopy with mucosal biopsies.

Results

Twenty-three patients, of which 14 women (61%), with a median (IQR) age of 67 years (58-80.5) were included. The median time from dysphagia onset was 7 years (4-11.5).

All patients presented with dysphagia at diagnosis and 30% had lost weight. The endoscopic findings were a single esophageal stricture in 56% of the cases, localized in the upper third in 83% of the cases. Mucosal sloughing was described in 26% of the cases and ulcers in 34% cases. Eighty-seven percent of the patients received endoscopic treatment by repeated dilatations for 90% and local steroid injection for 25%. Esophageal biopsies concluded to lichen planus aspect in 30% of the cases, parakeratosis in 17% of the cases, lymphocytic esophagitis in 17%. For 12 of 23 patients (52% of patients), oral involvement (n = 11), skin lesions (n = 7) or vulvo-anal lesions (n = 8) were found on dermatological examination. Six patients received systemic treatment, based on corticosteroids for all patients, immunosuppressive drugs for 2 patients and plasmapheresis for one patient. Skin biopsies concluded to a lichenoid aspect for three patients and inflammatory exocytosis was described for 4 patients. One patient had a positive direct immunofluorescence on skin biopsy, leading to diagnose bullous pemphigoid. This patient also had positive anti-basement membrane antibodies while the anti-BP 180 and 230 antibodies were negative in all patients for whom it was sampled (n = 11).

Conclusion

Cryptogenic esophageal strictures are a challenge to the gastroenterologist because of the poor contribution of mucosal esophageal biopsies and the lack of standardized and effective treatment. in our experience, dermatological evaluation helped in 50% of cases to introduce a systemic treatment leading to reduce the frequency of endoscopic treatments.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.12

P0014 Natural History of Autoimmune Atrophic Gastritis: A Retrospective, Tertiary Centre Experience From A High-Risk Area For Gastric Cancer

M Garrido ^1,^✉, A Oliveira ², I Pedroto ^1,², R Marcos-Pinto ^1,²

Introduction

Autoimmune atrophic gastritis (AAG) is a chronic inflammatory condition that results in a progressive replacement of the corpus parietal cell mass by atrophic and metaplastic mucosa. It is considered a pre-malignant condition due to increased risk of gastric neuroendocrine neoplasms (g-NENs) and gastric adenocarcinomas. Hence, endoscopic surveillance is recommended every 3 to 5 years. However, data on clinical outcomes in histologically confirmed AAG is scarce, particularly in high-risk regions for gastric cancer, as the north of Portugal.

Aims & Methods

To characterize the clinical, analytical, endoscopic and pathological phenotype of patients with AAG and to evaluate the risk of progression of pre-malignant gastric conditions and the occurrence of gastric neoplasia during the follow-up (f-up) by a retrospective identification of adult patients with positive anti-gastric parietal cell (anti-GPC) and/or anti-intrinsic factor (anti-IF) antibodies, from 01/2014 to 08/2019 (n=585) and inclusion of those with histologic findings consistent with AAG.

Results

A total of 145 patients (pts) were included (71.7% female sex) with a mean age of 55.8±15.1 years. 27.6% had another autoimmune disease, 11.9% (14/117) reported a family history of gastric adenocarcinoma and 43.1% (59/137) infection with H. pylori. 70.3% showed anti-GPC (+) and 5.5% anti-IF positivity alone; 24.1% showed both autoantibodies (+). At diagnosis, 67.6% had anaemia, 62.8% vitamin B12 deficiency (19.2% PA) and 46.2% iron depletion.

At the first endoscopic evaluation (T-0), gastric body biopsies revealed intestinal metaplasia (IM) in 79.7% and chronic atrophic gastritis (CAG) in the remaining. Antrum biopsies found premalignant conditions in 44.2% (23.9% CAG; 20.3% IM). Gastric dysplasia (g-DYS) was diagnosed in 5 (3.45%) pts (4 low-grade; 1 high-grade dysplasia; up to 22mm). Entero-chromaffin like (ECL) cell hyperplasia was found in 9 (6.2%) and ECL dysplasia in 2 (1.4%) pts. 13 g-NENs were diagnosed in 11 (7.6%) pts (most up to 5mm (n=10), all grade 1 (G1) and stage I g-NENs, except for one 13mm g-NEN, G1, stage II, resected by endoscopic submucosal dissection). Pts had a mean clinical f-up time of 5.06±3.95 years. 84 pts were submitted to endoscopic f-up during a mean time of 4.24±2.87 years. During this period, a significant progression of gastric pre-malignant conditions was not found. No g-DYS or adenocarcinoma were detected. Overall, 18 g-NENs were detected (up to 7mm; 15 G1, 3 G2; all stage I) among 8 pts, including 13 g-NENs out of 5 patients with g-NEN at T-0. The mean time to g-NEN development was 44.8 months (maximum 81 months). The incidence rate of new g-NENs was 9.7 per 1000 person-years. 4 pts died, none related to AAG.

In bivariate analysis, both ECL hyperplasia (28.6% vs 7.6%, p=0.012) and dysplasia (100% vs 7.1%, p< 0.001) were associated with g-NETs. Pts with ECL hyperplasia had a 4.84 higher OR of developing g-NENs [CI 95% 1.28-18.24]. Male gender (9.8% vs 1.9%, p=0.033) and H. pylori infection (8.5% vs 1.3%, p=0.042) were associated with g-DYS.

Conclusion

ECL hyperplasia and dysplasia were associated with the development of g-NETs, whereas male gender and H. pylori infection were associated with gastric dysplasia. Overall, 14.5% of AAG pts developed gastric neoplasms (g-NEN 9.66%; g-DYS 3.45%). All g-NENs and gastric dysplasia were early lesions amenable to endoscopic management. There was no AAG related mortality during the median 5-year f-up time, confirming the overall benign disease course when support treatment and endoscopic follow-up are offered.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.13

P0015 Immune Response and Macrophage Phenotype Regulation in Gastroesophageal Reflux Disease with Pulmonary Manifestations

S Lyamina ^1,^✉, S Kalish ¹, I Malyshev ¹, I Maev ¹

Introduction

Respiratory system inflammation and Th1/Th2 immune response imbalance are the key components of pulmonary manifestations in gastroesophageal reflux disease (pGERD) pathogenesis. Immune response disorders and inflammation depend greatly on the combination of macrophage phenotypes (MPh) in respiratory tract. MPh is specified by the cell microenvironment and one of significant bivalent regulators in alveolar macrophages (AM) phenotypes is surfactant protein D (SP-D). So quantitative and qualitative SP-D analysis is one of the factors influencing macrophage phenotype and plasticity in pGERD patients.

Aims & Methods

This study evaluated pooled data of AM phenotype (AMPh) and plasticity and quantitative/qualitative composition of SP-D in broncho-alveolar lavage (BAL) in pGERD patients as compared to pGERD + asthma and healthy volunteers (HV). Pooled AMPh analysis in patients with pGERD (n=21, 44,46±3,52 y.o.), combination of pGERD and asthma (n=19, 47,62±4,38 y.o.) and healthy volunteers (HV) (n=10, 51,83±3,52 y.o.) included receptor (CD80/CD206) and secretory characteristics (pro-/anti-inflammatory/bivalent M1/M2 cytokines) in AM culture medium assessed by flow cytometry (Beckman Coulter FC500). Quantitative SP-D analysis in BAL was performed by ELISA. Qualitative SP-D oligomeric forms were assessed by western blot analysis with tris-acetate gels (Invitrogen, NuPAGE, # EA03752BOX).

Results

Analysis of AM phenotype by M1/M2 ratio in patients with pG-ERD, pGERD with asthma vs. HV showed that pooledM1/M2 ratio of AM CD markers and cytokine production was 2.28 and 2.71, 0.86 and 0.93 vs. HV (1.0), respectively. The results indicate AMPh shift to M1 phenotype with predominate M1 plasticity in pGERD and to M2 phenotype with predominant M2 plasticity in pGERD+asthma as compared to HV. SP-D level in pGERD patients was 2.5 times decreased vs patients with pGERD+asthma (162.31±20.42 ng/ml vs 405.77±38.75 ng/ml, p< 0.05) and 3.7 times decreased vs. HV (162.31±20.42 ng/ml vs 600.54±46.22, p< 0.05). Qualitative oligomeric SP-D forms analysis showed predominance of monomeric forms both in pGERD and pGERD+asthma vs HV with monomeric and multimeric SP-D oligomers.

Conclusion

There are significant discrepancies in AMPh, AM plasticity and SP-D concentration and qualitative composition in pGERD, combination of pGERD and asthma and healthy volunteers. AMPh shift to M1 vs healthy and maximum decreased SP-D level with predominant monomeric forms are typical for GERD with pulmonary manifestations, whereas shift of AMPh to M2 and less decreasing SP-D level in BALF are specific for pGERD+asthma. Qualitative SP-D analysis showed no significant difference between pGERD and pGERD+asthma, but differed greatly in these groups as compared to healthy volunteers.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.14

P0016 Role of Mirnas in Gastric Atrophy, Autoimmunity and Disease Progression

G Maddalo ^1,^2,^✉, M Fassan ³, R Cardin ¹, F Pelizzaro ¹, F Farinati ¹

Introduction

MicroRNAs (miRNAs) are small non coding RNAs working as key regulators in biological processes. Their dysregulation seems to be involved in autoimmunity, inflammation and cancer. The autoimmune gastritis (AIG) and the multifocal H.pylori-related gastritis (MAG) are pre-neoplastic conditions eventually leading to gastric cancer with a different risk of transformation, being greater for MAG compared to AIG. Furthermore, in AIG the enterochromaffin cells hyperplasia, can further develop into gastric carcinoid, a neuroendocrine tumor (NET).

Aims & Methods

Based on evidence in the literature, we selected five specific miRNAs (miR-21, miR-155, miR-142-3p, miR-146, miR-223), involved in autoimmunity and neoplastic progression, in order to evaluate their tissue expression in chronic atrophic gastritis (AIG and MAG) and to compare their expression in patients without atrophic changes (controls). We wanted to evaluate, the different expression between AIG and MAG with the aim to investigate their possible pathogenic role in autoimmune etiology. Finally, we analyzed if a different miRNAs expression could correlate with OLGA stages, identifying a possible biomarker of neoplastic progression.

We performed an upper GI endoscopy in all patients with biopsy sampling, with staging by experts pathologists according to the OLGA. We used a qRT-PCR technique (quantified by the Livak method) to determinate the expression of miRNAs. Statistics were performed by the Kolmogorov-Smirnov test and using parametric and non parametric tests.

Results

We studied 10 AIG, 10 MAG and 10 controls.

•
Analyzing the expression of each single miRNA among AIG, MAG and controls, a significant difference was obtained for all miRNAs (p< 0.05).
•
Analyzing AIG and controls all miRNAs were overexpressed
•
(p <0.008), as well as in the comparison between MAG and controls (p <0.05). Only miR-155, -142, -223 were significant overexpressed in AIG vs MAG (p < 0.05).
•
No differences were found in miR-21 and miR-146 (p=ns).
•
We observed a significant statistical difference in the miR-21 expression when comparing controls with all atrophic patients (both AIG and MAG) at early (OLGA I-II) and advanced (OLGA III) atrophic stages (p <0.0001).

Conclusion

MiRNA are overexpressed in gastric atrophy with chronic inflammation, assuming their role in the immunity-cancer axis. All miRNAs, excepted miR-21, were overexpressed in AIG compared to MAG. Especially for miR-155, -142, -223 we can hypotesize a pathogenetic role in AIG, as they are involved in the control of Treg-Th17.

Homeostasis loss has already been postulated as a possible pathogenetic event in AIG.

The overexpression of miR-21 in MAG vs AIG could be explained by the greater risk of gastric cancer.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.15

P0020 Fecal Microbiota Transplantation Results in Both Engraftment and Loss of Bacteria in Recipients

F Cold ^1,^2,^3,^✉, PD Browne ¹, S Günther ⁴, SI Halkjær ², AM Petersen ^2,⁵, AH Christensen ³, LH Hansen ¹

Introduction

Decreased diversity of the fecal microbiota is recognized as a part of gut dysbiosis [1]. Hence treatments increasing microbial diversity, such as fecal microbiota transplantation (FMT), have attracted much attention in recent years.

In many studies FMT has increased the fecal alpha-diversity, a sign of possible engraftment of new bacteria, which has been correlated to improved clinical outcomes [2]. The loss of bacteria from the gut microbiota caused by the introduction of new bacteria through FMT has not been investigated.

Aims & Methods

The aim of our research was to investigate the engraftment and loss of bacteria caused by FMT.

To investigate this we analysed samples from a previously published placebo-controlled randomized clinical trial investigating the effects of 12 days of 25 daily multidonor FMT capsules treating 52 patients with IBS (Irritable Bowel Syndrome) [3].

We tested fecal samples from baseline, and at 15 days, 1, 3 and 6 months following the commencement of treatment using 16S RNA sequencing. We redid the analysis using Amplicon Sequence Variants (ASVs) instead of (97% clustered) OTUs. The patients were divided into FMT and Placebo responders and non-responders based on the predefined definition of response of at least a 50 points reduction in the IBS-severity symptom score (IBS-SSS) after 3 months. Criteria were composed to define ASVs as present or absent in a group of samples in a manner accounting for (i) differences in numbers of samples in each group and (ii) the differences in the numbers of sequencing reads per sample. An ASV was defined as engrafting when it was present in the Donors, was absent in the patients at baseline and was present in the patients at a following time-point. An ASV was defined as lost when it was present in a group of samples at baseline and not present at a later time-point.

Results

The FMT patients acquired (15 to 18 depending on time-point) ASVs present in the donors while the placebo patients didn't (0 to 1). The FMT group also lost (43 to 66) ASVs at a much higher rate than did the Placebo group (13 to 24 ASVs). The FMT responders and the FMT non-responders acquired similar numbers of ASVs, but the FMT responders seemed to lose ASVs at a higher rate (67 to 101) than the FMT non-responders (35 to 46). Looking at ASVs that were found engrafted at all time-points, Prevotella copri accounted for 2 of the 8 ASVs in the FMT group, 7 of the 13 ASVs in the FMT responders and 2 of the 12 ASVs in the FMT non-responders.

Conclusion

FMT induced both engraftment and loss of bacteria in the recipients. in particular Prevotella copri had the potential to engraft into the FMT responders’ microbiota. Whether the loss or engraftment of certain bacteria are correlated with beneficial clinical effects in IBS patients is still unanswered.

Disclosure

Nothing to disclose

References

1.Kriss M., Hazleton K.Z., Nusbacher N.M. et al. Low diversity gut microbiota dysbiosis: drivers, functional implications and recovery. Current opinion in microbiology. 2018. Aug; 44: 34–40. doi: 10.1016/j.mib.2018.07.003. PubMed PMID: 30036705; PubMed Central PMCID: PM-CPMC6435260. eng. [DOI] [PMC free article] [PubMed] [Google Scholar]
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United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.16

P0022 Circulating Microbiome Singatures in Patients with Gastric Cancer

R Gedgaudas ^1,^2,^✉, J Skieceviciene ², A Franke ³, M Urba ², L Kupcinskas ^1,², J Kupcinskas ^1,²

Introduction

Gastric cancer (GC) is one of the most lethal gastrointestinal malignancies. Up until now there are no reliable biomarkers for early identification of GC patients. Strong evidence suggests mucosal microbi-ome to play a crucial role in carcinogenesis. Emergic studies shows that microbial DNA can be detected in the blood circulation and may represent the microbiome of distant sites or serve as potential biomarkers of various dieases.

Aims & Methods

In this study we have aimed to detect changes in circulating blood microbiome in gastric cancer patients. Our study was conducted in Department of Gastroenterology of Lithuanian University of Health Sciences, Kaunas Clinics and included a cohort of 31 patients with GC and 41 healthy control (HC) subjects. 16S rRNA gene sequencing of V1-V2 variable regions was used to determine bacterial composition of blood plasma samples.

Results

Taxonomic composition analysis at the phylum level revealed that blood microbiome in both GC patients and HC subjects was predominated by Proteobacteria, Bacteroidetes, Actinobacteria and Firmicutes. a-diversity was significantly increased GC patients. Bacterial community structure showed significant clustering between HC and PH patients. Differential abundance analysis revealed Escherichia/Shigella, Pepto-niphillus, Polynucleobacter to be associated with gastric cancer. Levels of Paracoccus was positively correlated while Bacteroides, Ruminoccocus, Oscillibacter were inversely correlated with TNM stage. Random forrests classification between GC and HC based on circulating microbiome profiles yielded an area under receiver operating characteristic curve of 0.7.

Conclusion

Circulating blood microbiota comprises of four main phyla Proteobacteria, Bacteroidetes, Actinobacteria and Firmicutes. Circulating microbiome of GC patients is significantly altered in comparison to HC subjects.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.17

P0023 Microbiome Analysis of Gastric Cancer Tissue At Dna and Rna Levels

D Nikitina ^1,^✉, R Vilchez-Vargas ², LV Jonaitis ³, M Urba ³, J Kupcinskas ³, A Link ², J Skieceviciene ¹

Introduction

Gastric cancer (GC) is still one of the most common and fatal cancers worldwide. The pathogenesis of GC is involved with Helicobacter pylori infection, but only 1-2% of those infected develop this tumor. Recent studies have shown that in addition to H.pylori in the stomach, there are many other potentially pathogenic bacteria whose composition is altered in GC [1][2].

Aims & Methods

The aim of this study was to perform a microbiome analysis of gastric biopsies at the DNA and RNA levels in GC. in total, 337 samples from 91 individuals were included in this study, 23 of them were control individuals and 68 patients with GC. Biopsies were taken from damaged tumor mucosa and tumor adjacent mucosa at least 5 cm from the tumor tissue. From all biopsies RNA and DNA were extracted. RNA was reverse transcribed into cDNA. V1-V2 region of bacterial 16S rRNA gene from all samples were amplified and sequenced on an Illumina MiSeq platform. To construct sample-similarity matrices abundances of taxonomic ranks in each sample type were used by applying Bray-Curtis algorithm. For significant differences between groups Permutational multivariate analysis of variance (PERMANOVA) and Mann-Whitney test followed by false-discovery rate test were used.

Results

After taxonomic annotation, 10496 phylotypes, belonging to 463 genera and 22 different phyla were identified. No significant differences between tumor and tumor adjacent tissue biopsies both at the DNA and RNA levels were identified. Significant differences were found only in comparison with the control group. We detected 15 and 27 bacteria in GC which significantly differed from the control group at the DNA and RNA levels, respectively. in control group most abundant bacteria made up to 18% at the DNA level and up to 40% at the RNA level. in GC group most abundant bacteria increased till 99% at the DNA level and 100% at the RNA level. The bacterial communities in the tumor tissue biopsies were characterized by decreased richness and heterogeneity (measured by the Shannon and Simpson indexes) than in control group samples. Some of the bacteria (Actinomyces, Atopobium, Prevotella, Veillonella) were present at higher abundance at the DNA level than at the RNA level. H.pylori were present in tumor adjacent tissue biopsies at higher abundance compared to tumors tissue biopsies and even more compared to healthy tissue biopsies.

Conclusion

In a microbiome analysis of GC differences were found between tumor tissue biopsies and control group, which differed not only in bacterial composition, but also in number and diversity. An microbiome analysis of GC and control groups at the RNA level revealed more bacteria with less abundance.

Disclosure

Nothing to disclose

References

1.Engstrand L., & Lindberg M. (2013). Helicobacter pylori and the gastric microbiota. Best practice & research Clinical gastroenterology, 27(1), 39–45. [DOI] [PubMed] [Google Scholar]
2.Schulz C., Schütte K., Koch N., Vilchez-Vargas R., Wos-Oxley M. L., Oxley A. P., … & Pieper D. H. (2018). The active bacterial assemblages of the upper GI tract in individuals with and without Helicobacter infection. Gut, 67(2), 216–225. [DOI] [PubMed] [Google Scholar]

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.18

P0024 The Microbiome of The Esophagus, Stomach and Duodenum in Patients with Gastroesophageal Reflux Disease - Pilot Study

L Kunovsky ^1,^2,^✉, J Lochman ^3,⁴, Z Kala ⁵, J Dolina ¹, R Kroupa ¹, V Prochazka ², T Grolich ², J Vaculova ¹, P Litzman ¹, T Deissova ³, M Hanslianova ⁶, P Jabandziev ^7,⁸, O Slaby ⁸, L Izakovicova Holla ^3,⁹, P Borilova Linhartova ^3,⁹

Introduction

These days gastroesophageal reflux disease (GERD) represents one of the significant health problems of western countries as a result of several lifestyle factors. Prolonged GERD leads to esophageal inflammation and significantly increases the risk of Barrett's esophagus (BE) and the subsequent development of esophageal adenocarcinoma (EAC). There is an association between the esophageal microbiome and several esophageal diseases. However, it remains unclear whether the change in microflora leads to esophageal disease, or if this is a side effect of the highly acidic environment created by GERD.

Our pilot study aimed to describe oral bacterial biota in patients with GERD and healthy controls from different parts of the esophagus, stomach and duodenum. Detailed microbiome analysis could contribute to early diagnosis and to the application of effective treatment in patients with GERD.

Aims & Methods

Tissue samples were taken from each patient with biopsy forceps from several sites in the esophagus, stomach and duodenum. From a total of 74 biopsy specimens obtained via endoscopic examination of 2 patients with GERD, 4 with BE, 4 with EAC and 6 healthy controls, nucleic acid was isolated using the All Prep DNA / RNA / miRNA Universal Kit (Qiagen). The composition of the bacterial community was analyzed by sequencing the 16S rDNA PCR products of the V3-V4 regions on the Illumina MiniSeq platform.

Results

The sequence provided 8,335,646 pair-end reads passing quality filters. To describe the bacterial community richness in the collected samples, their alpha diversity was estimated, calculated using normalized rarefaction values. Specific pathological conditions did not significantly change alpha diversity measures (Shannon's diversity 2.52 Control; 2.48 RE; 2.51 BE; 2.32 EAC); however, there was a trend towards decreased diversity in EAC samples. The relative abundances of the five most abundant phyla in each sample collected were estimated to describe shifts in the bacterial community structure with different conditions. On average, the five most commonly represented bacterial genera were: Firmicutes (39%), Proteobacteria (45%), Bacteroidetes (9%), Actinobacteria (3%), and Fuso-bacteria (1%). Comparison of bacterial communities made using a non-metric multidimensional scaling (NMDS) plot (based on Jaccard similarity, with 97% identity) shows an apparent clustering of esophagus and stomach/duodenum samples. Distribution of taxonomic abundances showed that esophagus samples were dominated by Streptococcus and Prevotella with a lower representation of Veillonella, as reported previously. On the other hand, we did not observe significant clustering of samples from individual pathological conditions but only an increasing trend in gramnegative taxa (Fusobacterium, Campylobacter) was found in esophagus samples from RE and BE patients. Further, an increase in taxa Campylo-bacter and Lactobacillus taxa was observed in the group of EAC patients.

Conclusion

In our pilot study, we demonstrated the feasibility of a testing procedure in clinical practice. Our findings are consistent with recent studies presenting the predominant colonization of the esophagus with the bacteria Streptococcus and Prevotella ans a lower proportion of Veillonella. Due to the small number of patients of the same age in the individual groups tested, we were not able to prove significant clustering in a metagenomic analysis. For this reason, we are currently conducting a more extensive study under physiological and pathological conditions in patients with GERD, whose results will be presented.

Disclosure

References

Pilato Di et al. The esophageal microbiota in health and disease. Annals of the New York Acasemy of Scienes. 2016; 1381(1): 21–33. [DOI] [PubMed] [Google Scholar]
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United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.19

P0025 Characteristics of Donors For Faecal Microbiota Transplantation of A High-Volume Stool Bank: A 7-Year Experience

G Ianiro ¹, S Bibbò ², L Masucci ³, L Quaranta ³, S Porcari ^2,^4,^✉, CR Settanni ², G Fancello ³, P Vaccarello ², F Scaldaferri ⁵, LR Lopetuso ⁶, E Bocchino ², P Palumbo ², M Sanguinetti ⁷, A Gasbarrini ², G Cammarota ²

Introduction

Donor screening is an essential step of the fecal microbiota transplantation (FMT) workflow. Over years, methods of screening have become stricter, based on evolving recommendations, and recruitment have become accordingly more difficult.

Aims & Methods

Our aim is to describe the characteristics of stool donors from the establishment of our FMT centre to date, along with changes in recruitment and screening protocol. All donors pre-screened (investigating their willingness to donate and potential logistical issues) and screened from July 2013 to May 2020 at our FMT centre were included. Our donor screening protocol was first based on available evidence and, from 2016, based on available guidelines. Its last version dates back to 2019, and includes: donor questionnaire; blood and stool testing; questionnaire and rapid stool assay at each donation. Demographics of all included subjects, as well as specific reasons for exclusion, were recorded.

Results

In the study period, five hundred and fifty-two potential donors were evaluated. of them, 238 were not available to donate because of age out of range, personal or logistic issues. of the 314 remaining potential donors, 183 failed the clinical questionnaire, mainly because of recent antibiotic use, medical comorbidities, elevated BMI. One-hundred and twenty-one donors underwent blood and stool testing. of them, 53 individuals were excluded, mainly because of positivity at stool culture of at rapid stool assay. Overall, only 78 of 552 potential donors (14%) were enrolled to donate.

Conclusion

In our FMT centre, only a small rate of potential donors were finally included to donate. Our results suggest that recruitment of stool donors for FMT can challenging if strict and rigorous screening protocols are followed. Stool donation should be promoted and encouraged among general population, and dedicated incentive to stool donors are advocated.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.20

P0026 Gastrointestinal Symptoms and Outcomes of Hospitalised Sars-Cov-2 Patients. A Retrospective Study From A Large University Hospital in The West Midlands, Uk

A Bannaga ^1,^2,^✉, M Tabuso ¹, A Farrugia ^2,³, S Chandrapalan ^1,², K Somal ¹, VK Lim ¹, S Mohamed ¹, G Jalayeri Nia ¹, J Mannath ¹, J Wong ⁴, A Noufaily ², B Disney ¹, RP Arasaradnam ^1,²

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a respiratory contagious infectious disease that lead to a global pandemic in a matter of few months. Gastrointestinal (GI) symptoms were reported between 3 to 61% in affected patients [1-5]. The pathogenic mechanism of SARS-CoV-2 is yet to be discovered.

Aims & Methods

This study aimed to look for GI symptoms and outcomes of hospitalised SARS-COV-2 patients. Between 24/01/20 to 13/04/2020, SARS-CoV-2 cases were searched. A case was defined by a positive real time - reverse transcriptase Polymerase Chain Reaction (RT-PCR) for viral RNA of SARS-CoV-2 from nasal swab/sputum. Data was analysed by both IBM SPSS and R statistics software. Covariates of interest were analysed using logistic regression.

Results

321 patients were identified. Age range was 14 to 104 years. Mean age was 68.95 years. The most commonly admitted patient with the disease was aged 80 years. There were 189 males (58.9%). Caucasian origin represented (77%), while the black, Asian, and minority ethnic (BAME) groups represented 23%. Mean body mass index (BMI) was 24.2 Kg/M². Commonest symptoms were dyspnoea (62.9%), fever (59.1%), and cough (56%). Abnormal chest radiograph was found in (58.6%). 4.3% had history of chronic liver disease and only 1.2% of patients had history of inflammatory bowel disease. At presentation, the gastrointestinal symptoms were reported in 38 patients (11.8%). in more detail; abdominal pain in 15 patients (4.6%), diarrhoea in 14 patients (4%) and nausea and vomiting in 15 patients (4.6%). 44 patients were admitted to intensive care unit (ICU) of these diarrhoea was present in 4.4% of the patients, while nausea, vomiting and abdominal pain were present in 2.2%. Mean admission time was 10.28 days. The overall mortality was 32.4%. There was significant correlation between increasing age and death (correlation coefficient of 0.330 and P=0.01). Regression analysis revealed that the non-survivors had lower albumin (median of 37, IQR 32.0 to 39.0 g/l) compared to survivors (median of 38, IQR 34.2-41 g/l) (P=0.002). Also, non-survivors had higher CRP levels (median of 129, IQR 51 to 222 mg/l) compared to survivors CRP (median of 61.5, IQR 25.7 to 125 mg/l) (P=0.000). The neutrophil lymphocyte ratio (NLR) was significantly higher in non-survivors (median of 7.2, IQR 4.6 to 13) compared to survivors (median NLR of 5.7, IQR 3 to 9) (P=0.028). However, when the logistic regression analysis was adjusted for age only CRP (P=0.000) and Albumin (P=0.005) were predictive of mortality while the NLR became non-significant (P=0.198) and the age adjustment revealed that NLR was actually increasing with age.

Conclusion

GI symptoms were not commonly reported during the presentation of SARS-CoV-2 patients. The disease had high mortality among hospitalised patients. GI symptoms did not seem to affect requirement for admission to ICU. CRP and albumin could be predictors of mortality.

Disclosure

Nothing to disclose

References

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United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.21

P0027 Predictive Factors of Rebleeding After Endoscopic Hemostasis in The Treatment of Gastroduodenal Peptic Ulcers in Japanese Patients

K Adachi ^1,^✉, N Ogasawara ¹, S Inoue ¹, Y Kawamura ¹, T Sugiyama ¹, T Yosimine ¹, Y Yamaguchi ¹, Y Hijikata ¹, M Ebi ¹, Y Funaki ¹, M Sasaki ¹, K Kasugai ¹

Introduction

Endoscopic hemostasis is the first treatment for acute upper gastrointestinal (UGI) ulcers, and it can avoid emergency surgery. However, it can be difficult to completely achieve in some patients, and excessive hemorrhage from UGI ulcers can be fatal. Endoscopic hemosta-sis is carried out for UGI bleeding (Forrest classification Ia, Ib and IIa) with high dose proton pump inhibitors or potassium-competitive acid blocker. Despite improvements in endoscopic hemostasis and pharmacological therapies, UGI ulcers repeatedly bleed in 10% to 20% of patients, and those without early endoscopic reintervention or definitive surgery might be at a high risk for mortality. Therefore, determining which factors are involved in rebleeding after an initial endoscopic hemostasis is extremely important for patients with bleeding UGI ulcers. in addition, understanding the factors that contribute to intractable or in sufficient initial endoscopic hemostasis is needed to advance the management of such ulcers.

Aims & Methods

This study aimed to determine the risk factors for intractability to initial endoscopic hemostasis. We analyzed 638 patients who underwent emergency endoscopic hemostasis for bleeding UGI ulcers (Forrest classification Ia, Ib and IIa) within 24 hours of arrival at our hospital between April 2000 and March 2019. We retrospectively documented the patients’ backgrounds, and evaluated the ulcer location, size of exposed vessels on the bottom of the ulcer size, and Forrest bleeding patterns. To determine the factors involved in intractability to the initial endoscopic hemostasis, we compared patients whose bleeding UGI ulcers were successfully treated with the hemostasis with those who were intractable.

Results

Durable hemostasis was achieved in 538 patients (84.3 %) by using initial endoscopic procedures. Ninety-six patients (15.0 %) with Forrest types Ia, Ib, and IIa at the second look endoscopy were considered intractable to initial endoscopic hemostasis. Two patients (0.4%) who underwent emergency surgery because of failure to the initial endoscopic hemostasis and three patients (0.4 %) who died right after the initial endoscopic hemostasis. Two patients caused heart failure and one patient caused bleeding death. Multivariate analysis indicated that shock upon admission (odds ratio [OR], 2.47; 95% confidence interval [CI], 1.35 to 4.51), hemoglobin upon admission < 8.0 mg/dl (OR, 1.71; 95% CI, 1.02 to 2.88), serum albumin upon admission < 3.3 g/dL (OR, 2.03; 95% CI, 1.16 to 3.55), exposed vessels with a diameter of ≥ 2 mm on the bottom of ulcer (OR, 2.54; 95% CI,1.60 to 4.03), and Forrest types Ia (OR, 1.83; 95% CI,1.04 to 3.23) predicted intractable endoscopic hemostasis.

Conclusion

Shock upon admission, hemoglobin < 8.0 mg/dL, serum albumin < 3.3 g/dL, exposed vessels ≥ 2 mm on the ulcer bottom, and Forrest types Ia were identified as independent risk factors associated with initial intractable endoscopic hemostasis in patients with peptic UGI bleeds. Careful observation after initial endoscopic hemostasis is important for patients at a high risk for incomplete hemostasis.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.22

P0029 Management of Upper Gastrointestinal Bleeding in A Swedish Hospital: The Use of Glasgow-Blatchford and Rockall Scores

M Milevska ¹, A Bajor ¹, N Mottacki ^2,^✉

Introduction

In Western Europe the yearly incidence of upper gastrointestinal (GI) bleeding is around 0.1%. Mortality is 3-14% per episode(1,2). Scoring systems stratify potential outcomes; the Glasgow-Blatchford score classifies patients as high-risk/low-risk for requiring endoscopic intervention and assists in determining the urgency of endoscopic investigation (3). The Rockall Score (4) includes pre-endoscopic and endoscopic variables to predict mortality. These scores are not widely used in Sweden.

Aims & Methods

We aimed to assess endoscopic intervention and mortality in patients with upper GI bleeding, and whether the use of scoring systems would have impacted management. Patients who underwent an oesophagogastroduodenoscopy (OGD) at our unit in 2016 were assessed and those with pre- or post-operative ICD10 codes of upper GI bleeding were selected. Demographics, hepatic pathology and comorbidities were documented as well as OGD reports (source of bleeding, interventions and repeat endoscopy during the same admission). Pre-operative Blatchford and Rockall scores were calculated and outcomes were assessed.

Results

We reviewed 2247 OGDs. 680 had bleeding as a suspected or postoperative diagnosis. 208 had verified bleeding on the OGD report. Patients were stratified as Blatchford < 6 points or > 6 points. There was no difference in age (66 vs. 68 years) or heart rate (94 vs. 90). Mean systolic blood pressure and Hb on admission were significantly lower in both patients requiring endoscopic intervention and in those with > 6 points (p < 0.05). Patients requiring intervention had an odds ratio of 2.2 (95% CI 1.2-4.1) of having Blatchford > 6 compared to others. All patients had a similar median delay between admission and OGD (1 day); in those with Blatchford > 6 fewer patients suffered longer delays (p < 0.05). 16 patients died during the admission; upper GI bleeding (and co-morbidities) was the cause of death in all. Positive predictive value increased with rising Rockall Score (14.7% at 8 points) but X2-testing did not show a significantly increased mortality even at a cut-off of 8 points. At this cut-off, mean systolic BP was lower and heart rate higher on admission than in those patients with Rockall < 8 (p < 0.05). At cut-offs of 6 and 4 points, sensitivity increased (81.3% and 100% respectively) but specificity (42.3% and 13.4%) and PPV (10.4% and 8.7%) decreased.

Conclusion

The Blatchford score is a better predictor of outcome than the Rockall score. Patients who would have exceeded the commonly used cut-offs for these scoring systems had deviated clinical markers (blood pressure, Hb and heart rate) which are almost universally measured at admission. Those patients in our study who would have had a higher Blatchford score were referred for more urgent investigation and intervention, suggesting that these scoring systems may aid in predicting the need for urgent endoscopy and intervention but are not vital for doing so.

[Patient characteristics and outcomes (*p<0.05 compared to all other patients)]

	All patients (n=280)	Blatchford > 6 (n=106)	Rockall > 8 (n=10)	Required intervention (n=77)	No intervention (n=131)
Median age (range)	71.5 (21-101)	70.5 (27-101)	84 (61-90)	71 (27-101)	72 (21-94)
Gender M/F	118/90	65/41	4/6	48/29	70/61
Blatchford score (median, range)	6 (0-13)	8 (6-13)	6.5 (1-12)	7 (0-13)	4 (0-12)
Rockall score (median, range)	6 (3-10)	6 (3-10)	9 (9-10)	6 (3-10)	6 (3-9)
Number of patients with melena	93 (44.5%)	54 (50.9%)	3 (30%)	36 (46.8%)	57 (43.5%)
Number of patients with syncope	21 (10%)	14 (13.2%)	2 (20%)	8 (10.4%)	13 (9.9%)
Number of patients with known hepatic disease	21 (10%)	19 (17.9%)	0 (0%)	12 (15.6%)	9 (6.9%)
Number of patients requiring endoscopic intervention (%)	77 (36.8%)	49 (46.2%) *	5 (50%)	-	-
Number of patients with rebleeding (%)	26 (12.4%)	22 (20.7%) **	2 (20%)	19 (24.7%) **	7 (5.3%)
Mortality during admission (%)	16 (5.7%)	13 (12.3%) *	3 (30%)	6 (7.8%)	10 (7.6%)

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Disclosure

Nothing to disclose

References

1.Hreinsson J.P., Kalaitzakis E., Gudmundsson S., Björnsson E.S. Upper gastrointestinal bleeding: incidence, etiology and outcomes in a population-based setting. Scand J Gastroenterol. 2013; 48(4): 439–447. doi: 10.3109/00365521.2012.763174. [DOI] [PMC free article] [PubMed] [Google Scholar]
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3.Blatchford O., Murray W.R., Blatchford M. A risk score to predict need for treatment for uppergastrointestinal haemorrhage. The Lancet. 2000; 356(9238): 1318–1321. doi: 10.1016/S0140-6736(00)02816-6. [DOI] [PubMed] [Google Scholar]
4.Rockall T.A., Logan R.F., Devlin H.B., Northfield T.C. Risk assessment after acute upper gastrointestinal haemorrhage. Gut. 1996; 38(3): 316–321. doi: 10.1136/gut.38.3.316. [DOI] [PMC free article] [PubMed] [Google Scholar]

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.23

P0030 Clinical Outcome and Prognostic Indicators in Super Elderly Patients with Upper Gastrointestinal Bleeding in A 1,132 Japanese Patient Cohort

M Fujita ^1,^✉, N Manabe ², T Murao ², M Suehiro ², J Nakamura ², M Ayaki ², T Kamada ³, H Kawamoto ⁴, A Shiotani ², K Haruma ²

Introduction

In Japan, the population of over 75 years exceeded 13%, and the population has been rapidly increasing. with the recent technological advances in the field of hemostatic treatments, the prognosis of patients with gastrointestinal (GI) bleeding has been improved. Generally, the clinical outcome in patients receiving antithrombotic therapies with upper GI bleeding (UGIB) have a worse outcome compare to that in those without receiving antithrombotic therapies. However, there have been no large studies regarding prognostic indicators in patients with UGIB over 75 years.

Aims & Methods

The aim of this study was to evaluate the differences in clinical outcomes of patients with UGIB over 75 years (super elderly group) compared with patients under 65 years (non-elderly group) and evaluate the factors related to their prognosis. Medical records of patients who had undergone emergency endoscopy for GI bleeding from Jan/01/2011 to Des/31/2017 were retrospectively reviewed. The severity of GI bleeding was evaluated using the Glasgow-Blatchford (GB) and AIMS65 scores. Patients in whom obvious GI bleeding relapsed and/or presented persistent iron deficiency anemia in spite of emergency endoscopy were considered as having a poor clinical course, while the other cases were defined as those with good clinical course.

Results

A total of 1,132 UGIB patients were consecutively enrolled: 470 patients (41.5%) in the super elderly group and 248 patients (21.9%) in the non-elderly group.

Clinical characteristics

GB and AIMS65 score in the super elderly group were significantly higher compare to the non-elderly group (P< 0.001). The number of patients receiving antithrombotic therapy were significantly more in the super elderly group compare to that in the non-elderly group (P< 0.001), however antithrombotic therapy did not affect their clinical courses.

Factors associated with clinical course

Multivariate analysis (odds ratio [95% confidence intervals]) showed that GB score was not associated with clinical courses in the non-elderly group, but significantly associated with those in the super elderly group (1.67 [1.07-2.60]). The other factors were no association with their clinical courses in both groups.

Conclusion

The severity of UGIB in super elderly patients was significantly higher compare to that in non-elderly patients. Although antithrombotic therapy has been considered as one of the risk factors for UGIB, there was no association between antithrombotic therapy and clinical course. in super elderly patients with UGIB, the prognostic indicator can be patients’ general condition at the time of emergency endoscopy regardless of the patients’ background.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.24

P0031 Hemosuccus Pancreaticus: An Infrequent Cause of Life-Threatening Haemorrhage

P Karagyozov ^1,^✉, I Tishkov ¹, I Boeva ¹, V Mitova ¹, V Gelev ²

Introduction

Hemosuccus pancreaticus (HP) is a rare but life-threatening cause of upper gastrointestinal bleeding through the main pancreatic duct. This condition most commonly follows pseudoaneurysm formation secondary to acute or chronic pancreatitis. It is still considered a surgical problem but advances in medical therapy may enable clinically stable patients to undergo less-invasive methods.

Aims & Methods

The aim of our study is to highlight the challenges in the diagnosis and management of HP and to formulate a protocol to effectively and safely manage this condition - minimally invasive. We present a case series of five patients (N=5, tree men and two woman, mean age 55 yrs) admitted to our unit wih gastrointestinal bleeding subsequently found to be HP for the period between 2017-2019y.

Results

HP occurred in 3 patientes with chronic and in two with acute alcoholic pancreatitis.

All of the patients presented overt digestive bleeding (two with melena, one with hematochezia and haematemesis, one with hematochezia and one hemorrhagic shock).

All of the patients undergo an initial gastroduodenoscopy and CT angiog-raphy.

Selective digestive angiography was done in 4 patients: Arterial embolization was attempted in one patient. Due to partial re-canalization of the vessel and re-bleeding 18 days after first procedure, re-intervention was done with additional embolization. Placement of nitinol SEMS covoring the pseudoaneurysm was done in two patients. Due to the persistence of leakage to pseudoaneurysm, a second stent graft was implanted in one of the patients. in one of the patients the angiography was only diagnostic. ERCP with pancreatic duct stenting and tamponade was performed in two patients. in one of the patients ERCP was combinated with angiography and self-expandalbe stent placement. None of the patients required surgical treatment.

Technical and long-term clinical success was achieved in 75% of the patientes.

There was one death due to multiple organ failure and hemorrhagic shock.

Conclusion

Although the early diagnosis of HP is challenging, use of appropriate diagnostic studies plays a significant role in reducing mortality and morbidity. We recommend an interventional procedure for the initial treatment of HP, and feel that surgical treatment should only be considered when angiography shows no abnormal findings, when ERCP with stent placement is not suitable option, or when the interventional therapy is not successful.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.25

P0032 Incidence, Predictive Factors and Outcomes of Non-Variceal Upper Gastrointestinal Bleeding: A Prospective Multicenter Population-Based Study From Hungary

L Lakatos ¹, L Gonczi ^2,^✉, F Izbéki ³, A Patai ⁴, I Racz ⁵, B Gasztonyi ⁶, L Varga-Szabó ⁷, F Rozsa ², BD Lovasz ², A Ilias ², PL Lakatos ^2,⁸

Introduction

Acute upper gastrointestinal (GI) bleeding is associated with significant morbidity and mortality.

Aims & Methods

Our aim was to evaluate characteristics and prognostic factors in the management of acute upper GI bleeding in a large multi-center study from Hungary. The present prospective one-year study involved six major community hospitals in Western Hungary covering a population of 1,263,365 persons in 2016. Data collection included demographic characteristics, vital signs at admission, comorbidities, medications, time to hospital admission and endoscopy, laboratory results, endoscopic management, including endoscopic therapy and second look endoscopy, risk assessment using Glasgow-Blatchford Score (GBS), Rockall Score (RS) and the American Society of Anesthesiologists (ASA) Physical Status Score, transfusion requirements, length of hospital stay and mortality.

Results

688 cases (incl. 117 in-hospital cases) of acute upper non-variceal GI bleeding were registered, resulting an estimated incidence rate of 54.42 (CI95% 50.5-58.6) per 100,000 population per year in Western Hungary. Time from symptom onset to presentation at the Emergency Department (ER) was < 6 hours in 35.9% and < 12 hours in 52.7% of the cases. Time from hospitalization to endoscopy was < 6 hours in 55.7% and < 12h in 71.8%. Frequent diagnoses were duodenal ulcer (20.6%), gastric ulcer (19.0%), gastroesophageal reflux disease (GERD) (11.1%), erosive gastritis/ duodenitis (9.9%) and Mallory-Weiss syndrome (8.2%), malignancy (4.0%) and arteriovenous malformation (AVM) (3.8%). Therapeutic intervention on initial endoscopy was performed in 37.1%, while 35.9% of patients required second look endoscopy. Intravenous proton-pump inhibitor (PPI) was applied in 78.8%, while blood transfusion was given to 65.7% of the patients. Hospitalization stay exceeded 7 days in 50.3%, and 5.3% of the patients required surgery. Mortality was 11.6% among patients with bleeding episode presenting outside the hospital, while the overall mortality rate (including in-hospital bleedings) was 13.5%. Longer time to presentation at the ER predicted transfusion requirements (p=0.038), while weekend presentation was associated with transfusion (p=0.047), surgery (p=0.016) and mortality (p=0.021). Presentation with vegetative symptoms at admission (i.e. tachycardia, hypotension or syncope) was associated with increased transfusion needs (p< 0.001), longer in-hospital stay (p< 0.001) and mortality (p=0.017). Patients on anticoagulant, antithrombotic or non-steroidal anti-inflammatory drug (NSAID) medications had higher transfusion needs (p< 0.001) and longer in-hospital stay (p=0.004), but no increased mortality (p=0.571). The GBS was predictive of transfusion (AUC: 0.82; cut-off: GBS >7points; sensitivity: 71.9% specificity: 78%), while mortality was strongly associated with the post-endoscopic RS (AUC: 0.75; cutoff: RS >5points; sensitivity: 68.8% specificity: 68.9%). Presence of comorbidities and ASA stage correlated with transfusion requirements (ASA 1-2 vs. ASA 3-4: OR 2.9, CI95% 2.1-4.1; p< 0.001), endoscopic intervention (OR 1.4, CI95% 1.1-1.9; p=0.033), mortality (OR 9.0, CI95% 4.7-17.2; p< 0.001) and hospitalization length (p< 0.001).

Conclusion

Incidence rates of acute upper GI bleeding in Western Hungary are in line with international trends. The ASA-score, GBS and RS predicted outcomes and transfusion requirements. We observed higher mortality rates, which can partially be explained by the high comorbidity rates in this population, but warrant optimization of the management of acute non-variceal upper GI bleeding.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.26

P0033 Incidence, Predictive Factors and Outcomes of Variceal Upper Gastrointestinal Bleeding - A Prospective Multicenter Population-Based Study From Hungary

L Lakatos ¹, L Gonczi ^2,^✉, F Izbéki ³, A Patai ⁴, I Racz ⁵, B Gasztonyi ⁶, L Varga-Szabó ⁷, F Rozsa ², BD Lovasz ², A Ilias ², PL Lakatos ^2,⁸

Introduction

Acute variceal gastrointestinal (GI) bleeding is associated with significant morbidity and mortality.

Aims & Methods

Our aim was to evaluate characteristics and prognostic factors in the management of acute upper GI bleeding in a large multi-center study from Hungary. The present prospective one-year study involving six major community hospitals in Western Hungary covering a population of 1,263,365 persons in 2016. Data collection included demographic characteristics, vital signs at admission, comorbidities, medications, time to hospital admission and endoscopy, laboratory results, endoscopic management, including endoscopic therapy and second look endoscopy, risk assessment using Glasgow-Blatchford Score (GBS), Rockall Score (RS) and the American Society of Anesthesiologists (ASA) Physical Status Score, transfusion requirements, length of hospital stay and mortality.

Results

108 cases of acute variceal GI bleeding were registered, providing an estimated incidence rate of 8.54 (CI95% 7.08-10.32) per 100,000 population per year in Western Hungary. Time from symptom onset to presentation at Emergency Department (ER) was < 6 hours in 41.4%, and < 12 hours in 64.6% (n=99). Time from hospitalization to endoscopy was < 6 hours in 66.7%, and < 12h in 81.5%. Endoscopy revealed grade 3-4 varices in 63% of patients according to the Paquet's classification of varices. Endoscopic therapeutic intervention was performed in 57.4%, and 38.0% of patients required second look endoscopy. On initial endoscopy, 39.8% of patients were treated with sclerotherapy, 18.5% had ligation and 5.6% balloon tamponade. 76.9% of the patients required blood transfusion. Hospitalization length exceeded 7 days in 45.4% of the patients. Mortality was 18.2% among patients with bleeding episode presenting outside the hospital, while the overall mortality rate (including in-hospital bleedings) reached 24.1%. There was no significant difference in mortality or transfusion requirements based on prehospital time or weekend management (p=NS). Presentation of vegetative symptoms at admission (i.e. tachycardia, hypotension or syncope) was associated with increased rates of transfusion (p=0.003). The Paquet's grade of varices was correlated with the transfusion needs (p=0.036), endoscopic therapy (p< 0.001), and showed similar trend for mortality (p=NS). The increased international normalized ratio (INR) and creatinin levels were associated with mortality (p=0.001 and p=0.002). The GBS best predicted transfusion requirements (AUC: 0.793; cut-off: GBS >8 points; sensitivity: 72.3% specificity: 76%). The frequency of known ETOH dependency and systemic comorbidity was 84.3% and 98.1% in this population. The patients’ ASA stage was associated with transfusion requirements (ASA 1-2 vs. ASA 3-4: OR 7.6, CI95% 2.7-21.6; p< 0.001), endoscopic intervention (OR 12.6, CI95% 3.4-46.5; p=0.033), and showed similar trend with mortality (OR 3.6, CI95% 0.8-16.7; p< 0.095).

Conclusion

Incidence rates of acute variceal GI bleeding in Western Hungary are high. The ASA-score, GBS predicted outcomes and transfusion requirements. Although comorbidities are very high in this population, the observed high mortality rates, coupled with relatively low rates of endoscopic ligation warrant optimization of management strategies in acute variceal GI bleeding.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.27

P0034 Positive White Nipple Sign On Esophageal Varices - Petty Or Exigent!

PN Desai ^1,^✉, C Patel ¹, MV Kabrawala ¹, S Nandwani ², R Mehta ², P Kalra ², R Prajapati ², N Patel ²

Introduction

During endoscopy variceal haemorrhage is identified when we see active bleeding from the varices. But majority of the times active bleeding has ceased when we introduce the scope. So, all endoscopists should be well versed with identifying the signs of recent variceal haemorrhage.

The most commonly seen stigmata are red color signs, including red wale marks (longitudinal red streaks on varices that resemble red corduroy wales), cherry red spots, and hematocystic spots (raised discrete red spots on the surface of varices that appear as blood blisters). A less commonly recognized stigma of recent variceal haemorrhage is a white nipple-like projection from a varix into the esophageal lumen. This is a platelet-fibrin plug. It is referred to as the ‘white nipple sign’ and is a stigma of a site of recent bleeding. Recognition of this stigma of recent bleeding is necessary to manage that varix endoscopically to prevent further variceal bleeding or intra procedural bleeding and its incipient complications. This sign is not well described in literature and its importance to endoscopists treating esophageal varices still not clear. Our experience with this sign, recognizing it on endoscopy and dealing with it differently than those cases without the white nipple sign has been the aim of our retrospective analysis. It will definitely be useful to shed light on this important but no much-discussed perspective of esophageal variceal management.

Aims & Methods: Aim

To assess if White Nipple Sign on esophageal varices is petty (no prognostic Significance) Or Exigent (Mandates more attention).

Methods

2601 patients from 2008 to January 2020 with variceal bleed. Management protocol: Glue injection GOV1, GOV 2 and IGV1. 0.5ml glue + 1.5ml to 3ml distilled water. Esophageal varices - EVL. Thoroughly looked for positive white nipple sign. Varix distal to it injected with glue. First band applied on varix with nipple using a special technique.

If active spurt from nipple. EVL performed. If Severe bleeding - identify site. Tamponade with cap. Still not localized- endotracheal intubation and EVL. Banding fails again, inject cyanoacrylate glue just below spurt, then in it. Fully covered Denis Ella stent if everything fails. Repeat endoscopy after 24 hours, remove stent and treat varices.

Results

Total - 2601. Timing of endoscopy- 4 -8 hours. Positive White Nipple sign- 631(24.3%).

Blood in stomach- 1124 (43.2%), Nipple sign in this group- 575 (51.2%), No blood in stomach- 1477 (56.8%), Nipple sign in this group - 56 (4.9%). Active spurt from nipple- 137 /631 (21.7%), Endotracheal Intubation- 39 (28.4%), Aspiration -12 (8.8%), Successful EVL - 594 (94.1%), EVL Unsuccessful needing Glue Injections - 35 (5.5%).

Persistent Bleed - 2 (0.3%), Denis Ella FCSEMS 2 (0.3%). Mortality - 3 (0.5%).

Conclusion

White Nipple Sign is not only a predictor of recent bleed, but it signifies significant bleed with increase morbidity and mortality and has to be managed differently with more caution and with specific strategy. Not petty but exigent!

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.28

P0035 No Difference Between Oral and Intravenous Proton Pump Inhibitors For Bleeding Peptic Ulcers: A Systematic Review and Meta-Analysis

E Csiki ^1,^2,^✉, H Szabó ^1,², L Hanák ¹, Z Szakács ¹, S Kiss ¹, P Hegyi ¹, E Hegyi ¹, D Pécsi ^1,³, B Eróss ¹

Introduction

Current guidelines recommend intravenous proton pump inhibitor therapy in peptic ulcer bleeding. We aimed to compare the efficacy of oral to intravenous administration of proton pump inhibitors (PPI) in peptic ulcer bleeding.

Aims & Methods

We performed a systematic search in PubMed, Cochrane, Embase, Scopus databases for randomized controlled trials which compared the outcomes of oral PPI therapy to that of intravenous PPI therapy for bleeding peptic ulcers. The primary outcome was 30-day mortality. Odds ratios (OR) with 95% confidence intervals (CI) were calculated for dichotomous outcomes, while weighted mean differences (WMD) with CI were calculated for continuous outcomes in meta-analysis. The protocol of the study was registered a priori onto PROSPERO.

Results

A total of 13 RCT reported 1751 peptic ulcer patients, 881 and 870 of which were in the control and intervention groups, respectively. There were no statistically significant differences between treatments regarding 30-day mortality (OR=0.72, CI, 0.29-1.76); 30-day rebleeding rate (OR, 0.91, CI, 0.59-1.38); length of hospital stay (WMD = -0.34 days, CI: -1.17-0.49); transfusion requirements (WMD = -0.05 PRBC unit, CI: -0.28-0.18); need for surgery (OR = 0.91, CI: 0.40-2.07); further endoscopic therapy (OR = 1.04, CI: 0.56-1.93); and need for re-endoscopy (OR = 0.83, CI: 0.51-1.33). Heterogeneity was negligible in all analysis, except for that on the length of hospitalization (I²=81.2%, p< 0.001).

Conclusion

Recent evidence suggests that the oral administration of PPIs is not worse than the currently recommended intravenous PPI treatment in bleeding peptic ulcers after endoscopic assessment, warranting guideline revision.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.29

P0036 Upper Gi Bleeding in Covid-19 Patients: Characteristics and Management in A Multicenter Experience From Northern Italy

A Mauro ^1,^✉, F De Grazia ¹, MV Lenti ¹, R Penagini ², R Frego ³, S Ardizzone ⁴, EV Savarino ⁵, P Occhipinti ⁶, M Bosani ⁷, F Radaelli ⁸, A Amato ⁸, M Dinelli ³, F Ferretti ⁴, E Filippi ², S Orlando ⁶, M Vecchi ², M Bardone ¹, L Pozzi ¹, L Rovedatti ¹, E Strada ¹, A Di Sabatino ¹

Introduction

Outbreak of the novel SARS-CoV-2 infection, leading to coronavirus disease 2019 (COVID-19) has been declared an official pandemic by WHO on March 11, 2020. COVID-19 patients have an increased susceptibility to develop thrombotic complications, and therefore thromboprophylaxis is routinely administered. The widespread of anticoagulant treatment and the exposure to stress ulcer risk may increase the occurrence of upper gastrointestinal bleeding (UGIB). Timing of upper GI endoscopy should be carefully evaluated given the risk of respiratory worsening in non-intensive care unit (ICU) patients.

Aims & Methods

To retrospectively evaluate the medical and endoscopic management of UGIB in non-ICU COVID-19 patients referred to eight COVID Hub Centers from Northern Italy. COVID-19 inpatients (positive nasopharyngeal swab or bronchoalveolar lavage) older than 18 yrs with overt sign of UGIB were enrolled in the study in the period from March 5^th to April 30^th. Demographic and clinical characteristics at admission were evaluated. Type of anticoagulant and/or antiplatelet therapy were acquired. Severity of CO-VID-19 pneumonia was classified according to the type of oxygen support. Glasgow Blatchford score was calculated at onset of signs of GI bleeding. Timing between onset of signs of GI bleeding and execution, if performed, of upper GI endoscopy was evaluated. Endoscopic characteristics and outcome of patients were evaluated overall or according to the execution or not of an upper GI endoscopy before and after 24 hr. Chi-square test with Fisher test and Mann-Whitney test were used when appropriate.

Results

23 patients (18 male; 75 yrs; IQR 64-78) were included in the study. Antiplatelet therapy was present in 7/23 patients whereas 18/23 (78%) were on anticoagulant therapy before or during hospital stay (35% on prophylactic therapy and 44% in full dose anticoagulant) and 65% of them had two or more comorbidities (78% hypertension or chronic heart disease, 48% diabetes and 9% cirrhosis). 69% of patients had a significant respiratory involvement (high flow oxygen or non-invasive positive pressure support). Signs of upper GI bleeding appeared in a median time of 4 days (0.6-7) during hospital stay being presence of tarry stool the most common finding (52%).. in 11 patients (48%) upper GI endoscopy was performed within 24 hr (4 had haematemesis), whereas it was not performed because of complete resolution of bleeding with medical management in 4 patients, and because of severe respiratory worsening in one. Peptic ulcer was the most common finding (8/18) followed by erosive or haemorragic gastritis (4/18), Mallory-Weiss or Dieulafoy lesion (4/18) and vari-ceal bleeding (1/18). Endoscopic treatment (adrenaline injection + clips in 5 and cyanoacrylate injection in one) was necessary in 6/18 patients. Mortality rate was 21.7%. Mortality (2 vs 3 patients) and rebleeding (2 vs 1 episodes) were not different between patients having upper GI endoscopy before or after 24 hr/not performed. Need of endoscopic treatment was more common in patients in which upper GI endoscopy was performed before 24 hr (6 vs 1 patients, p=0.02) although Glasgow Blatchford score was similar between the two groups (13;12-16 vs 12;9-15).

Conclusion

Upper GI bleeding is not a common complication in COVID-19 patients although the widespread of thromboprophylactic therapy, and peptic ulcer disease is the most common finding. Conservative management with optimization of medical therapy and delay of endoscopy could be an option in patients that are at risk of respiratory complications.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.30

P0037 Use of A Machine Learning Algorithm To Predict Rebleeding and Mortality For Esophageal Variceal Bleeding in Cirrhotic Patients

J Soldera ^1,^✉, F Tomé ², LL Corso ³, MM Rech ¹, AD Ferrazza ¹, AZ Terres ¹, BT Cini ¹, LZ Eberhardt ¹, JIL Balensiefer ¹, RS Balbinot ¹, ALF Muscope ¹, ML Longen ¹, B Schena ¹, GL Rost Jr ¹, RG Furlan ¹, RA Balbinot ¹, SS Balbinot ¹

Introduction

Esophageal variceal bleeding (EVB) is one of the most common complications of cirrhosis. Its mortality rates range around 15%-20% in the first episode. Given EVBs high rates, identifying patients with a high chance to survive is paramount in order to allocate resources into treatment with accuracy.

Aims & Methods

The purpose of this study is to use a machine learning algorithm to predict rebleeding and mortality for EVB in cirrhotic patients and to analyze its accuracy.

A historical cohort study was conducted, analyzing data from hospital charts from Jan 2010 to Dec 2016. Patients were found by searching every use of terlipresin in the period. Paper and electronic medical charts were hand- analyzed. Patients over 18 years old with laboratory and imaging data supporting the diagnosis of cirrhosis and with a definitive diagnosis of EVB were included.

This analysis used data from 74 cirrhotic patients, taking into account 36 variables, which had EVB as a complication. The preliminary analysis of the study was Pearson Correlation, which compared the 36 variables in study with the outcomes of death and rebleeding. This was in order to verify the linear correlation strength, positive or negative. When Artificial Intelligence (AI) was applied, an Artificial Neural Network (ANN) was utilized to recognize patterns of the outcomes through supervised learning. The results were analyzed based on a confusion matrix, which presented the probabilities of the Positive Predictive Value, Negative Predictive Value, Sensitivity, Specificity and Network Accuracy. A Receiver Operating Characteristic (ROC) curve analysis was then performed.

Results

Electronic search retrieved 177 hospital admissions with use of terlipresin. 101 were due to EVB. All- cause mortality was 36%, 41.5% and 50.4% for 30-, 90- and 365-day, respectively. Mean age was 56 years-old, 79% were male. Most common cause of cirrhosis was alcohol abuse, followed by hepatitis C.

The Pearson Correlation analysis showed the variables have values of linear correlation ranging from -0.34 to 0.30 to mortality and -0.31 to 0.21 to rebleeding. Both values represent weak correlations with the outcomes. Thus, it is notably difficult to define which variables are the ones with major leverage on the outcomes. Ergo, the use of AI could be a key-tool to identify the patterns in such a complex data-evolved situation. For patients who had a mortality outcome, the specificity value shows that the ANN was able to identify 95.0% of them. The predictive value shows when the ANN predicted mortality, 95.0% of the patients did indeed perish. The overall accuracy was 97.4% and the Area Under the curve ROC (AUROC) was 0.993, which demonstrates a high performance of the network.

For patients who had a rebleeding outcome, the specificity value shows that the ANN was able to identify 66.7% of them. The predictive value shows when the ANN predicted rebleeding, 100% of the patients did indeed rebleed. The overall accuracy was 97.4% and the AUROC was 0.942.

Conclusion

The ANN could more accurately predict mortality by EVB when compared with two other assessment tools, CLIF-SOFA and MELD Score. The literature has already reported that the CLIF-SOFA has better predictive characteristics than the MELD Score. The AUROC of the CLIF-SOFA found in the literature for the outcome death was 0.943 and the AUROC of the MELD score was 0.80. While, the AUROC of the ANN was 0.993. Therefore, Machine Learning could be a useful tool in order to improve clinical practice, perhaps outperforming the current tools.

Disclosure

Nothing to disclose

References

Wong M.W., Chen M.J., Chen H.L., Kuo Y.C., Lin I.T., Wu C.H. et al. Application of chronic liver failure-sequential organ failure assessment score for the prediction of mortality after esophageal variceal hemorrhage post endoscopic ligation. PLoS ONE. 2017; 12(8): e0182529. doi: 10.1371/journal.pone.0182529 /// [DOI] [PMC free article] [PubMed] [Google Scholar]
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United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.31

P0038 Hemospray in The Treatment of Variceal Bleeds: Outcomes From The International Hemospray Registry

M Hussein ^1,^✉, D Alzoubaidi ¹, M Weaver ², C Makahamadze ³, A de la Serna ⁴, J Ortiz-Fernandez-Sordo ⁵, JW Rey ⁶, B Hayee ⁷, E Despott ⁸, A Murino ⁸, S Moreea ⁹, P Boger ¹⁰, J Dunn ¹¹, I Mainie ¹², D Graham ³, D Mullady ², D Early ², K Ragunath ⁵, J Anderson ¹³, P Bhandari ¹⁴, M Goetz ¹⁵, E Rodriguez ⁴, T Gonda ¹⁶, R Keisslich ¹⁷, E Coron ¹⁸, LB Lovat ¹, R Haidry ³

Introduction

Early treatment for variceal bleeding is recommended within 12 hours to improve outcomes. Endoscopic therapy in acute vari-ceal bleeding can be technically difficult and is not always successful and therefore a bridge is sometimes required towards definitive endoscopic therapy or Trans jugular intrahepatic portosystemic shunt (TIPS). Hemo-spray (Cook Medical, North Carolina, USA) is an endoscopic haemostatic powder for Gastrointestinal (GI) bleeding.

The aim of this study was to look at outcomes in patients with upper gastrointestinal bleeds (UGIB's) secondary to varices.

Aims & Methods

Data was collected prospectively (January 2016- November 2019) from 16 centres in the USA, UK, Germany, France and Spain. Hemospray was used during emergency endoscopy for a variceal UGIB as a monotherapy, dual therapy with standard haemostatic techniques or rescue therapy once standard methods have failed. Haemosta-sis was defined as cessation of bleeding within 5 minutes of hemospray application. Rebleeding was defined as a sustained drop in Hb (>2g/l), haematemesis or melaena with haemodynamic instability following index endoscopy.

Results

12 patients had Hemospray treatment following a variceal upper GI bleed (10 males, 2 female). 10 were oesophageal varices and 2 gastric varices. The median Rockall score was 8 (IQR, 7-8). The median Blatchford score was 15 (IQR, 13-17).

There was an immediate haemostasis rate of 75%. There were no re-bleeds following treatment with Hemospray. 4 patients were treated with Hemospray monotherapy, 3 with combination therapy and 5 with rescue therapy (Table 1). Hemospray was always given after oesophageal banding or injection sclerotherapy in the combination/rescue therapy cohorts. 4/9 patients died within 7 days, 3 out of these 4 patients did not achieve initial haemostasis with Hemospray.

Table 1.

Outcomes in the Hemospray subgroups

	Monotherapy (n=4)	Combination (n=3)	Rescue(n=5)
Median Blatchford score	15 (IQR, 14-16)	15 (IQR, 8-17)	12 (IQR, 11-14)
Median Rockall score	8 (IQR, 8-9)	8 (IQR, 6-9)	8 (IQR, 7-8)
Haemostasis (%)	3/4 (75%)	2/3 (66%)	4/5 (80%)
Rockall 7 and 8 predicted re-bleeding rate 25-40%
Re-bleed	0	0	0
Rockall 8 predicted mortality rate 40-45%
7-day mortality (%)	1/3 (33%)	2/3 (66%)	1/3 (33%)

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Conclusion

The outcomes from the registry showed an immediate hae-mostasis rate of 75% in variceal UGIBs following treatment with Hemospray. in those cohort of patients there is no re-bleeding. This suggests that Hemospray may play a potential role as a bridging therapy in variceal bleeds which are difficult to control, towards repeat definitive endoscopic therapy or TIPS. Larger trials are required to validate these results.

Disclosure

Laurence B Lovat: Minor shareholder in Odin Vision. Research grants from Medtronic, Pentax Medical, DynamX. Scientific Advisory Boards: Dynamx, Odin Vision, Ninepoint Medical. Rehan Haidry: Received Educational grants to support research from Medtronic Ltd., Cook Endoscopy (fellowship support), Pentax Europe, C2 Therapeutics, Beamline diagnostics

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.32

P0039 Patients with Upper Gastrointestinal Bleeding and Previous Use of Anrithrombotic Drugs Have Less Need For Endoscopic Therapy

R Jiménez-Rosales ^1,^✉, EJ Ortega-Suazo ¹, JM López-Tobaruela ¹, JG Martínez-Cara ¹, E Redondo-Cerezo ¹

Introduction

Upper gastrointestinal bleeding (UGIB) remains a significant cause of hospital admission with changing epidemiology: aging population, with multiple comorbidities and increased use of antithrombotic (AT) drugs. AT drugs are a recognized risk factor for UGIB (1); however, few studies have evaluated their effects on patient outcomes with controversial results. Previous studies show no differences (2,3) or a higher need (4) for endoscopic therapy (ET) in AT vs. non-AT (NAT) users in non-variceal UGIB. Gao et al. showed more active bleeding in AT users (5) whereas Teles-Sampaio et al. found no differences (2).

Aims & Methods

The aim of our study is to evaluate the effect of AT use on relevant outcomes of patients with UGIB.

This was a prospective study on consecutive UGIB patients (variceal and non-variceal) treated in Virgen de las Nieves University Hospital (2013-2019). All patients underwent upper endoscopy. We considered AT users all patients on antiplatelets (low dose aspirin, thienopyrimidines) and/or anticoagulants (vitamin-K antagonist, direct-acting anticoagulants, heparin). Information regarding clinical, biochemical data and procedures was collected. Documented clinical outcomes were in-hospital and delayed (6-months) mortality, rebleeding and delayed (6-months) hemorrhagic and cardiovascular events. Descriptive, bivariate and multivariate logistic regression analysis was carried out.

Results

698 UGIB patients were included (63.6% males), 258 (37%) were taking AT drugs (161 antiplatelets, 115 anticoagulants) at presentation. AT differed from NAT group in age (72vs.60;p< 0.001), comorbidities (90.7%vs.45.7%;p< 0.001), ASA classification (3.05vs.2.49;p< 0.001), AIMS65 score (1.77vs.1.18;p< 0.001), GB score (11.09vs.10.08;p=0.001), heart rate (86.96vs.91.35;p=0.018), hemoglobin levels (9.19vs.9.64;p=0.027), variceal etiology (9.3%vs.22.5%;p< 0.001), active bleeding in endoscopy (25.2%vs.33.2%;p=0.027), need for ET (33.3%vs.43.6%;p=0.007) and in-hospital complications (19.8%vs.13.4%;p=0.026). There were no significant differences in gender, systolic blood pressure, non-variceal etiology, rebleeding (7.8%vs9.6%;p=n.s), need for interventional radiology or surgery (2.3%vs.4.8%;p=n.s), blood transfusions, hospital stay and acute mortality (8.5%vs.10%;p=n.s).

Analyzing the cause of death between AT and NAT groups, acute mortality related to UGIB was 3.5% vs.6.1 % (p=n.s) and to another cause 4.7% vs.3.9% (p=n.s), respectively.

Regarding of delayed events, patients on anticoagulants had more cardiovascular ones (26.1%vs.14.6%; p=0.002) with no differences found in antiplatelets users. No differences were found regarding hemorrhagic events and mortality in AT users.

After adjustment for age and comorbidities, independent predictors for need for endoscopic therapy were AT use (OR 0.595;95%CI 0.40-0.87;p=0.045), active bleeding (OR 15.56;95%CI 9.18-26.38;p< 0.001), variceal bleeding (OR 3.18;95%CI 1.46-6.95;p=0.004),and GB score (OR 1.10; 95%CI 1.01-1.20,p=0.026).

Conclusion

Despite being older, with higher ASA, GB and AIMS65 score, lower hemoglobin levels at admission, and more comorbidities as well as in-hospital complications; patients who have UGIB and take AT drugs have lower heart rate, active bleeding in endoscopy and need for endoscopic therapy compared with non-AT users. Both had similar rates of rebleeding, need for surgery or interventional radiology, transfusions, hospital stay and acute mortality. Importantly, we also found that the need for endoscopic therapy was lower in AT users, even after adjusting for potential confounding factors, acting as a protective factor.

Disclosure

Nothing to disclose

References

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United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.33

P0040 An Analysis of The Mortality in Patients with Upper Gastrointestinal Bleeding and No Terapy Applied in The Index Endoscopy

R Jiménez-Rosales ^1,^✉, EJ Ortega-Suazo ¹, JG Martínez-Cara ¹, F Vadillo-Calles ¹, E Redondo-Cerezo ¹

Introduction

Upper gastrointestinal bleeding (UGIB) is a true emergency, associated with significant morbidity, mortality and healthcare costs. The basis of the management nowadays are hemodynamic stabilization and performance of an upper endoscopy within 24 hours after presentation.

Criteria for endoscopic therapy in UGIB has been well established, especially for ulcer related bleeding. However, the rate of endoscopic hemo-stasis in UGIB patients undergoing endoscopy is variable between series, ranging from 20% to 40% (1,2).

Aims & Methods

Our aim was to analyze mortality in patients undergoing an upper endoscopy because of upper GI bleeding, with no hemostatic treatment applied, causes and improvement strategies. We use data from a prospective database including consecutive UGIB patients treated in “Virgen de las Nieves” University Hospital from January 2013 to September 2017. All patients underwent upper endoscopy. Information regarding clinical and biochemical data and procedures was collected. Documented clinical outcomes were rebleeding, in-hospital mortality (distinguishing between bleeding related death and due to another event) and delayed (6-months) mortality. Descriptive, inferential and multivariate logistic regression analysis was carried out.

Results

638 patients (66.1% male) underwent upper endoscopy within 24 hours; 249 (39%) received endoscopic hemostasis, whereas 389 (61%) did not. Active bleeding was present in 6.9% of patients who did not receive endoscopic hemostasis. Mortality in this last group was 5.9%, compared to 14.5% among the patients who received endoscopic therapy (p< 0.0001; OR 2.69; IC 95% 1.55-4.66). Among the patients who did not received endo-scopic therapy, 13 (3.3%) had a bleeding-related death and 9 (2.3%) died because of previous comorbidities. Within the patients who did not received endoscopic therapy and had a bleeding-related death, causes were esophageal varices (5, two of them had esophageal ulcer too), obscure origin GI bleeding (4), peptic ulcer (3) and neoplasm (1). Logistic regression showed that independent predictors for in-hospital mortality in UGIB patients who did not received endoscopic therapy were esophageal varices (OR 5.53; CI95% 1.43-21.39; p=0.013), obscure origin GI bleeding (OR 4.83; CI95% 1.11-20.97; p< 0.036), esophageal ulcer (OR 16.6; CI95% 2.01-131.93; p=0.008) and a MAP(ASH) score above 2 (OR 1.79; CI95% 1.33-2.42; p< 0.0001).

Conclusion

In-hospital mortality in UGIB patients is lower in those who did not receive endoscopic treatment, due to less severe bleeding. However, 5.9% of these patients died, and 3.3% had a bleeding related death. in this group, the most usual cause of death was variceal bleeding, followed by occult GI bleeding that, along with esophageal ulcers and a MAP(ASH) score above 2 were independent risk factors for mortality. in conclusion, we should lower the threshold to apply hemostatic treatment in patients in whom an UGIB is suspected and we found small varices or varices without bleeding stigmata, as well as with esophageal ulcers; especially if they have a MAP(ASH) score greater than 2.

Disclosure

The authors have no conflict of interest. This abstract has been previously presented at national meeting.

References

1.Stanley A.J., Laine L., Dalton H.R., Ngu J.H., Schultz M., Abazi R. et al. Comparison of risk scoring systems for patients presenting with upper gastrointestinal bleeding: international multicentre prospective study. Bmj. 2017; 356: i6432. [DOI] [PMC free article] [PubMed] [Google Scholar]
2.Redondo-Cerezo E., Vadillo-Calles F., Stanley A.J. et al. MAP(ASH): A new scoring system for the prediction of intervention and mortality in upper gastrointestinal bleeding. J Gastroenterol Hepatol. 2020; 35: 82–89. [DOI] [PubMed] [Google Scholar]

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.34

P0041 Adjuvant Effect of New Hemostatic Spray ‘Nexpowder’ On Conventional Endoscopic Treatment in Managing Non-Variceal Upper Gastrointestinal Bleeding: A Prospective, Multi-Center, Randomized Controlled Trial

YI Choi ^1,^✉, KO Kim ², Y-W Shin ³, H-K Kim ³, K-S Kwon ³, WJ Ko ³, SH Kim ⁴, SJ Hong ⁴

Introduction

Nexpowder (Nextbiomedical CO., Incheon, South Korea) is a newly developed endoscopic hemostatic powder generating gelation effect on bleeding focus.

Aims & Methods

This study was to evaluate adjuvant effect of Nexpowder though comparing acute and subacute re-bleeding rates between Nex-powder with conventional endoscopic therapy (N+CET, study) group vs conventional endoscopic treatment only (CET, control) group in patients with acute non-variceal upper gastrointestinal bleeding (UGIB). This prospective, multicenter, and randomized trial conducted from March 2019 to March 2020 in Korea. Consecutive patients (>18 years) with acute UGIB (Forrest classification Ia, Ib, and IIa) who achieved immediate hemostasis through CET were randomized 1:1 to N+CET group or CET only group. Primary outcomes were defined as re-bleeding rate in 3 days and 30 days after therapy and secondary outcomes were safety profiles for Nexpowder.

Results

After exclusion of ineligible criteria, total of 141 patients were randomized into N-CET (n=71) vs CET only (n=70) group. Baseline characteristics including age (study vs control: 63.7± 14.0 vs 63.6 ± 14.7, p=0.6), female proportion (15(21.1%) vs 21(30.0%), p=0.3), anticoagulant use history (16(22.5%) vs 20(28.6%)), p=0.5) were not statistically different between groups. Main reason of bleeding (study vs control: peptic ulcer, 68(95.8%) vs 61(87.1%), p=0.2), initial bleeding control method before randomization (Argon plasma coagulation, 43(60.6%) vs 44(62.9%), p=0.9), Glasgow-Blatchford bleeding score (10.21±4.2 vs 11.0 ± 3.9, p=0.2) did not showed statistically difference between groups. Re-bleeding in 3 days occurred in 3 patients (4.2%) in N+CET group and 11 patients (15.7%) in CET only group with statistical significance (p< 0.001). Re-bleeding rate in 30 days showed 8.5% (n=6) in the N+CET group while 24.3% (n=17 patients) in CET only groups (p< 0.001). There was no reported Nexpowder related adverse events during study period.

Conclusion

Nexpowder application with conventional endoscopic therapy was safe and effective in achieving acute and subacute hemostasis for UGIB. Nexpowder application during conventional endoscopic control might be promising choice for physicians to care in acute emergent UGIB setting.

(Trial registration number: NCT04124588)

Disclosure

Nextbiomedical company supported financial support to Professor Kyoung Oh Kim, but Kyoung Oh Kim did not have any conflict of interest in this study.

References

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United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.35

P0042 Diagnosis of Pharyngeal Cancer On Endoscopic Video Images By Artificial Intelligence

M Kono ^1,^✉

Introduction

A favorable outcome can be expected when pharyngeal cancers are detected at an early stage and they are treated with minimally invasive methods such as endoscopic resection.

Aims & Methods

We therefore aimed to develop an artificial intelligence (AI) system for the real-time diagnosis of pharyngeal cancers. Methods: Endoscopic video images and still images of pharyngeal cancer treated in our facility were collected. A total of 4559 images of pathologically proven pharyngeal cancer (1243 using white light imaging and 3316 using narrow band imaging/blue laser imaging) from 276 patients were used as a training dataset. The AI system used a convolutional neural network (CNN) model typical of the type used to analyze visual imagery. Supervised learning was used to train the CNN. The AI system was evaluated using an independent validation dataset of 25 video images of pharyngeal cancer and 36 video images of normal pharynx taken at our hospital.

Results

The AI system diagnosed 22/25 (88%) pharyngeal cancers as cancers and 24/36 (67%) non-cancers as non-cancers. The transaction speed of the AI system was 0.03 seconds per image, which meets the required speed for real-time diagnosis. The sensitivity, specificity, and accuracy for the detection of cancer were 88%, 67%, and 75% respectively.

Conclusion

Our single-institution study showed that our AI system for diagnosing cancers of the pharyngeal region had promising performance with high sensitivity and acceptable specificity. Further training and improvement of the system are required with a larger dataset including multiple centers.

Disclosure

T. Tada is a shareholder of AI Medical Service Inc. All other authors disclosed no financial relationships relevant to this publication.

References

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United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.36

P0043 in Tertiary Care Patients with Functional Dyspepsia, Postinfectious Onset Is A Risk Factor For Weight Loss

J Schol ^1,^✉, F Carbone ¹, K Van den Houte ¹, E Colomier ¹, I-H Huang ¹, T Vanuytsel ^1,², J Tack ^1,²

Introduction

Functional dyspepsia (FD) is a prevalent disease and presents with symptoms located in the epigastric region. The Rome IV criteria differentiate the subgroups postprandial distress syndrome (PDS), mainly characterized by early satiation, postprandial fullness and other postprandial symptoms, and the epigastric pain syndrome (EPS) characterized by epigastric pain or burning. Acute gastroenteritis and H. Pylori infection have been identified as risk factors for FD, in the former case referred to as postinfectious FD (PI-FD). It is unclear how these risk factors relate to Rome IV subgroups and clinical impact. Our aim was to study the association of PI-FD and H. pylori status with clinical profiles, including PDS or EPS, and the amount of weight loss.

Aims & Methods

Consecutive FD patients filled out questionnaires to assess symptom frequency and severity. Patients were identified as PDS, EPS or overlap subgroup according to severity scores of epigastric pain, early satiety or postprandial fulness. Additionally, the postinfectious history and H. Pylori status were determined. Analyses were performed using Chi-square test or ANOVA. Results were considered significant if p< .05. Data are described as mean ± standard error of the mean.

Results

In a cohort of 459 patients with functional dyspepsia (71% females, 39±0.7 ys, 22.2±0.2 kg/m^A2), 36% were characterized as PDS (n=167, 68% females, 39±1 ys, 21.9.1±0.3 kg/mA2), 9% as EPS (n=40, 60% females, 42±2.6ys, 23.3±0.7 kg/mA2) and 55% showed overlap (n=252, 75% females, 38±1 ys, 22.2±0.3 kg/mA2). Age and BMI were similar in the three subgroups (p=.33 and p=.22 respectively).

Postinfectious onset of symptoms was reported by 20% of patients, 17%, 18% and 23% in the PDS, EPS and overlap subgroups respectively(p=.31). H. Pylori status was positive in 14% of patients, with 12%, 10% and 16% in PDS, EPS and overlap groups respectively (p=.40). Hence, PI onset and active H. Pylori infection were no risk factors for any of the subgroups. Significant weight loss, defined as more than 5% of the original body weight, was reported by 57% of patients, distributed as 63% in PDS, 36% in EPS and 56% in the overlap group. PI-FD patients were more likely to experience weight loss in the total patient group (OR 2.27, p=.0013) and in the overlap group (OR 3.38, p=.0003) but not in the EPS (OR 2.0, p=.44) or PDS (OR 1.21, p=.70). Only early satiety was associated with significant more weight loss in the PDS (p=.0002) and overlap group (p< .0001).

Conclusion

In this large cohort study, postinfectious onset of symptoms of FD is a risk factor for weight loss, especially in the overlap group, but is not associated with the symptom patterns of PDS, EPS or overlap subgroups.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.37

P0044 Functional Dyspepsia and Its Subgroups: Prevalence and Impact in The Rome Iv Global Epidemiology Study

J Tack ^1,^✉, OS Palsson ², S Bangdiwala ³, F Carbone ⁴, K Van den Houte ⁵, D Drossman ⁶, DL Dumitrascu ⁷, X Fang ⁸, S Fukudo ⁹, U Ghosal ¹⁰, J Kellow ¹¹, R Khatun ¹², E Okeke ¹³, E Quigley ¹⁴, MJ Schmulson Wasserman ¹⁵, M Simrén ¹⁶, WE Whitehead ², P Whorwell ¹⁷, AD Sperber ¹⁸

Introduction

Functional Dyspepsia (FD) is a common Disorder of Gut-Brain Interaction (DGBI), with varying reported population prevalences. The definitions of FD and its subgroups postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) were updated in the Rome IV consensus.

Aims & Methods

Our aim was to study their prevalences and impact on individuals in an internet survey, as part of the recently completed Rome Foundation Global Epidemiology Study of DGBIs.

54127 adults (26578 females; mean age 43.7, range 18-97 years) in 26 countries completed an Internet survey that included Rome IV FD diagnostic questions, the Patient Health Questionnaire-4 (PHQ-4) psychological distress questionnaire, the PROMIS Global-10 quality of life measure, demographics, and selected medical history. Survey participants were identified and provided by Qualtrics, LLC (Provo, UT). Quota-based sampling was used to ensure a generally comparable sex ratio and age group distributions between countries. Respondents reporting a history of relevant organic disease (peptic ulcer, celiac disease, bowel cancer, or inflammatory bowel disease) were excluded from FD case definition.

Results

Pooled mean Rome IV FD prevalence in the entire sample was 7.2% (95% CI 7.1-7.4). FD rates ranged from 2.2% (Japan) to 12.3% (Egypt). FD prevalence was significantly higher in women, with an odds ratio of 1.56 (1.46, 1.67). FD prevalence decreased with age, from 9.5% in those 18-35 years, to 3.9% in those above 65 (Table). Quality of life physical and mental scores were significantly lower in those fulfilling FD criteria compared to the rest of the population (physical 12.38 (12.30 vs. 12.47) vs. 14.63 (14.61, 14.65)) and mental (11.84 (11.73, 11.95) vs. 13.69 (13.66, 13.72)). The most prominent subtype was PDS, with a distribution of 66.6% PDS, 15.3% EPS and 18.1% overlapping PDS and EPS. Both PDS and EPS were more prevalent in women and decreased with age (Table). Comorbid Rome IV IBS was present in 26.1% of those fulfilling FD criteria, with lowest prevalence in PDS and highest in the overlap group (13.1% in PDS, 42.2% in EPS, 60.2% in overlap). Functional heartburn and chronic nausea/vomiting criteria were fulfilled in respectively 9.0 and 7.0% of FD cases, with highest prevalence in the overlap group (respectively 26.7 and 18.2%). Fulfilling FD symptom criteria was significantly associated with clinically relevant anxiety (30.4% (28.9, 31.9) to 10.2% (10.0%, 10.5%) and depression (30.2% (28.8, 31.6) vs. 9.9% (9.6, 10.2)) on the PHQ-4.

Prevalence of meeting criteria for Rome IV FD and its subtypes (% and 95% CI) by sex and age groups in the internet sample of adults in 26 countries.

	Sex			Age group
		18-34	35-49	50-64	65+	All ages
FD	Females:	10.8 (10.1, 11.4)	8.8 (8.2, 9.5)	7.4 (6.7, 8.1)	5.2 (4.5, 5.9)	8.7 (8.4, 9.1)
	Males:	8.0 (7.4, 8.6)	6.2 (5.7, 6.8)	4.5 (4.0, 5.1)	2.9 (2.5, 3.4)	5.7 (5.5, 6.1)
	Overall:	9.5 (9.1. 9.9)	7.5 (7.1, 7.9)	5.9 (5.5, 6.4)	3.9 (3.5, 4.3)	7.2 (7.0, 7.4)
PDS	Females:	9.3 (8.7, 9.9)	7.5 (6.9, 8.1)	6.3 (5.7, 7.0)	4.5 (3.8, 5.1)	7.5 (7.2, 7.8)
	Males:	6.9 (6.4, 7.5)	5.1 (4.6, 5.5)	3.7 (3.2, 4.2)	2.5 (2.0, 2.9)	4.8 (4.6, 5.1)
	Overall:	8.2 (7.8, 8.6)	6.3 (5.9, 6.6)	4.9 (4.5, 5.3)	3.3 (2.9, 3.7)	6.1 (5.9, 6.3)
EPS	Females:	3.2 (2.8, 3.5)	3.3 (2.9, 3.6)	2.4 (2.0, 2.9)	1.7 (1.2, 2.1)	2.8 (2.6, 3.0)
	Males:	2.4 (2.1, 2.8)	2.6 (2.2, 2.9)	1.7 (1.4, 2.0)	0.8 (0.6, 1.0)	2.0 (1.8, 2.2)
	Overall:	2.8 (2.6, 3.1)	2.9 (2.7, 3.2)	2.0 (1.8, 2.3)	1.2 (0.9, 1.4)	2.4 (2.3, 2.5)

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Conclusion

FD according to Rome IV criteria is highly prevalent on a global scale, affecting more women than men and with declining prevalence with age. FD has a major impact on quality of life and is associated with significant anxiety and depression co-morbidity. PDS is the dominant subgroup, present in over 80% of the FD sufferers. Overlap with IBS, (functional) heartburn and nausea or vomiting is present in only a minority of subjects, and highest in the overlap group.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.38

P0045 The Correlation Between Electronic Cigarette Smoking and Dyspepsia

AFMZ Zein ^1,^✉, D Nauphar ², U Khasanah ³, TM Pratamawati ², RS Brajawikalpa ⁴, CS Sulistiyana ⁵, E Suhaeni ⁶, E Ayuningtyas ⁷, A Hamzah ⁸

Introduction

Dyspepsia is one third case in daily clinical practice and has multiple lifestyle associated risk factors. Tobacco smoking is associated with dyspepsia but the relationship between electronic cigarette (e-cig) smoking and dyspepsia is unknown.

Aims & Methods

This study was aimed to investigate the correlation between e-cig smoking and dyspepsia. This cross-sectional study enrolled 86 adult e-cig smoker in Cirebon City, West Java, Indonesia. We used consecutive sampling method in this study. The data collection used validated Short-Form Leed Dyspepsia Questionnaire (SFLDQ) in Indonesian language. The dyspepsia was defined as SFLDQ score cutoff ≥4. We also measure the consumption of e-cig smoking, the duration of consumption, and the dose of consumption. Data analysis was using Spearman's rank correlation test.

Results

The prevalence of dyspepsia in this study 38.3%. There is weak correlation between duration of e-cig smoking and dyspepsia (r = 0.34; 95%CI:; p = 0.03) but there is no significant correlation between the dose of e-cig smoking and dyspepsia (r = 0.106; 95% CI:; p = 0.082).

Conclusion

The dyspepsia in e-cig smoker is prevalent. Further, there is weak correlation between duration of e-cig smoking and dyspepsia. Further studies are needed to determine the correlation between e-cig smoking and dyspepsia and its associated factors.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.39

P0047 Investigation of Esophageal Epithelial Tissue Integrity and Molecular Epithelial Markers On Diabetic Gerd Patients

S Bor ^1,^✉, S Kipcak ², P Ergun ³, Selvi Gunel N, Ege Reflux Study Group ⁴

Introduction

Epidemiologically, both Diabetus Mellitus and gastro-esophageal reflux disease are the between most common diseases and have significant impact on public health. The incidence of overlap of these diseases should be high and needs particular attention. We showed that diabetic rabbit EE is more resistant to harmful agents and more powerful LES muscle contractions (1). Therefore it is important to evaluate the pathophysiological mechanisms in the esophageal epithelium (EE) in GERD patients with DM.

Aims & Methods

We evaluated the changes and mechanisms at the EE in two groups of patients (DM+GERD, GERD without DM) and healthy controls. All subjects were underwent 24h pH-MII, esophageal high resolution manometry, upper GI endoscopy and 9 esophageal biopsies in total 57 subjects; healthy controls n=15, GERD n=20, DM+GERD (Type 1 DM n=4, Type 2 DM n=18) n=22. The electrophysiological properties of the esophageal tissues were examined with mini ussing chamber system and the permeability properties were examined with fluorescein spectrophotometri-cally. E- cadherin and tight junctions mRNA expression levels were determined by quantitative RT-PCR and protein expressions were detected via western-blot and ELISA methods.

Results

: Tissue resistances (R) of DM-GERD have been shown to be significantly higher than GERDs (p≤0.05), they are also numerically above healthy controls (p>0.05). Diffusion studies revealed that the changes were related with the expansion in the intercellular spaces. When the molecules that play a role in the pathogenesis of DIS were evaluated, the expressions of e-cadherin, ZO-2, Claudin-1, Occludin increased compared to the controls in patients with DM + GERD. Compared to GERD group, ZO-2 and Claudin-1 significantly increased in DM + GERD group. Protein expression results suggest that ZO-2, Claudin-1 increase, and even higher in the presence of DM (Table).

Table.

		E- cad	ZO-1	ZO-2	Claudin1	Claudin 4	Occludin
*Gene Expression (foia change} ^p≤0.05**	GERD / Control	2.08 ^#	-1.85	1.15	-1.35	1.06	1.09
	DM+ GERD/GERD	1.45	1.85	1.75 &	-1.12	1.39	-1.02
	DM+GERD/Control	3.01^*	1.00	2.02^*	-1.5	1.47^*	1.07
		E- cad (area ±SD)	ZO-1 (area ±SD)	ZO-2 (ng/mL±SD)	Claudin1 (ng/mL+SD)	Claudin 4 (ng/mL±SD)	Occludin (area ±SD)
*Protein Expression Level ^p≤0.05**	Control (n=15)	0.88 ± 0.46^*	0.71 ± 0.43	1.2 ± 0.9 ^*	1.7 ± 0.9 ^*	3.7 ± 5.4	0.94 ± 0.58^*
	GERD (n=20)	1.17 ± 1.11	1.07 ± 0.64	1.7 ± 2.4 &	2.4 ± 2.9 &	3.6 ± 5.3	1.62 ± 1.51
	DM+GERD (n=22)	1.68 ± 1.62^*	0.96 ± 0.87	4.1 ± 4.1^* &	4.3 ± 2.8 ^* &	5.0 ± 4.0	2.01 ± 1.46^*

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^*

Control vs DM+GERD

^#

Control vs GERD, & GERD vs DM+GERD

Conclusion

Presence of DM increased the esophageal epithelial resistance in GERD. This might be related with the changes at upregulation of the molecules especially ZO-2, Claudin 1, Occludin, E-cadherin in the intracellular spaces. It is important for a chronic and years-long disease such as DM to improve molecular properties of EE. These mechanisms of protective changes in the presence of DM in GERD cases also brings the possibility of the target of noxious agents in the epithelium as well as reversing the changes that GERD creates in the esophageal epithelium.

Disclosure

Nothing to disclose

References

1.Capanoglu D., Coskunsever D., Olukman M., Goksel S., Bor S. The effect of diabetes mellitus on esophageal epithelia and LES muscle of rabbit. Dig Dis Sci. 2016; 61(7): 1887. [DOI] [PubMed] [Google Scholar]

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.40

P0048 Differential Effects of Duodenal Bile Salts On Mucosal Physiology and Symptoms in Functional Dyspepsia Patients

M Ceulemans ^1,^✉, L Wauters ¹, A Accarie ¹, J Toth ¹, R Mols ², P Augustijns ², J Tack ¹, T Vanuytsel ¹

Introduction

Despite increasing evidence for duodenal epithelial hyper-permeability and low-grade inflammation in functional dyspepsia (FD) patients (Vanheel et al. Gut 2014), the role of luminal changes has scarcely been studied.

Aims & Methods

We aimed to study duodenal bile salt (BS) concentrations in relation to duodenal mucosal changes and symptoms in FD patients (Rome IV criteria) compared to healthy controls (HC). Duodenal fluids were aspirated via a nasoduodenal tube after endoscopic collection of duodenal biopsies. BS concentrations were measured in fasted state, and in fed state (every 15 min during 1 h; Fortimel®, 300 kCal) using LC-MS/MS. Paracellular passage of a fluorescein-labeled dextran (4 kDa) was recorded in Ussing chambers, and eosinophils were counted on H&E-stained sections per high-power field (HPF; 0.24 mm²). All subjects filled out the Patient Assessment of Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM). Multilevel (mixed) models were constructed with BS concentrations as dependent and time as independent variables. Univariate and correlation analyses were performed between groups. Finally, mediation analysis was done to study whether mucosal factors (paracellular passage and eosinophilia) mediated the relationship between BS (total, primary or secondary) and symptoms (PAGI-SYM), with computation of the direct and indirect effect via bootstrapping with 95% confidence interval (CI) using Hayes’ PROCESS in SAS.

Results

In total, 24 FD patients (21 female) and 25 HC (16 female) were included with similar age and BMI (Table). A significant effect of time was found for the change in total BS concentrations (F= 23.4, p< 0.0001), with a similar evolution for primary and secondary BS in FD patients and HC. Similar total, primary and secondary BS concentrations were found in fed state (45 min) with significantly higher duodenal mucosal permeability, eosinophils and symptoms in FD patients compared to HC (Table). Significant correlations were found between passage and both primary (r= -0.52, p= 0.02) and secondary BS (r= -0.44, p< 0.05) in FD patients but not HC. While only a direct effect of primary BS on PAGI-SYM was seen in FD (β= 0.01 ± 0.004, p= 0.01), a significant indirect effect was found of secondary BS on PAGI-SYM, mediated by paracellular passage (β= 0.08 ± 0.05, 95% CI [0.012;0.19]). When testing the effect of BS on symptoms through duodenal eosinophils in FD, only a direct effect was found for primary BS (β= 0.01 ± 0.004, p= 0.008) with no association between eosinophils and secondary BS (p= 0.92).

Between-group comparison of variables of interest

Variable, median (IQR)	FD patients (n= 24)	Healthy controls (n= 25)	FD vs. controls (p-value)
Age (years)	28 (23 - 34)	26 (24 - 32)	0.64
BMI (kg/m²)	22.3 (19.8 - 23.8)	23.3 (20.1 - 25.7)	0.29
Fed total bile salts (mM)	8.9 (6.1 - 15.6)	8.4 (2.4 - 15.2)	0.39
Fed primary bile salts (mM)	8.1 (5.1 - 12.5)	5.6 (1.7 - 12.5)	0.47
Fed secondary bile salts (mM)	1.1 (0.5 - 2.5)	0.8 (0.2 - 2.3)	0.35
Paracellular passage (pmol)	22.2 (16.1 - 33.0)	19.5 (8.4 - 22.1)	0.02
Duodenal eosinophils (/HPF)	12 (9 - 15)	3 (2 - 4)	<0.0001
PAGI-SYM symptom scores	2.5 (2.0 - 2.9)	0.1 (0.0 - 0.3)	<0.0001

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Conclusion

In FD patients, fed state concentrations of total, primary and secondary BS were similar compared to controls. Fed state primary BS concentrations are associated with symptom severity, independent of duodenal permeability or eosinophils. in contrast, the association of secondary BS with symptoms involved duodenal permeability but not eosinophils. The role of BS in duodenal barrier function, symptom generation, and as a therapeutic target in FD warrant further investigation.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.41

P0049 Dextran Sodium Sulphate-Induced Gastrointestinal Injury Affects Impact of Donepezil On The Gastric Myoelectric Activity in Experimental Pigs

J Bures ^1,^✉, J Kvetina ¹, E Peterova ¹, I Tachecí ¹, V Radochova ², D Kohoutova ^1,³, M Valis ¹, V Knoblochova ¹, S Rejchrt ¹, T Douda ¹, M Kopáčová ¹, J Zdarova Karasova ²

Introduction

Donepezil, a potent reversible cholinesterase inhibitor, has still been used as a preferred treatment of Alzheimer disease. Its gastrointestinal side effects, like dyspepsia, nausea, vomiting or diarrhoea, occur in 20-30 % of patients. Pathogenesis of these motility disorders has not been fully clarified yet. Ageing has a significant impact on the gastrointestinal tract (GIT), even in healthy seniors. Its function can be further deteriorated by an underlying disease. Experimental pigs can be used in preclinical studies due to their similar gastrointestinal functions compared with humans. Experimental dextran sodium sulphate (DSS)-induced injury affects function of different parts of the GIT, including the stomach and small bowel.

Aims & Methods

The aim of this study was to assess the effect of a single and repeated doses of donepezil on porcine gastric myoelectric activity with and without DSS-induced injury. Eighteen adult female pigs (mean weight 38.7±1.0 kg) were enrolled. Donepezil hydrochloride was given as a single intragastric dose (group A: 5 mg; group B: 10 mg). The third group (C) received a 7-day donepezil (5 mg per day; in a dietary bolus) with an extra intragastric dose in the morning on day 8 (10 mg). DSS was administered to overnight fasting animals in another dietary bolus in the morning for 7 days (10 g per day). Gastric myoelectric activity was investigated by means of electrogastrography (EGG) on day 1 (A and B) and day 8 (C), using an EGG stand (MMS, Enschede, the Netherlands). All EGGs were performed in propofol general anaesthesia. Basal (15 min.) and study recordings (330 min.) were evaluated by MMS software (version 8.19). Running spectral analysis was used for a standard evaluation of EGG. Results were expressed as dominant frequency of gastric slow waves (DF; cycles per minute - cpm), power analysis (areas of amplitudes; |iV^A2) and power ratio assessment: fraction of the areas of amplitudes after (numerator) and before (nominator) the study drugs.

Results

Altogether 6210 one-minute EGG recordings were evaluated, each in DF, power and power ratio. Groups A and B revealed similar trends. DF decreased from basal values (median: 3.1; interquartile range: 1.1-3.1; and 3.1; 1.2-3.5 cpm) down in group A (0.9; 0.7-1.2; p< 0.001) and group B (1.4; 0.9-2.8; p< 0.001) after 60 min. in group C, DF increased from basal values (2.2; 0.9-3.1) significantly after 105 min. (3.1; 2.8 - 7.0; p< 0.001). Higher DF sustained for next 165 min. (3.3; 3.3-4.0; p< 0.001). Power and power ratio had a corresponding pattern.

In group A, power ratio decreased from its highest values 30 min. after drug administration (1.1; 0.4-5.3) to low levels after 120 min. (0.2; 0.1-0.4; p< 0.001). Group B showed a similar profile. in group C, power ratio dropped significantly from higher values 30 min. from the start (1.0; 0.5-4.7) to low levels after 120 min. (0.4; 0.1-1.1; p< 0.001). Power ratio raised again after the next 60 min. (1.0; 0.3-6.4; p< 0.001), finishing with decreased values after 315 min. (0.5; 0.2-0.7; p< 0.001).

Conclusion

Donezepil alone revealed an unfavourable effect on porcine myoelectric activity assessed by gastric power. It can be a plausible explanation of a donepezil-associated dyspepsia in humans. DSS caused an undesirable increase in dominant frequency and decreased EGG power. That may indicate that underlying disease in elderly humans can have aggravate the effect of donepezil on gastric myoelectric activity.

Disclosure

Nothing to disclose

Acknowledgement

The study was funded by a Research Grant GACR (18-13283S).

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.42

P0050 The Impact of Nabumetone On Gastric Myoelectric Activity in Experimental Pigs with and Without Gastrointestinal Injury Induced By Dextran Sodium Sulfate

S Rejchrt ^1,^✉, J Kvetina ¹, E Peterova ¹, I Tachecí ¹, V Radochova ², D Kohoutova ^1,³, M Nobilis ⁴, V Knoblochova ¹, T Douda ¹, M Kopacova ¹, J Bures ¹

Introduction

Prostaglandins regulate motility of the stomach. Their inhibition induced by non-steroidal anti-inflammatory drugs may alter gastric motor function. Both, enhanced motility and delayed gastric emptying were described in humans. Nabumetone is a potent, preferentially cyclo-oxygenase-2 inhibitor. Its non-acidic nature and pro-drug formulation (no entero-hepatic circulation of its active metabolite 6-methoxy-2-naph-thylacetic acid) contribute to improved gastrointestinal tolerability of this drug. Experimental dextran sodium sulfate (DSS)-induced injury can have an impact, both, function and morphology of different parts of the gastrointestinal tract, including the stomach and small bowel, and thus affect gastric motor function and intestinal drug absorption.

Aims & Methods

The aim of current study was to investigate the impact of nabumetone on porcine gastric myoelectric activity assessed by a noninvasive surface electrogastrography (EGG) in the setting of presence or absence of injury induced by DSS. Experimental pigs are widely used in preclinical studies owing to their similar gastrointestinal functions compared to humans.

Sixteen experimental adult female pigs (3-month-old; mean weight 38.7 ± 2.3 kg, median 39.0) were divided into three groups treated with nabumetone: A (n=6; a single intragastric (i.g.) dose 1000 mg); B (n=6; a single i.g. dose 2000 mg) and C (n=4; a single i.g. dose 2000 mg after a 7-day DSS administration; 10 g per day, as a morning dietary bolus). All endoscopic intragastric administrations of nabumetone and EGG recordings were carried out in fasting animals under general anaesthesia. Basal (15 min.) and study recordings (eight 15-minute intervals) were accomplished using an EGG stand (MMS, Enschede, the Netherlands). MMS software (version 8.19) was used to assess EGG. Running spectral analysis was used for basic evaluation of EGG. The results were expressed as dominant frequency of slow waves (DF; cycles per minute - cpm). EGG power analysis (areas of amplitudes; μV^2)) was accomplished in all animals.

Results

A total of 2160 one-minute EGG recordings were evaluated, each in both parameters. Basal DF of the group C after one-week of DSS administration (mean: 1.9 ± std dev 1.2 cpm) was significantly higher compared with basal DF in groups A (1.5±1.0; p=0.048) and B (1.5±1.2; p=0.013). DF raised in all groups, up to 3.5±3.1 cpm by the end of study recording (p=0.041; p< 0.001; p< 0.001). For several times, an increase of DF up to 10 cpm, lasting a few minutes, was recorded in different intervals in all groups. Similarly, the basal power of group C was significantly higher (median: 2350; inter-quartile range: 1067-3571; |VA2) compared to groups A (973; 334-2321; p< 0.001) and B (738; 352-3451; p< 0.001). EGG power decreased in all groups by the end of study recording (A: 282; 177-550; p< 0.001; B: 260; 158-968; p< 0.001; C: 757; 391-2581 μV^2); p< 0.001).

Conclusion

A single intragastric dose of nabumetone lead to an undesirable increase in dominant frequency and a decrease of EGG power. One-week of DSS administration did not influence the increase of dominant frequency after the administration of nabumetone, but attenuated the fall in EGG power.

Disclosure

Nothing to disclose

Acknowledgement

The study was supported by the Research Project MH CZ-DRO (UHHK, 00179906).

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.43

P0051 Gastric Emptying Time Using Smartpill Wireless Motility Capsule Correlates with Hunger Contractions and High Ghrelin

M-U Din ^1,^✉, HO Diaz-Tartera ², D-L Webb ³, PM Hellström ⁴

Introduction

Many studies quantify gastric emptying with acetaminophen absorption, yielding gastric emptying rate (GER), typically assayed temporally in plasma samples and quantified from time to peak or AUC. For both research and clinical investigations, the SmartPill wireless motil-ity capsule (WMC) is increasingly used to quantify gastric emptying time (GET). Although the two methods are intended to measure essentially the same parameter, physiological variables affecting results can differ. Correlation data between GET and acetaminophen was therefore pursued. in a separate group, correlations between GET, hunger contractions and the metabolic response to a meal in terms of plasma glucose and peptide hormones were studied.

Aims & Methods

WMC recordings with acetaminophen absorption (n=21) and metabolic response (n=41) were obtained from healthy volunteers. Fasted subjects ingested a 260-kcal mixed meal, 1.5g acetaminophen and the WMC. Plasma was obtained -10, 0 (meal intake), 10, 20, 30, 40, 50, 60, 90, 120, 180 and 240 min and stored at -80 °C for later analyses of acetaminophen, glucose, insulin, ghrelin, glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). WMC recordings were analyzed with MotiliGI 3.0 software to obtain GET based on pH drop in stomach followed by neutralization upon reaching duodenum. GET was confirmed by last hunger contractions (LHC) by pressure recordings within 5 min before GET. Correlations of GET to LHC, plasma glucose, insulin, ghrelin, GIP, GLP-1 and PYY as evaluated by plasma concentrations as time to peak (Tmax), maximum concentration (Cmax) and exposure (AUC) were quantified by Pearson correlation coefficients.

Results

In all cases, LHC closely reflected GET (R ∼0.99). Hence, GET obtained by WMC likely reflected the actual time of WMC migration into the duodenum. By contrast, despite a clear acetaminophen peak 72±4 |iM, correlation between GER and Tmax was weak (R ∼0.18). Neither did acetaminophen Cmax or AUC correlate with GET. Peptide hormone analyses showed ghrelin to be strongly correlated to LHC (R 0.74; p< 0.0001) and further related to GET (R 0.41, p < 0.02). The timing of GLP-1 meal response approached significance (R 0.24, p< 0.07), but not Cmax or AUC. Neither did Cmax, Tmax or AUC of glucose, insulin, GIP, or PYY reveal any correlations to GET.

Conclusion

GET as measured by SmartPill WMC displays a robust correlation to hunger contractions occurring at high ghrelin levels, but does not correlate to gastric emptying as measured by acetaminophen absorption, nor to metabolic parameters glucose absorption or insulin release. Hence, hunger contractions seem to be a strong physiological force behind gastric emptying time of the WMC.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.44

P0052 Saccharomyces Boulardiicncmi-745 Improves Gut-Brain Axis Dysfunction in A Humanized Mouse Model of Ibs with Co-Morbid Anxiety

M Constante ^1,^✉, G De Palma ¹, J Lu ¹, J Jury ¹, S Collins ¹, L Rondeau ¹, A Caminero ¹, P Bercik ¹, E Verdu ¹

Introduction

IBS is frequently associated with psychiatric co-morbidities such as anxiety and depression and has been considered a disorder of gut-brain axis communication. We previously developed a humanized mouse model of IBS and co-morbid anxiety (IBS+A) by colonizing germ-free mice with fecal microbiota of IBS+A patients. Bacterial probiotics have been tested in gut-brain axis modulation, but the effects of yeast probiotics such as Saccharomyces boulardii CNCM I-745 have not been investigated yet in our humanized mouse model of IBS+A.

Aims & Methods

Our aim was to test the effect of the probiotic yeast Saccharomyces boulardii CNCM I-745 (S. bou) in preventing gut dysfunction and anxiety like-behavior in our mouse model and investigate underlying mechanisms. Germ-free Swiss-Webster mice were colonized with fecal microbiota from an IBS+A patient or from a healthy subject (HC: healthy controls). Three weeks later, mice were gavaged daily for two weeks with 3g/ kg/day of the probiotic S. bou (Biocodex-France) or water. Mouse anxietylike behavior was assessed using the light/dark preference test and the step down test. Mouse gastrointestinal (GI) transit was measured by fluoroscopy after intragastrical gavage with 5 small steel beads and barium sulfate. Barrier function was assessed by Using chamber technique. Gene expression assessed by Nanostring Counter Gene Expression and qRT-PCR. Microbiota was characterized by 16S rDNA and rRNA quantification by Illumina sequencing and qRT-PCR, respectively. Indole quantification was assayed by absorption using Kovak's reagent.

Results

IBS+A mice developed 30% faster gastrointestinal transit (P< 0.05) and had a 3-fold longer latency time in the step-down test (P< 0.001), indicative of anxiety-like behavior compared with controls. S. bou treatment normalized gastrointestinal transit (P< 0.05) and shortened by 50% the step-down latency (P< 0.01), compared with water-treated mice. Expression of Trpv1, implicated in visceral hypersensitivity and anxiety, was 2-fold higher in IBS+A mice than in controls (P< 0.001), and its expression was decreased by S. bou treatment (P=0.05). Abundance of Enterococcus, Eubacterium, Unc. Erysipelotrichaceae, Collinsella, Butyricicoccus and Unc. Coriobacteriaceae was higher, while Weissella, Fructobacillus and Oscillo-spira genera were lower in IBS+A mice that were gavaged with water, compared with HC mice. Treatment with S bou normalized those differences. Predicted function analysis suggested higher number of genes implicated in indole biosynthesis in S. bou-treated mice (P=0.01). in addition, co-culture of fecal microbiota from SPF mice with S. bou in vitro resulted in 20% higher levels of indoles, and 50% higher levels of Lactobacillus (which correlated between them - R²=0.76, P< 0.001).

Conclusion

Saccharomyces boulardii CNCM I-745 improves the intestinal and behavioral phenotype induced by IBS+A microbiota in mice. Putative mechanisms include regulation of host Trpvl gene expression, modulation of the microbiota and indole production. The results prompt investigation of S. bou in IBS patients with co-morbid anxiety.

Disclosure

Presented as a poster at the Canadian Digestive Diseases Week on March 2020 Supported by a grant from Biocodex - Gentilly - France

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.45

P0053 Impaired Regulation of Autonomic Nervous System in Globus Pharyngeus

P Lipták ^1,^✉, M Duricek ², P Banovcin ², R Hyrdel ¹, I Tonhajzerová ³

Introduction

Globus pharyngeus is one of the more common functional gastrointestinal disorder (FGID). The pathophysiological mechanisms of FGID are complex. However data considering possible cause of globus pharyngeus are scarse. Accumulating evidence indicates that autonomic dysregulation contributes to FGID but whether this is true for globus is still unknown. The symptoms of FGID are often triggered by stress, however, the mechanisms of autonomic dysregulation in FGID, especially in response to stress are incompletely understood.

Aims & Methods

The aim of this study was to assess potential changes of autonomic nervous regulation in patients suffering from globus pharyngeus in response to distinct types of stressors (passive physical stress vs. active mental stress).

Methods

Studied population included 7 patients diagnosed with globus and 10 sex- and age-matched healthy controls. All patients were diagnosed according to ROME IV criteria for functional gastrointestinal disorders. Blood pressure (BP) and heart rate were continuously recorded using Finometer MIDI (FMS, Netherlands) at rest and during two distinct stressors - mental arithmetic test and cold pressor test (cooling of forearm in 1-3^oC water bath for 5 min). Evaluated parameters:

1) baroreflex sensitivity (BRS, calculated from spontaneous heart rate variability and BP variability) reflex vagally-mediated heart rate regulation in response to changes of BP,

2) spectral power in low-frequency band of systolic BP variability (LF-SBP) reflecting sympathetic alpha-adrenergic stimulation of vascular smooth muscles,

3) systolic and diastolic BP, and

4) mean heart rate.

Results

BRS (reflecting vagal function) in patients with globus was substantially reduced compared to controls at rest and in response to both mental arithmetic test and to cold pressor test (p< 0.001 for all comparisons). in contrast, LF-SBP (reflecting sympathetic function) was normal at baseline, but had tendency to be increased in globus group compared to controls during both stress tests. No differences were found in systolic and diastolic BP and heart rate.

Conclusion

Our data show impaired dynamic sympatho-vagal balance in patients with globus pharyngeus at rest and in response to different types of stressors. The vagal function is strongly reduced at baseline and not influenced by stress, while the sympathetic response have tendency to be exaggerated by stress.

These findings support the hypothesis of altered autonomic regulation as a potential mechanism worsening the symptoms of globus with possible contibution of stress as factor. We suggest that comprehensive evaluation of autonomic response using noninvasive methods could help to better understand the role of autonomic dysregulation in functional gastrointestinal disorders.

Support: Slovak Scientific Grant Agency [VEGA 1/0044/18 and 1/0190/20]; project Ministry of Health of the Slovak Republic under the project registration number 2018/20-UKMT-16

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.46

P0054 Brain Functional Connectivity Changes in Irritable Bowel Syndrome Using A Lactulose Pain Provocation Test and Resting-State Fmri

B Halandur Nagaraja ^1,^2,^✉, B Berentsen ^1,³, T Hausken ^1,³, A Lundervold ^2,⁴

Introduction

Irritable bowel syndrome (IBS) is a heterogenous chronic gastrointestinal disorder characterized by chronical abdominal pain associated with altered bowel habits, in the form of diarrhea, obstipation or a mix between the two. The brain-gut axis (BGA) play an important role in IBS, and neuroimaging techniques are useful in the study of brain-gut interactions [1]. Herein, we used resting state functional magnetic resonance imaging (rs-fMRI) to analyse the functional connectivity changes in IBS patients.

Aims & Methods

Eighteen patients with IBS and nine healthy controls (HC) underwent high-resolution anatomical T1-weighted imaging followed by resting state BOLD fMRI scan, twice. After the first scan subjects were administered lactulose (10 mg per os) as a pain provocation test known to induce symptoms in patients with IBS, and the second scan was performed after two and half hours.

Pre-processing of rs-fMRSI signals consisted of, removing first two time points, despikeing, slice timing correction, co-registration to T1-weighted anatomical images, head motion correction, blurring and nuisance regression. T1-weighted structural MR images were processed using Freesurfer [2] to obtain cortical reconstruction and volumetric segmentation. The T1-weighted MRI segmentations were transformed to fMRI space for extracting the regions of interest (ROIs).

To calculate the functional connectivity (FC) the seed signal was obtained by averaging the pre-processed rs-fMRI time-series from all the voxels in the Freesurfer-segmented insular gyrus region of the left hemisphere. All pre-processing of rs-fMRI signals and the estimation of FC maps were performed using Analysis of Functional NeuroImages software package [3].

Results

Mean of FC values were calculated for the 177 ROIs obtained from Freesurfer segmentation. To identify the ROI with significant changes in FC, two tailed t-tests were performed between mean FC values of IBS patients and healthy controls. Table 1 shows the average FC values over all the IBS patients and HC for some of the brain regions. IBS patients had significantly lower FC values in both the amygdala and the right hippocampus regions. Also, IBS patients have significantly higher FC in right insular cortex compared to healthy controls. Administration of lactulose resulted in significant lower FC values in the amygdala region in healthy controls. However, no significant changes were observed in IBS patients. in the hippocampus regions, FC values of IBS patients were increased, whereas FC values in the same region were reduced in healthy controls.

Table.1.

Mean FC values of IBS patients and healthy controls from both before lactulose (BL) and after lactulose (AL) rs-fMRI scans.

	Right Amygdala	Left Amygdala	Right Hippocampus	Left Hippocampus	Right Short Insular cortex	Right Thalamus proper
IBS	BL:0.125	BL:0.134	BL:0.079	BL:0.074	BL:1.075	BL:0.121
IBS	AL:0.181	AL:0.194	AL:0.170	AL:0.163	AL:1.024	AL:-0.149
HC	BL:0.437	BL:0.500	BL:0.315	BL:0.245	BL:0.768	BL:0.083
HC	AL:0.193	AL:0.171	AL:0.145	AL:0.142	AL:0.886	AL:0.152
p-value (BL)	0.037	0.006	0.023	0.115	0.038	0.748

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Conclusion

The IBS patients have significantly different insular cortex resting state functional connectivity maps compared to healthy controls. Also, the administration of lactulose affects the brain differently in IBS patients and healthy controls. in future, comprehensive study of brain activation and connectivity maps using more healthy controls and IBS patients is planned.

Disclosure

This work is supported by the Norwegian Research Council FRIMEDBIO276010, and Helse Vest's Research Funding 2017

References

1.Mayer Emeran A. et al. “Role of brain imaging in disorders of brain-gut interaction: a Rome Working Team Report.” Gut 68.9 (2019): 1701–1715. [DOI] [PMC free article] [PubMed] [Google Scholar]
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United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.47

P0055 Transcutaneous Vagal Nerve Stimulation As A Potential Treatment For Functional Gastrointestinal Disorders: A Meta-Analysis of Neuroimaging Evidence

R Rajiah ^1,^✉, K Takahashi ¹, J Ruffle ¹, Q Aziz ¹

Introduction

Autonomic nervous system dysfunction is common in functional gastrointestinal diseases (FGIDs). Attributed to complex underpinning pathophysiology, limited options exist for their medical management. Considering the pivotal role of the vagal nerve in the ‘brain-gut axis’, transcutaneous vagal nerve stimulation (tVNS) has been proposed as a novel treatment option. However, its precise central mechanism is unknown, which must be concretely ascertained before its widespread uptake in clinical practice.

Aims & Methods

The aim was to identify the reproducible neural correlates of tVNS by meta-analysis. A total of 157 studies were identified from the Web of Science and PubMed databases. 4 neuroimaging studies, encompassing 60 subjects (17 male, 27 female and 16 not provided) aged 18-45, met the inclusion criteria. Using GingerALE meta-analysis of imaging data, activation likelihood estimation (ALE) at the cluster level was calculated. Studies were reviewed for concordance of brain activity in thee domains: (1) tVNS vs. baseline; (2) sham stimulation vs. baseline; and (3) tVNS vs. sham stimulation.

Results

tVNS consistently activated regions comprising the insula, thalamus, caudate, medial frontal gyrus and cingulate gyrus and deactivated clusters within the parahippocampal gyri and brainstem (p< 0.0005 Table 1). These findings are consistent with brain regions indicated in vagal nerve activity, interoception and pain processing.

Table 1.

Meta-analytic regions of brain activation and deactivation for tVNS vs. baseline and tVNS vs. sham stimulation in 60 healthy participants

Cluster Ranking	X	Y	Z	ALE score	P-value	Z-score	Location
Brain activation for tVNS vs. baseline
1	-40	-6	4	0.0111	0.0000	4.2076	Insula (L)
1	-48	44	-16	0.0080	0.0002	3.6020	Middle Frontal Gyrus (L)
1	-42	40	0	0.0077	0.0002	3.4906	Inferior Frontal Gyrus (L)
1	-58	-18	16	0.0074	0.0005	3.2849	Transverse Temporal Gyrus (L)
1	-60	-20	30	0.0074	0.0005	3.2849	Inferior Parietal Lobule (L)
Brain deactivation for tVNS vs. baseline
1	-30	-46	-8	0.0116	0.0000	4.7882	Parahippocampal Gyrus (L)
1	-6	-28	-24	0.0079	0.0000	3.9969	Brainstem
Brain activation for tVNS vs. sham stimulation
1	-12	26	44	0.0080	0.0001	3.6600	Cingulate Gyrus (L)
1	-12	38	34	0.0079	0.0001	3.6374	Medial Frontal Gyrus (L)
1	-12	-2	16	0.0074	0.0005	3.3079	Caudate Body (L)
1	-10	-16	10	0.0074	0.0005	3.3079	Thalamus Medial Dorsal Nucleus (L)
Brain deactivation for tVNS vs. sham stimulation
1	-6	-28	-30	0.0116	0.0000	5.51540	Brainstem

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Conclusion

tVNS reproducibly activates brain areas implicated in the regulatory central autonomic network and deactivates pain processing nodes. Considering the centrality of dysautonomia to FGID pathophysiology, further therapeutic exploration of tVNS is warranted to determine if it can have therapeutic benefit in visceral pain.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.48

P0056 in Patients with Heartburn, Superficial Mucosal Afferent Nerves Express Transient Receptor Potential Vanilloid Subfamily Member-1 (Trpv1), and Oesophageal Epithelial Cells Express Acid-Sensing Ion Channel 3 (Asic3)

A Ustaoglu ^1,^✉, P Woodland ¹, M Peiris ¹, D Sifrim ¹

Introduction

Heartburn is a characteristic symptom of gastro-oesoph-ageal reflux disease. This unpleasant symptom is generated at the oe-sophageal mucosa, where noxious contents of the refluxate interface with nociceptors within the superficial epithelium [1]. We have recently demonstrated superficial afferent nerves in the oesophageal mucosa of patients with non-erosive reflux disease (NERD), but deeper lying nerves in erosive oesophagitis, functional heartburn, and healthy controls [2]. Thus far, these nerves have not been further characterised. Transient receptor potential vanilloid subfamily member-1 (TRPV1) and acid sensing ion channel 3 (ASIC3) are ion channels that can respond to acid and have been implicated in the pathogenesis of GORD [3,4]. TRPV1 mRNA and protein levels are increased in patients with NERD and erosive oesophagitis, and acid-induced activation of ASIC3 sensitises primary oesophageal epithelial cells in culture. The expression of TRPV1 and/or ASIC3 on superficial oesophageal mucosal nerves would strongly support the role of these nerves in heartburn pathogenesis.

Aims & Methods

We aimed to characterise TRPV1 and ASIC3 expression on oesophageal mucosal afferent nerves in patients with heartburn. We studied 35 patients with heartburn symptoms, and phenotyped them endoscopically and with objective reflux studies into erosive oesophagitis (N=10), NERD (N=10), functional heartburn (N=7), and Barrett's oesophagus (N=8) groups. Mucosal biopsies taken at endoscopy were co-stained with TRPV1 (Alomone, ACC-050, 1:400) or ASIC3 (ThermoFisher Scientific, PA5-61898, 1:200), and CGRP (ThermoFisher Scientific, PA1-30927, 1:400) or E-cadherin (Sigma-Aldrich, 1:100). qPCR was used to assess TRPV1 (Qia-gen, QT01010219) and ASIC3 (Qiagen, QT01012557) gene expression in RNA extracted from these mucosal biopsies. Co-localising pixels between TRPV1 and CGRP were quantified with Manders coefficient, and ASIC3-im-munoreactive cells were counted using FIJI. Statistical significance among GORD phenotypes was analysed with one-way ANOVA.

Results

In keeping with our previous studies, we found superficial sensory mucosal nerves (within 8 cell layers of the lumen) most commonly in NERD patients (90% of NERD vs 40% in FH). Deep nerves (approx. 22 layers from lumen) were found in 46% of the samples assessed and were most frequently intra-papillary regardless of disease phenotype. Superficial sensory nerves expressed TRPV1 most significantly in NERD (p=0.0057). Deep intrapapillary CGRP positive nerve endings did not express TRPV1 in all phenotypes studied. TRPV1 was occasionally found expressed on epithelial cells. in contrast, ASIC3 was not expressed on nerves, but was expressed on epithelial cells in 43% of samples. ASIC3 was more often expressed in NERD and erosive oesophagitis patients (p=< 0.0001).

Conclusion

Superficial oesophageal mucosal nerves, found most frequently in NERD, express TRPV1. Moreover, ASIC3 is expressed predominantly in epithelial cells of NERD and erosive oesophagitis patients. This suggests that superficial mucosal nerves and oesophageal epithelial cells drive acid and pain hypersensitivity. Superficial localisation of TRPV1-immunoreactive nerves and expression of ASIC3 on epithelial cells raise the enticing possibility of topical antagonists as a therapeutic option in treatment of NERD.

Disclosure

Nothing to disclose

References

1.Van Oudenhove L. et al. Best Pract. Res. Clin. Gastroen-terol., vol. 18, no. 4, pp. 663–680, Aug. 2004. [DOI] [PubMed] [Google Scholar]
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3.Guarino M. P. L. et al. Neurogastroenterol. Motil., vol. 22, no. 7, pp. 746–e219, Jul. 2010. [DOI] [PubMed] [Google Scholar]
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United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.49

P0057 Assessment of The Reflex Response of The Lower Esophageal Sphinter Through High Resolution Manometry

O Moralejo Lozano ^1,^✉, JA Pérez de la Serna y Bueno ², A León Ruíz de ², C Sevilla Mantilla ², A Zataráin Valles ², M Aparicio Cabezudo ², C Ciriza de los Ríos ², AJ Barrajón Masa ¹, M Colmenares Bulgheroni ¹

Introduction

Hypotonia, increases in abdominal pressure (AP), and transient lower esophageal sphincter relaxations (TLESR) are the main etio-pathogenic factors of gastroesophageal reflux disease (GERD). The objective of the study is to assess the possibility of detecting the reflex response of the lower esophageal sphincter (LES) to different stimuli during high-resolution manometry (HRM).

Aims & Methods

A group of patients referred for evaluation of GERD by means of solid state HRM (Medtronics) and 24h pHmetry are studied. Patients with esophageal gastric surgery or major esophageal motor disorders were excluded. 2 groups were defined: Group 1: patients who underwent two abdominal pressure increase maneuvers (manualcompression of the abdomen [MCA], and leg elevation [LE]), and Group 2: in which a change in the position from supine position into a sitting position to trigger TLESR.

Results

73 patients were included: group 1, 35 (19 women) and group 2, 38 (28 women). in group 1, the HRM allowed to identify and quantify the increases in intragastric pressure and the LES reflex response. The mean of the basal gastric pressure was similar in men and women. Gastric pressure increases during LE are much higher than those obtained with MCA (25.7 ± 12 vs. 8.9 ± 3.6). The contractile response was produced mainly by the diaphragmatic component during LE and by the intrinsic LES with MCA. These differences are appreciable only when the 2 components of the gastro-esophageal junction (hiatal hernia) are identified. in group 2, change in position triggered TLESR in 23/38 patients, regardless of the LES resting pressure. The pHmetry showed pathological GER in 14 patients in group 1 and in 19 in group 2. in both the tests were positive more frequently in these patients, although without statistically significant differences, probably due to the small number of cases.

Conclusion

Carrying out these tests during the HRM is easy, does not excessively prolong the study, does not add significant discomfort to the patient, and allows identifying those with an inadequate LES reflex response. The abdominal pressure increases are greater with the LE test, during which the LES response is produced mainly by the diaphragmatic component, unlike what happens during the MCA in which most of the contractile response is carried out by the component intrinsic to the LES.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.50

P0058 Pathophysiology of The Inability To Belch Syndrome: Observations Made with Prolonged Esophageal Pressure and Impedance Monitoring

R Oude Nijhuis ^1,^✉, J Snelleman ², BF Kessing ³, J Oors ¹, D Heuveling ², L ten Cate ⁴, JM Schuitenmaker ¹, A Smout ¹, A Bredenoord ¹

Introduction

Symptoms of inability to belch are occasionally reported in gastrointestinal and otorhinolaryngological clinical practices. Although the phenomenon has previously been associated with dysfunction of the cricopharyngeal muscle, its underlying etiology is unclear. Esophageal and pharyngeal air transport patterns and the role of the upper esopha-geal sphincter (UES) have never been objectively investigated.

Aims & Methods

The aim of this study was to evaluate pathophysiological mechanisms underlying symptoms of inability to belch using prolonged esophageal pressure and impedance monitoring. Consecutive patients presenting with symptoms of inability to belch were included. VAS scores were collected to evaluate esophageal symptoms. All patients underwent prolonged stationary esophageal high-resolution impedance manometry (HRIM) to assess esophageal motility, UES and lower esophageal sphincter (LES) pressures and relationships with air transport patterns in the pha-ryngoesophageal region. Patients drank 500 mL of carbonated water to stimulate belching. A subsequent ambulatory pH-impedance study was performed to assess gas reflux patterns and esophageal air presence time over 24 hours. Statistics were presented as medians with range.

Results

We included nine patients, age 25 (18 - 37) years, of whom 5 were male. Gurgling noises from the throat (100%; VAS 8.8 (6.0-10.0)) and bloating (89%; VAS 7.8 (6.4 - 9.1)) were the most frequently reported symptoms. in 8 out of 9 patients, motility was classified as ineffective or absent (distal contractile integral 339.5 (0-753) mmHgxcmxs; integrated relaxation pressure 7.2 (3.7-16.2) mmHg). in the majority of patients (89%), UES resting and residual relaxation pressures during wet swallows fell within the normative range (114.0 (71.7-224.9) mmHg and 2.0 (0 - 9.5) mmHg, respectively). After ingestion of the carbonated water, a median number of 42 (14-69) gas reflux episodes up to the level of the lower border of the UES were observed, but none resulted in UES opening. Most events (64%) were followed by a secondary peristaltic contraction. During 24-h pH impedance monitoring, patients reported 10 (5-174) symptom episodes of inability to belch. The majority of these episodes (100% (50-100)) were associated with gas reflux impedance patterns. Moreover, periods of continuous high impedance levels, indicating air entrapment, were observed in all patients. The 24-h esophageal air presence time was 19.9% (2.3-32.6). in all patients, the number of mixed and pure liquid reflux episodes and total acid exposure time were normal (13 (1 - 68) and 1.8% (0.0- 20.2), respectively).

Conclusion

Prolonged HRIM recordings confirm the existence of a syndrome characterized by an inability to belch and support the hypothesis that ineffective UES relaxation, and consequent esophageal air entrapment, may lead to pharyngoesophageal symptoms.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.51

P0059 Achalasia Is Associated with Atopy in Patients Under 40 Years of Age

D King ^1,^2,^✉, J Chandan ², T Thomas ³, N Bhala ², N Adderley ², K Nirantharan ², N Trudgill ¹

Introduction

Achalasia is an uncommon motility disorder of the esophagus of unknown aetiology. Associations with autoimmune disorders have been described. Eosinophilic esophagitis (EoE) is associated with atopic conditions such as asthma and eczema. Patients with features of achalasia who are subsequently diagnosed with eosinophilic esophagitis (EoE) and respond to glucocorticosteroids have been previously reported.

Aims & Methods

The aim of this study was to examine associations between achalasia and atopic and autoimmune diseases. A retrospective cohort study using a national primary-care database examined associations between achalasia subjects at both diagnosis and during follow-up, with atopic, autoimmune and neurodegenerative conditions compared with age/sex matched controls. Models were adjusted for age, sex, deprivation, body mass index and smoking status. Due to potential confounding between atopic and autoimmune conditions, subjects with atopic conditions at baseline were excluded when examining associations with autoimmune conditions and vice versa.

Results

Between 1995 and 2018, 2,593 participants with achalasia (median age 57 (IQR 42-72) years; 52% male) were identified, and matched to 10,402 controls. This included 1,082 incident cases, matched to 4,322 controls. At diagnosis, achalasia subjects were at increased risk of autoimmune conditions with 57 (9%) autoimmune conditions in 654 achalasia cases compared to 176 (6%) in 2,866 controls (Odds Ratio 1.39 (1.02-1.90), p=0.039). At diagnosis of achalasia, in the whole cohort, there was no association with atopic conditions with 311 (32%) atopic conditions in 964 achalasia subjects compared to 1,133 (28%) in 3,995 controls (OR 1.16 (1.00-1.37), p=0.53). However, achalasia subjects under 40 years of age had a 40% increased risk of atopy with 76 (39%) atopic conditions in 195 achalasia cases and 240 (30%) in controls (OR 1.4 (95%CI 1.00-1.95), p=0.047). Few incident conditions of interest in achalasia subjects were observed, and no increase in incident rate ratio (IRR) was observed for atopic, autoimmune or neurodegenerative conditions between achalasia subjects and controls. However, an increased IRR was seen for both rheumatoid arthritis and vitiligo individually (2.02 (1.16-3.5), p=0.012 and 3.21 (1.07-9.62), p=0.037 respectively).

Conclusion

This study suggests that in a subset of younger achalasia patients there is an association with atopy that may have aetiological significance.

Disclosure

KN reports grant from AstraZeneca, personal fees from Sanofi and Boehringer Ingelheim, outside the submitted work. NJA reports grants from MSD and AstraZeneca, outside the submitted work. NT reports grants from Dr. Falk, MSD, AstraZeneca and Pfizer, outside the submitted work. Other authors have no conflicts of interest to declare.

References

Spechler S.J., Konda V., Souza R. Can Eosinophilic Esophagitis Cause Achalasia and Other Esophageal Motility Disorders? Am J Gastroenterol. 2018; 113(11): 1594–1599. doi: 10.1038/s41395-018-0240-3 [DOI] [PubMed] [Google Scholar]

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.52

P0060 Systemic Diseases Associated with Absent Esophageal Contractility Disorder, It Is Not Always Scleroderma

L Alcala ^1,^✉, A Jimenez Masip ², L Relea ³, E Barba Orozco ¹

Introduction

Absent contractility is characterized by aperistalsis (100% of swallows with failed peristalsis) and normal median integrated relaxation pressure (IRP). The mechanism and pathogenesis of this disorder is unknown. Absent contractility is associated with systemic autoimmune diseases, especially scleroderma (SSc) and frequently with severe gastro-esophageal reflux (GERD), but the evidence is limited on other systemic diseases associated with this esophageal disorder, and only one study has addressed this issue.

Aims & Methods

The aims of this study were to describe the systemic diseases associated with absent contractility and to describe the clinical and manometric characteristics of these patients.

Methods

We performed a retrospective study of all patients diagnosed with absent contractility in our center. We reviewed all high resolution esophageal manometry (HREM) studies performed between May 1st 2018 and February 29th 2020. After careful selection of patients, clinical, demographic, endoscopic and esophageal manometry data were obtained from the electronic medical records.

Results

A total of 1317 HREM were performed in the study period and 72 patients with absent contractility were included for analysis. Overall, 43 (59.7%) were female, with a mean age of 55.4 (+- 15.0) years. Indications for HRM were dysphagia in 23 (31.9%) suspicion of GERD in 23 (31.9%), suspicion of autoimmune disease in 18 (25.0%) and miscellaneous in 8 (11.1%).

A comprehensive overview of systemic disorders associated with absent contractility is shown in Table 1.

Table 1.

systemic disorders associated with absent contractility

Etiology	cases
Autoimmune disease, n (%)	31 (43.1)
Limited scleroderma, n (%)	14 (19.5)
diffuse scleroderma, n (%)	8 (11.1)
Mixed connective tissue disease, n (%)	6 (8.3)
Sjogren, n (%)	1 (1.4)
LES, n (%)	1 (1.4)
Anti-synthetase syndrome, n (%)	1 (1.4)
Acid-reflux associated, n (%)	25 (34.7)
GERD, n (%)	20 (27.7)
Post-nissen, n (%)	4 (5.6)
Post vagotomy, n (%)	1 (1.4)
Others, n (%)	10 (13.9)
Chronic idiopathic pseudoobstruction, n (%)	3 (4.2)
Steinert myopathy, n (%)	2 (2.7)
CVID / esophageal candidiasis, n (%)	1 (1.4)
Eosinophilic esophagitis, n (%)	1 (1.4)
Chagas disease, n (%)	1 (1.4)
presbyesophagus, n (%)	1 (1.4)
Rumination syndrome, n (%)	1 (1.4)
Unknown, n (%)	6 (8.3)
anti smooth muscle positive, n (%)	1 (1.4)
all test negative	5 (6.9)

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HREM metrics showed a hypotensive LES in 43 (59.7%), with a mean LES resting pressure of 13.9(±11.5) mmHg and a mean integrated relaxation pressure 3.2(±3.4) mmHg, there were no significant differences between groups, interestingly, the presence of a hiatal hernia was more frequent in GERD patients than patients without GERD (36.0% vs 14.9% p = 0.04).

Conclusion

We found that 34.7% of patients had a different etiology of absent contractility other than GERD or SSc, and even after an extensive evaluation, a definite diagnosis could not be reached in 8.3% of patients.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.53

P0061 Basal Pressure of Les and Ues: Should We Determine At The Beginning Or End of High Resolution Esophageal Manometry?

C Arieira ^1,^2,^3,^✉, M Freitas ^1,^2,³, F Dias de Castro ^1,^2,³, J Berkeley Cotter ^1,^2,³

Introduction

Manometric parameters of High Resolution Esophageal Manometry (HREM) are defined according to the Chicago Classification (CC). The determination of the basal pressure of the Upper Esophageal Sphincter (UES) and Lower Esophageal Sphincter (LES) is traditionally performed at the beginning of the HREM in a period of 30 seconds at rest. The invasiveness of intubation and the need to inhibit dry swallowing during determination seems to be the cause of changes in these parameters.

Aims & Methods

To evaluate differences in baseline pressures of the UES and LES when the acquisition of these parameters was made simultaneously at the beginning (standard) and at the end (additional) of HREM. Included patients who underwent HREM with a 36-channel solid state probe (Manoscan®) in supine position, in which an additional assessment of the baseline pressure of UES and LES was carried out at the end of HREM.

Results

Included 76 patients, 60.5% female, with a mean age of 56.6 ± 14.9 years. Most HREM were performed due to GERD (56.6%). in 44.7% of the patients there was a motility disorder according to CC and in 44.7% there was a hiatal hernia. The baseline pressure of the UES (99.6 vs 69.6mmHg; p < 0.001) and LES was statistically different at the beginning and end of the HREM (19.5 vs 17.1mmHg; p < 0.001). At the beginning of the HREM, 40.8% presented hypertensive UES and 3.9% hypotensive, at the end 11.8% hypertensive and 11.8% hypotensive. Regarding the LES, at the beginning of the HREM, 14.5% was hypertensive and 15.8% was hypotensive, at the end, 11.8% was hypertensive and 26.3% was hypotensive.

Conclusion

The baseline pressures of the UES and the LES seem to be statistically higher at the beginning of the HREM when compared to those obtained at the end of the study. These findings may reflect a better patient adaptation throughout the study to the procedure and, probably, the baseline pressure obtained at the end of the procedure maybe more reliable.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.54

P0062 Esophago-Gastric Junction Contractile Integral (Egj-Ci) May Predict Response To Treatment in Patients with Esophageal Achalasia

N de Bortoli ^1,^✉, F Bronzini ¹, S Santi ², S Tolone ³, M Frazzoni ⁴, P Visaggi ¹, L Mariani ¹, M Bellini ¹, R Penagini ⁵, S Marchi ¹, EV Savarino ⁶

Introduction

achalasia is defined by the inability of the lower esophageal sphincter to relax in the setting of absent peristalsis. Treatment is focused on reducing symptoms, improve quality of life and prevent complications. Treatments options are actually suggested according to achalasia pattern at high resolution manometry (HRM).

Aims & Methods

The aim of this study was to evaluate the esophagogastric junction contractile integral (EGJ-CI) and integrated relaxation pressure (IRP) during high and low volume provocative test in a series of patients with achalasia who underwent PD or HDM. We evaluated consecutive patients with achalasia. All patients underwent upper endoscopy, X-ray and esophageal HRM, Eckdart score. During HRM we evaluated mean EGJ pressure, IRP and EGJ-CI. All patients underwent provocative testing: low volume (multiple rapid swallow, MRS) and high volume 200ml (rapid drinking challenge, RDC) tests. The values of IRP during MRS and RDC were collected in all patients. Treatment options were decided according to achalasia HRM pattern, age, anesthesiologic risk and patient choice. All patients were evaluated with X-Ray and Eckardt symptom score 6-month after treatment. According to the treatment efficacy, all patients were divided in: Group A (responder) characterized by no residual dysphagia and normal X-Ray; Group B (non-responder) residual dysphagia and barium retention.

Results

We enrolled 56 patients (27 female) with mean age 60.6±17.8 yrs. All patients had dysphagia and barium retention during X-Ray at baseline. Twenty-eight patients were treated with PD and the same number with HDM. The HRM pattern was: 20 patients with type I, 33 patients type II and 3 type III. According to the patients’ outcome, we had 35 patients (18 female) considered as responder and 21 patients (9 female) as non-responder. EGJ-CI were higher in non-responder (p< 0.001). During provocative test IRP was lower in responder group (p< 0.001). Results detailed in Table 1.

A ROC analysis showed that EGJ-CI (cut-off value 88.95 mmHg-cm) had the best performance (AUC 0.975, sensibility 95.5% and specificity 100%) to predict response to treatment in patients with achalasia undergoing en-doscopic or surgical treatment.

Table 1.

data collected during HRM

	Responder (35)	Non-Responder (21)	p
Male/Female	18/17	12/9	0.934
Mean age (yrs)	59±19.5	60.3±20.2	0.852
EGJ mean (mmHg)	41.4±21.2	56.7±30.4	0.06
Mean IRP-SS (mmHg)	36.5±15.9	43.5±22.7	0.168
EGJ-CI (mmHg-cm/s)	71.9±40.6	120.3±31.1	<0.001
IRP-MRS (mmHg)	31.9±13.7	44.6±14.4	0.0014
Pressurization RDC	13/35	20/21	<0.001
Esophageal dilation (x-Ray)	18/35	10/21	>0.99
Heled-Dor Miotomy	22	8	0.09

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Conclusion

Our data suggest that EGJ-CI has the greater diagnostic performance in distinguishing responder to non-responder and should be routinely evaluated in order to choose the best treatment approach for these patients.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.55

P0063 Dysphagia: Has Standardising Our Test Meal Increased Our Diagnostic Yield During High Resolution Oesophageal Manometry?

C Sykes ^1,^2,^✉, A Davidson ^1,², J Blake ², A Dhar ^1,³, M Fox ^4,⁵, H Parker ²

Introduction

Non-achalasia major motility disorders (MMD) are part of the diagnostic algorithm of the Chicago Classification for high resolution manometry (HRM) and are notably difficult to manage¹. Further still, few patients presenting with oesophageal dysphagia related to MMD report symptoms when swallowing small amounts of water². Inclusion of a standardised solid test meal (rice STM) has been shown to increase the diagnostic sensitivity and specificity for MMD^2,3. An alternative approach used clinically is to ask patients to attend for HRM with foods that usually cause them symptoms; however, it is not known if this provides equivalent results.

Aims & Methods

The primary aim of this diagnostic study was to compare diagnostic yield for MMD of the rice STM with a non-standardised meal, selected by the patient or physiologist. A secondary aim was to compare the likelihood that symptoms were triggered by the test meal. 190 consecutive patients referred for investigation of oesophageal dys-phagia underwent oesophageal HRM (24-channel, water-perfused catheter, MUI Scientific, Canada) at the University Hospital of North Durham, UK (Apr 2016-Mar 2020). The presence of symptom-associated major dys-motility during test meals was recorded (symptoms registered within 10s of objective dysmotility). Excluded patients included those with previous MMD diagnosis, previous surgery and failure to complete the HRM study. Half of the cohort received a non-standardised test meal and half were served the rice STM with established reference intervals⁴. Meals required at least 10 swallows to complete. Patients were categorised based on manometric findings (no MMD or MMD). Differences between groups were assessed using the Chi-squared test.

Results

79 dysphagia patients (42%) met the inclusion criteria for the study. Exclusions were predominantly diagnosis of achalasia (n=50 patients) or diagnosis of a non-achalasia MMD during water swallows (n=36). of those included, 39 underwent a non-standardised test meal and 40 the rice STM. There was no difference in diagnostic yield or symptom reporting between the two test meals (Table 1). An additional 17 (22%) patients with normal motility or ineffective motility (IEM) during single water swallows had a non-achalasia MMD as a result of solid meal inclusion. Approximately half of these patients, (n=8, six with outflow obstruction), irrespective of test meal had positive “symptom association dysmotility” during the study. A similar number of patients (n=11) had symptoms associated with repeated failed or ineffective oesophageal motility, indicative of clinically relevant IEM⁴.

Table 1.

Manometric findings and symptom associations during test meals.

	Standard test meal (n=40)	Non-standard test meal (n=39)	Significance
Total symptomatic (%)	16 (40%)	13 (33%)	p = 0.54
Total major motility disorder (%)	9 (23%)	8 (21%)	p = 0.83

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Conclusion

The inclusion of a standardised test meal or non-standard testing with solids selected by the patient or physiologist both increased the diagnostic yield of MMD from single water swallow HRM studies by the same extent (overall 22%, in line with prospective case series⁴). The number of patients who reported oesophageal dysphagia during the standardised and non-standard test meals was also similar. These findings confirm that the inclusion of a test meal significantly increases the diagnostic yield of HRM studies; however, as long as sufficient solid swallows are taken (minimum 10), the choice of test meal may not be critical.

Disclosure

Nothing to disclose

References

1.Tutuian R., & Castell D. O. Esophageal motility disorders (Distal esophageal spasm, nutcracker esophagus, and hypertensive lower esophageal sphincter): Modern management. Curr. Treat. Options Gastro-enterol. 9, 283–294 (2006). [DOI] [PubMed] [Google Scholar]
2.Sweis R., Anggiansah A., Wong T., Brady G., & Fox M. Assessment of esophageal dysfunction and symptoms during and after a standardized test meal: Development and clinical validation of a new methodology utilizing high-resolution manometry. Neurogas-troenterol. Motil. 26, 215–228 (2014). [DOI] [PubMed] [Google Scholar]
3.Ang D. et al. Diagnostic yield of high-resolution manometry with a solid test meal for clinically relevant, symptomatic oesophageal motility disorders: serial diagnostic study. Lancet Gastroenterol. Hepatol. 2, 654–661 (2017). [DOI] [PubMed] [Google Scholar]
4.Hollenstein M. et al. Pharyngeal swallowing and oesophageal motility during a solid meal test: a prospective study in healthy volunteers and patients with major motility disorders. Lancet Gastroenterol. Hepatol. 2, 644–653 (2017). [DOI] [PubMed] [Google Scholar]

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.56

P0064 Overlap Syndrome of Gerd and Dyspepsia in The Organized Urban Population of Khakassia

V Tsukanov ^1,^✉, O Rzhavicheva ², N Butorin ³, A Vasyutin ¹, J Tonkikh ¹

Introduction

One of the most actual clinical problems is overlap syndrome of GERD and dyspepsia.

Aims & Methods

In Abakan, a cross sectional study was performed in 1411 people, of whom 905 were alien (Caucasoids, 402 men and 503 women, average age 44.9 years) and 506 indigenous (Khakasses, 276 men and 230 women, average age 41.3 years) inhabitants, which amounted to 93% of the Abakanvagonmash enterprise list. Heartburn was diagnosed in accordance with the Montreal Consensus [1], Barrett's esophagus in accordance with the British Society of Gastroenterology guidelines [2]. Diagnosis of dyspepsia was performed according to the Rome IV criteria [3]. Esophagogastroduodenoscopy was performed in 813 patients in a 50% random sample. Diagnosis of esophagitis was based on the Los Angeles Classification [4].

Results

The prevalence of dyspepsia was 24.3% in Caucasoids and 17.8% in Khakasses (OR=1.48; 95% CI 1.13-1.95; p=0.006). Heartburn was registered in 14.7% of alien inhabitants and in 10.3% of indigenous people (OR=1.50; 95% CI 1.07-2.10; p=0.02); esophagitis - in 3.4% of Caucasoids and 1.9% of Khakases (OR=1.75; 95% CI 0.70-4.35; p=0.3). The frequency of heartburn was 34.5% in Caucasoids with dyspepsia and 8.3% in Cau-casoids without dyspepsia (OR=5.79; 95% CI 3.93-8.52; p< 0.001); 31.1% in Khakases with dyspepsia and 5.5% in Khakases without dyspepsia (OR=7.64; CI 4.16-14.02; p< 0.001). Among Caucasoids, esophagitis was recorded in 12.5% of patients with dyspepsia and 0.5% of people without dyspepsia (OR=22.01; 95% CI 5.69-85.17; p< 0.001). in Khakasses, these indicators were, respectively, 8.9% and 0% (OR=55.85; 95% CI 3.04-1025.76; p< 0.001).

Conclusion

The incidence of dyspepsia and GERD was higher among Caucasoids compared with Khakasses. Overlap GERD and dyspepsia were registered in both populations.

Disclosure

Nothing to disclose

References

1.Vakil N., van Zanten S.V., Kahrilas P. et al. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006; 101(8): 1900–20. [DOI] [PubMed] [Google Scholar]
2.Fitzgerald R.C., di Pietro M., Ragunath K. et al. British Society of Gastroen-terology guidelines on the diagnosis and management of Barrett's oesophagus. Gut. 2014; 63(1): 7–42. [DOI] [PubMed] [Google Scholar]
3.Stanghellini V., Chan F.K., Hasler W.L. et al. Gastroduodenal Disorders. Gastroenterology. 2016; 150(6): 1380–92. [DOI] [PubMed] [Google Scholar]
4.Lundell L.R., Dent J., Bennett J.R. et al. Endoscopic assessment of oesopha-gitis: clinical and functional correlates and further validation of the Los Angeles classification. Gut. 1999; 45(2): 172–80. [DOI] [PMC free article] [PubMed] [Google Scholar]

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.57

P0065 Esophageal Motility Patterns After Peroral Endoscopic Myotomy (Poem) in Patients with Achalasia

Z Vackova ^1,^2,^✉, J Mares ¹, J Krajciova ¹, Z Rabekova ¹, L Zdrhova ³, P Loudova ⁴, J Spicak ⁵, P Štirand ¹, T Hucl ⁶, J Martinek ⁷

Introduction

Several studies have reported partial recovery of peristalsis in patients with achalasia after myotomy.

Aims & Methods

The aim of our study was to analyze esophageal motility patterns after peroral endoscopic myotomy (POEM) and to assess the potential predictors and clinical impact of peristaltic recovery. We performed a retrospective analysis of prospectively collected data of consecutive patients with achalasia undergoing POEM at a tertiary center. High-resolution manometry (HRM) studies prior to and after POEM were reviewed and the Chicago Classification (CC) was applied.

Results

A total of 237 patients were analyzed. The initial HRM diagnoses were achalasia type I: 42 (17.7%); type II: 173 (73.0%); type III: 22 (9.3%). Before POEM, peristaltic fragments were present in 23 (9.7%) patients. After POEM the CC diagnoses were: 112x absent contractility, 42x type I achalasia, 15x type II, 11x type III, 26x ineffective esophageal motility, 18x esophagogastric junction outflow obstruction, 10x fragmented peristalsis and 3x distal esophageal spasm. Altogether 68 patients (28.7%) had signs of contractile activity, but the contractions newly appeared in 47 patients (47/214, 22.0 %). Type II achalasia showed a trend for appearance of contractions (p=0.097). Logistic regression analysis did not identify any predictors of peristaltic recovery. The post-POEM Eckardt score was not different between patients with and without contractions nor was the parameters of timed barium esophagogram.

Conclusion

More than 20% of achalasia patients have signs of partial recovery of esophageal peristalsis after POEM. It occurs predominantly in type II achalasia but the clinical relevance seems to be negligible.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.58

P0067 Endoscopic Clips Versus Endoscopic Suture For Mucosal Closure After Per-Oral Endoscopic Pyloromyotomy: A Prospective Study

R Hustak ^1,^✉, Z Vackova ¹, J Krajciova ¹, J Spicak ¹, J Martinek ¹

Introduction

G-POEM is an emerging method for treatment of gastropa-resis. Safe mucosal closure is necessary to avoid adverse events.

Aims & Methods

The aim of this study was to compare the effectivity of two closure methods: clips and endoscopic suturing (ES) in patients undergoing G-POEM. A single center, prospective study (NCT:03679104). The closure method was assigned at the discretion of an endoscopist prior to the procedure. The main outcome was the proportion of subjects with successful closure. Unsuccessful closure was defined as a need for a rescue method, or a need for an additional intervention. Secondary outcomes were easiness of closure (measured by a visual analogue scale VAS; 0=impossible, 10=very easy, scored by endoscopist and nurse) and closure time.

Results

A total of 29 patients [M:F/13:16,mean age,range: 49.7 (26-74)] have been included; 17 received ES and 12 clips (mean 6; range 4-19). All patients with ES had successful closure. One patient with clips needed a rescue method (KING closure with endoloop) and another two patients needed additional clipping, in one because of a leak on POD1 and another because of periprocedural mucosotomy dehiscence. The remaining 9 patients (75%) had a successful closure with clips. Closure with clips tender to be quicker (mean closure time 10.9 min (range 4-20) vs 14.3 (5-21); p=0.064). Endoscopist tended to assess closure with ES easier compared to clips (mean VAS for ES 7.4 (3-10) vs. 6.4 (3-10) for clips; p=0.18). A nurse assessed easines of both closure methods as comparable (p=0.93).

Conclusion

Endoscopic suturing system may be more reliable than clipping for mucosal closure in patients undergoing G-POEM. Besides clips, centers performing G-POEM should have an alternative (rescue) closure method. (Supported by a grant from the Czech Ministry of Health 17-28797A).

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.59

P0068 Post Deglutitive Upper Esophageal Sphincter Manometric Characteristics Analyzed with Swallow-Gateway in Patients with Achalasia

A Dell'Era ^1,^2,^✉, A De Bernardi ¹, S Passaretti ³, E Ribichini ³, N Pizzorni ^1,⁴, A Schindler ^1,⁴, PA Testoni ³, S Ardizzone ^1,²

Introduction

Abnormal findings of the upper esophageal sphincter (UES) on high resolution manometry (HRM) have been described in patients with achalasia (1,2). in particular, the finding of high UES residual pressure has been postulated to be a protective reflex of the UES to prevent esophago-pharyngeal regurgitation.

Aims & Methods

The aim of our study was to evaluate the post-deglutition UES manometric findings in patients with achalasia to assess the role of UES in preventing esophago-pharyngeal reflux after deglutition.

Methods

retrospective analysis of prospective patients who underwent esophageal HRM in Digestive Physiopathology Unit of ASST Fatebene-fratelli Sacco and San Raffaele Hospital of Milan with diagnosis of acha-lasia according to Chicago 3 classification; the control group included of patients with diagnosis of normal HRM. HRM analysis was conducted using the Manoview software; UES metric were analyzed using Swallow-Gateway, a dedicated web-based application. Data are reported as means±SEM. Student's t test, Mann-Whitney U and chi-square were used as appropriate. P value ≤ 0.05 was considered statistically significant.

Results

18 patients with achalasia and 32 in control group were analyzed. Table 1 reports manometric characteristics of the two groups. Patients with achalasia have higher UES residual pressure and longer UES relaxation; no significant difference was observed for the other parameters evaluated. in particular no difference was observed for baseline and post-deglutitive UES-contractile integral (CI) and UES peak pressure.

Table 1.

Manometric characteristics of UES

	Achalasia	Control	p
UES basal pressure (mmHg)	94.8±12.7	87.0±8.2	n.s.
UES residual pressure (mmHg)	9.1±1.3	3.6±1.2	0.005
UES time to nadir pressure (msec)	216.3±26.7	172.6±16.7	n.s.
UES duration of relaxation (msec)	847.3±43.3	706.1±31.5	0.011
UES time of recover (msec)	630.9±36.4	533.3±32.7	n.s.
UES-CI baseline (mmHgseccm)	113.7±22.1	126.6±24.5	n.s.
UES-IRP median (mmHg)	7.0±1.0	5.6±1.1	n.s.
UES-CI post deglutitive (mmHgseccm)	930.0±98.9	797.2±38.3	n.s.
UES peak pressure (mmHg)	305.4±16.2	303.9±13.6	n.s.

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Conclusion

Our study confirms previous findings of higher UES residual pressure in patients with achalasia compared to control subjects. No difference was observed in the post-swallowing UES characteristics, suggesting that the protective reflex may be present only during the opening of the UES.

Disclosure

Nothing to disclose

References

1.Yoneyama F., Miyachi M., Nimura Y. Manometric findings of the upper esophageal sphincter in esophageal achalasia. World J Surg. 1998; 22: 1043–6. discussion 1046-7 [DOI] [PubMed] [Google Scholar]
2.Blais P et al. Upper esophageal sphincter (UES) metrics on high-resolution manometry (HRM) differentiate achalasia subtypes. Neurogastroenterol Motil. 2017. Dec; 29(12). doi: 10.1111/nmo.13136. [DOI] [PMC free article] [PubMed] [Google Scholar]

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.60

P0069 Fundoplication in Patients Born with Oesophageal Atresia: Pre-Operative Workup and Fundoplication Outcomes

M Van Lennep ^1,^✉, E Chung ^2,³, A Jiwane ⁴, R Saoji ⁵, R Gorter ⁶, M van Wijk ^1,⁷, U Krishnan ^2,³

Introduction

Oesophageal atresia (OA) patients have a higher risk of having a fundoplication compared to other patients with gastro-oesophageal reflux disease (GORD). Fundoplication increases resistance to oesopha-geal bolus flow, which is already hampered by abnormal oesophageal motility in OA patients. We hypothesized that children born with OA suffer from more post-fundoplication complications including dysphagia compared to non-OA patients.

Recent international guidelines for OA recommend to perform oesopha-gogastroduodenoscopy (OGD) with biopsies to exclude eosinophilic oesophagitis (EoE), contrast oesophagram to assess upper gastrointestinal anatomy and pH (+/-impedance) measurement to confirm severity of GORD prior to fundoplication (1).

Aims & Methods

The aim of this study was twofold. First we evaluated which of these diagnostic tests were performed prior to fundoplication in OA patients in earlier days. Second, we aimed to compare fundoplication outcomes in OA patients with age- and sex-matched peers without OA. Medical records from OA patients and age- and sex-matched controls without OA who underwent fundoplication between 2006-2016 in three international centres (in Australia, The Netherlands and India) were retrospectively reviewed.

Results

40 OA patients (median 1.1 [0.1 - 17.0]yrs; 88% type C; follow-up 7.9 [0.6-12.0]yrs) and 40 controls (1.3 [0.3 - 17.0]; follow-up 7.5 (0.6-12.0) yrs) were included (table). Preoperative investigations in OA patients included OGD in 34 (85%), contrast oesophagram in 35(88%) and pH(+/-impedance) measurement in 11 (28%). Seven patients 18%) underwent all three investigations. Pre-operative OGD (n=34) was abnormal in 12(30%) children, including oesophageal strictures in 6 (18%), EoE in 4 (12%), hiatal hernia in 2(6%), intestinal metaplasia in 2 (5.9%), reflux oesophagitis in 1(3%) and diverticulum in 1(3%).

Post-fundoplication, 33(83%) OA patients had newly developed symptoms including dysphagia(43%), gagging(35%), food aversion(30%), bloating(40%) and/or dumping(8%). No associations between fundoplication outcome and type of fundoplication were found. OA patients had significantly more postoperative dysphagia, bloating and oral aversion compared to controls (table). Recurrent GORD symptoms were seen in 38(95%) OA patients and 13(33%) children developed (recurrent) strictures. in the OA cohort, median time to symptom recurrence was 60 [0-360] days, 95% were back on proton pump inhibitors (PPI) within 2 months post-surgery and 10% had redo-fundoplication.

Conclusion

Our study is the first to examine preoperative diagnostic workup and post-fundoplication outcomes in paediatric OA patients and compare outcomes with a matched control group. Diagnostic workup for fundoplication in OA patients varies greatly and is often incomplete. Postoperatively, all OA patients had symptoms, including recurrent GORD in 95% who all were back on PPI within two months of surgery. OA patients had significantly more dysphagia, bloating and food aversion post-fundo-plication compared to matched controls. The role of fundoplication in OA patients should be re-evaluated. Prospective data is needed to confirm our findings and to develop a tailored treatment paradigm for GORD in OA patients based on symptoms and results of investigations.

Table.

Fundoplication outcome in patients born with OA and age- and sex-matched controls

Newly developed symptoms	OA patients	Controls	P-value
Dysphagia	17 (42.5)	5 (12.5)	0.005
Gagging	14 (35.0)	9 (22.5)	ns
Dumping	3 (7.5)	1 (2.5)	ns
Food difficulties	12 (30.0)	2 (5.0)	0.006
Bloating	16 (40.0)	7 (17.5)	0.047

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Disclosure

Nothing to disclose

References

1.Krishnan U., Mousa H., Dall'Oglio L. et al. ESPGHAN-NASP-GHAN Guidelines for the Evaluation and Treatment of Gastrointestinal and Nutritional Complications in Children with Esophageal Atresia-Tracheoesophageal Fistula. J Pediatr Gastroenterol Nutr 2016; 63(5): 550–70. [DOI] [PubMed] [Google Scholar]

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.61

P0070 Antroduodenal Motility Patterns in Patients with Gastroparesis: Differences By Etiology

MJ Hereijgers ¹, D Keszthelyi ¹, J Kruimel ¹, AA Masclee ¹, JM Conchillo ^1,^✉

Introduction

Gastroparesis (GP) is a common gastrointestinal disorder associated with significant morbidity and considerable health care costs. GP patients form a heterogeneous population with diverse etiology. Treatment is often challenging due to a poorly understood underlying pathophysiology.

Aims & Methods

Therefore, the aim of this study is to assess antroduodenal motility patterns among the different GP etiologies. in this retrospective analysis, we reviewed antroduodenal manometry (ADM) recordings and medical records of patients with confirmed GP between 2009-2019 at Maastricht University Medical Centre. Gastroparesis was diagnosed based on prolonged gastric emptying as measured by scintigraphy or C13 gastric emptying breath test. The following data were collected from medical records: age, gender, BMI, GP etiology and severity grade. ADM was performed using a 36-channel high-resolution manometry catheter. After 30 minutes recording in fasting conditions, patients were given a standardized meal. After the ingestion of the meal, data were recorded for 6 hours, during which patients were not allowed to eat or drink. ADM measurements were evaluated for antral and duodenal amplitudes (mmHg) and motility index (MI), fed period duration (min), number and duration of phase III contractions and migrating motor complexes (MMCs), and presence of neuropathic patterns (i.e. bursts, retrograde propagation, clustered contractions, absence of phase III contractions). Antral hypomotility was defined as antral MI < 13.67.

Results

A total of 167 GP-patients (142 women, median age 45 [31-57]) with confirmed delayed gastric emptying were included. The following GP etiologies were identified: idiopathic n= 101; post-surgery n= 36; diabetes n= 30. A lower percentage of female patients was found in the post-surgery GP-group compared to the other groups (p < 0.01). No differences were found between GP-groups regarding age, BMI, gastric half emptying time, antral and duodenal amplitudes, and MI. Fed period duration was significantly longer in idiopathic (p < 0.01) and diabetic GP-patients (p < 0.05) compared to post-surgery GP-patients.

Furthermore, the number and duration of phase III contractions, and the number of MMCs was significantly lower in idiopathic and diabetic patients compared to post-surgery GP-patients (p < 0.01). Likewise, absence of MMCs during 6-hr recording were more often observed in idiopathic and diabetes GP-patients compared to post-surgery GP-patients (resp. p <0.01 and p <0.05). No significant differences between GP-subgroups were found regarding number of bursts, clustered contractions, retrograde propagation and absence of phase III contractions.

Conclusion

Antroduodenal motility patterns are different between GP etiologies. A disease severity spectrum was identified ranging from post-surgery GP with milder dysmotility patterns to diabetic and idiopathic GP with more severe dysmotility patterns. These differences suggest different pathophysiologic pathways and possible targeted treatment options.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.62

P0071 Gastric Electric Stimulation in Patients with Treatment Refractory Nausea and Vomiting: A 5 Year Follow-Up Study

E Sundelin ^1,^✉, S Kilincalp ², J Brun ², F Jabarkel ², G Ringström ², H Abrahamsson ², M Simrén ², H Törnblom ²

Introduction

Gastric electrical stimulation (GES) is a treatment option for patients suffering from chronic, refractory nausea and vomiting. It is approved for use in patients with gastroparesis (delayed gastric emptying), but also in patients with normal gastric emptying after positive symptom response during temporary percutaneous GES The number of patients treated worldwide and studies reporting the long term effects of GES therapy are limited.

Aims & Methods

In this retrospective single-center cohort study, our aim was to investigate the effect of GES over a 5-year period after implantation. All patients implanted with a GES device since 2000 with at least one year of follow-up and at least three self-reported symptom diaries were included.

We have used the same two-week diaries at eight predefined time-points after GES implantation; 1, 3 and 6 months, 1 year and thereafter annually. Symptoms at each time-point were compared with baseline symptoms before GES implantation. A responder to GES treatment was defined by at least 50% reduction in weekly nausea time or weekly vomiting frequency at each time-point.

Overall, patients were considered as complete responders if satisfying the response criteria at ≥75% of the time-points, non-responders ≤25%, and partial responders >25% but < 75%. All patients with normal gastric emptying time were selected for treatment after a positive symptom response during temporary percutaneous GES.

Results

Data fulfilling inclusion criteria for symptom reports was available in 68 patients (55 females, median age 43.5 (range 20-81) years), of whom 36 (53%) had five years of follow up. Before GES implantation, the median weekly vomiting frequency was 9.2 (0-177) and weekly nausea time

23 (1-141) h. with our definition of overall long-term treatment response, 42 (62%) patients were classified as complete responders, 21 (31%) patients as partial responders and five (7%) patients as non-responders. The non-responders primarily had idiopathic gastroparesis and were younger (p=.045). There was no difference in gender distribution (p=0.45) between the response groups (see Table 1). At the last symptom registration time-point, the responder group had reduced their weekly vomiting frequency (median 0 (0-34)) and weekly nausea time (5 (0-133)h) significantly (p< 0.001 for both), the partial response group showed a trend towards a reduced weekly nausea time (15 (0-49)h) (p=0.08), but not for weekly vomiting frequency (7 (0-102)) (p=0.84).

The response distribution was similar when comparing patients with delayed vs. normal gastric emptying; complete response 28/46 (61%) vs. 14/23 (61%), partial or non-response 18/46 (39%) vs. 9/23 (39%

Table 1.

	Responders	Partial responders	Non-responders
Patients (n)	42	21	5
Sex females/males (%females)	36/6 (86)	15/6 (71)	4/1 (80)
Age, years (median, range)	44 (20-68)	44(24-81)	27(21-50)
Diagnosis
Diabetic gastroparesis	16	10	0
Idiopathic gastroparesis	5	2	4
Post-surgical gastroparesis	7	2	0
Enteric dysmotility,	7	1	1
Functional vomiting or nausea	7	6	0

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Conclusion

GES has a favorable long-term response in a substantial proportion of patients with chronic severe, refractory nausea and vomiting. However, about one third of patients have partial or incomplete response to treatment with a significant persisting symptom burden. Gastric emptying rate cannot predict the treatment response to GES.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.63

P0073 Standardizing Long-Term Gastrointestinal Motility Recordings in Children; Comparison Between Healthy Adults and Two Pediatric Populations

G Gulliksson ^1,^✉, F Dylèn Lilljekvist ², N Nyström ³, M Scholing ², E Gustafson ², PM Hellström ⁴

Introduction

The most valid method for examining small bowel motility in children is 24-hour antroduodenojejunal manometry. Evaluation of pediatric controls is ethically problematic due to the wearisome procedure of stationary manometry.

Our aim was to evaluate whether 8-hour control recordings from healthy adults can be used as reference for diagnosing pediatric antroduodenojejunal motility disorders.

Aims & Methods

Three groups of subjects underwent antroduodenojejunal manometry; one control group of healthy adult volunteers (n=43) and two clinically investigated pediatric groups, one control group with unspecific abdominal pain (n=15) and one case group with motility disorders (n=17).

Characteristics of phase III and coordinated antroduodenal propagation were compared. Correlation for age was tested for all variables. Ethics approval no. 2020-02496.

Results

The control groups showed recurring MMCs. Children had higher peak pressures of phase III compared to adults (40.1; 36.7-46.9 vs. 31.1; 27.3-44.2 mmHg; p< 0.01) and shorter duration of phase III (4.8; 4.0-5.7 vs. 6.0; 4.6-7.0 min; p< 0.07). Frequency and antroduodenal propagation were similar. Within control groups, we found negative age correlation for frequency (p< 0.03) and positive age correlation for duration of phase III (p< 0.01). No correlation was found for pressure or antroduodenal propagation. in the pediatric group with motility disorders, highly irregular motility patterns were discerned with numerically higher peak pressures (43.4; 37.1-55.8) and reduced antroduodenal propagation. PIPO-cases (n=8) showed a significantly lower frequency of phase III and prevalent abnormal motility patterns.

Conclusion

The normal phase III in children and adults is not significantly different, except for higher luminal pressures in children. The age correlations within control groups suggest that phase III undergoes changes with growth. We suggest that control values of phase III obtained from healthy individuals can be used across all ages for analysis of antroduodenojejunal motility disorders.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.64

P0074 Development of A Score That Predicts Manometric Alterations in Patients with Systemic Sclerosis

J Silva ^1,^✉, A Peixoto ², P Costa-Moreira ³, G Macedo ⁴

Introduction

Systemic Scleroses (SSc) comprehends a spectrum of related disorders that share a characteristic of excess of collagen fibers accumulation in tissue. The esophagus is the most frequently affected part of the gastrointestinal (GI) tract. Abnormal esophageal manometry (EM) is present in the majority of patients with SSc. Direct measurement of esophageal motility is usually reserved for patients with symptoms refractory to empiric trial of proton pump therapy. However, approximately 30 percent of patients with EM alterations are asymptomatic.

Aims & Methods

Our aim is to evaluate the relationship between esophageal manometric findings and different clinical and laboratorial findings in patients with SSc and the construction of a model that predicts alterations in EM. We performed a retrospective Cohort study of patients with SSc and EM from a period of 12 years (2008-2020).

We analyzed different clinical characteristics, biochemical, immunologic, electromyographic, echocardiographic and electrocardiographic findings and pulmonary function testing. EM alterations related to SSc were defined as hypotensive lower esophageal sphincter, ineffective motility or absent contractility. Univariable analysis was performed with Man-Whitney for continuous analysis and Qui-square for categorical analysis. We construct a predictive model using backward logistic regression.

Results

We included 71 patients in our study. Eighty-eight were female, median age was 54 (42-64) years. Diffuse cutaneous SSc was present in 10.5%; limited cutaneous SSc in 39.5%; SSc without sclerodermia in 1.3% and overlap syndrome with SSc in 42.1%. GI symptoms were present in 82% of the patients (mostly dysphagia, 63%). Upper endoscopy was performed in 75% and endoscopic findings were found in 25% of patients

(erosive esophagitis in 8%, erosive gastritis in 7% and esophageal candi-diasis in 3%). EM alterations here present in 40.8% of patients. in univariable analysis, EM alterations relates to Raynaud syndrome (RR 3.6, CI₉₅% 1.3-5.3; p=0.024), diffuse cutaneous SSc (RR 2.5, CI₉₅% 1.5-4.5; p=0.007), anti-nuclear antibody (RR 3.6, CI₉₅% 1.8-4.6, p=0.034), abnormal cardiac study (RR 2.2, CI₉₅% 1.3-4.7, p=0.045) and abnormal CO defuse capacity (RR 1.8, CI₉₅% 1.3-3.2, p=0.021). Abnormal EM was not related to presence of GI symptoms (RR 1.4, CI₉₅% 0.6-3.4, p=0.234). We constructed a model using 4 variables [diffuse cutaneous SSc (1 ponto),anti-nuclear antibody (2 pontos),cardiac study (2 pontos) and CO defuse capacity (4 pontos)], with an area under the curve of 0.748 (p=0.002). Using the cut-off of 5 points, this model presented a sensibility of 86% and a specificity of 74% for detection of EM alterations.

Conclusion

In our population, despite 82% of patients presented with GI symptoms, only 40.8% presented with EM alterations. GI symptoms was not related to EM alterations. Other findings should be considered in order to predict EM alterations. Our model is able to predict EM alterations in patients with SSc. External validation is necessary.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.65

P0075 Ineffective Esophageal Motility: Is Severe Compromise Relevant?

A Oliveira ^1,^✉, AO Ferreira ², C Palmela ²

Introduction

Ineffective esophageal motility (IEM) is a heterogeneous disorder, considered minor by the Chicago classification, as it is not consistently associated with symptoms. It has recently been proposed to analyze this entity using 3 parameters: severely compromised motility (above 70% ineffective waves), multiple rapid swallows (MRS) and its distal contractile integral (DCI) compared to single swallow (SS), could reveal functional reserve (MRS:SS DCI> 1).

Aims & Methods

Evaluation of these new 3 parameters on IEM patients. Retrospective study of patients with a manometric diagnosis of IEM from 2012 to 2019. We used a high-resolution manometry solid state probe with 36 channels and Sandhill software. Patient with reflux symptoms also performed 24h impedance pH monitoring. Extracted data was further analyzed with SPSS v21.0.

Results

We included 40 patients, 60% (n = 24) female, mean age 56 ± 15 years. The main complaints were heartburn (58%, n = 23) and dysphagia (35%, n = 14), 26 patients underwent pH analysis and 42% (n=11) were positive for pathological gastroesophageal reflux. The MRS:SS DCI ratio was > 1 in 52% of the population.

Severe MEI was identified in 68% of the cases, and was associated with a lower median DCI (255 vs 350 mmHg.s.cm, p = 0.001) but not related to a lower MRSDCI (Severe: 299 vs non-severe: 192 mmHg.s.cm, p = NS), and also not associated with loss of functional reserve (MRS:SS DCI> 1, severe: 70% vs non-severe: 61%, p = NS). Severe MEI was not associated with pathological gastroesophageal reflux (Severe: 35% vs non-severe: 55%, p=NS).

Conclusion

Patients with severe IEM, under this new classification, may still have a preserved functional reserve and were not found to have higher rates of pathological gastroesophageal reflux.

Patients with ineffective motility and reflux could benefit from a complementary study of MRS and their reserve function when being candidates for a potential intervention.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.66

P0076 Upper Esophageal Sphincter Changes in Achalasia Measured with Pressure-Flow Metrics

E Karaoguz ^1,^✉, S Bor ²

Introduction

Achalasia is a primary esophageal motility disorder characterized by impaired peristalsis and inadequate relaxation of the lower esophageal sphincter (LES). The main pathophysiological findings are smooth muscle dysfunction in the distal esophagus and lower esophageal sphincter but the whether the disease also affects the upper esophageal function in achalasia is still not clear. Pressure-flow analysis is a new technique which gives a good opportunity to evaluate upper esophageal sphincter (UES) and pharyngeal area by using pressure-flow metrics.

Aims & Methods

The aim of this study was to evaluate UES and area of pharynx by using pharyngeal impedance-pressure manometry in patients with achalasia and to compare with the healthy control group. Achalasia was diagnosed with the measurement of esophageal body and LES with highresolution manometry (HRM), and classified according to Chicago III cassification, timed barium swallow and upper gastrointestinal endosco-py in all patients. High resolution pharyngeal manometry was performed in 27 (16 men; 55,6 ± 15,6 years) naive patients with achalasia and 12 (2 men; 36,5 ± 9,1 years) healthy volunteers.

Different pressure-flow metrics were evaluated. A solid state catheter with 36 pressures and 16 impedance channels was used and calibrated with Software Version 9.4 Medical Measurement Systems (MMS) database. Procedures were performed in semi-sitting position with receiving 3 times 5 ml and 3 times 10 ml isotonic liquid swallows. After the UES and pharynx values were recorded, the procedure was terminated and the catheter was removed. The manometry tracings were uploaded to Swallow Gateway system. This webpage and incorated software spesifically design for the evaulation of mesurements a combined impedance measurements.

Results

Upper esophageal sphincter relaxation pressure (U-IRP), hypopharyngeal intrabolus pressure (H-IBP) and pharyngeal pressures (PHCI) significantly higher in patients with Achalasia compared to HC. There were no significant differences between two groups in terms of UES Maximum-Admittance (Max. Adt.) and Bolus Presence Time (BPT) metrics (Table).

Table.

		Patient Group (mean±SD)	Healty Control (mean±SD)
5 ml	Max. Adt. (mmHg)	2.94±0.84	4,59±0,75
5 ml	H-IBP (mmHG)	10,12±10,72^*	3,32±6,30
5 ml	U-IRP (mmHg)	8,58±10,91^*	-1,42±8,12
5 ml	BPT (sn)	0,57±0,11	0,57±0,07
5 ml	PHCI (mmHg^s^cm)	497,70±210,00^*	334,58±120,71
10 ml	Max. Adt. (mmHg)	5,81±0,01	5,56±0,56
10 ml	H-IBP (mmHG)	10,11±10,92^*	3,15±7,01
10 ml	U-IRP (mmHg)	10,81±10,08^*	-,17±7,76
10 ml	BPT (sn)	0,64±0,23	0,61±0,12
10 ml	PHCI (mmHg^s^cm)	516,43±222,8^*	331,79±109,50

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^*

p< 0.05 compared to controls

Conclusion

UES relaxation was significantly insufficient in patients with achalasia compared to HC. We speculate that in order to facilitate the passage of UES bolus against the difficulty of relaxation, pharyngeal pressures and intrabolus pressure increased. The insufficiency at UES relaxation might be explained with two possibilities; 1) There might be similar but lesser degree pathology within UES nerves and muscles to constraint against a sufficient relaxation 2) Because of the accumulaton of food and secretions inside the esophagus, intraesophageal pressure increases in Achalasia patients and this facilitates the aspiration of the content. Inc-reaced U-IRP might be reflection of protection of upper airways. Further studies comparing UES pressure flow metrics before and after succesful management might be helpful.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.67

P0077 The Effect of Proton Pump Inhibitor Plus Alginate Therapy On High-Resolution Manometry Parameters in Gastroesophageal Reflux Patients with Ineffective Esophageal Motility

A Celebi ^1,^✉, G Sirin ¹, AE Duman ¹, H Yilmaz ¹, S Hulagu ¹

Introduction

The ineffective esophageal motility (IEM) in according to the Chicago classification is that the distal contractile integral (DCI) is below 450 mmHg.s.cm. in more than half of wet swallows. IEM detected on highresolution manometry (HRM) is the most common esophageal motility disorder in gastroesophageal reflux patients. However, the direction of association between reflux disease and IEM is unclear.

Aims & Methods

We aimed to show the effect of PPI (twice a day) plus alginate (four times a day) therapy on esophageal motility in gastroesophageal reflux patients with IEM in our study.

The effects of six months PPI plus Alginate therapy on HRM parameters in gastroesophageal reflux patients with IEM were retrospectively analyzed.

Results

Sixteen gastroesophageal reflux patients with IEM who underwent post-treatment HRM were found. Eight of patients(50%) were female, the mean age was 48±14.4 years. IEM was not detected in 11 of 16 patients (69%) in post-treatment HRM analysis. The weak peristaltic contraction percentage decreased in three of the remaining five patients and in two patients did not change. The mean DCI was found to be significantly higher in the post-treatment HRM than pretreatment procedure (609.1 ±317.1 vs 349.9 ± 200.9 mmHg.s.cm. respectively, p=0.01). in the HRM examination performed after the treatment, the percentage of normal peristaltism in wet swallows was statistically significantly higher than the percentage of normal peristaltism before treatment (75±15.9 vs 45.6±30.8, respectively. p=0.002).

Conclusion

In reflux patients with IEM six months PPI (twice a day) plus alginate (four times a day) therapy increases the mean DCI in the esophageal body and improves IEM in 69% of patients.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.68

P0078 The Relation Between Changes in Gastric Emptying Rate and Improvement of Simultaneously Measured Symptoms with Prokinetic Agents; An Analysis of 8 Treatment Trials

F Carbone ^1,^✉, K Van den Houte ¹, J Schol ¹, E Colomier ¹, A Huang ¹, N Goelen ¹, J Tack ²

Introduction

Meta-regression analyses have failed to show a significant relationship between improvement of gastric emptying rate (GE) and improvement of symptoms with prokinetic agents in idiopathic gastropare-sis (IGP)/functional dyspepsia (FD).However, significant effects emerge when a selection of agents and tests is applied (Janssen 2013; Vijayvargiya 2019). The potentially strongest link between effects on GE and symptoms is found when both are measured simultaneously. We studied this relationship at the individual patient level in treatment intervention studies performed by our unit.

Aims & Methods

Data from 6 placebo-controlled cross-over trials and 2 open label studies involving ghrelin, prucalopride, cisapride, botulinum toxin (BT), buspirone, erythromycin, clonidine and octreotide;(2 acute, 6 repeat administration) in 140 FD/IGP patients, were analysed. All patients underwent a standardized GE breath test (13C-octanoic acid) during which the intensity (0-4) of fullness, bloating, nausea, belching, epigastric pain and burning (EB) were scored every 15 min for 4 hours. Meal-related severity of individual symptoms (ISS) was obtained by summing all scores for that symptom and the overall meal-related symptom severity (OSS) was defined as the sum of all individual symptoms scores. The relationship between change in GE T1/2 and change in symptom score was assessed via Spearman correlation in individual and pooled studies.

Results

Overall, GE improved during treatment (p< 0.001), OSS (88±7 to 63±6,p< 0.0001) and all ISS except EB were improved (all p< 0.005). OSS as well as ISS did not correlate significantly with GE T1/2, at baseline/placebo or during active treatment (respectively R=0.01 and R=-0.03). The change in GE T1/2 did not correlate with the change in OSS (Fig.1) or the change in ISS (all R-values < 0.12). Individual studies with BT, erythromycin and prucalopride showed significant improvement in GE T1/2, but no significant positive correlation was found for the studies separately (respectively R=-0.42,-0.28 and 0.23) or pooled together (R=-0.13).

Conclusion

Even in the closest apposition between measurement of GE and symptom assessment in FD/IGP, no correlation was found between the degree of symptom improvement and the improvement of GE. The observed symptomatic significant benefit must be attributed to effects other than enhanced GE.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.69

P0079 Endoscopic Novel Combo Technique: Long-Term Outcomes in Treating Patients with Primary Achalasia

E Bedewy ^*,^✉, A Elgendi ², M Kamel ³

Introduction

Achalasia is a primary esophageal motility disorder characterized by the absence of esophageal peristalsis and impaired relaxation of the lower esophageal sphincter (LES) in response to swallowing.

Aims & Methods

Evaluating combined Botulinum toxin injection, pneumatic dilation and mechanical dilation by retro-flexion of the endoscope (COMBO) as a suggested novel treatment for achalasia.

Methods

The study included 44 Egyptian patients suffering from achalasia of the cardia (AC). The suggested COMBO technique is done in single step endoscopic setting three-steps procedure:

1- Injection of 100 Units Botulinum toxin type A (Botox-Allergan), 25 units circumferentially in anterior, posterior and lateral esophageal wall.

2- Wait about 1-2min and pass the scope to the stomach and then graded dilatation using Achalasia balloon over guide wire starting from 35 mm to be followed 3 min later by 40 mm balloon dilation, time of inflation should not less than 1 min.

3- Inspecting the cardia carefully after balloon dilatation then retroflexion of the scope and inspecting the cardia and rinse it thoroughly with water then approaching the cardia carefully with the scope retro-flexed with right axis deviation by using the right -left knop of the scope and trying to gently insinuate the scope to the esophagus through the cardia but only 2/3 of the retroflexed portion (the maximum circumference of the semicircular part) of the scope and not the entire endoscopic shaft so the semicircular portion of the retroflexed part is kept dilating the cardia for about 30 seconds with rotating the scope in a gentle way 180 ^oC gently during this period using hand and body rotation to rotate the scope and repeat it at least three time. (The action is not allowed if there is a difficulty insinuating the retroflexed scope through the cardia).

Finally good endoscopic inspection of the dilated lower esophageal sphincter must be done for detecting any complications mainly bleeding or perforation, so we recommended better rinsing with methylene blue to exclude any area of perforation that was done for all cases after dilatation.

Results

The Combo endoscopic method showed a very good and satisfactory response in 42/44 of patients (response rate 95.5%) form the first session with a follow up period ranging from at least 48 weeks to maximum of 240 weeks.

All Patients showed significant improvement of almost all the clinical symptoms especially dysphagia, regurgitation, choking and postprandial vomiting even the patient who experienced iatrogenic post Heller myotomy (follow up 50 weeks), 8/44 (18.1%) patients still experienced infrequent non-annoying retrosternal chest pain, 12/44 (27.2%) suffered intermittent heart burn and mild regurge.

No complications were reported during or after the procedure as perforation or bleeding.

Conclusion

COMBO endoscopic technique could be suggested as a novel and effective method for treating achalasia as a stepwise way before proceeding to more risky invasive methods as Peroral Esophageal Myotomy (POEM) or surgical procedure or in high risky patients at least.

Disclosure

Conflict of interest and funding: Non

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.70

P0081 Endoscopic Findings At The Time of Foreign Body Impaction Removal: A 7 Year Retrospective Audit

C Gofton ^1,^2,^✉, YS Kim ³, K Rasouli ¹, B Reynaulds ¹, G Hawken ⁴, Gastroenterology Department CCLHD

Introduction

Foreign body impaction (FBI) is a frequent gastroenterological emergency. The management of FBI usually requiring urgent endoscopy to retrieve the obstruction, but is also useful in the potential diagnosis of the underlying cause for FBI. Currently, limited studies detail an underlying cause for FBI at initial endoscopy for removal of the obstruction.

Aims & Methods

This study aimed to assess the endoscopic diagnosis of the underlying cause for FBI at initial endoscopy. Details of all patients who presented with FBI to Central Coast Local Health District (Gosford Hospital and Wyong Hospital) from 2013 to 2020 were reviewed from a retrospective database. Detailed admission and endoscopic findings were examined for patients admitted under the Gastroenterology team.

Results

From January 2013 to January 2020, 311 patients presented with food bolus impaction to Gosford or Wyong hospitals during the audit period. The majority of these patients were male, at 76.3%. The average age at presentation was 56.5, and the age of presentation trended towards younger age groups however, this was non-significant. of those patients presenting with FBI, 277 (89%) underwent endoscopy, with 34 (11%) patients spontaneously clearing their impaction. On endoscopy, 234 (75%) patients had food product present in their oesophagus requiring removal. 37 (15%) patients had a diagnosis for the underlying cause of their food bolus obstruction made. These were eosinophilic oesophagitis (17), reflux stricture (5), ill-defined stenosis (3), hiatus hernia (3), pill oesophagitis (3), tortuous oesophagus (2), Zenkers diverticulum (1), pharyngeal pouch (1), Schatzki ring (1), and carcinoma (1). 197 patients had no cause identified for FBI on initial endoscopy.

Conclusion

75% of patients presenting with FBI had food product present on initial endoscopy. Only 15% of patients who presented with food bolus obstruction had a clear diagnosis for the underlying cause identified on initial endoscopy. This study reaffirms the need for further endoscopic investigation following FBI to identify an underlying diagnosis for the obstruction.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.71

P0082 Clinical Spectrum and Treatment Outcomes of Eosinophilic Oesophagitis in Durham and Tees Valley, Including Initial Results of Orodispersible Budesonide (Jorveza®)

JC Lee ^1,^✉, M Hussien ², M Stothard ³, M Johnston ³, K Dasgupta ², I Beintaris ², H Dallal ³, A Dhar ³

Introduction

Eosinophilic oesophagitis (EoE) is common in pts with dysphagia or food bolus obstruction. Swallowed steroids have been the mainstay of treatment until Orodispersible tablet (ODT) Budesonide (Jorveza®) became available in 2018. The real world outcomes of ODT budesonide are awaited.

Aims & Methods

This retrospective study, designed after the launch of ODT budesonide in the UK, aimed to (1) analyse the current clinical pre-sentation,(2) endoscopic diagnosis,and (3) treatment outcomes with proton pump inhibitors (PPI), swallowed steroids (Fluticasone or Budesonide inhalers) and ODT Budesonide (Jorveza®).

Patients with histologically confirmed EoE (defined by a eosinophil count of >15/hpf) between Jan 2018 - Jun 2019, were identified from a histology database at 2 large University hospitals. Clinical presentation, endoscopy findings, treatments and outcomes were extracted from electronic patient records. Patients with eosinophil counts of 5-15/hpf were included as “possible EoE”. Symptom improvement was defined as >50% reduction in dysphagia episodes weekly.

Results

59 pts (38M, 21F) with confirmed or possible EoE were identified. 44% were between ages 40-60yrs. 64% were male. 54% had history of atopy - asthma and hayfever being common. 10% pts reported food allergy. 71% pts were non-smokers. Dysphagia was the presenting symptom in 84%, predominantly to solids (76%). 40% reported having some form of food bolus obstruction. Other symptoms included heartburn (47%), regurgitation (40%), and vomiting (31%). Endoscopy EREFS Scores were: 0=18, 1=26, 2=12, 3=3. Biopsy (Bx) distribution was 1-2 Bx =17pts, 3-4 Bx =30, 5-6 Bx = 12. No strictures requiring dilatation were present. 40/59 patients had been trialed on a PPI with only 32.5% improvement. 21/59 pts were treated with swallowed corticosteroids, 18 pts had >6month follow up, with 56% symptom resolution. 20 pts were treated with ODT budesonide for 12 weeks, 6 after non-response to swallowed steroids. Overall symptom resolution in this group was 50% (9/18). 100% response in treatment naïve pts, and 67% response in those who had previously received swallowed steroids. Response rates between Jorveza treated and swallowed steroid pts was not statistically significant, due to small sample sizes, p=0.74.

Conclusion

Eosinophilic oesophagitis is still being diagnosed at a later age of between 40-60yrs. There is significant variability in the number of oesophageal biopsies taken at endoscopy. The initial results of ODT Budesonide treatment are promising, especially in treatment naïve patients.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.72

P0083 Relationship Between Symptoms and Clinical Features in Patients with Esophageal Eosinophilia

H Hosaka ^1,^✉, S Kuribayashi ¹, K Sato ¹, K Nakata ¹, Y Hashimoto ¹, M Sekiya ¹, H Tanaka ¹, Y Shimoyama ¹, T Uraoka ¹

Introduction

There are patients with eosinophilic esophagitis (EoE) who have symptoms such as chest pain or dysphagia, while there are asymptomatic patients with esophageal eosinophilia. It is known that EoE patients are likely to have esophageal motility abnormalities that may cause their symptoms. However, a relationship between symptoms and clinical features in patients with EoE are not known.

Aims & Methods

The aim of the study was to reveal the association between symptoms and clinical features in patients with esophageal eosino-philia.

A total of 20 patients with esophageal eosinophilia(eosinophil infiltrations in the esophageal mucosa ≥15/HPF) who underwent both esophagogas-troduodenoscopy (EGD) and esophageal high-resolution manometry (HRM) were enrolled between 2009 and 2018. Dysphagia, chest pain, and heartburn were classified as typical symptoms and nausea, abdominal pain, bloating were classified as atypical symptoms. Characteristic EGD findings (circular rings, linear furrowing, white exudates), HRM findings evaluated by Chicago classification, and treatments were assessed by each patient's symptom.

Results

Dysphagia (9 cases,45%), chest pain (7 cases,35%), heartburn (5 cases,25%), and atypical symptoms (5 cases,25%) were observed. HRM revealed abnormal esophageal motility (11 cases,55%): esophagogastric junction outflow obstruction (EGJOO)(3 cases,15%), Jackhammer esophagus (2 cases,10%), distal esophageal spasm (1 case,5%), ineffective esophageal motility (IEM)(5 cases,25%), and normal (9 cases,45%). Patients with dysphagia had significantly higher integrated relaxation pressure (IRP) (12.9mmHg) and higher distal contractile integral (DCI) (3789.6mmHg-cm-s) than patients without dysphagia (9.1mmHg, 1069mmHg-cm-s, P< 0.05 each). Patients with only atypical symptoms had lower IRP(7.46mmHg vs. 11.95mmHg, P< 0.05). Dysphagia was related to EGJOO and spastic disorders than IEM and normal. The type of symptom was not associated with any endoscopic finding nor eosinophil counts in esophageal epithelium.. Regarding the treatments, 2 patients did not take any medication, 13 patients only had proton pump inhibitor (PPI) therapy, and 5 patients needed steroid after PPI trial. Patients with chest pain tended to be treated with steroid (P< 0.05).

Characteristics of clinical data in each symptom in patients with esophagealeosinophilia *: p<0.05

	Dysphagia		Chest pain		Heartburn		Atypical symptom
	+	-	+	-	+	-	+	-
No of patients	9	11	7	13	5	15	5	15
Age, y	48.1 ±6.7	46.7±12.2	49.0±8.7	46.5±10.7	50.4±4.9	46.3±10.8	42.8±16.7	47.8±6.6
Sex(M:F)	6:3	9:2	4:3	11:2	4:1	11:4	4:1	11:4
Endoscopic finding +	6(67%)	7(64%)	4(57%)	9(69%)	4(80%)	9(60%)	3(60%)	10(67%)
HRM parameters: IRP (mmHg)	12.9±3.1	9.1±2.9*	11.9±3.4	10.3±3.6	12.9±3.5	10.1±3.3	7.46±2.8	12.0±3.0*
DCI (mmHg-cm-s)	3789.6±4724.2	1069.0±904.3*	3429.1±5520.0	1681.7±1490.2	1901.4±1411.1	2423.9±3913.1	1259.0±1356.0	2638.1±3862.6
EGJOO/spastic/IEM/normal	2/3/0/4	1/0/5/5*	2/1/2/2	1/2/3/7	2/1/1/1	1/2/4/8	0/1/2/2	3/2/3/7
Treatment: PPI/steroid after PPI trial	6/3	7/2	2/4	11/1*	3/2	10/3	4/1	9/4

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Conclusion

Esophageal motility abnormalities with higher IRP and DCI are suggested to be related to dysphagia. PPI therapy might be ineffective to relieve chest pain and patients with chest pain tended to need steroid therapy in patients with esophageal eosinophilia.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.73

P0084 Lipid Profiling in Patients with Eosinophilic Esophagitis

C Schmöcker ^1,^2,^✉, H Gottschall ², M Mainka ³, A Pietzner ¹, D Hartmann ⁴, NH Schebb ³, KH Weylandt ¹

Introduction

Eosinophilic esophagitis (EoE) is the second most common inflammatory disease in the esophagus [1]. EoE is an antigen-driven immune-mediated reaction clinically characterized by symptoms of esophageal dysfunction and histologically defined by an eosinophil-predominant inflammation in the esophagus [2]. Long lasting eosinophilic inflammation leads to fibrosis with stricture formation as presented by dysphagia and bolus obstruction [3, 4]. Until now mechanisms of inflammation in EoE are not fully understood. Some findings indicate a role for lipid mediators in these inflammatory processes.

For instance, it has been shown that 15-lipoxygenase (LOX), a key-enzyme in the arachidonic acid cascade, is up-regulated in esophageal tissue in active EoE. Additionally, PGD₂ receptor antagonists [5] may serve as therapeutic options besides topicals steroids and elemental diet.

Aims & Methods

We have recently shown that comprehensive lipid mediator profiling is feasible in gastrointestinal (GI) tract tissue biopsies [6]. Therefore, we now aim to get deeper insights into lipid mediator modification occurring in EoE.

Oxylipine patterns in esophageal tissue of 13 patients with active EoE compared to healthy tissue of 15 patients without EoE were analyzed. Lipid metabolite profiles were determined by liquid chromatography coupled with tandem mass spectrometry.

Results

We detected significantly elevated levels of cycloxygenase-(COX) derived prostanoids of the D and E series in active EoE. Furthermore, we found significantly increased levels of 15-HETE, 15-HETrE, 17-HDHA and other hydroxy-PUFA which can be formed by 15-LOX and COX,in active EoE esophageal tissue compared to controls.

Conclusion

Our findings support the hypothesis that COX- and 15-LOX-derived lipid mediators are part of the inflammatory processes occurring in EoE. These findings warrant further research to investigate their role as potential therapeutic targets.

Disclosure

Nothing to disclose

References

1.Arias A. et al. Systematic review with meta-analysis: the incidence and prevalence of eosinophilic oesophagitis in children and adults in population-based studies. Aliment Pharmacol Ther, 2016. 43(1): p. 3–15. [DOI] [PubMed] [Google Scholar]
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6.Gottschall H. et al. Aspirin alone and combined with a statin suppresses eicosanoid formation in human colon tissue. J Lipid Res, 2018. 59(5): p. 864–871. [DOI] [PMC free article] [PubMed] [Google Scholar]

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.74

P0085 Provocative Tests During High-Resolution Manometry May Be Helpful To Distinguish Patients with Eosinophilic Esophagitis Responding To Ppi Therapy

N de Bortoli ^1,^✉, F Rettura ¹, M Frazzoni ², S Tolone ³, L Frazzoni ⁴, G Sciume ¹, E Vichi ¹, C Cecchini ¹, M Bellini ⁵, S Marchi ¹, EV Savarino ⁶

Introduction

Eosinophilic esophagitis (EoE) is an up-and-coming condition histologically characterized by 15 eosinophil x HPF from esophageal biopsies. Proton pump inhibitor (PPI) represents the first line approach of this condition. No demographic or clinical parameters have found able to predict response to treatment. Standard high-resolution manometry (HRM) did not show any specific motor findings in patients with EoE.

Aims & Methods

The aim of this study was to evaluate the role of low (multiple rapid swallow, MRS) and high volume (rapid drinking challenge, RDC) provocative tests in predicting histologic remission after PPI therapy in patients with EoE

We evaluated consecutive patients with EoE who underwent HRM and reflux monitoring (impedance-pH) to exclude GERD. HRM was performed according to Italian guidelines. All patients had 3 MRS (5 wet swallows of 2ml of water in less than 10s) and one RDC (200ml of water swallowed rapidly).

Thereafter, the same treatment with high dose PPI (80mg esomeprazole for 8 weeks) was administered to every patient, which was followed by a routine endoscopy with 6 esophageal biopsies. According to histology patients were categorized in: responder (< 15 Eos x HPF; Group A) and non-responder (>15 Eos x HPF). The results of HRM and MII-pH were evaluated to better understand differences between the two groups.

Results

We evaluated 29 patients (6 females; mean age 29.7±11.7 years; mean BMI 21.5±1.2). Group A was composed by 14 patients (4 females; with mean age of 26.6±10.3); Group B was composed by 15 patients (2 females; with mean age of 32.4±13.4) (p< 0.05). GERD was excluded in all patients and impedance-pH did not show any significant differences between the two groups. HRM did not show any difference between the two groups in terms of esophagogastric junction parameters and esophageal body motility during the 10 wet swallows. However, MRS and RDC showed a lack of inhibition of esophageal body with frequent panesophageal pres-surization (p< 0.001). Data from HRM were summarized in Table 1.

Conclusion

Provocative tests during standard HRM seem able to distinguish responder from non-responder to PPI treatment. These preliminary results, if confirmed by larger and prospective studies, will be useful to choose steroids or diet as first-line approach for treating EoE patients.

Disclosure

Nothing to disclose

Table 1.

data collected during HRM

	Group A (14pts)	Group B (15 pts)	p
Mean DCI-SS	2482.7±911.4	1915.1±589.4	0.052
Mean IRP-SS	10.6±2.6	13.6±4.1	0.131
Mean DCI-MRS	2408.5±1014.6	1802.1±992.7	0.173
Mean IRP-MRS	10.5±3.3	13.1±3.2	0.067
Failed MRS	2	9	0.02
Panesophageal pressurization-MRS	1	10	0.001
DCI-RDC	705.8±214.9	684.3±116.8	0.768
IRP-RDC	11.6±2.6	14.3±4.1	0.076
Failed RDC	5	13	0.007
Panesophageal pressurization-RDC	1	11	<0.001

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United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.75

P0086 Fibrotic Features in The Eosinophilic Esophagitis Endoscopic Reference Score in The Diagnosis and Response To Proton-Pump Inhibitor Therapy

P Navarro ^1,^✉, EJ Laserna-Mendieta ^1,^2,³, D Guagnozzi ^4,⁵, S Casabona-Francés ^2,⁶, MA Perello ⁷, EV Savarino ⁸, S de la Riva ⁹, E Rey-Iborra ¹, N Serrano Moya ¹, C Alcolea-Valero ¹, C Santander ^2,⁵, AJ Lucendo ^1,^2,⁵

Introduction

The eosinophilic esophagitis (EoE) Endoscopic Reference Score classification system is proposed to standardize the reporting of major endoscopic features of EoE, which are included in the acronym EREFS. The validated EREFS system may help to identify inflammatory (edema, exudates and furrows) versus fibrotic features (rings and strictures) in the esophagus of EoE patients. Proton-pump inhibitor (PPI) therapy is recognized as an anti-inflammatory treatment option for patients with EoE, able to reduce symptoms and eosinophilic infiltration. Recent research has suggested that PPI will have limited impact on subepithelial EoE processes such as fibrosis, because lack of inhibition of Th2 cytokine-stimulated eotaxin-3 expression by esophageal fibroblasts.

Aims & Methods

To investigate the potential effect of PPI therapy in reducing endoscopic features of EoE and in reverting fibrotic features after a short-term course. Data on the effectiveness of PPI to induce remission of EoE were collected from EoE CONNECT, a multicenter, prospectively-maintained registry of patients with EoE. Patients who received PPI therapy to induce EoE remission either as initial therapy or after failure to a previous dietary or drug-based option were included in the study. Patients who were under esophageal dilation were excluded. Clinical remission was defined by a decrease of >50% in Dysphagia Symptom Score; histologic remission was defined as a peak eosinophil count below 15 eosino-phils per high-power field (eos/hpf). EREFS was scored by the severity of 5 endoscopic findings at baseline endoscopy and after a short course of PPI drugs. Changes in EREFS overall score and fibrotic subscore (presence of rings and/or strictures) were compared between EoE responders and non-responders to PPI treatment by t-test analyses. The potential additional benefit of achieving deep esophageal remission (<5 eos/hpf at post-treatment endoscopy) was also investigated.

Results

Data on 169 patients with EoE who received PPI therapy to induce remission of EoE and have registered information on clinical, histologic and endoscopic findings before and after PPI therapy were analyzed. Double dose of PPI were used in most cases (88%). At baseline endoscopy, 96 patients presented rings and 26 esophageal strictures. Eighty seven patients (51.5%) accomplished for histologic remission and symptomatic response together and were considered as PPI-responders. Mean±SD overall EREFS score at baseline were not different for PPI responder and non-responder patients, but reduced significantly only in PPI respond-ers (2.59±1.73 to 1.06±1.01, p< 0.001), with no changes found among no responders (2.85±1.68 to 2.16±1.86). PPI responder associated to reduction from baseline in mean±SD rings’ subscore (0.74±0.85 vs. 0.41±0.62; p=0.001) and strictures’ subscore (0.10±0.29 vs. 0.01±0.11; p=0.007). Overall, the combined fibrotic score was significantly lower from baseline in EoE patients who responded to PPI therapy compared to those who did not (being 2.16 ±2.00 vs 1.28±1.08; p=0.009). Deep histologic remission provided no significant additional reductions of rings’ and strictures sub-scores from baseline compared with partial histological remission (5-15 eos/hpf), but the combined fibrotic score showed a near-significant decrease (1.43±1.25 vs. 0.93±0.89, p=0.05).

Conclusion

Effective PPI therapy for EoE associates to significant endoscopic improvement overall, and reduces significantly endoscopic features of esophageal fibrosis in the short term. Deep histologic remission tended to produce increased benefits.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.76

P0087 Dupilumab Normalizes Expression of Genes Associated with Type 2 Inflammation in Patients with Eosinophilic Esophagitis

JD Hamilton ^1,^✉, MH Collins ², WK Lim ¹, S Hamon ¹, MF Wipperman ¹, A Radin ¹, M Chehade ³, I Hirano ⁴, ES Dellon ⁵, S Harel ¹, W Brian ⁶, LP Mannent ⁷, ME Rothenberg ²

Introduction

Eosinophilic esophagitis (EoE) is chronic type 2 inflammatory disease resulting in eosinophilic inflammation of the esophagus, remodeling, and barrier dysfunction. Patients with EoE have an altered esophageal transcriptome compared with healthy controls, including changes in genes associated with type 2 inflammation, eosinophils, and mast cells. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4 and IL-13, key and central drivers of type 2 inflammation in multiple diseases. in a double-blind, placebo-controlled, phase 2 study (NCT02379052), adults with active EoE were randomized 1:1 to receive 12 weeks of subcutaneous dupilumab 300 mg weekly or placebo. Dupilumab significantly improved dysphagia and histological and endoscopic measures of disease with an acceptable safety profile. This analysis assessed the effect of dupilumab on the expression of type 2 inflammatory genes in patients enrolled in the EoE phase 2 study.

Aims & Methods

Pinch biopsies were collected from proximal, mid, and distal esophagus at baseline and Week 12 of 41 patients, and RNA was extracted for transcriptome sequencing. Mean gene expression of the 3 esophageal regions for each patient was examined at baseline and Week 12, then compared across patients with the published EoE and healthy transcriptomes. A relative change from baseline of ≥ 2-fold, q < 0.05 was considered significant, reflecting appropriate adjustment for multiple testing.

Results

Overall, dupilumab 300 mg weekly modulated 1,302 genes, with very similar transcriptomes in all 3 analyzed esophageal regions. Dupilumab significantly normalized the expression of genes associated with type 2 inflammation. This includes genes associated with type 2 inflammatory cell responses (e.g. CCR4, POSTN, and ALOX15), proinflammatory cytokine production (e.g. SPINK7), and mucins (e.g. MUC5B). Dupilumab also significantly normalized genes associated with eosinophils and mast cells, by downregulating genes associated with eosinophil recruitment (e.g. CCL26 and CCR3) and genes encoding eosinophil (e.g. SIGLEC8) and mast cell surface proteins (e.g. IL1RL1), which are all dysregulated in the EoE transcriptome. The post-dupilumab transcriptome more closely resembled that of healthy controls than the published EoE transcriptome. No changes in gene expression in the placebo group met significance thresholds.

Conclusion

In this phase 2 study, dupilumab reversed the EoE disease transcriptional signature, and normalized multiple genes associated with type 2 inflammation, eosinophils, and mast cells. This confirms the congruence of the mechanism of action of dupilumab and the mechanism of disease, highlighting the IL-4/IL-13 pathway as a central mediator of EoE pathogenesis.

Disclosure

Hamilton JD, Lim WK, Hamon S, Wipperman MF, Radin A, Harel S: Regeneron Pharmaceuticals, Inc. - employees and shareholders. Collins MH: Allakos, AstraZeneca, BMS, Esocap, GSK, Regeneron Pharmaceuticals, Inc., Shire - consultant; Receptos/BMS, Regeneron Pharmaceuticals, Inc., Shire - research funding. Chehade M: Adare, Allakos, Nutricia, Regeneron Pharmaceuticals, Inc., Shire - consultant; Allakos, Regeneron Pharmaceuticals Inc., Shire - research funding; Medscape, Nutricia - honoraria for lectures. Hirano I: Adare, Receptos/BMS, Regeneron Pharmaceuticals, Inc., Shire - consultant; Meritage, Receptos/BMS, Regeneron Pharmaceuticals, Inc., Shire - research funding. Dellon ES: Abbott, Adare, Aimmune, Alivio, Allakos, Arena, AstraZeneca, Banner, Biorasi, Calypso, Enumeral, EsoCap, Gossamer Bio, GSK, Receptos/BMS, Regeneron Pharmaceuticals, Inc., Robarts, Salix, Shire/Takeda - consultant; Adare, Allakos, GSK, Meritage, Miraca, Nutricia, Receptos/BMS, Regeneron Pharmaceuticals, Inc., Shire - research funding; Allakos, Banner, Holoclara - educational grant. Brian W, Mannent L: Sanofi - employees, may hold stock and/or stock options in the company. Rothenberg ME: Allakos, AstraZeneca, BMS, ClostraBio, Pulm One, Spoon Guru - consultant; ClostraBio, Pulm One, Spoon Guru – equity interest; Teva Pharmaceuticals - royalties from reslizumab; Mapi Research Trust - royalties from PEESSv2; UpToDate - royalties; an inventor of patents owned by Cincinnati Children's Hospital.

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.77

P0088 Achalasia and Obstructive Motor Disorders Are Not Uncommon in Patients with Eosinophilic Esophagitis

M Ghisa ¹, G Laserra ^1,^✉, E Marabotto ², S Ziola ², S Tolone ³, ND Bortoli ⁴, M Frazzoni ⁵, A Mauro ⁶, R Penagini ⁷, V Savarino ⁸, EG Giannini ⁸, P Zentilin ⁸, CP Gyawali ⁹, EV Savarino ¹⁰

Introduction

Eosinophilic Esophagitis (EoE) is a chronic disease that has been associated with various esophageal motility disorders, ranging from hypo- to hyper- contractile motility abnormalities. Recently, a potential association has been reported between eosinophilic esophagitis (EoE) and achalasia and other obstructive motor disorders.

Aims & Methods

We aimed to estimate the incidence of overlap between EoE and obstructive motor disorders including achalasia in a large cohort of consecutive EoE patients who underwent HRM as part of the initial evaluation. Furthermore, we aimed to assess the clinical course of both diseases and determine response to treatment.

We included consecutive patients with a new diagnosis of EoE who underwent HRM during initial evaluation at academic institutions in Padua, Genoa, Pisa and Naples, between 2012 to 2019. Demographic, clinical, en-doscopic and histological characteristics were recorded at baseline and during management. EoE and esophageal motility disorders were diagnosed according to established international criteria. Treatments offered included proton pump inhibitors and topical steroids for EoE, pneumatic dilation and myotomy for achalasia.

Results

Of 109 consecutive patients (mean age 37 years, 82 male), 68 (62%) had normal HRM. Among 41 patients with motor disorders, 24 (59%) had minor motor disorders while 17 (41%) major motor disorders (including 8 with achalasia: type 1=1 patient, type 2=4 patients, and type 3=3 patients). Achalasia and non-achalasia obstructive motor disorders (DES=1 patient, jackhammer esophagus=2 patients, EGJOO=5 patients) had 14.7% prevalence in EoE. Achalasia was more frequent in females, with longer diagnostic delay and abnormal esophagogram (p< 0.05) compared to EoE without achalasia or obstructive motor disorders. Clinical features and endoscopic findings were similar between EoE patients with or without achalasia and obstructive motor disorders (p=ns); on the contrary, abnormalities on esophagogram were seen more often in achalasia and obstructive motility disorders (p< 0.001). Achalasia patients resembled those with other obstructive motility disorders, with no differences in demographic features, symptoms, endoscopic and histologic characteristics (p=ns) but they present a longer diagnostic delay (p=0.038). Concerning therapies, while there were no differences in PPI response between patients with achalasia and obstructive motility disorders and the other ones (p=0.104), the former responded less well to topical steroids (p=0.005). No differences in response to PPI and topical steroids between achalasia and other obstructive motor disorders (p=1 and p=0.592, respectively) were found. Invasive endoscopic or surgical treatments were required for symptom relief in 50% of patients with achalasia and obstructive motor disorders. After mean follow-up of 30 months, clinical, endoscopic and histological benefit from therapy was observed in 15 of 16 (94%) patients with achalasia and obstructive motor disorders. Only one patient with DES had persistent dysphagia and eosinophilic inflammation, likely related to noncompliance.

Conclusion

Achalasia and obstructive motor disorders are not uncommon in EoE, suggesting a potential causal link between these disorders. HRM is of value in patients with suspected EoE during the initial diagnostic work-up.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.78

P0089 Oesophageal Mucosa Innervation in Paediatric Eosinophilic Oesophagitis

K Nikaki ^1,^✉, A Ustaoglu ¹, C Lee ¹, P Woodland ¹, D Sifrim ¹

Introduction

The mechanism for symptom generation in eosinophilic oesophagitis (EoE) is not completely clear. Together with mechanical obstruction due to decreased oesophageal wall distensibility, oesophageal hypersensitivity has been noted. Hypersensitivity can be due to impairment of mucosal integrity and/or sensitization of mucosal nerves.

Aims & Methods

The aim of our study was to delineate the mucosal innervation in the proximal and distal oesophagus in paediatric EoE and control subjects and correlate this with the histological findings. We prospectively recruited children undergoing an upper GI endoscopy for clinical reasons and identified a subgroup with normal histology +/-normal impedance pH-metry that served as controls and a patient group with histologically confirmed EoE. We obtained oesophageal biopsies from 3-5cm above the lower oesophageal sphincter and from the proximal/upper third. The biopsies were immunohistochemically stained for CGRP and TRPV1. CGRP positive nerve fibres were identified and their position relative to the lumen was determined (expressed as median number of cell layers from the lumen for all sections examined). The peak eosinophilic count per high power field (HPF) was used as proxy of disease activity in EoE.

Results

19 children were included (12M:7F, median age: 11 years) in the control group and 12 in the EoE group (9M:2F, median age: 12 years). in the control group, CGRP positive nerve fibres were identified at a median of 19.5 cell layers from the lumen in the proximal and 19 cell layers in the distal oesophagus (Image 1). in the EoE group, CGRP positive nerve fibres were identified at a median of 14 cell layers in the proximal and 12.6 cell layers in the distal oesophagus (p=0.0009 and 0.01 respectively). There is a weak correlation between the number of eosinophils per HPF and the position of the nerve fibres in the oesophageal mucosa (r=-0.46). None of the nerve fibres identified expressed the TRPV1 receptor.

Conclusion

The oesophageal mucosa innervation in children with EoE is similar in the proximal and distal oesophagus with more superficial lying nerve fibres compared to controls. The superficiality of the nerve fibres may be driven by the underlying inflammation. These findings may contribute to the oesophageal hypersensitivity noted in EoE despite histologi-cal remission.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.79

P0090 Acid Suppressant Medications and Eosinophilic Esophagitis: Are They Friends Or Foes?

O Alaber ¹, R Sabe ², A Swi ³, B Dahash ^1,^✉, V Baez ², T Sferra ²

Introduction

Eosinophilic esophagitis (EoE) is an atopic-immune mediated, inflammatory process isolated to the esophagus leading to symptoms of esophageal dysfunction. Treatments are elimination diets, topical steroids, and proton pump inhibitors (PPI). A recent report suggests that acid suppression therapy (AST) with PPI and histamine-2 receptor antagonist (H2RA) exposure during infancy is a risk factor for EoE.

Aims & Methods

To investigate whether AST at any age is associated with an increased risk of EoE.

Data were obtained from a commercial medical database (IBM Explorys Solutions, IBM, Inc.) that has patient information from 27 U.S. healthcare networks from 1999 to present. Patients who underwent esophagogastro-duodenoscopy (EGD) were identified using Systematized Nomenclature of Medicine - Clinical Terms (SNOMED-CT). Cases were defined as patients who underwent an EGD and started AST (PPI or H2RA) for the first time after at least 90 days from the initial EGD for a period of three months then underwent a second EGD and were subsequently diagnosed with EoE. Controls were patients who underwent an EGD and never received AST. Patients with a pre-existing diagnosis of EoE or previously received AST were excluded from the analysis. The 90-day period after the initial EGD was used to exclude patients who received AST prior to the final diagnosis of EoE (based on a past clinical guideline to exclude PPI-responsive eosin-ophilia). Odds ratio (OR) and 95% confidence interval (CI) for the OR were calculated for the association of AST and development of EoE.

Results

2,225,060 (3.5%) of individuals (64,417,480) within the database underwent an EGD.

The overall population prevalence of EoE was 5 in 10,000 (32,220 cases), this is consistent with previous population studies. The risk of being diagnosed with EoE in a patient who never received AST (controls) was 0.37%. Compared to controls (Table 1), those who received any AST had a 1.2 (CI: 1.1 - 1.3) times higher odds of having a new diagnosis of EoE; those who received PPIs had a 1.6 (CI: 1.5 - 1.7) higher odds; and individuals who received H2RAs did not have an increased risk of EoE (OR: 1.1, CI: 0.9 - 1.4). Receiving both ASTs conferred a 3.0 (CI: 2.7 - 3.2) higher odds of being diagnosed with EoE compared to controls. Subgroup analysis (Table 1) comparing both and any ASTs to individual PPI/H2RA revealed the effect of H2RAs to be minimal when used alone and additive if combined with PPIs.

Table 1.

Main Analysis and Subgroup Analysis

	Cases N (Risk %)	OR	95% CI
EGD + no AST's (Controls)	2130 (0.37%)
EGD + H2RA only	80 (0.41%)	1.12	0.90 - 1.41
EGD + PPI only	1680 (0.58%)	1.60	1.50 - 1.70
EGD + Both AST's (H2RA and PPI)	650 (1.08%)	2.97	2.72 - 3.24
EGD + Any AST's (H2RA or PPI)	1720 (0.44%)	1.18	1.11 - 1.26
EGD + Both AST's (H2RA and PPI) vs H2RA only		2.64	2.10 - 3.33
EGD + Both AST's (H2RA and PPI) vs PPI only		1.87	1.71 - 2.05
EGD + Any AST's (H2RA or PPI) vs H2RA only		1.05	0.84 - 1.32
EGD + Any AST's (H2RA or PPI) vs PPI only		0.75	0.70 - 0.80

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Conclusion

Although PPIs are a treatment for EoE, our findings suggest the use of a PPI at any age is a risk factor for the development of EoE. H2RA therapy alone is not a risk for EoE. However, the use of both ASTs increases the risk over PPI therapy alone. This effect might be due to more severe symptoms in EoE patients leading to more aggressive therapy. The pathophysiology for this increased risk of EoE is unclear.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.80

P0091 Anti-Tumor Necrosis Factor Therapy and Eosinophilic Esophagitis: Is There Any Connection?

O Alaber ¹, R Sabe ², B Dahash ^1,^✉, V Baez ², T Sferra ²

Introduction

Eosinophilic esophagitis (EoE) is an atopic-immune mediated, inflammatory process isolated to the esophagus leading to symptoms of esophageal dysfunction. Eosinophilic esophagitis has been increasingly reported to be associated with other immune mediated disorders (IMD). It is unknown whether this association is due to a common underlying immune dysregulation or due to other factors associated with IMDs. We hypothesized that anti-tumor necrosis factor-a therapy (anti-TNF) is one of the IMD associated factors leading to the development of EoE.

Aims & Methods

To investigate whether anti-TNF therapy is a risk factor for EoE.

Data were obtained from a large commercial medical database (IBM Ex-plorys Solutions, IBM, Inc.) that contains patient information from 27 U.S. healthcare networks from 1999 to present. Systematized Nomenclature of Medicine - Clinical Terms (SNOMED-CT) were used to extract patient information. We defined cases as patients without a pre-existing diagnosis of EoE who had an office visit (index event) and subsequently received an anti-TNF (etanercept, adalimumab, or infliximab) regardless of indication. We defined the comparator group as those who had a diagnosis of EoE and never received an anti-TNF. We performed subgroup analyses for inflammatory bowel disease (IBD) and other immune mediated diseases (rheumatoid arthritis, ankylosing spondylitis, psoriasis, Behcet's syndrome, hidradenitis suppurativa, and uveitis) and for individual diagnoses (only those diseases with sufficient numbers in the database were analyzed). Odds ratio (OR) and 95% confidence interval (CI) were calculated for the association of anti-TNF therapy and the development of EoE.

Results

135,630 (0.21%) of all patients (64,417,480) within the database were prescribed an anti-TNF. Cases (those prescribed an anti-TNF for any indication) had a 2.22 (CI: 1.92 - 2.56) higher odds of being diagnosed with EoE compared to controls who never received an anti-TNF (Table 1). Cases with IBD had a 1.84 (CI: 1.1 - 2.25) higher odds of having EoE when compared to patients with IBD who never received anti-TNF therapy. Cases with other IMDs had a 1.65 (CI: 1.32 - 2.06) higher odds of developing EoE when compared to those with an IMD and never prescribed an anti-TNF (Table 1). Cases with Crohn's disease (OR: 1.94, CI: 1.48 - 2.52), rheumatoid arthritis (OR: 1.69, CI: 1.24 - 2.27), and psoriasis (OR: 1.95, CI: 1.39 - 2.73) had a higher odds of developing EoE as compared to controls. Ulcerative colitis (OR: 1.02, CI: 0.51 - 1.86) and ankylosing spondylitis (OR: 1.49, CI: 0.73 - 3.05) did not have higher odds of EoE (Table 1).

Conclusion

The initiation of an anti-TNF in patients with IMD was associated with an increased occurrence of EoE in our population. The underlying pathophysiologic mechanism of this increased risk of anti-TNF therapy requires further investigation.

Disclosure

Nothing to disclose

Table 1.

Association of anti-TNF therapy and development of EoE in immune-mediated diseases

	Cases N (Risk %)	Comparator N (Risk %)	OR	95% CI
All patients	190 (0.17%)	20850 (0.07%)	2.22	1.92 - 2.56
IBD	110 (0.31%)	740 (0.17%)	1.84	1.51 - 2.25
Other IMD	90 (0.12%)	620 (0.07%)	1.65	1.32 - 2.06
Ulcerative colitis	10 (0.15%)	170 (0.15%)	1.02	0.51 - 1.86
Crohn's disease	70 (0.34%)	260 (0.18%)	1.94	1.48 - 2.52
Rheumatoid arthritis	50 (0.10%)	280 (0.06%)	1.69	1.24 - 2.27
Ankylosing spondylitis	10 (0.15%)	30 (0.10%)	1.49	0.73 - 3.05
Psoriasis	40 (0.15%)	210 (0.08%)	1.95	1.39 - 2.73

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United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.81

P0092 Mental Distress Among Adult Patients with Eosinophilic Esophagitis

WE de Rooij ^1,^✉, F Bennebroek Evertsz’ ², A Lei ¹, AJ Bredenoord ¹

Introduction

Data on the prevalence of mental distress among adult eosinophilic esophagitis (EoE) patients are scarce. Also, a significant gap remains in understanding of the degree to which clinical and socio-demo-graphic variables are related to significant psychological symptoms.

Aims & Methods

Adult EoE patients were invited to complete standardized measures on anxiety and depressive symptoms (HADS) and general psychopathology (SCL-90-R). All scores were compared to General Population (GP) norms, stratified by age and sex. Socio-demographic and clinical factors were assessed by means of a self-reported questionnaire. Factors with p-value < 0.2 in univariate analysis, or factors that were considered clinically relevant, were entered into a multivariate logistic regression model.

Results

In total, 147 adult EoE patients (61% males, median age 43 (IQR 29 - 52) years were included (response rate 71%). No difference with GP values was found for total anxiety and depressive symptoms (7.8±6.6 vs 8.3±0.21; P = 0.35). A total of 38/147 (26%) patients reported high levels of anxiety and/or depressive symptoms (HADS-A: 35/147 (24%) and HADS-D: 14/147 (10%) ≥ 8), indicative of a psychiatric disorder. in a multivariate analysis, age between 18-35 years was independently associated with high levels of anxiety (≥ 8 HADS-A) (OR 3.0 | 95 % CI 1.307 - 6.881; P = 0.01) The SCL-90-R Global Severity Index (GSI) was significantly higher compared to the GP (P < 0.001). Also the dimensions; depression, somatization, insufficiency of thinking and acting, hostility, sleep disturbance, anxiety and sensitivity were all significantly higher compared to the GP (P < 0.05). in total, 43 (29%) patients reported to have current or past mental problems, of which 23 (53%) felt it was related to EoE.

Conclusion

A considerable prevalence of mental distress was observed in adult patients with EoE, with a 3-fold risk of features of significant anxiety in those patients younger than 35 years. Therefore, a pro-active approach in the management of EoE towards these symptoms seems warranted.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.82

P0093 Eosinophilic Oesophagitis - Clinical, Endoscopic and Histological Scoring Systems in Initial Diagnosis After Remission Induction and in Remission Maintenance Under Topical Corticosteroids

NJ Lorenz ^1,^✉, A Link ¹, C Thon ¹, P Czapiewski ², U von Arnim ¹

Introduction

Eosinophilic oesophagitis (EoE) is a chronic inflammatory, allergenic/immune-mediated disease of the esophagus. EoE is characterized clinically by symptoms of esophageal dysfunction and histologically by an eosinophil-predominant inflammation restricted to the esophagus. Clinical (Straumann Dysphagia Index, SDI), endoscopic (EREFS) and his-tological (EoE-HSS) scoring systems exist to determine disease activity. Topical corticosteroids (tCS) are effective in inducing clinico- histological remission (RI) and maintenance of remission (RM) in active EoE. However, often symptoms, endoscopic and histological findings do not correlate.

Aims & Methods

Correlation of SDI, EREFS and EoE-HSS at initial diagnosis (ID) of EoE, after RI and in RM with tCS among each other as well as in the course of therapy.

Retrospective cohort analysis of 2006-2020 in patients with active EoE with follow-up intervals up to 6 years. SDI, EREFS and EoE-HSS were collected at the time of ID, after RI and during RM (Definition: remission: ≤15 Eos/HPFand reduction SDI ≥3). The evaluation based on descriptive statistics, Friedman test and Bonferroni-adjusted post-hoc comparisons.

Results

At the time of RI, all scores were analyzed in 29 of 60 patients (62% male, mean age 48). All EoE patients were treated with tCS for a mean of 13 weeks until RI. 19 complete data sets were evaluated in RM after a mean duration of therapy with tCS of 21 months. The EREFS showed significant correlations to EoE-HSS in RI (Spearman correlation r=0.56; p=0.013) as well as in RM (r=0.61; p=0.006). The pairwise comparison using Bonferroni-adjusted post-hoc tests reveals significant differences between ID and RI for SDI (r=-0.035; p< 0.001) and EoE-HSS (r=0.268; p=0.028), but not for EREFS. No statistical significance of the three scores was detected between RI and RM.

Conclusion

Clinical, endoscopic and histological scores to determine activity in EoE do not correlate at time of ID.

The comparison of the respective scoring systems after induction therapy reveals significant differences at the time of ID and RI symptomatically and histologically, but not in RM under tCS therapy. These results underline the effectiveness of tCS in RI and RM therapy of active EoE.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.83

P0094 Long-Term Treatment with Proton Pump Inhibitors and Topical Steroids in Eosinophilic Esophagitis: Efficacy and Factors Influencing Response

G Laserra ^1,^✉, M Ghisa ¹, B Barberio ¹, F Zingone ¹, S Tolone ², ND Bortoli ³, V Savarino ⁴, EV Savarino ¹

Introduction

Eosinophilic esophagitis (EoE) is a chronic disorder. While induction therapy is well defined, evidence about long-term management and factors influencing the course of the disease are still lacking.

Aims & Methods

The aim of this study was to evaluate the long-term outcome of EoE patients who started proton pump inhibitors (PPIs) or topical steroids as induction therapies. Prospectively collected data from 58 EoE patients (42 Male, mean age at diagnosis 33yo), with a mean follow-up of 2 years and 10 months, were analysed. All patients had symptoms suggestive of EoE (i.e. dysphagia and bolus impaction) and after endoscopic/histological confirmation of EoE were treated with high-dose PPI therapy. in case of eosinophilic infiltration persistence at 8-weeks upper endoscopy, treatment with topical steroids was started. Thereafter, patients repeated the upper endoscopy to confirm the histological remission (i.e. eosinophilic peak < 15/HPF). During follow-up, 3 different patterns of therapeutic response were identified: continuous responders (CR; histological remission in more than 75% of endoscopic evaluation carried out every year from the diagnosis), intermittent responders (IR; remission in 25-75% of endoscopic evaluations), non-responders (NR; remission in less than 25% of endoscopic assessments). Risk factors for relapse were calculated.

Results

Seventeen (29%) patients achieved clinical and histological remission using PPI (PPI-R), 32 (56%) responded to topical steroids (TS-R), 3 (5%) to diet and 6 did not respond to any therapy (10%). Remission was durable in 60% of PPI-R patients who maintained maximal dose therapy, and in 58% of those attempting a tapering. Among TS-R patients, remission was maintained in 56% of those taking maximum dosage and in 50% of those who tapered. No significant difference in maintenance of remission between those who tapered therapy (PPI or TS) and those who did not, was observed (p=0.633 and p=0.912). No different risk of relapse between who tapered and who did not, both for PPI (p>0.99, OR=2, I=0.24-29.80) and for TS (p=0.38, OR=2.25, I=0.46-10.61), emerged. in terms of long-term efficacy, 64% were CR, 26% were IR, 10% NR. Considering CR, IR and NR, there was a significant difference in terms of age at diagnosis and diagnostic delay (p=0.044 and 0.011, respectively). The mean age at diagnosis was 36yo for CR, 30yo for IR and 20yo for NR. Diagnostic delay was 3years and 6months for CR, 2 years and 7 months for IR, 8years and 7months for NR.

Conclusion

Our data demonstrated that PPI and TS are effective therapies to induce remission and to maintain histological response in the long term in most patients (90%), even after tapering. Only a small proportion of patients do not respond to available treatments. Characterization of these patients could help, in the future, to improve therapeutic outcome.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.84

P0095 Serum Biomarkers in The Diagnostics of Patients with Suspected Eosinophilic Esophagitis - Preliminary Report

J Sarbinowska ^1,^✉, D Wasko-Czopnik ¹, B Wiatrak ²

Introduction

Invasive diagnostic tests monitoring the effectiveness of eo-sinophilic esophagitis (EoE) therapy, i.e. according to current standards, periodic panendoscopy with specimens for histopathological examinations, encourage the search for alternative, less invasive methods suggesting broadening the diagnosis leading to diagnosis, but also monitoring the course of the disease. in the light of previous studies, we do not have a biomarker of blood serum with sufficient diagnostic accuracy.

Aims & Methods

The aim of the study is to assess the correlation of serum biomarkers concentration with the diagnosis of EoE. To date, 56 people have been studied, each of whom had serum levels of interleukin 5 (IL-5) and 13 (IL-13), transforming growth factor beta 1 (TGF-β1), eotaxin 3, as well as panendoscopy with specimens collection from the esophagus for histopathological examination. The criteria for diagnosing EoE according to the current UEG, EAACI ESPHAGAN and EUREOS guidelines (2017) and Updated international consensus diagnostic criteria of the AGREE conference (2018) was esophageal biopsies of ≥15 eosinophils per high-power field, in co-occurrence of esophageal dysfunction symptoms and absence of other causes of esophageal eosinophilia. Patients who did not meet these criteria constituted the control group. Quantification of biomarkers was performed using an enzyme immunoassay (ELISA). in data analysis, p < 0.05 was considered statistically significant.

Results

Only 15 people with dysphagia symptoms and suspected EoE were diagnosed with the disease (26,79%). The median TGF-β1 concentration was significantly increased in patients with EoE compared to the control group [11025,00 pg/ml (interquartile range - IQR: 7170,0-14100,00) vs. 7839,00 pg/ml (IQR: 6297,0-9195,00),p = 0,022], the median eotaxin 3 concentration was on the upper limit of significance [96,00 pg/ml (IQR: 43,80-182,00) vs. 50,00 pg/ml (IQR: 27,70-100,40),p=0,054], while for the other markers no statistical significance was obtained: IL-13 [2,50 pg/ml (IQR: 1,28- 3,30) vs. 3,70 pg/ml (IQR: 1,00),p=0,185], IL-5 [4,07 pg/ml (IQR: 3,10) vs. 4,30 pg/ml (IQR: 3,90),p=0,452].

Conclusion

The increase in serum TGF-β1 concentration correlates with the diagnosis of EoE, which suggests a potential role in recognizing, and perhaps also controlling the course of the disease. Due to the small group of patients and promising results of analyzes, it seems advisable to continue the study, further recruitment of participants, inclusion of additional biomarkers in the determinations, as well as to continue to observe changes in their concentrations during EoE therapy. From the obtained data, in further analysis, it is advisable to develop, among others decision tree, which can be a tool supporting the diagnosis, monitoring and forecasting of the course of EoE in clinical practice, not on the basis of the concentration of individual biomarkers, but their group and interrelationships.

Disclosure

This study was funded by the Wroclaw Medical University Research Program for Young Scientists (Project: STM.C130.17.045). The authors do not report any financial or personal affiliations to persons or organizations that could negatively affect the content of this publication or claim to have rights to this publication.

References

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United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.85

P0096 Defining An Eosinophilic Leukocyte Count Per Mm² Threshold For The Diagnosis of Eosinophilic Esophagitis Using A Digital Pathology Platform

C Molnár ¹, T Micsik ², ÁV Patai ^3,^4,^✉

Introduction

Eosinophilic esophagitis (EoE) is a chronic, antigen-mediated disease causing severe dysphagia. Diagnosis relies on clinical symptoms and eosinophilic leukocyte count (EoL) per High Power Field (HPF). However, histology samples frequently may not fill the whole objective and there is an almost 2.5-fold difference in HPF area of different microscopes. Thus, a standardized number of EoL/mm² may decrease diagnostic discrepancies and may facilitate better diagnostic rate.

Aims & Methods

Our aim was to analyze EoL/mm² and other histopatho-logic features in EoE using a digital pathology platform, and compare these to gastroesophageal reflux disease (GERD) to define a EoL/mm² threshold for the diagnosis of EoE.

45 EoE and 45 matched GERD cases were selected retrospectively from the archives of the Pathology Departments of Semmelweis University, Budapest, Hungary. Clinicopathological data were collected, slides were digi-talized using Pannoramic^TM P250 Flash digital slide scanner (3DHISTECH Ltd., Budapest, Hungary) and re-analyzed by 2 independent GI histopa-thologists. Epithelial and subepithelial compartments and EoLs were annotated digitally with CaseViewer.

Results

45 EoE patients were 66% males; mean age was 23.5 ± 19.7 years. Most common endoscopic manifestations were rings (36.8%) and longitudinal furrows (21.1%). Histopathologic EoE findings were: eosinophilic cell degranulation 86.6%, spongiosis 75.5%, eosinophilic aggregate formation 66.7%. Average sample areas were similar in both groups, whereas digital image analysis showed significantly higher EoL/mm² count in both epithelial (171.2±177.2 vs 3.3±11.6) and subepithelial (61.1±67.11 vs 4.5±13.22) compartments of EoE as compared to GERD cases. ROC analysis found a reliable threshold for differentiating EoE from GERD at 33 EoL/mm² (AUC=0.993) in the epithelial and 16 EoL/mm² in the subepithelial compartment (AUC=0.882).

Conclusion

In 2018 a consensus paper of international experts suggested an estimated 60 EoL/mm² threshold for diagnosing EoE instead of 15 EoL/HPF. Our study with numerical counting of EoLs on a digital platform found that a lower, 33 EoL/mm² threshold might be reliably differentiate EoE from GERD. Further prospective studies are needed to validate these findings.

Disclosure

Nothing to disclose

References

Dellon E.S., Liacouras C.A., Molina-Infante J. et al. Updated International Consensus Diagnostic Criteria for Eosinophilic Esophagitis: Proceedings of the AGREE Conference. Gastroenterology. 2018; 155(4): 1022–1033. [DOI] [PMC free article] [PubMed] [Google Scholar]

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.86

P0097 Endoscopic and Radiological Abnormalities Are Common in Patients with Eosinophilic Oesophagitis and Are More Likely with Increased Oesophageal Sampling - A Single Centre Longitudinal Experience

HN Haboubi ^1,^✉, R-I Rusu ¹, T Wong ¹, JM Dunn ¹, SS Zeki ¹

Introduction

Eosinophilic Oesophagitis (EoE) is a chronic allergic disorder of the oesophagus, associated with an inflammatory infiltrate of eosinophils into the oesophagus, and associated with submucosal fibrosis and dysphagia. A high index of suspiscion is needed at endoscopy and targeted biopsies from areas of mucosal abnormality in addition to standard multiple level sampling strategies, yielding the best results.

Aims & Methods

We aimed to evaluate the endoscopic, pathologic and radiologic features of patients with EoE over a 3-year investigative period. A retrospective study of patients with a pathological diagnosis of eosinophilic oesophagitis between 2015 - 2017 was undertaken following a data extraction of results using the Electronic Patient Record (EPR) system. Baseline characteristics were interrogated, in addition to endoscopic findings, associated radiological abnormalities, management strategies and patient outcomes.

Data was extracted and analysed using Rstudio.

Results

A total of 225 patients with a new diagnosis of EoE were made during the time period studied. Median age distribution was 25-30 years, with the oldest patient diagnosed at 75-years of age. The main indication for endoscopy was dysphagia (47%), followed by odynophagia (27%). Food bolus obstruction was present in 25 individuals (11%). The most common endoscopic finding was stricture (40%). A normal oesophagus was described in 18% of individuals with trachealisation seen in 15% of cases. A schatzki ring was present in 10% of cases with endoscopic evidence of oesophagitis described in 45%.

Eosinophil counts ranged from 15-72 eos/hpf with furrows and exudates associated with higher mean eosinophil counts/hpf (55 and 52 respectively) than other endoscopic features, and mucosal oedema associated with lower counts (mean 32 eos/hpf).

Number of biopsies taken ranged from 1-20. Taking more biopsies was associated with a higher chance of spongiosis as well as fibrosis being commented on during histopathological analysis (p< 0.001 and p=0.013 respectively).

Conclusion

Eosinophilic Oesophagitis is becoming an increasingly more commonly diagnosed condition and is associated with significant patient morbidity. Heightened awareness of endoscopic features of disease as well as enhanced biopsy protocols maximise the chances of successful diagnosis.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.87

P0099 Gastroesophageal Refluxes Depend On Nutrients Consumption in Children

G Borodina ^1,², S Morozov ^3,^✉

Introduction

In contrast to adults, association of number and types of gastroesophageal refluxes with usual nutrients consumption is not widely studied in children.

Aims & Methods

The aim of the study was to evaluate the correlation between types and number of gastroesophageal refluxes and nutrients consumption in children and adolescents.

The study was approved by IEC. The data of examination of 219 children (7-17 y.o.), 147 with GERD and 72 controls served as a source for the study. The amount and types of GER were determined using 24-hours esopha-geal pH-impedansometry (Ohmega, MMS, The Netherlands). Food frequency questionnaire was used to evaluate level of nutrients consumption. To make possible comparison of data obtained in different age and sex groups of children, direct levels of nutrients consumption were converted to a percentage deviation from the recommended daily allowance rates. Spearman rank correlation analysis was performed with the use of Statistica 10 (StatSoft Inc., USA) to clear out whether association exists between usual nutrition and number of gastroesophageal reflux episodes, their acidity and duration in children.

Results

Statistically significant (p< .05) correlation of Acid exposure time was found with amounts of PUFA (Spearman R=-0.334), ω-3 (R=-0.33), ω-6 (R=-0.3); retinols (R=-0.34), niacin (R=-0.28) and ascorbic acid (R=-0.37) consumption.

The number of acid refluxes correlated with energy values of the ration (R=0.269), amount of total protein (R=0.279), total fat (R=0.272), total carbohydrates (R=0.152), and added sugar (R=0.157) consumption. The number of weak-acid refluxes was not correlated with any of the parameters of actual nutrition.

We found significant correlation between the number of non-acid refluxes and amount of PUFAs (R=0.19), u-6 (R=0.151), u-3 (R=0.19); sodium (R=0.158), phosphorus (R=0.166), vitamin B1 (R=0.17), niacin (R=0.19), and ascorbic acid (0.23).

Conclusion

We found that types and number of gastroesophageal refluxes, as well as acidification of the lower part of oesophagus may be associated with usual nutrition. Our results may mean that different nutrients have different impact on esophageal motility in children. The results may have practical outcome for planning non-pharmacological intervention in children with GER.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.88

P0101 Epithelial Permeability and Inflammatory Process of Esophageal Mucosa After Anti-Reflux Surgery in Patients with Gastro-Esophageal Reflux Disease

P Ergun ^1,^✉, S Kipcak ², V Gorgulu ³, E Sozmen ⁴, S Bor ⁵, Ege Reflux Study Group

Introduction

Two major injury mechanisms among others proposed for causing mucosal damage in esophageal epithelium of patients with gastroesophageal reflux disease (GERD); gastric acid, pepsin, other noxious agents, and cytokine-mediated inflammation. Laparoscopic anti-reflux surgery (LARS) has restrain reflux effectively and symptoms rapidly disappear. Therefore, LARS patients are the most effective model to study esophageal mucosa absence of harmful agents.

Aims & Methods

We aim to evaluate the tissue resistance and inflammatory process of esophageal mucosa of the cases before and after LARS and compare with healthy controls (HC) in order to understand the underlying pathophysiologic mechanism of GERD.

Upper GI endoscopy, esophageal high resolution manometry, 24h pH-MII monitoring were performed in all patients. Nine esophageal biopsies from 22 patients pre- and post- LARS (13 men; 42,9 ± 11,5 years), 23 healthy controls (7 men; 41,9 ± 10,8 years) were taken. Four biopsies used for Ussing chamber studies, three homogenized for inflammatory studies, rest for measure dilated intercellular spaces (DIS). Upper GI endoscopy and biopsies were repeated 3-4 months after LARS. All patients were symptom-free. Biopsies were analysed in Multiplex Immunoassay System (Bio-Plex®) to scan 40 chemokines and studied in Ussing chambers to measure transepithelial resistance (TEER) and tissue permeability with fluorescein diffusion.

Results

TEER results following LARS were significantly higher than HC and pre-LARS (Table). Additionally, HC were significantly increased compared to pre-LARS. Mucosal permeability of post-LARS was significantly decreased versus pre-LARS and HC. The levels of C-C Motif Chemokine Ligand (CCL-) 1, 3, 4, 7, 8, 17, 21, 24, 26, 27, interleukin (IL-) 1b, 10, C-X-C motif Chemokine Ligand (CXCL)-2,-6,-8 Interferon gamma (IFNG) and macrophage migration inhibitory factor (MIF) of post-LARS were increased compared to pre-LARS (p< 0.05). IL-8 and TARC levels of pre-LARS was significantly higher than HC. DIS score of HC (0,97 ± 0,21 urn) was significantly lower (p< 0.0001) than pre- and post-LARS. DIS of post-LARS (1,27 ± 0,26 um) insignificantly decreased versus pre-LARS (1,32 ± 0,24 um).

Conclusion

The TEER and permeability results implicate that LARS made very efficient recovery within esophageal epithelium resistance in patients with GERD even though higher than HC. Higher levels of anti-inflammatory chemokines (IFNG, IL-10 and CCL-7) and tissue healing markers (CCL-17, -22, IL-4, -10) may indicate the role of macrophages and neutrophils during recovery phase in post-LARS. Similar results of pre- and post-LARS patients for DIS measurements implicates that short-term recovery phase may not enough to indicate perceptible difference in tissue level or these changes might be irreversible.

We concluded that LARS improves the permeability of esophageal mucosa in short term follow-up possibly related with the assistance of anti-inflammatory chemokines (IFNG, IL-10 and CCL-7) and tissue healing markers. DIS might not recover at all or need long-term healing process to recover since we measured maximum of 4 months after surgery. To the best of our knowledge, there is no study about epithelial permeability and inflammatory mechanisms together and before and after LARS, which is an ideal model for recovery of EE, there is a need for more data to evaluate patho-genesis of GERD.

Disclosure

Nothing to disclose

Table.

Transepithelial resistance and permeability results of the groups

	HC	Post-LARS	Pre-LARS
TEER (Ohms)	176,9 ± 39,2 c	206,1 ± 40,7 a, b	151,0 ± 38,7
Permeability (pmols)	41,2 ± 16,3	29,7 ± 18,1 d, e	43,3 ± 19,2

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a; p=0.0001 vs pre-LARS, b; p=0.031 vs HC, c; p=0.047 vs pre-LARS, d; p=0.028 vs pre-LARS, e; p=0.046 vs HC

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.89

P0103 Microscopic Esophageal Injury Contributes To Heartburn Perception in Patients with Gerd

P Banovcin ^1,^✉, M Duricek ², P Lipták ¹, L Nosáková ¹, R Hyrdel ¹

Introduction

Heartburn is the most prominent feature of GERD. Multiple receptors have been identified responsible for heartburn perception, with TRPV1 receptor activated by acid being best described. Intensity of heartburn, however, varies greatly among the patients as various pathophysiological mechanisms are involved. Although mucosal integrity plays a key role in the pathophysiology of GERD, its direct involvement in the perception of heartburn has not been established yet.

Aims & Methods

We hypothesized that the infusion of noxious stimuli into the esophagus induces heartburn of intensity that is proportionate to the mucosal integrity in patients with heartburn. TRPV1 activator acid (HCl solution, pH=1, 10 min.) was infused (8ml/min.) into the esophagus via a transnasal tube with the opening placed 5 cm above the manometri-cally determined LES. The intensity of sensations was recorded every 2 min. by visual analogue scale (VAS, range 0-10). 12 patients with chronic heartburn were included. All patients had 24 hour pH/impedance off PPI. We reviewed the pH impedance tracings and determined MNBI values as the average value of three 10 min. intervals (1:00, 2:00 and 3:00 a.m.) in the periods without reflux events and/or swallowing. We analyzed the correlation between the MNBI value and the dynamics of heartburn perception based on VAS.

Results

12 subjects received acid infusion. Infusion induced heartburn in all patients. Maximal VAS score was 7.1±2.6 (N=12). 6 patients had positive pH/impedance study (AET>6%). in order to avoid the contribution of hypersensitivity in the heartburn perception we determined the dynamics of heartburn development. We defined it as the ratio between the intensity of heartburn in the 2. min. of the infusion (VAS) and the maximal intensity of heartburn (VAS). We obtained the MNBI values for 6 impedance segments and performed correlations between the dynamics of heartburn and MNBI values. Mean MNBI values were 2727±2750, 2841±2890, 2148±227n, 2244±266n, 2363±3260 and 2274±3160 in Z1-Z6, respectively. We observed significant correlation between the dynamics of heartburn (as determined by the ratio value) and the MNBI value in the most distal (Z6) impedance segment (R=0.7, p=0.01). No significant correlation was found for MNBI values in Z1-Z5 (R values were 0.34, 0.39, 0.2, 0.24, 0.48, respectively, p=NS). Interestingly, correlations between the maximal VAS values and MNBI revealed no statistical significance (data not shown).

Conclusion

Impaired mucosal integrity seems to directly contribute to heartburn perception in patients with chronic heartburn. Importantly, this relationship seems valid for the whole heartburn patients group (regardless of the degree of acid exposure). Rather the dynamics of heartburn development than the heartburn intensity itself is determined by the mucosal integrity.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.90

P0105 Effect of High Acid Exposure On The Esophagus in Children with Gastroesophageal Reflux Disease: Ph-Impedance, Clinical and Endoscopic Parallels

M Aksionchyk ^1,^✉, K Marakhouski ²

Introduction

Gastroesophageal reflux disease (GERD) is common in children and has a varied clinical manifestation with a wide range of typical gastroesophageal and atypical extra-esophageal symptoms. pH-imped-ance testing makes possible the assessment of pH and other parameters of GERD together with disease symptoms and the diagnosis of GERD [1].

Aims & Methods: Aim

it was to assess the parallels between the clinical gastroesophageal reflux disease (GERD) - symptoms (typical and atypical), endoscopic findings and the data of the pH-impedance monitoring in pediatric patients with an abnormal esophageal reflux. Methods: criteria for inclusion of patients in the study: the presence of GERD related symptoms (typical and/or atypical); abnormal esophageal reflux burden on the pH-impedance monitoring. Los Angeles classification was used to assess the endoscopy findings. The assessment of pH-impedance monitoring data performed from November 2017 till November 2019 revealed abnormal esophageal reflux burden in 93 patients (acid exposure time - AET > 7%, total number of reflux episodes > 70/100 - in children aged > 1 year/infants) [2-4].

Calculating the average AET in this group resulted in the index of 10.64 (CI% 9.46 - 12.11); 75%o = 12.6 (CI% 11.3286 to 16.5000). For this reason AET = 11.33 was selected as the lower limit of the esophagus high degree of acidification.

The study included 27 patients with AET > 11.33%. Male - 18 (66.7%), female - 9 (33.3%), aged 1 - 17 years (average age =6,37). Male/female ratio = 18: 9.

Results

Based on the results of clinical symptoms and endoscopic findings the patients were divided into 5 groups: reflux esophagitis (RE) - 8, non-erosive GERD (NERD) - 11, eosinophilic esophagitis (EoE) - 1, esophageal atresia (EA) - 6, 3 of them have RE), polyp of the esophagogastric junction (EGJ)- 1.

Clinical symptoms:

- EA: typical symptoms - 2, atypical symptoms - 2, mixed - 2;

- RE: typical - 3, atypical - 2, mixed - 3;

- NERD: typical - 0, atypical - 9, mixed - 2;

- EoE: typical - 1;

- polyp of the EGJ: typical - 1.

Typical symptoms: heartburn, dysphagia, belching, vomiting, abdominal pain, nausea.

Atypical symptoms: cough, obstructive bronchitis, frequent pneumonia. Clinical symptoms in general: typical - 6, atypical - 14, mixed - 7. The Kruskal-Wallis test was perfomed in groups of patients with RE, NERD and EA. As a result of this test a significant difference revealed - p = 0.011397 in the duration of the longest reflux in the group with EA compared with the groups of RE and NERD - Post-hoc analysis (Dunn). No significant difference in indicators of AET, number of reflux episodes and age is revealed.

Conclusion

1 - atypical symptoms prevail in the group of NERD;

2 - males mostly suffer from the abnormal esophageal reflux burden;

3 - the average duration of the longest reflux episode in the group with EA is significantly higher than in groups with NERD and RE.

Demographic characteristics and pH-impedance data of patients with GERD.

Groups	Male/female	age	AET (%)	Total number of reflux episodes	Duration of the longest reflux
RE	8/-	8,2 95% CI 4,4-11,9	18,11 95% CI 11,68-25,54	128,9 95% CI 46,3- 211,9	31,7 95% CI 22,9 - 40,5
NERD	5/6	6,1 95% CI 3,8-8,2	18,48 95% CI 13,62-23,34	64,3 95% CI 44,8-83,8	33,0 95% CI 26,9 - 39,1
EA	4/2	3,7 95% CI -0,2-7,6	21,28 95% CI 9,58-32,97	79,3 95% CI 25,1-133,6	82,0 95% CI 32,5 - 131,6
Polyp EGJ	-/1
EoE	1/-

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Disclosure

Nothing to disclose

References

1.Shay S., Tutuian R., Sifrim D., Vela M., Wise J., Balaji N., Zhang X., Adhami T., Murray J., Peters J., Castell D. Twenty-four hour ambulatory simultaneous impedance and pH monitoring: A multicenter report of normal values from 60 healthy volunteers. Am J Gastroenterol 2004, 99, 1037–1043. [DOI] [PubMed] [Google Scholar]
2.Rosen R., Vandenplas Y., Singendonk M. et al. Pediatric gas-troesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr 2018; 66: 516–554. [DOI] [PMC free article] [PubMed] [Google Scholar]
3.Pilic D., Frohlich T., Noh F. et al. Detection of gastroesophageal reflflux in children using combined multichannel intraluminal impedance and pH measurement: data from the German Pediatric Impedance Group. J Pe-diatr 2011; 158: 650–4. [DOI] [PubMed] [Google Scholar]
4.Indications, Methodology, and Interpretation of Combined Esophageal Impedance-pH Monitoring in Children: ESPGHAN EURO-PIG Standard Protocol. Tobias G. Wenzl, Marc A. Benninga, Clara M. Loots, Silvia Salvatore, Yvan Vandenplas, on Behalf of the ESPGHAN EURO-PIG Working Group. JPGN 2012; 55: 230–234. [DOI] [PubMed] [Google Scholar]

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.91

P0106 Impact of The Minimum Duration of The Reflux Episodes in Phmetry in The Reference Values

O Moralejo Lozano ^1,^✉, C Sevilla Mantilla ², JA Pérez de la Serna y Bueno ², C Ciriza de los Ríos ², M Colmenares Bulgheroni ¹, AJ Barrajón Masa ¹, A Ruíz de León ²

Introduction

The minimum duration used in the analysis of reflux episodes in pHmetry varies considerably depending on the software and the recorders used. in older equipments, due to technical limitations, the minimum duration to consider an episode is 4-8 seconds for wired pHmetry and 6 seconds for wireless pHmetry. Modern equipment usually uses a sampling rate of 1 data per second and usually sets the minimum duration of episodes to 2 seconds. However, reference values are generally used without taking this variable into account, which modifies the results and their possible interpretation.

Aims & Methods: Objective

To determine the implications of the variability in the minimum duration to consider a reflux episode in the analysis of the pHmetry records.

Material and method

The pHmetry records, without eliminating the intake periods, of 10 control subjects and 20 patients with reflux were studied, applying values of minimum duration of one episode of: 2, 4, 6 and 8 sec. and the modifications of the acid exposure time (AET), generic score (GS) and its repercussion in the consideration of conclusive evidence of pathological reflux according to the criteria of the Lyon Consensus are evaluated. All the studies were performed with a Digitrapper pH-Z recorder (MEDTRONICS) and Accuview pH-Z 5.2 software, modifying in the analysis a single element, the duration of the reflux episode.

Results

Control group of 10 subjects (mean age 22.6 ± 1.2 a.). Patients group (mean age 53.6 ± 12.2 a.). The increase in the minimum time to consider an episode of reflux was associated with a decrease in the number of episodes, of the AET and of the GS, both in the controls and in patients with reflux and the total group (TABLES WOULD BE PROVIDED).

Conclusion

Reducing the minimum time to consider a reflux episode to 2 seconds produces a significant increase in the number of episodes, with a wide standard deviation; which may affect the results of the parameters that relate reflux and symptoms (symptomatic sensitivity index, probability of symptomatic association) and the so-called undetermined group of the Lyon criteria, 10% of which would change diagnosis with criteria of minimum duration 2 or 4 seconds, a percentage that doubles when comparing 2 with 6 seconds.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.92

P0107 Mean Nocturnal Baseline Impedance Correlates with Reflux Disease Severity and Symptom Perception

H Abdul-Razakq ^1,^✉, A Raeburn ¹, K Patel ¹, O Femi ¹, A Vales ¹, A Emmanuel ¹, N Zarate ¹, R Sweis ¹

Introduction

The Lyon Consensus 2018 describes nocturnal baseline impedance (MNBI) as a reflection of oesophageal mucosa permeability, with lower values found in erosive and eosinophilic oesophagitis¹; however it is not clear how MNBI correlates with symptoms. This study aims to determine the relationship of MNBI with symptoms across three common presentations of reflux; Barrett's oesophagus, non-erosive reflux disease (NERD) and functional heartburn (FH).

Aims & Methods

Between 2014 and 2020, pH-Impedance measurements and symptom index (SI) were collected for 37 consecutive patients with at least 3 cm of Barrett's oesophagus. Results were compared with 37 consecutive patients with NERD and 37 with FH were used as disease controls. MNBI was calculated from sensors at 3 and 5cm above the LOS over 3x10 minute intervals during the nocturnal period.

Results

There was no significant difference between Barrett's and NERD in median acid exposure time (AET) [Barrett's 14.0% (6.3%-23.5%) vs. NERD 8.9%(5.6%-13.5%) (p=0.497)], total number of impedance-measured reflux events [Barrett's (108.5±79.8) vs. NERD (87±52.2) (P=0.444)] or bolus exposure time (BET) [Barrett's (2.49±3.2) vs. NERD (1.29±0.9) (p=0.096)]. By definition, AET 1.9(0.7%-2.7%), number of reflux events (41.24±23.5) and BET (0.48±0.3) were all within normal limits for FH. Barrett's patients reported the fewest symptoms overall (7.5; 0-24), whereas NERD (15; 6-41) and FH (13.5; 6-28) reported a similarly increased number of symptoms. On the other hand, NERD patients were more likely to have a positive SI (12/37; 32.4%) compared to Barrett's (7/37; 18.9%) (p=0.048). Similarly, the median SI for NERD was highest (32.3%; 6.4-54.5%) compared to Barrett's (6.25%; 0-38%) (p< 0.008). FH, by definition, had a negative SI (0%; 0%-8.2%).

MNBI was lowest in Barrett's compared to NERD and FH (p< 0.0001) (Figure 1) There was no difference in MNBI between the 10 patients with persistent (>3cm) Barrett's who had attempts at therapy (ablation, mucosal resection) compared to the 27 who had not received therapy (p=0.96). There was a moderately inverse correlation between median Barrett's segment length (5cm (3cm,9cm)) and MNBI (r = -0.436; p=0.038).

Conclusion

This study suggests that MNBI was able to differentiate between the 3 groups, despite the similar AET, total number of reflux events and BET seen across Barrett's and NERD patients. Furthermore, the impact of reflux disease on mucosal permeability (MNBI) appears to have an influence on symptom perception. This study also provides further validation to the Lyon consensus definition of MNBI as a measure of reflux disease severity.

Median and IQR MNBI for 3 presentations of reflux

	Barrett's oesophagus MNBI (ohms)	NERD MNBI (ohms)	Functional Heartburn MNBI (ohms)	P-value
IQR (25th percentile)	248	2764	3809.25	p<0.0001*
Median	398	1160	3355	p<0.0001*
IQR (75th percentile)	777	964.5	2866.5	p<0.0001*

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Disclosure

Nothing to disclose

References

1Gyawali C.P., Kahrilas P.J., Savarino E. et al. Modern diagnosis of GERD: the Lyon Consensus. Gut 2018; 67: 1351–1362. [DOI] [PMC free article] [PubMed] [Google Scholar]

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.93

P0108 Evaluating Clinical Features and Reflux Symptom Index As Diagnostic Indicators of Extra-Oesophageal Gastro-Oesophageal Reflux Disease

R *Kumar ^1,^✉, SR Saifuddin ^1,^*, CH Lim ², YT Wang ²

Introduction

There is currently no gold standard investigation for Extra-Oesophageal Gastro-Oesophageal Reflux Disease (EOGORD). Identifying this condition relies heavily on clinical diagnosis and invasive investigations such as oesophageal pH monitoring and manometry. We aim to: (1) establish clinical factors associated with pathological EOGORD; and (2) assess the accuracy of Reflux Symptom Index (RSI) questionnaire, a commonly employed tool, in detecting pathological EOGORD.

Aims & Methods

We analysed data of all patients who completed an RSI questionnaire while attending a 24-hour impedance-pH study at a major tertiary centre between January 2016 to July 2018. Pathological EOGORD was defined as those who reported extra-oesophageal symptoms (cough, burp, sour taste, globus pharyngeus), and DeMeester Score >14.72 or Symptom Index ≥50% or Symptom Association Probability ≥95%. An RSI ≥13 was taken to be indicative for clinically significant extra-oesophageal reflux symptoms.

The association between gender, hiatus hernia, and BMI with pathological EOGORD were calculated using a Chi-Squared test, while age association with EOGORD was evaluated using an independent sample t-test. Performance of RSI was assessed using sensitivity, specificity, and positive and negative predictive values. Statistical analyses were performed on SPSS version 25.

Results

72 patients fulfilled the inclusion criteria, with 35 patients meeting our definition for pathological EOGORD. BMI ≥25 was significantly associated with an increased risk of pathological EOGORD when compared to patients with BMI <25 (66.7% vs 40.4%, p=0.036). Gender (Female 50.0% vs Male 47.1%, p=0.803), age (No EOGORD 50.5 ±16.5 vs EOGORD 50.4 ±14.6, p=0.963), and hiatus hernia (Present 60.0% vs Absent 51.2%, p=0.614) were not found to be independent predictors of pathological EO-GORD.

The performance characteristics analysis of RSI in detecting pathological EOGORD showed a sensitivity of 54.3%, a specificity of 75.0%, a positive predictive value of 67.9%, and a negative predictive value of 62.8%.

Table 1.

Clinical characteristics of study cohort and association with Pathological EOGORD

		Pathological EOGORD		p-value
		Absent (n=37)	Present (n=35)
RSI	<13	27	16	N.A.
Note: 1 patient did not complete RSI	≥13	9	19
Gender	Male	18	16	p=0.803
	Female	19	19
BMI	<25	28	19	p=0.036
Note: 1 patient's BMI not recorded	≥25	8	16
Hiatal hernia	Absent	21	22	p=0.614
Note: unable to obtain information for 19 patients	Present	4	6
Age	Mean (years)	50.5 (±16.5)	50.4 (±14.6)	p=0.963

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Conclusion

In our cohort, higher BMI (BMI≥25) is linked to a higher risk of EOGORD. We found RSI to be unreliable in predicting pathological EO-GORD and is not a satisfactory replacement for established GORD assessment.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.94

P0109 Artificial Intelligence Automates Evaluation of Baseline Impedance From Ph-Impedance Studies and Augments Prediction of Treatment Outcome in Gastro-Esophageal Reflux Disease

B Rogers ^1,^✉, S Samanta ², K Ghobadi ², A Patel ³, EV Savarino ⁴, S Roman ⁵, D Sifrim ⁶, CP Gyawali ⁷

Introduction

Artificial intelligence (AI) automates several gastroenterologist tasks, including interpretation of endoscopic images, but has not been evaluated for pH-impedance studies. Baseline impedance (BI) is a measure of esophageal mucosal integrity, but calculation of BI from pH-impedance studies is only possible during artifact free nocturnal periods (mean nocturnal BI, MNBI). AI has potential to streamline BI acquisition, including from upright periods of the pH-impedance tracing.

Aims & Methods

We determined feasibility of automated AI in BI extraction (AIBI), and compared AIBI with acid exposure time (AET), mean nocturnal BI (MNBI), and GERD outcome.

Raw data from pH-impedance studies were acquired from symptomatic patients studied off (n=117, 53.1±1.2 yr, 66%F) and on (n=93, 53.8±1.3 yr, 74%F) antisecretory therapy at two tertiary care centers and from an international cohort of asymptomatic volunteers (n=115, 29.3±0.8 yr, 47%F). Data were uploaded into dedicated prototypical AI software designed to automatically extract AIBI. Manual corroboration of 2 test studies by two investigators (BDR, CPG) demonstrated almost 90% accuracy of the program in identification of swallows, reflux episodes, and belches; these events, meal periods and artifacts were digitally discarded in calculating AIBI. Manually extracted MNBI values, corresponding total, upright and recumbent AIBI, and the upright:recumbent AIBI ratio were recorded. AIBI was separately calculated from the first 30 and 60 min of the upright and recumbent pH-impedance monitoring periods for additional analysis. AIBI values were compared to AET and MNBI in controls and GERD patients, and ≥50% symptom improvement on validated questionnaires in GERD patients.

Results

Recumbent AIBI was similar to MNBI (p=ns). AIBI ratio was higher when AET>6% (median 1.18, IQR 1.0-1.5), compared to < 4% (0.95, IQR 0.84-1.1), 4-6% (0.89, IQR, 0.72-0.98) and controls (0.93, IQR 0.80-1.09, p£0.04). While MNBI, total AIBI, and the AIBI ratio off PPI were significantly different between responders and non-responders to GERD management (p< 0.05 for each comparison), only AIBI ratio segregated management responders from other cohorts. On ROC analysis, off therapy AIBI ratio had AUC of 0.661, comparable with AET (AUC 0.715), and better than MNBI (AUC 0.313); AIBI ratio outperformed AET when AET >6% (AUC 0.766 vs. 0.606) and 4-6% (AUC 0.563 vs. 0.516). Off therapy AIBI acquired from the first 30 and 60 min of the recumbent pH-impedance monitoring period resembled MNBI (p≥0.10); 30 min upright AIBI was lower than overall upright AIBI (p=0.007), but 60 min values were similar (p=0.07). Additionally, AIBI ratio calculated from the first 30 and 60 min of the upright and recumbent periods resembled overall AIBI ratio (p≥0.36 for each comparison); however, performance characteristics in predicting symptom response were less robust (30 min AIBI ratio: AUC 0.594, 60 min AIBI ratio: AUC 0.590).

Conclusion

BI calculation can be automated using AI, and can be evaluated during both upright and recumbent periods. Novel AI metrics show potential in predicting GERD treatment outcome.

Table.

Comparison of Reflux Metrics 5 cm above LES between Controls and GERD Patients. *p<0.05 compared to no response; †p<0.05 compared to controls

	Controls	Off PPI		On PPI
		Response	No Response	Response	No Response
	n=115	n=57	n=57	n=39	n=48
Total AET (%)	0.6 (0.2-1.2)	4.5 (2.0-9.4) †*	1.9 (0.7-4.2) †	0.3 (0.0-6.9)	0.4 (0.1-1.8)
MNBI (ohms)	2497 (2170-3029)	1378 (922-2027) †*	2128 (1493-2885)	1645 (1015-2571)†	1968 (1165-2593)†
Total AIBI (ohms)	2398 (1985-2908)	1513 (1058-2248) †	1968 (1535-2374) †	1785 (1274-2241) †	1865 (1543-2231) †
Upright AIBI (ohms)	2329 (1938-2834)	1450 (1025-2206) †*	1828 (1423-2272) †	1656 (1239-2245) †	1826 (1528-2127) †
Recumbent AIBI (ohms)	2468 (2111-2953)	1425 (1051-2085) †*	2070 (1623-2627) †	1621 (1052-2292) †	1835 (1428-2525) †
U:R AIBI ratio	0.93 (0.80-1.09)	1.05 (0.83-1.22) †*	0.89 (0.79-1.06)	0.96 (0.87-1.24)	0.97 (0.85-1.15)

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Disclosure

BDR: no disclosures; SS: no disclosures; KG: co-founder of ClearifiRx; ES: Lecture Fee: Medtronic, Takeda, Janssen, MSD, Abbvie, Malesci; Consulting: Medtronic, Takeda, Janssen, MSD, Reckitt Bencik-ser, Sofar, Unifarco, SILA, Oftagest; SR: consulting Medtronic, research support Diversatek Healthcare, Medtronic; DS: research grants: Reckitt Benckiser UK, Jinshan Technology China, Alfa Sigma Italy; CPG: Consulting: Medtronic, Diversatek, Isothrive, Ironwood, Quintiles

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.95

P0110 Reflux Monitoring with Impedance-Ph-Metry: New Set of Normal Values Obtained From Consensus Analysis of Tracings From Healthy Asymptomatic Subjects: A Multicentre International Collaborative Study

D Sifrim ^1,^✉, S Roman ², EV Savarino ³, CP Gyawali ⁴

Introduction

Existing normal values for pHmetry and impedance-pH me-try have limitations, including limited sample size of normative studies from typically one or two countries, significant technical problems from inclusion of pH drops due to meals/artefacts, and identification of impedance reflux events using inconsistent rules, leading to large inter-reviewer variability. Software for automated analysis also has significant limitations, resulting in over-diagnosis of particularly non-acidic reflux.

Aims & Methods

We aimed to obtain a new set of normal values for impedance-pH-metry based on consensus analysis of tracings from a large number of healthy asymptomatic subjects collected from multiple countries in five continents.

Methods

A total of 541 Impedance-pHmetry tracings from healthy asymptomatic subjects from Africa, Asia, Europe, North America, and South America were collected and de-identified. Included studies were performed with two different systems: Diversatek (Boulder, Colorado, US) (ex Sandhill) and Medical Measurement Systems (MMS, Enchede, Netherlands). Tracings with technical artefacts, marked esophageal symptoms and features of behavioural disorders (aerophagia, supragastric belching and rumination) were excluded. The included tracings were manually analysed by two expert reviewers working together either in-person or through video-conference. Analysis included 1) editing of pH drops (to exclude artefacts and meal/drink induced pH drops), 2) recognition of impedance reflux events using strict pre-established criteria, 3) Measurement of distal mean nocturnal baseline impedance (MNBI). 4) Identification and scoring of post reflux swallow-induced peristaltic waves (PSPW).

Results

After exclusions, consensus analysis was performed in 391 tracings (Diversatek n=265, MMS n=126), mean age 32.7 yrs (range 18-71), 212 females/179 males. Males had more acid exposure, reflux episodes and lower MNBI at 3 cm above the LES. Subjects older than 40 yrs had lower MNBI in distal esophagus. Normal values for Diversatek and MMS systems are displayed in the table. Comparing normal values between Western countries, Asia, South America and South Africa (using identical imped-ance-pH-metry systems) we observed significant regional differences 1. using Diversatek, higher PSPW scores in Western countries, and higher MNBI in Asia; 2. using MMS, higher acid exposure in the Netherlands, higher MNBI in Asia and South Africa, and low MNBI in Turkey. Comparison between systems in similar world regions showed that MMS measures higher MNBI both in Western countries and Asia.

Conclusion

We established normal values for impedance pH metry based on a large number of tracings from healthy asymptomatic subjects that could be used worldwide, obtained using manual consensus analysis and consistent criteria for inclusion of pH drops, reflux recognition, MNBI and PSPW. We identified both regional and system related differences, indicating that clinical impedance-pH interpretation needs to use normal thresholds valid for the system utilized and world region. We anticipate that these normal values will contribute to development of software algorithms for more precise and clinically useful automated impedance-pH analysis.

Table.

Normal values of impedance-pHmetry obtained with Diversatek (ex Sandhill) and MMS systems

	total acid exposure	total number of reflux	PSPW score	MNBI 5 cm above LES	MNBI 3 cm above LES
	SAN / MMS	SAN / MMS	SAN / MMS	SAN / MMS	SAN / MMS
5 percentile	0.0 / 0.0	2.0 / 2.4	15 / 19	1395 / 1794	1384 / 1542
25 percentile	0.1 / 0.3	10 / 12	34 / 35	2207 / 2410	2281 / 2334
Median	0.4 / 1.4	21 / 30	49 / 49	2630 / 3201	3001 / 3014
75 percentile	1.2 / 2.5	34 / 43	60 / 60	3179 / 4397	2623 / 4098
95 percentile	2.8 / 5.0	55 / 78	80 / 78	3944 / 5768	4510 / 5586
	p < 0.001	p < 0.02	ns	p < 0.001	ns

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Disclosure

This study was performed without financial support from companies producing impedance-phmetry systems

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.96

P0113 Defining Reference Ranges For Prolonged (96-Hour) Wireless Ph Monitoring Using Healthy Controls and Patients with Erosive Esophagitis: Validation of The Lyon Classification For Gerd Diagnosis

R-I Rusu ^1,^✉, M Fox ², E Tucker ³, SS Zeki ¹, JM Dunn ¹, J Jafari ¹, T Wong ¹

Introduction

Technology now allows up to 96-hr wireless pH-recording in clinical practice. This is desirable because there is high day-to-day variability in esophageal pH-measurements, and it has been shown that prolonged pH-studies increase the diagnostic yield and reproducibility of gastro-esophageal reflux disease (GERD) diagnoses (Scarpulla AJG 2007). However, reference ranges and diagnostic thresholds for this methodology have not been established.

Aims & Methods

This study analysed prolonged esophageal pH recordings from healthy controls (HC) and patients with objective, endoscopic evidence of GERD. Results were used to validate the recently published Lyon Consensus Classification for GERD Diagnosis (Gyawali Gut 2018). HC underwent prolonged, wireless pH studies (Bravo™, Medtronic) at two tertiary centres. Bravo™ was inserted under sedation at endoscopy. Median and 95th percentile values were calculated for acid exposure time (AET) over 24, 48, 72 and 96-hr and compared against the “worst 24-hrs” (most pathological day). Retrospectively, the same analysis was applied to results from consecutive patients with erosive esophagitis that completed 96-hr wireless pH studies off acid suppressants for >1 week, categorized by the Los Angeles (LA) classification. Linear regression and receiver operating curve (ROC) analysis were performed with the area under the ROC curve (AUC) and Youden's index to define optimal diagnostic cut-offs.

Results

62 asymptomatic HC were studied, of whom 40 (age 28±9 years, 72% F) completed 96-hr pH recording. Median AET was 1.4% (upper 95th percentile 4.8%) for any study day and 2.6% (7.4%) for the worst day. 136 patients with reflux esophagitis completed the 96-hr study (61 LA A, 60 B, 15 C-D). Results are summarized in Table 1.

Linear regression analysis revealed a correlation between endoscopic findings, average AET (p< 0.0001, R2=41.7%) and worst day AET (p< 0.0001, R2=33%) after adjusting for gender and age. ROC analysis for the average AET differentiated the group with definite, endoscopic evidence of GERD (LA B, C, D) from HC (sensitivity 87%, specificity 93%, positive predictive value (PPV) 90%, negative predictive value (NPV) 91% for a cut-off AET of 4.4%; AUC 0.94). Similar results were present for the “worst 24-hrs” analysis (sensitivity 86%, specificity 95%, PPV 93%, NPV 90% for a cut-off AET of 7.0%; AUC 0.94).

Conclusion

This study defines the reference (“normal”) range for prolonged, 96-hr ambulatory wireless pH monitoring. Additionally, pathological thresholds were identified that accurately discriminate between HC and patients with conclusive GERD diagnosis, based on the presence of erosive esophagitis. The findings provide conditional support for diagnostic criteria proposed by the Lyon Consensus, specifically that AET < 4% refutes and AET >6% supports GERD diagnosis. By comparison, ROC analysis based on the data presented indicates that the optimal diagnostic threshold that discriminates between HC and patients with reflux esophagitis (LA B, C, D) was 4.4% based on average AET and 7.0% based on worst day AET.

Disclosure

Nothing to disclose

Table 1.

Acid Exposure Time (AET) in healthy controls and patients with erosive reflux esophagitis

	96 h Average Day	96 h Worst Day
Healthy Controls (n)	40	40
Median % AET (95th Percentile range)	1.40 (0.11-4.84)	2.60 (0.41-7.47)
Reflux Esophagitis
LA A (n)	61	61
Median % AET (95th Percentile range)	6.10 (0.80-15.50)	9.80 (1.14-23.56)
LA B (n)	60	60
Median % AET (95th Percentile range)	8.23 (1.61-18.41)	11.65 (2.31-28.37)
LA C-D (n)	15	15
Median % AET (95th Percentile range)	9.95 (4.07-24.90)	13.50 (7.30-33.50)

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United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.97

P0114 Analysis of Ions and Organic Acids in Saliva in Diagnostics of Gastroesophageal Reflux Disease

S Konecny ^1,^2,^✉, V Dosedelova ³, P Durc ^3,⁴, J Dolina ^1,², F Foret ³, P Kuban ³

Introduction

Gastroesophageal reflux disease (GERD) is a disease caused by backflow of gastric contents into the esophagus due to the failure of physiological antireflux mechanisms and can lead to esophageal and ex-traesophageal symptomatology. At the current time, the gold standard in diagnostics of GERD is 24-hour multichannel intraluminal impedance and pH monitoring (MII-pH) that is invasive, time consuming and expensive diagnostic method with not clear relevance in diagnostics of extraesopha-geal reflux (EER) and there is a need for new faster, cheaper and more sensitive diagnostic method for detection of EER.

New potential target in diagnostic of GERD is saliva. One of the saliva's protective mechanism during a reflux episode is neutralization of gastric acid by various buffering systems. Bicarbonate and phosphate constitute major salivary buffering components. Since reflux episodes occur more frequently and have a longer duration in patients having GERD, our study investigates the hypothesis that bicarbonate and phosphate ions might be elevated in saliva.

Aims & Methods

In this work, we developed a new method for the analysis of saliva samples. We analyzed two major salivary buffering compounds bicarbonate and phosphate and seven additional anions including chloride, nitrite, nitrate, sulfate, thiocyanate, acetate and butyrate using an in-house built capillary electrophoresis instrument with capacitively coupled contactless conductivity detector (CE-C⁴D). The developed method was used to compare the levels of these compounds in saliva samples from 12 healthy controls and 20 patients with GERD to investigate the applicability of saliva in diagnostics of GERD.

Results

We found that chloride, phosphate, bicarbonate, and acetate were the major ions with mean concentrations in saliva of 20.1, 6.4., 5.7, and 4.6 mM, respectively. Concentrations of nitrite, nitrate, sulfate, and butyrate were lower than 1 mM.

We found that there was no significant difference in phosphate concentration between healthy and GERD patients (mean values of 6.4 and 5.7 mM, p = 0.272). On the other hand, there was a statistically significant difference in bicarbonate concentration. The mean bicarbonate concentration was significantly higher in saliva from GERD patients than in healthy controls (i.e. 8.1 and 5.7 mM, respectively, p = 0.004), confirming the initial hypothesis that the buffering ions in saliva might be elevated in GERD patients due to the need for more buffering action due to the more frequent and more prolonged reflux episodes.

Concerning all other studied analytes in saliva, there was significant difference only in nitrite concentration between the two studied groups. However, it must be noted that in many cases, the nitrite levels were below LOD that could have influenced the statistical analysis.

Conclusion

In this work, we first optimized a separation electrolyte for sensitive analysis of phosphate, bicarbonate, and other inorganic and organic ions by CE-C⁴D. in total, nine ions were analyzed in saliva samples from healthy volunteers and patients suffering from GERD. Statistically significantly elevated bicarbonate levels were found in the group of GERD patients, confirming our hypothesis that natural saliva buffering compounds might be elevated in patients due to recurrent acid reflux episodes. The developed CE-C⁴D method might be useful in a non-invasive diagnostics of GERD and might contribute to a simplification of the diagnostic procedure.

Disclosure

The authors acknowledge the financial support from the Ministry of Health of the Czech Republic (Grant No. 17-31945A).

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.98

P0115 The Influence of Crural Diaphragm On Esophagogastric Junction Function and Gastroesophageal Reflux Disease Features. A Prospective Study with High Resolution Manometry and Impedance-Ph Monitoring

S Parisi ¹, EV Savarino ², N de Bortoli ³, M Frazzoni ⁴, M Ghisa ⁵, L Frazzoni ⁶, G Gualtieri ¹, G Terracciano ⁷, M Lanza Volpe ¹, V Savarino ⁸, S Tolone ^9,^✉

Introduction

A normal esophagogastric junction (EGJ) is essential in preventing gastroesophageal reflux disease (GERD). Crural diaphragm (CD) is responsible for a part of the antireflux barrier. High-resolution manometry (HRM) provides information on axial separation between LES and CD (e.g. hiatal hernia, HH) and can evaluate the EGJ antireflux barrier thanks to the esophagogastric contractile integral (EGJ-CI). However, comprehensive data about the correlation between presence of LES-CD separation, EGJ-CI and GERD features, such as symptoms, esophagitis and reflux patterns determined at impedance-pH monitoring (MII-pH) are scarce.

Aims & Methods

To verify if a increasing distance of LES-CD separation and a decreasing EGJ-CI could better correlate with a positive MII-pH, with reflux symptoms and with different grades of esophagitis. Secondary aim point was to verify the usefulness of a new metric to determine the CD's barrier function.

Consecutive patients with typical GERD symptoms (heartburn and/or regurgitation) and a recent upper endoscopy were enrolled. Esophagitis was defined according to Los Angeles classification. The presence of further symptoms and PPIs response were recorded. All patients underwent HRM assessing EGJ morphology, EGJ-CI, esophageal peristalsis and EGJ function. EGJ Type I was further divided into Type I-CO, a complete overlap of LES and CD, and Type I-MS, a minimal separation, with LES located from the upper border of CD (in correspondence of pressure inversion point, 0.0 cm) to 1 cm above. Also, intra-hernia pressure and contractile integral of CD (CD-CI, using a DCI toolbox for three respiratory cycles and then dividing for the durance in seconds, when distinguishable from LES, e.g. not in Type I-CO) were recorded.

The patients then underwent impedance-pH testing off-therapy. We recorded the esophageal acid exposure time (AET), number of total impedance-detected reflux episodes, mean nocturnal baseline impedance (MNBI), post-reflux swallow-induced peristaltic wave index (PSPW, + if< 53%) and symptom association analysis using symptom association probability (SAP+ if ≥95%) and symptom index (SI+ if ≥50%). McNemar test and Anova test were performed among the four group determined according to LES-CD separation.

Results

We enrolled 203 [96M/107F; mean age 46 (17-82)] consecutive patients and identified 72 (35.4%) EGJ Type I-CO, 54 (26.6%) Type I-MS, 42 (20.7%) Type II and 35 (17.2%) Type III. Patients with Type III EGJ had lower EGJ-CI, decreased mean DCI, a higher median number of reflux episodes, a greater mean AET, a lower MNBI and PSPW and had more frequently a positive symptoms association compared to patients with Type II and Type I-CO/MS (Table 1). Type I-MS had a higher number of reflux episodes (48 vs. 29, p< 0.03), a greater mean AET (4.8 vs. 2.7, p< 0.05) and a greater positive symptom association (55% vs. 26%, p< 0.02) compared to Type I-CO. A low value of CD-CI was present in 55% of HH and the lower the values, greater were the number of refluxes or AET values. At Anova, PPI response was significantly linked to EGJ Type III, whereas dysphagia presence was linked to higher intra-hernia pressure and higher CD-CI values.

Conclusion

With increasing separation between the LES and the CD patients had a gradually and significantly increase of reflux episodes and esophageal acid exposure. Even a minimal separation can be responsible for GERD development and supports the role of the CD in preventing reflux. Assessing contractility integral for CD could be important for evaluating both presence of severe GERD (when low) and dysphagia (when high).

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.99

P0116 Ogj-Ci Complements Reflux Disease Severity and Gives Insight Into The Pathophysiology of Reflux in Barrett'S

H Abdul-Razakq ^1,^✉, A Raeburn ¹, K Patel ¹, O Femi ¹, A Vales ¹, A Emmanuel ¹, N Zarate ¹, R Sweis ¹

Introduction

Oesophagogastric junction contractile integral (OGJ-CI) is a novel parameter that assesses barrier function during high resolution manometry (HRM); however its utility has not yet come into routine clinical use. We assessed OGJ-CI values across three common presentations of reflux; Barrett's oesophagus, non-erosive reflux disease (NERD) and functional heartburn (FH), to determine how OGJ-CI complements disease severity. Analysis was replicated across 2 common HRM systems and catheter types in consecutive patients.

Aims & Methods

Consecutive HRM studies between 2014 and 2020 were collected from a tertiary referral unit in London; 63 patients (21 Barrett's, NERD and FH each) used a water-perfused catheter (Medical Measurement System, Netherlands) and 48 patients (16 Barrett's, NERD and FH each) used a solid state catheter (Sierra Scientific Instruments, USA). OGJ-CI was calculated using the distal contractile integral (DCI) tool over 3 respiration cycles at 20mmHg isobaric contour. DCI of the oesophageal body was used as a measure of peristaltic effectiveness. Manometry was followed by 24 hour catheter-based pH monitoring to measure acid exposure time (AET) and is presented as (median; interquartile range).

Results

Overall, AET was greatest in patients with Barrett's (14%; 5.8-23.6%) followed by NERD (9.3%; 5.8-13.6%) and FH (1.9%; 0.8-2.8%) (p< 0.0001). Similar OGJ-CI and DCI pressure trends were seen across both manometry systems and catheter types. There was no statistical difference in OGJ-CI between NERD and FH (Sierra p=0.9; MMS p=0.614) but OGJ-CI was significantly lower in patients with Barrett's compared to NERD and FH (Sierra: p=0.014; MMS: p=0.017) (Figure 1). Similarly, DCI was higher in NERD (Sierra 659mmHg.s.cm; MMS 588mmHg.s.cm) and FH (Sierra 1202mmHg.s.cm; MMS 736mmHg.s.cm) while in Barrett's, DCI was significantly lower (Sierra 417mmHg.s.cm; MMS 198mmHg.s.cm) (Sierra p=0.002; MMS p< 0.0001). A weak negative correlation was observed between Barrett's length and OGJ-CI (r=-0.18, p=0.5).

Median OGJ-CI (mmHg.cm) with 95% Confidence Interval (CI) across 3 presentations of reflux,using MMS and Sierra

	MMS Barrett's oesophagus OGJ-CI (mmHg.cm)	MMS NERD OGJ-CI (mmHg.cm)	MMS Functional Heartburn OGJ-CI (mmHg.cm)	Sierra Barrett's oesophagus OGJ-CI (mmHg.cm)	Sierra NERD OGJ-CI (mmHg.cm)	Sierra FH OGJ-CI (mmHg.cm)
95% CI (Upper limit)	17.9	39.6	37.0	7.6	40.0	31.7
Median	13.0	29.1	27.1	4.2	24.0	19.8
95% CI (Lower limit)	8.0	18.7	17.3	0.8	8.0	7.9

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Conclusion

OGJ integrity and peristaltic effectiveness correlate well with acid reflux burden but the mechanism differs between reflux disease states; OGJ-CI is the same between NERD and FH but markedly reduced in Barrett's. Further, DCI is higher in NERD and FH than in Barrett's. Furthermore, this pattern is similar across two of the most commonly used HRM systems and are independent of catheter characteristics. This study suggests that in Barrett's, disruption of OGJ anatomy may result in an increased volume of reflux compounded by reduced peristalsis effectiveness (and in turn, clearance), whereas in NERD, the increased frequency of reflux is more likely to be cleared by an intact peristaltic contraction.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.100

P0117 Mean Nocturnal Baseline Impedance Values Do Not Correlate with Symptoms and Signs of Laryngopharyngeal Reflux and Do Not Predict Response To Ppi Therapy

M Duricek ^1,^✉, P Banovcin ¹, P Lipták ¹, L Nosáková ¹, R Hyrdel ¹

Introduction

24 hour pH impedance has been increasingly used for the diagnosis of laryngopharyngeal reflux (LPR). However, no criteria for the pathologic number of LPR episodes have been widely accepted yet. Therefore reflux symptom index (RSI), reflux finding score (RFS) and therapeutic PPI trial have remained the gold standard of diagnosis and treatment. Recently, mean nocturnal baseline impedance (MNBI) gained substantial evidence for the diagnosis of GERD. Nevertheless, the evidence of MNBI for its use in LPR patients is scarce. We therefore formulated the hypothesis that lower MNBI values are associated with higher symptom burden, more severe reflux laryngitis and predict response to PPI therapy in patients with LPR.

Aims & Methods

Patients referred for suspected LPR were screened and those with positive reflux finding score (RFS>7), as determined by flexible laryngoscopy and/or positive reflux symptom index (RSI>13), and at least one acidic LPR episode during 24 hour pH/impedance study were enrolled. We recruited patients at least 30 days without PPI treatment. Appropriate distance between pH sensors was chosen based on manometri-cally determined upper and lower esophageal sphincter. We reviewed the pH impedance tracings and determined MNBI values as the average value of three 10 min. intervals (1:00, 2:00 and 3:00 a.m.) in the periods without reflux events and/or swallowing. We gained these values for 6 impedance segments (Z1 - most proximal to Z6 - most distal). We established the correlation between the MNBI values and RSI/RFS using Pearson correlation coefficient (R value). Then we recommended PPI treatment twice daily for 3 months. Subsequently we determined RSI values and evaluated symptomatic response. We determined those who achieved RSI normalization or > 50% decrease of RSI as PPI responders. Those that did not fulfill these criteria were the non-responders group. We compared the pre-treatment MNBI values in these groups of patients using Students T-test.

Results

27 patients (20M/7F) completed the study. RSI in RSI positive patients 25.4[24-33.5] and RFS in RFS positive patients was 10[9-11]. Average MNBI values before PPI treatment were 2816±135n, 3361±162n, 3376±196n, 2490±171n, 2469±2520 and 2974±320n for segments Z1-Z6, respectively. There was no correlation between MNBI and RSI in any impedance segment (R=0.15, -0.08, -0.12, 0.02, 0.07 and -0.14, for segments Z1-Z6, respectively, p=NS in all cases). There was also no correlation between MNBI and RFS (R=-0.05, 0, -0.09, -0.22, -0.26, -0.2 for segments Z1-Z6, respectively, p=NS in all cases). 18 patients completed 3 months treatment. 8 patients were PPI responders and 10 patients were PPI non-responders. There was significant increase of MNBI values in Z4-Z6 (p< 0.04 in all three segments), and no significant increase of MNBI in Z1-Z3 compared to pretreatment values (N=18). There was no statistical difference between pretreatment MNBI values in the responders compared to non-responders group in any impedance segment (p=0.28, 0.79, 0.94, 0.72, 0.79, 0.92 in Z1-Z6, respectively).

Conclusion

Direct relationship between the microscopic mucosal injury and the symptoms and signs of laryngopharyngeal reflux is improbable. Moreover, MNBI values do not predict symptomatic response to PPI. This suggests that other aspects of LPR than those that are detectable on 24 hour esophageal pH/impedance might be of importance.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.101

P0118 Extraesophageal Symptoms of Gerd: Can Microscopic Esophagitis Improve The Diagnosis?

D Costa ^1,^2,^✉, M Sousa ², M Gonçalves ¹, S da Silva Mendes ¹, B Arroja ¹, D Fernandes ¹, I Costa ^3,^✉, N Lamas ², R Gonçalves ¹, C Rolanda ^1,²

Introduction

Establishing causality between Gastroesophageal reflux disease (GERD) and extraesophageal symptoms is extremely challenging. Current diagnostic tests suffer from either lack of sensitivity or specificity and have limited associated treatment outcomes. Combination of different methods is often needed to support or refute this diagnosis.

Aims & Methods

We aimed to evaluate the performance of a standardized protocol to identify microscopic esophagitis and to determine its role in supporting laryngopharyngeal reflux (LPR) diagnosis related to GERD. Thus, a unicentric, observational, prospective study was performed between April and October 2019 in the Otorhinolaryngology (ORL) department of Braga Hospital, with 39 patients with suspected LPR according to clinical symptoms and signs. The Reflux Symptom Index (RSI) questionnaire and the Reflux Finding Score (RFS) on nasopharyngolaryngoscopy evaluation were obtained. Upper gastrointestinal endoscopy with microscopic esophageal evaluation as defined by the Esohisto consensus guidelines, conventional esophageal manometry and combined esophageal pH-impedance monitoring were also performed off Proton Pump Inhibitor (PPI).

Results

From the 39 suspected LPR, most patients were female (87,2%), with a mean age of 57,7 years old, with concomitant esophageal symptoms in 92,3% and only 25,6% responded to IBP treatment. The mean RSI and RFS were 23,4 and 11, respectively. GERD was confirmed in 45,7% of patients. The RSI item coughing after eating/lying down showed to be a significant predictor for GERD in patients with suspected LPR (OR:1.6; p=0.036). The total RSI score displayed an AUC of 0.696 (SE=0.09, p=0.036), with a sensitivity of 81,3% and specificity of 57,9%, when a cut-off of 20 was selected. Microscopic esophagitis revealed a sensitivity of 35,7% and specificity of 70,0% in our sample, though severe esophagitis (n=2) was only found in GERD patients.

Conclusion

The Esohisto histological score revealed a low performance to identify patients with LPR related to GERD, though it may improve upper endoscopy performance

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.102

P0121 A Chinese Subgroup Analysis of The Asian Phase 3 Study To Evaluate The Efficacy and Safety of Vonoprazan 10 Or 20 Mg Compared with Lansoprazole 15 Mg in The Maintenance Treatment of Asian Patients with Erosive Esophagitis

Y Xiao ^1,^✉, J Qian ², S Zhang ³, N Dai ⁴, N Funao ⁵, Y Sakurai ⁵, L Dong ⁶, L Xie ⁶, M Chen ⁷

Introduction

Proton pump inhibitors (PPIs) such as lansoprazole are standard therapy for short-term and maintenance treatment of erosive esophagitis (EE). However, PPIs show variable time to onset of action and high relapse rate of healed EE. Vonoprazan, a potassium competitive acid blocker, offers maximum acid-inhibitory effects in first dose compared with lansoprazole. Previous phase III study had shown the non-inferiority of vonoprazan to lansoprazole in non-Japanese Asian EE patients during the initial therapy phase. However, whether vonoprazan was also non-inferior to lansoprazole during the maintenance phase of EE therapy in non-Japanese Asian patients was not clarified. A study was conducted to assess the safety and efficacy of vonoprazan in Non-Japanese Asian patients with healed EE. in this sub-group analysis, the non-inferiority of vonoprazan compared to lansoprazole in the maintenance phase of healed EE in Chinese patients was evaluated.

Aims & Methods

A phase III, double-blind, parallel-group, multicenter study was conducted to demonstrate the non-inferior efficacy and safety of vonoprazan to lansoprazole in non-Japanese Asian patients with healed EE (NCT02388737). Adult patients with endoscopically confirmed EE were randomized (1:1:1) to receive oral vonoprazan 10 or 20 mg once daily (QD) or lansoprazole 15 mg QD as maintenance therapy for 24 weeks. Primary end point was EE recurrence rate during the 24 weeks, which is defined as endoscopically confirmed Los Angeles classification grade A-D EE. Additional end points included subjective measures of EE symptoms, health-related quality of life (HRQoL), and safety. in this subgroup analysis, we report the efficacy and safety of vonoprazan (10 and 20 mg) compared with lansoprazole (15 mg) in Chinese patients with healed EE.

Results

In the Chinese cohort, 491 patients randomly received oral vonoprazan 10 mg (N=163) or 20 mg (N=159) QD or lansoprazole 15 mg QD (N=169) as maintenance therapy for 24 weeks. Endoscopically confirmed EE recurrence rates during 24 weeks were 13.8% (17 of 123) in the vono-prazan 10-mg group, 14.0% (17 of 121) in the vonoprazan 20-mg group, and 25.0% (31 of 124) in the lansoprazole 15-mg group. Vonoprazan 10 mg (treatment difference: -11.2%, 95% CI: -20.9, -1.4) and 20 mg (treatment difference: -11.0%, 95% CI: -20.8, -1.1) were non-inferior to lansoprazole in preventing recurrences of EE after 24 weeks. As the upper limit of 95% CIs was ≤0%, both doses of vonoprazan showed superiority to lansoprazole. EE symptoms were improved in all treatment groups from baseline, with no significant between-group difference (P>.05). HRQoL measures assessed using EQ-VAS scores were significantly greater in the vonoprazan 10-mg group than in the lansoprazole 15-mg group (P=.004). Treatment-emergent adverse event (TEAE) rates were 71.8%, 78%, and 72.2% for vonoprazan 10 mg, vonoprazan 20 mg, and lansoprazole 15 mg, respectively, out of which the incidence rates for drug-related TEAEs were 23.9%, 28.3%, and 16.6%, respectively; 4.9%, 4.4%, and 5.3% of patients in the three groups, respectively, reported serious adverse events, although none of them were related to the study drug. Treatment discontinuation due to TEAEs was 6.1% with vonoprazan 10 mg, 5.7% with vonoprazan 20 mg, and 4.1% with lansoprazole. Upper respiratory infection was the most frequently reported TEAE in the vonoprazan 10-mg (17.2%), 20-mg (15.7%), and lansoprazole groups (11.8%).

Conclusion

Vonoprazan 10 and 20 mg are well tolerated and superior to lansoprazole 15 mg for preventing relapse in Chinese patients with healed EE.

Disclosure

This study was funded by Takeda Pharmaceutical Company Ltd. Nobuo Funao is an employee of Takeda Pharmaceutical Company, Japan; Yuuichi Sakurai is an employee of Takeda Pharmaceutical Company, Japan and hosts the Takeda stock; Lu Dong is an employee of Takeda (China) International Trading Co. Ltd.; Li Xie is an employee of Takeda (China) International Trading Co. Ltd. and holds the Takeda stock options. Yinglian Xiao, Jiaming Qian, Shutian Zhang, Ning Dai and Minhu Chen have no disclosures.

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.103

P0123 Understanding The Ppi-User Journey: Results of A Survey On Initiation of Ppi Treatment

K Plehhova ^1,^✉, N Paquette ², J Gould ³, C Coyle ¹

Introduction

PPIs are one of the most widely-prescribed classes of medication for the treatment of reflux¹. Under current guidance, patients with GORD or un-investigated dyspepsia should be initially offered lifestyle advice and antacid/alginate therapy². If unsuccessful, the next step is to is to offer empirical full-dose PPI therapy for 4-8 weeks². Long-term PPI use should be regularly reviewed and the lowest effective dose prescribed^2,3. Currently, however, physicians are inclined to prescribe a PPI early and for extended periods, which presents a barrier to appropriate reflux manage-ment¹.

Aims & Methods

The aim of this piece of research is to better understand the impact of current practice on patient attitudes and treatment journeys.

An online survey was conducted by Toluna/Harris Interactive with sufferers of gastroenterological conditions in the UK and Germany (DE) in December 2019. 6088 (UK) and 4640 (DE) respondents were screened and a total of 566 (n=372 UK; 194 DE) qualified for participation in the survey. Either a 5- or 20-minute survey was taken depending on the sample group. Respondents were included if they were either current or previous users of PPIs who: (1) Are currently using a PPI to treat reflux; (2) Have in the last year used a PPI to treat reflux; (3) Have in the last year used a PPI for another reason. Current users of PPI for any other reason were excluded. The following topics were covered (bold indicates responses from groups 1-3, otherwise only responses from groups 1&2): Steps taken before first visiting physician with reflux, Initial recommendations, PPI treatment initiation, Use of PPI, Management of reflux whilst taking a PPI, Ending PPI Treatment, Attitudes towards taking a PPI.

Study Limitations: This study explored individual recall of PPI treatment initiation and use thereafter. This methodology is appropriate as an insights tool; however, it is not a validated patient reported outcome (PRO) measure. Future research would be carried out using a validated PRO.

Results

Approximately 10% of the UK population and 5% in Germany (DE) are currently on, or recently completed, a PPI course (n=6088 UK; 4640 DE). The majority (7% UK; 3% DE) of these prescriptions were for reflux. 79% UK and 69% DE respondents reported being prescribed something at first visit; of these, 61% UK and 68% DE were prescribed a PPI either alone or in combination with another treatment. 20% of respondents (20% UK; 17% DE) reported not having tried any over-the-counter (OTC) medication prior to being prescribed a PPI. Those prescribed a PPI recalled being well informed about what dosage to take (70% UK;69% DE) and when to take it (56% UK;58%DE) when first prescribed a PPI; however, other safety and usage information was not as frequently discussed (Table 1).

Table 1.

Information Provided Alongside PPI Prescription

	UK	Germany (DE)
What dosage to take each day	70	69
When to take the PPI	56	58
How long you should keep taking the PPI	22	38
What to do if you get side effects	19	18
Interactions with other medications	18	27
Side effects	18	23
How long for the PPI to take effect	17	30
Possible symptoms once stop taking PPI	15	19
Nothing	8	5

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Conclusion

There is user-reported variability in treatment and prescription approach of PPIs as compared to standard guidance. Respondents recalled being commonly informed about dosing when first prescribed a PPI but other key pieces of safety and usability information were not as commonly reported as discussed.

Disclosure

The authors are employees of Reckitt Benckiser Healthcare Ltd.

References

1.Coyle C. et al. BJGP Open, 2019; [DOI] [PMC free article] [PubMed] [Google Scholar]
2.NICE Clinical guideline [CG184]; Last updated: 2019; [Google Scholar]
3.Freeberg et al. Gastroenterology 2017; 152: 706–715 [DOI] [PubMed] [Google Scholar]

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.104

P0124 Understanding The Ppi-User Journey: Results of A Survey On Ppi Treatment Experience

K Plehhova ^1,^✉, N Paquette ², J Gould ³, C Coyle ⁴

Introduction

PPIs are one of the most widely-prescribed classes of medication for the treatment of reflux¹. Under current guidance, patients with GORD or un-investigated dyspepsia should be initially offered lifestyle advice and antacid/alginate therapy². If unsuccessful, the next step is to is to offer empirical full-dose PPI therapy for 4-8 weeks². Long-term PPI use should be regularly reviewed and the lowest effective dose prescribed^2,3. Currently, however, physicians are inclined to prescribe a PPI early and for extended periods, which presents a barrier to appropriate reflux manage-ment¹.

Aims & Methods

The aim of this piece of research is to better understand the impact of current practice on patient attitudes and treatment journeys. An online survey was conducted by Toluna/Harris Interactive with sufferers of gastroenterological conditions in the UK and Germany (DE)

in December 2019. 6088 (UK) and 4640 (DE) sufferers were screened and a total of 566 respondents (372 UK; 194 DE) qualified for participation in the survey. Either a 5- or 20-minute survey was taken depending on the sample group. Respondents were included if they were either current or previous users of PPIs who: (1) Are currently using a PPI to treat reflux; (2) Have in the last year used a PPI to treat reflux; (3) Have in the last year used a PPI for another reason. Current users of PPI for any other reason were excluded. The following topics were covered (bold indicates responses from groups 1-3, otherwise only responses from groups 1&2): Steps taken before first visiting physician with reflux, Initial recommendations, PPI treatment initiation, Use of PPI, Management of reflux whilst taking a PPI, Ending PPI Treatment, Attitudes towards taking a PPI. Study Limitations: This study explored individual recall of PPI experience on initiation and use thereafter. This methodology is appropriate as an insights tool; however, it is not a validated patient reported outcome (PRO) measure. Future research would be carried out using a validated PRO.

Results

Most respondents reported taking their PPI for more than 2 months; up to two thirds have been taking PPIs continuously for over 1 year (64% UK rising to 78% aged 55+, 50% DE rising to 62% aged 55+). 1 in 3 (33% UK;29% DE) reported taking their PPI for 5 years or more (Table 1). 88% of UK and 80% of DE respondents prescribed PPIs either do not know how long they will be taking a PPI for (41% UK;48% DE) or expect to be taking their PPI for over 3 months (47% UK;32% DE). The majority of PPI users reported experiencing breakthrough symptoms (66% UK;80%DE). For half of this group, symptoms occurred once a week or more (47% UK;48% DE). in both countries, of those who had come off their PPI, half abruptly stopped treatment (49%UK;56%DE); the other half either reduced dose or frequency (51% UK;44% DE).

Table 1.

Reported duration of PPI use (numbers rounded)

Reported Duration of PPI Use	UK (%)	Germany (DE) (%)
Longer than 5 years	33	29
3-5 years	16	13
1-2 years	16	8
7-12 months	5	8
3-6 months	8	10
1-2 months	6	9
2-4 weeks	9	14
1 week	4	5
Cannot remember	4	5

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Conclusion

• Over two thirds of respondents experienced breakthrough symptoms, half of these at least once a week.

• PPI treatment duration exceeded guideline limits in most cases.

• Half of PPI users who stopped their PPI reported doing so abruptly.

References: References

1Coyle C et al. BJGP Open, 2019, 2NICE Clinical guideline [CG184]; Last updated: 2019, 3 Freeberg, et al, Gastroenterology 2017;152:706-715

Disclosure

The authors are employees of Reckitt Benckiser Healthcare Ltd.

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.105

P0129 Real World Risk of Acute Interstitial Nephritis in Patients On Acute Proton Pump Inhibitor Therapy

S Trujillo ¹, A Desai ¹, S Dalal ¹, D Sandhu ^1,^2,^✉

Introduction

Proton pump inhibitors (PPIs) are one of the most commonly prescribed medications for management of many gastrointestinal disorders, including gastroesophageal reflux disease, peptic ulcer disease, dyspepsia, Barrett's esophagus, and acute gastrointestinal bleeding. PPI are generally well tolerated and are thought to have a good safety profile. However, studies suggest a link between chronic PPI and renal dysfunction, specifically acute interstitial nephritis (AIN). Diagnosis is usually delayed due to its atypical and subtle presentation, which likely contributes to its progression to chronic kidney disease (CKD). There is limited data on whether acute PPI therapy causes AIN. Our primary aim was to evaluate the prevalence of AIN in patients for each acute PPI therapy medication. Our secondary aim was to compare the risk of AIN in patients on PPI compared to histamine H2-receptor blockers (H2 blockers) and compare adverse outcomes of acute PPI-induced AIN.

Aims & Methods

We performed a retrospective analysis in the IBM Explo-rys database 5 (1999-2020), a pooled, national, de-identified clinical database of over 72 million unique patients from 26 health care networks and 300 hospitals across the United States. Patient populations were identified using SNOMED and ICD codes. PPI included were esomeprazole, omeprazole, pantoprazole and lansoprazole. The development of AIN was evaluated within 8 weeks of PPI initiation. Patients on medications commonly implicated in AIN which included non-steroidal anti-inflammatory drugs, antibiotics, loops diuretic, H2 blockers, rifampin, and allopurinol were excluded from the study if prescribed within 30 days of initiation of PPI. Additionally, patients with systemic lupus erythematous, sarcoidosis, Granulomatosis with polyangiitis, and Sjogren's disease were also excluded from the study. The control group was defined as patients on H2 blockers with the above exclusion criteria. Adverse events (AEs) were defined as ICU admission within 7 days, hemodialysis within 2 weeks, new chronic kidney disease within 6 months of diagnosis of AIN, and new end stage renal disease within 1 year for PPI group and control group. Prevalence was reported for each PPI. Odds ratio with 95% CI were calculated for risk of AIN for each PPI compared to control group. Chi-squared test was used to compare the risk of AEs in the combined PPI group vs H2 blockers.

Results

Acute PPI-induced AIN comprised 0.56% (n=1410) of total AIN patients. Prevalence of AIN in Esomeprazole was 6 (per 10,000), Omeprazole was 6 (per 10,000), Pantoprazole was 18 (per 10,000) and Lansoprazole was 4 (per 10,000). Pantoprazole was the only PPI associated with an increased risk for AIN (OR 1.66, 95% CI 1.51-1.84) compared to the control group. There was no difference between risk of CKD and ESRD between PPI and H2 blocker groups. Patients in PPI group were more likely to be senior (age > 65), female gender, have Medicare insurance, hypertension, hyperlipidemia and heart failure.

Conclusion

Our study shows that AIN is a rare side effect of acute PPI therapy. Pantoprazole should be used with caution perhaps in patients with underlying CKD however this needs to be validated in future studies.

Demographics of patient on PPI and H2 blockers

Demographics	PPI (n=1410)	H2 blocker (n=770)	p value
Age > 65	590 (42%)	250 (33%)	<0.0001
Female	1210 (86%)	630 (82%)	0.013
Caucasian	1070 (76%)	570 (74%)	0.3
Obesity	650 (46%)	340 (44%)	0.37
Hypertension	1090 (77%)	540 (70%)	0.0003
Diabetes Mellitus	610 (43%)	310 (40%)	0.17
Heart failure	510 (36%)	210 (28%)	0.0002

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Disclosure

Nothing to disclose

References

Antoniou T. et al. “Proton Pump Inhibitors and the Risk of Acute Kidney Injury in Older Patients: a Population-Based Cohort Study.” CMAJ Open, vol. 3, no. 2, 2015, doi: 10.9778/cmajo.20140074. [DOI] [PMC free article] [PubMed] [Google Scholar]
Moledina Dennis G., and Mark A. Perazella. “Proton Pump Inhibitors and CKD.” Journal of the American Society of Nephrology, vol. 27, no. 10, 2016, pp. 2926–2928., doi: 10.1681/asn.2016020192. [DOI] [PMC free article] [PubMed] [Google Scholar]
Nehra Avinash K. et al. “Proton Pump Inhibitors: Review of Emerging Concerns.” Mayo Clinic Proceedings, vol. 93, no. 2, 2018, pp. 240–246., doi: 10.1016/j.mayocp.2017.10.022. [DOI] [PubMed] [Google Scholar]
Xie Yan et al. “Proton Pump Inhibitors and Risk of Incident CKD and Progression to ESRD.” Journal of the American Society of Nephrology, vol. 27, no. 10, 2016, pp. 3153–3163, doi: 10.1681/asn.2015121377. [DOI] [PMC free article] [PubMed] [Google Scholar]

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.106

P0130 Prevention of Esophageal Stricture After Circumferential Endoscopic Sub-Mucosal Dissection: Effect of A Self-Assembled Peptide in A Swine Model

S Oumrani ^1,^2,^3,^✉, M Barret ^2,^3,⁴, F Beuvon ⁵, C Chêne ², C Nicco ², E Abou Ali ^3,⁴, F Batteux ^2,³, F Prat ^2,^3,⁴

Introduction

Circumferential en bloc resection of esophageal mucosa using endoscopic sub-mucosal dissection (ESD) or endoscopic mucosal resection (EMR) could find its place in the treatment of Barrett's esophagus (BE) or extensive superficial neoplasia.

However, expansion of this treatment could be limited by the high risk of occurrence of an esophageal stricture. When resection exceed % of the circumference, the risk to develop a stricture rise to 90%. En bloc circumferential esophageal mucosa resection technique have been developed in a swine model.

The aim of this study was to assess the effect of a modified, pH = 2, self-assembled peptide matrix (4[Arg-Ala-Asp-Ala]) (SAP) on the development of esophageal stricture after circumferential endoscopic resection in a swine model.

Aims & Methods

We realized an endoscopic circumferential endoscopic sub-mucosal dissection (c-ESD) in 35 swine under general anaesthesia. Five animals were included in the control group, 11 animals received the SAP matrix immediately after a c-ESD and 11 received the SAP matrix associated to a local steroid (triamcinolone 10 mg/mL) immediately after the c-ESD. An endoscopy and an esophagogram were realized at day 14 and then the animals were euthanized. Partial en bloc esophagectomy was realized for pathology analysis. Four animals in the SAP matrix-steroid group and 11 animals in the SAP matrix alone group were kept alive until day 28 or euthanized before this date if they developed a symptomatic stricture. A blood sample was taken for all animals at day 0 and 14 and pro fibrotic cytokine level was determined. Our primary outcome was occurrence of an esophageal stenosis at day 14.

Results

At day 14, all animals in the control group, 10 animals in the SAPM-group (66%) and 11 (78%) animals in the SAPM-triamcinolone group had an endoscopic stricture which was symptomatic for 5 (100%), 4 (27%) and 7 (50%) of them respectively (p=0.008 for control vs SAP group, p=0.11 for control vs SAP-triamcinolone group).

Median (IQR) esophageal diameters were 8 (4.5-9.5) mm, 4.8 (3.1 - 7.7) mm and 3 (2-4) mm in the SAP, control and SAP-triamcinolone groups, respectively (p = 0.02 for control vs SAP group, p=0.11 for control vs SAP-triamcinolone group).

Concerning histological analysis, neoepithelium was longer in both treated groups than in control group (p=NS). There was no correlation between TGF-β blood levels and occurring of stenosis or fibrosis depth measured on histological slides of the esophageal tissue.

Conclusion

Application of a SAP matrix upon an endoscopic esophageal c-ESD in a swine model immediately at the end of procedure allowed a 73% significant reduction of the incidence of a symptomatic stricture at day 14, by delaying its occurrence. Adding triamcinolone brought no significant improvement.

Disclosure

The study was funded by 3-D Matrix Europe SAS.

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.107

P0131 Contribution of Hydrogen Sulfide-Producing Cystathionine-G-Lyase (Cth) in The Development of Barrett's Metaplasia-Specific Molecular Profile and Systemic Inflammation

E Korbut ^1,^✉, M Wierdak ¹, K Magierowska ^1,², U Glowacka ¹, D Wójcik ¹, T Brzozowski ¹, M Surmiak ³, VT Janmaat ², MP Peppelenbosch ², R Smits ², M Magierowski ^1,²

Introduction

Barrett's Esophagus (BE) is a premalignant condition of esophageal epithelium with characteristic molecular profile related to the expression of columnar epithelium-specific genes with special emphasis on KRT family. On the other hand, hydrogen sulfide (H₂S) releasing pharmacological tools have been shown to accelerate ulcer healing and to prevent gastric mucosa against NSAIDs-induced injury. H₂S is an endogenous gaseous molecule produced via L-cysteine metabolism due to activity of cystathionine-g-lyase (CTH) and two other enzymes. However, the involvement of H₂S-producing CTH activity in the development of BElike molecular profile in esophageal epithelium has not been investigated.

Aims & Methods

In vitro studies:

Human-derived esophageal keratinocytes (EPC2) and squamous esopha-geal epithelial cells (Het-1A) with or without CTH gene knock-outs (k/o) induced by CRISPR/Cas9 were treated with acidified bile mixture (BM) to induce BE-like molecular profile according to our previously optimized protocol reflecting clinically observed alterations. Additionally, wild type Het-1A and EPC2 cells were treated with D,L-propargylglycine (PAG, 50-1000 mM) as CTH inhibitor. BE-like molecular profile interpreted as alterations in mRNA expression of KRT genes (e.g. KRT4, KRT8, KRT15, KRT18) was assessed by real-time PCR. Cell viability after 3-days of treatment with PAG (50 uM-10 mM) was evaluated by thiazolyl blue tetrazolium bromide (MTT) assay.

In vivo studies:

Wistar rats with surgically-generated esophagogastroduodenal anastomosis (EGDA) were treated i.g. for 8 weeks with vehicle or with PAG (1-30 mg/kg). Esophageal lesions/metaplasia index (ELMI) was assessed macro-scopically and microscopically using H&E and PAS staining and standardized scale. Esophageal blood flow (EBF) was measured by laser flowmetry. Esophageal mRNA expression for BE-specific KRT genes was determined by real-time PCR. H₂S production by CTH activity in esophageal mucosa was assessed using methylene blue method. Serum content of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, TNF-a, IFN-y, and GM-CSF was screened by Luminex platform.

Results

In in vitro cell model, PAG treatment (50-1000 |iM) and CTH k/o did not affect Het-1A and EPC2 cell viability. Moreover, BM treatment of cells without genetic modifications administered with PAG, as well as Het-1A and EPC2 with CTH k/o further enhanced molecular changes characteristic for BE (e.g. KRT genes up/downregulation), previously observed in BM-treat-ed EPC2 and Het-1A wild type cells.

In animal model, daily treatment with PAG (as compared with vehicle) increased ELMI evoked by chronic reflux leading to BE-like metaplasia with the presence of goblet cells, decreased EBF and induced BE-like molecular profile. Further enhancement of decreased H₂S production was observed in esophageal mucosa of EGDA-rats treated with PAG. Pharmacological inhibition of CTH by PAG increased pro-inflammatory markers serum concentration.

Conclusion

We conclude that altered H₂S production by decreased enzymatic CTH activity in esophageal mucosa exposed to gastroesophageal reflux could be involved in the development of BE metaplasia followed by specific molecular profile changes. Pharmacological inhibition of CTH and/or CTH k/o further enhanced BE progression and inflammatory response in animal model and molecular profile alterations towards BE in human esophageal epithelial cells in vitro, respectively. These effects possibly involve vasodilatory and anti-inflammatory properties of endogenous H₂S. [Funding source: National Science Centre,Poland (UMO-2016/23/D/NZ4/01913)].

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.108

P0132 Mirna Biomarkers For A Non-Invasive Diagnosis of Barrett's Esophagus

N Masque Soler ^1,^✉, M Gehrung ², X Li ¹, C Kosmidou ¹, RC Fitzgerald ¹

Introduction

In developed countries, esophageal adenocarcinoma (EAC) incidence has increased six-fold in the last three decades. The outcome remains poor with a 5-year survival of under 20%. EAC can be preceded by Barrett's esophagus (BE). Screening the population at risk for BE would improve their surveillance schemes and help identify where early endo-scopic intervention is required. To date screening has not been recommended due to reliance on expensive and invasive endoscopy. The Cytosponge® is a minimally invasive, non-endoscopic cell sampling device for BE. Cytosponge is a capsule on a string that when swallowed dissolves to an expandable sponge which can sample cells from the entire oesophageal length. The presence of gastric cardia (GC) glands in the sponge is a quality control for distal esophagus sampling and a Cytosponge is classed as inadequate if it does not include GC. A fluid-based assay, such as miRNA applied to harvested cells could allow for greater multiplexing. We hypothesised that the combination of miRNAs with computer vision techniques could enable the determination of cell specific contributions to biomarker expression.

Aims & Methods

Cytosponge samples from the BEST2 trial were used.

i) RNA extracted from FFPE sections was probed with a custom 110-plex miRNA panel (Fireplex, Abcam) containing known and novel biomarker candidates. Cytosponges (n=117) comprised: 46 normal esophagus, 44 non-dysplastic BE (NDBE), 10 low grade dysplasia, 10 high grade dysplasia and 7 inadequate samples.

ii) H&E slides of Cytosponges were used for an in-house computer vision tool assessment which uses deep learning to quantify distinct tissue phenotypes. Thus, the amount of columnar and squamous epithelium present in each section was calibrated. Differentially expressed miRNA markers were validated with qPCR and via computer vision tool in an independent cohort (n=139) with 68 inadequate and 71 adequate samples, of which 35 were normal and 36 NDBE.

Results

Four miRNAs candidates had statistically significant higher expression in diseased compared to healthy samples in the test cohort. We observed a positive correlation (r=0.72-0.77) between the expression levels of each miRNA and the amount of columnar epithelium from both the gastric and BE epithelium. All 4 markers were not expressed in inadequate samples which did not contain any type of columnar epithelium. An independent cohort of 139 cases validated these results, where all 4 miRNAs were differentially expressed in inadequate vs. adequate samples (p=0.038-0.0001). A 5-fold cross validation of the 4 miRNAs for sample adequacy in terms of the glandular cell content showed an AUC-ROC of 0.91. Hence, these markers were informative for the presence of any columnar epithelium (including BE) in the sample.

These results have considerable implications in the discovery of new markers in Cytosponge samples since orthogonal characterization of sampled material can avoid biases in selection of novel molecular biomarkers.

Conclusion

The expression of 4 miRNAs are a potential quality control tool for Cytosponge samples. A combined experimental and computer vision approach enabled the underlying biology of miRNA biomarker expression to be determined with relevance to other biomarker studies.

Disclosure

Rebecca C Fitzgerald is one of the named inventors on patents pertaining to the Cytosponge and related assays and is the co-funder of Cyted together with Marcel Gehrung. Neus Masque-Soler has no disclosures.

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.109

P0133 Ethnic Features of The Barrett's Esophagus with Dysplasia Prevalence in The Population of Khakassia Administrative Center

V Tsukanov ^1,^✉, N Butorin ², E Kasparov ¹, A Vasyutin ¹, J Tonkikh ¹

Introduction

The incidence of esophageal cancer increasing rapidly in recent years, which makes actual the study of Barrett's esophagus (BE) [1].

Aims & Methods

From 2011 to 2015 in the endoscopic department of the republican hospital in Abakan were performed 11,615 endoscopic examinations in Caucasoids (5,537 men and 6,078 women, mean age 42.4 years), and 5,808 - in Khakases (2,774 men and 3,034 women, mean age 41.6 years) with video gastroscope Olympus GIF 180 using narrow-band imaging and magnifying technique. Heartburn was determined on the basis of the Montreal consensus [2], BE - British Society of Gastroenterology guidelines [3]. Diagnosis of esophagitis was based on the Los Angeles Classification [4]. Barrett's esophagus and dysplasia were diagnosed using the morphological study. Daily pH monitoring was performed in 21 Khakases (10 men and 11 women) and 25 Caucasoids (12 men and 13 women) with heartburn.

Results

We found the predominance of prevalence of BE, weekly heartburn and esophagitis in Caucasoids compared with Khakases (Table). Heartburn in both populations was observed more frequently in patients with BE compared with persons without BE. The BE risk factors in Cauca-soids and Khakases were male gender, increasing age and obesity. with daily pH monitoring, the average time with a pH< 4 during the day in the esophagus in Caucasoids with heartburn was 21.18±1.7%, in Khakasses with heartburn - 15.5±1.3% (p=0.007). The number of alkaline refluxes also prevailed among alien inhabitants (25.1±1.7) compared with the indigenous population (19.4±1.4; p=0.01).

Conclusion

Ethnic differences of BE and esophagitis prevalence suggest that genetic factors may play a significant role in the pathogenesis of GERD.

The prevalence of BE,esophagitis and weekly heartburn in the population of Khakassia

Population	Weekly heartburn	Esophagitis	BE	BE with dysplasia
	Abs.	%	Abs.	%	Abs.	%	Abs.	%
1. Caucasoids, n=11,615	1,440	12.4	486	4.2	163	1.4	28	0.24
2. Khakases, n=5,808	499	8.6	144	2.5	58	1.0	5	0.09
OR; 95% CI; p	1.5; 1.35-1.67; <0.001		1.71; 1.42-2.07; <0.001		1.40; 1.04-1.89; =0.03		2.60; 1.04-6.47; =0.04

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Disclosure

Nothing to disclose

References

1.Wani S., Rubenstein J.H., Vieth M., Bergman J. Diagnosis and Management of Low-Grade Dysplasia in Barrett's Esophagus: Clinical Practice Updates Expert Review From the Clinical Guidelines Committee of the American Gastroenterological Association. Gastroenterology. 2016; 151(5): 822–35. [DOI] [PubMed] [Google Scholar]
2.Vakil N., van Zanten S.V., Kahrilas P. et al. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006; 101(8): 1900–20. [DOI] [PubMed] [Google Scholar]
3.Fitzgerald R.C., di Pietro M., Ragunath K. et al. British Society of Gastroenterology guidelines on the diagnosis and management of Barrett's oesophagus. Gut. 2014; 63(1): 7–42. [DOI] [PubMed] [Google Scholar]
4.Lundell L.R., Dent J., Bennett J.R. et al. Endo-scopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification. Gut. 1999; 45(2): 172–80. [DOI] [PMC free article] [PubMed] [Google Scholar]

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.110

P0134 Radiofrequency Ablation of Barrett's Esophagus: The Real Practice Experience in A Tertiary Hospital. Is It The Best Technique For This Entity?

S García Mateo ^1,^✉, MJ Domper Arnal ¹, R Sandalinas Velamazan ¹, G Hijos Mallada ¹, D Abad ¹, N Saura Blasco ¹, M Hernández Aínsa ¹, P Cañamares Orbís ², E Alfaro ¹, V Laredo De La Torre ¹, A Ferrandez ¹, J Ducons García ¹

Introduction

Barrett's esophagus (BE) is a premalignant condition due to its capacity for progression to adenocarcinoma (EAC). Radiofrequency ablation (RFA) combined or not with other endoscopic procedures is the treatment of choice for BE. However, the risk of relapse exists in the medium term whether risk factors persist.

Aims & Methods

1) To determine the efficiency of RFA of BE and the prevalence of adverse events in a tertiary Hospital.

2) To evaluate the risk factors associated with a year-relapse of BE post-RFA.

Prospective observational cohorts study about patients with BE treated with RFA in the endoscopy unit of University Clinical Hospital Lozano Blesa in Zaragoza from 2012 to 2019. Data were analyzed by SPSS Statistics 22.0.

Results

50 patients with BE were included. Most of them were men (42/50; 84%) with a mean age of 56.44 ± 14.91 years old. Eight of them (8/50; 16%) without dysplasia, more than half with low-grade dysplasia (26/50; 52%), 18% with high-grade dysplasia (9/50), and 14% (7/50) with early cancer. The 92% (46/50) had a long length of Barrett segment (circumferential extent (C) 5.12 centimeters ± 3.63; maximum extent (M) 6.80 centimeters ± 3.00). Most of the patients had hiatal hernia (38/50; 76%). The patients underwent a median of 2± 1 RFA sessions, with a mean treatment time of 11.82 ± 10.76 months. Argon plasma coagulation (29/46; 58%) and multiband mucosectomy (12% (6/50)) were combined with RFA in most of the patients. There were any severity acute (during the procedure) or early (0-48 hours) complications such as perforation or death. However, there were 23% of mild complications including strictures (8/50; 16%) or mucosal ulcers (8/50; 16%). 41 of the 46 patients (92%) who ended the treatment were reevaluated after a year. Seven patients (14% (7/41)) had a recurrence of BE of which more than half needed Argon plasma coagulation (71.42% (5/7)), multiband mucosectomy was performed in 14.28% (1/7) and only one patient needed RFA (14.28%, 1/7). Most of BE recurrences were in males (5/7; 71.42%) with low-grade dysplasia (3/7; 42.85%). There were no significant association between the recurrence and the long length of Barrett segment (p=0.414) neither do high body mass index (more than 25) (p=0.117) nor sex (p=0.252). Some patients (8% (4/41)) had erosive esophagitis during the surveillance. Moreover, in three of them, Nissen's fundoplication was needed.

Conclusion

RFA in combination or not with other endoscopic procedures is highly effective near-term and has an excellent safety profile. However, long-term surveillance is highly recommended because the risk of recurrence is not negligible.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.111

P0136 Prospective Multicentre Randomised Controlled Trial Comparing The Safety and Effectiveness of The Endorotor® Mucosal Resection Device with Continued Ablation in The Treatment of Refractory Barrett's Oesophagus: Report of Initial Outcomes

M Hussein ^1,^✉, S Sami ¹, LB Lovat ¹, R Haidry ², KK Wang ³

Introduction

Endoscopic ablation therapy is recommended in patients with flat dysplastic Barrett's oesophagus (BE). A proportion will be refractory to treatment. This is associated with neoplasia recurrence. The EndoRotor® device (Interscope Medical Inc, Whitinsville, MA, USA) is a nonthermal resection device. The aim was to compare the safety and efficacy of EndoRotor with ablation in the treatment of refractory BE.

Aims & Methods

This is an on-going prospective, randomised trial in two centres in the UK and USA. Patients with refractory BE were randomised to EndoRotor resection or continued ablation (Cryotherapy/Radiofrequency ablation). All patients had Intramucosal adenocarcinoma/High grade or Low-grade dysplasia at initial baseline histology. Patients were followed up every 3 months with a maximum of 3 treatments. Primary outcome was BE length reduction. Secondary outcomes included pain post procedure (pain scores), stricture rates and complications. Refractory disease was defined as the presence of BE after at least 3 sequential sessions of first line ablative endotherapy or less than 50% reduction in BE after two sessions.

Results

A total of 11 patients were recruited thusfar. 5 randomised to EndoRotor and 6 to ablation.

In the EndoRotor arm the mean initial BE length was C 1.4 (SD 2.1) and M 3.5 (SD 1.9). Patients had a median number of 5 (IQR, 3-6) previous ablations. Patients had a mean of 2 EndoRotor procedures. The mean BE length post initial treatments is C 1 and M 1.9 thusfar. There were 14 procedures performed. Patients had mild (score =1- 4) discomfort post 3/14 procedures. There were no perforations/strictures during follow-up. There was one adverse event where intraprocedural bleeding was treated successfully with bipolar probes.

In the ablation arm the mean baseline initial BE length was C 0.7 (SD =1.2) and M 3.6 (SD 1.9). They had a median number of 4 (IQR, 3-5) previous ablations. They had a mean of 2 follow-up ablations. The mean current BE length post treatment is C 0.2 and M 3.2. There were 13 procedures performed. There was one report of mild discomfort post procedure.

Table 1.

Outcomes in the EndoRotor and ablation arm

	EndoRotor arm (N = 5)	Ablation arm (N = 6)
Median no. of previous ablations	5 (IQR, 3-6)	4 (IQR, 3-5)
Median number of procedures	2	2
Median follow up time (months)	6 (IQR, 3-6)	5 (IQR, 3-6)
Median procedure treatment time (Mins)	32 (IQR, 16-60)	6 (IQR, 5-9)
Median reduction in BE length (C) (mm)	4	5
Mean reduction in BE length (M) (mm)	16	4

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Conclusion

EndoRotor is safe to use in the treatment of refractory BE with no associated strictures and low pain scores. in this cohort of refractory patient's EndoRotor has slightly better outcomes in terms of BE length reduction. This data will be validated with more patients recruited and completed treatment sessions with histology and final BE lengths.

Disclosure

Laurence B Lovat: Minor shareholder in Odin Vision. Research grants from Medtronic, Pentax Medical, DynamX. Scientific Advisory Boards: Dynamx, Odin Vision, Ninepoint Medical. Rehan Haidry: Received Educational grants to support research from Medtronic Ltd., Cook Endoscopy (fellowship support), Pentax Europe, C2 Therapeutics, Beamline diagnostics.

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.112

P0137 Prospective Evaluation and Screening Guidelines For Barrett's Esophagus

O Alaber ^1,^✉, W Brock ¹, A Chandar ², J Dumot ², A Faulx ², P Thota ³, M Canto ⁴, P Iyer ⁵, J Wang ⁶, NJ Shaheen ⁷, M Anil Kumar ³, H Cosby ⁸, R Lansing ⁵, T Hollander ⁶, Y Ofori-Marfoh ⁷, H Moinova ², J Lutterbaugh ¹, J Barnholtz-Sloan ¹, J Willis ¹, S Markowitz ¹, A Chak ¹

Introduction

Recent guidelines recommending Barrett's Esophagus (BE) screening in selected patients with multiple risk factors have never been prospectively tested. We have initiated a multi-center study to detect BE in subjects who meet new screening guidelines and evaluate a novel non-endoscopic method for BE detection.

Aims & Methods

Patients with > 5 years of GERD over age 50 referred to gastroenterologists at 6 institutions are eligible either if they are white men or if they have three additional risk factors for esophageal adenocarcinoma (male gender, obesity, white race, smoking, family history). Those undergoing EGD are asked to undergo a non-endoscopic diagnostic test using Esocheck (Lucid Diagnostics, PavMed Inc.), a swallowable encapsulated balloon device that samples the distal esophagus. BE and esopha-geal adenocarcinoma (EAC) are detected by assaying DNA extracted from the distal esophagus for methylated VIM and CCNA1.

Results

BE has been detected in 6 (8.7%) of the 69 subjects who were eligible for study. Mean age of subjects is 60.4 years, 47 (68%) are men, and 60 (87%) are white. Thirty seven subjects agreed and had the non-endo-scopic encapsulated balloon test performed. The Esocheck sampling test took less than five minutes, was well tolerated, and could be performed by non-physicians as well as physicians. Preliminary methylated DNA marker assay results available on 20 subjects detected all 3 subjects with BE (100% sensitivity), was positive in 1 individual with intestinal metaplasia of the cardia, and was negative in 15 of 16 normal subjects (94% specificity).

Table 1.

Demographics Characteristics

Age (mean (SD))	60.31(10.35)
Male Gender (n (%))	47 (68.1%)
Female Gender (n (%))	22 (31.9%)
White Race	60 (87%)
African Americans Race	9 (13%)
Smoking History	45 (69%)
BMI	31.25 (6.77%)
Antacid Use	61 (88%)
Family history of BE	4 (6%)
Agreed to had the non-endoscopic encapsulated balloon test	37 (53.6%)

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Conclusion

To date EGD has detected BE in nearly 1 of 11 eligible subjects identified prospectively, confirming the validity of using screening guidelines. The Esocheck encapsulated balloon based distal esophageal sampling device coupled with methylated DNA markers demonstrates the feasibility of unsedated non-endoscopic office-based BE screening. This study is ongoing.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.113

P0138 First In-Human Study On The Safety, Tolerability and Efficacy of The Aquamedical Focal Rf-Vapor Ablation (Rfva) System, For The Eradication of Barrett's Esophagus (Be): The Steam-Be Dosimetry Study

S van Munster ¹, E Verheij ^1,^✉, RE Pouw ¹, BLAM Weusten ², JJ Bergman ³

Introduction

Radiofrequency ablation (RFA) is the preferred modality for ablation of dysplastic BE. Although highly effective, RFA has drawbacks such as multiple deployment steps; the need for direct contact with the esophageal wall; and generally multiple treatment sessions are required. Aqua RFVA System (AquaMedical, Inc.) is a novel ablation system that generates water vapor at 100^oC using an RF electrode to ablate tissue. It is a through-the-endoscope technique that acts without direct contact with the esophageal wall. We studied dosimetry using in-vitro lean-beef and porcine models and tested the feasibility, safety and efficacy in patients with flat dysplastic BE.

Aims & Methods

Aqua system includes an RFVA generator (60W), a 7Fr RFVA catheter and a syringe with saline. The catheter is passed through the biopsy channel of a standard endoscope and works in conjunction with a distal attachment cap to create focal (∼1 cm²) ablations in the esophagus. The Aqua system was tested in 3 successive phases; a lean-beef model; a porcine study (n= 6); and a first in-human study (n=15). in the lean-beef and porcine study, ablation depth at different dosages Vapor (dose = duration in seconds) was compared with focal RFA (1-4x 12J/cm²) at acute (0h) and subacute (48h) setting. Two doses were selected for further human testing in patients with flat dysplastic BE with 4 ablations (2 per dose) per patient. Patients were followed post-ablation for symptoms and adverse events. Follow-up endoscopy with histology was performed after 8 weeks to assess the proprtion of squamous conversion for each treatment area.

Results

None of the treatments in all study-phases resulted in any complications. As expected, in the lean-beef model (total 40 ablations), increasing doses of Vapor and RFA both resulted in deeper ablation. 2-5sec Vapor resulted in a mean depth ranging from 0.8 to 1.5mm, and was comparable to 1-4x 12J/cm² RFA (range 0.6-1.5mm). in the acute porcine evaluation, no differences were found for all doses and treatments tested. Vapor at 3 and 5 seconds (total 42 ablations) and 1-2x 12J/cm² RFA resulted in mean ablation depth of 0.48, 0.53, 0.49 or 0.50mm, respectively. However, as the treatment effect evolved over 48h (total 60 ablations), Vapor at 3 seconds dose (0.56mm) was comparable to 2x 12J/cm² RFA (0.45mm), whereas Vapor at 5 seconds produced slightly deeper ablation (0.72mm). We selected a conservative 1 & 3 seconds dose for the human study. A total of 60 ablations were technically successful applied in 15 patients. No adverse events occurred and the procedure was well-tolerated, with pain scores ranging from 0-2 out of 10 during 14 days post treatment. Follow-up endoscopy showed a median squamous conversion rate of 55% (IQR 13-91) for 1 second and 98% (IQR 61-100) for 3 seconds. All biopsies from endoscopically eradicated areas contained normal squamous epithelium without buried BE glands.

Conclusion

In this 3-phase study with lean-beef, porcine and the first inhuman application, the Aqua RFVA system was safe for focal esophageal ablation and successfully converted dysplastic BE into squamous epithelium. These preliminary yet promising results warrant further testing with RFVA devices.

Disclosure

This study was financially supported by Aqua Medical, Inc.

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.114

P0140 Poor Healing and Poor Squamous Regeneration After Radiofrequency Ablation Therapy For Early Barrett's Neoplasia: Incidence, Risk Factors, and Outcomes

S van Munster ^1,², CN Frederiks ^1,^3,^✉, L Alvarez Herrero ¹, A Bogte ³, A Alkhalaf ⁴, BE Schenk ⁴, EJ Schoon ⁵, WL Curvers ⁵, AD Koch ⁶, SEM van de Ven ⁶, PJ De Jonge ⁶, TJ Tang ⁷, WB Nagengast ⁸, FTM Peters ⁸, J Westerhof ⁸, M Houben ⁹, JJ Bergman ², RE Pouw ², BLAM Weusten ^1,³

Introduction

Although endoscopic eradication therapy (EET) with radio-frequency ablation (RFA) is effective in the majority of patients with Barret's Esophagus (BE), a subgroup of patients is unable to achieve complete eradication of BE. Some might experience delayed healing with visible ulcerations after RFA (“poor healing”; PH) and/or regeneration with BE mucosa (“poor squamous regeneration”; PSR). Little data is available for PH/ PSR and practical recommendations are lacking. We aimed to evaluate the incidence, risk factors, and outcomes of patients with PH/PSR after RFA.

Aims & Methods

We included all patients with at least 1 RFA treatment from a nationwide registry in the Netherlands with all patients who underwent EET for early BE neoplasia. All treatments were performed by specifically trained endoscopists according to a joint treatment and follow-up protocol. PH was defined as visible ulcerations ≥3 months post-RFA; PSR as < 50% regression 3 months after RFA. Treatment success was defined as a complete eradication of BE (CE-BE).

Results

1,386 patients were included with a median BE length of C2M5 containing LGD (27%), HGD (30%), or early cancer (43%) as worst histology. PH occurred in 10% of patients (134/1,386) and additional time +/- acid suppression resulted in complete healing in all patients. Upon complete healing, normal squamous regeneration was seen in 50% (67/134), 97% of which (65/67) achieved CE-BE. Overall, 5% of patients had PSR (74/1,386),

which was preceded by PH in 92% (67/74). 64% (47/74) of PSR patients failed CE-BE. 70% (33/47) of failures were free of neoplasia with 30/33 undergoing endoscopic follow-up. During mean 42 months 23% (7/30) progressed to early neoplasia all of which underwent curative endoscopic treatment. The remaining 30% of failures (14/47) had persisting neoplasia (HGD+). Overall, patients with PSR had a higher risk for progression to advanced cancer that exceeded boundaries for endoscopic treatment as compared to patients without PSR (15% vs. < 1% resp., P< 0.01). Risk factors for PSR include < 50% squamous regeneration after baseline endo-scopic resection (odds ratio (OR) 13.1 [95% confidence interval 6.8-25.9]), presence of reflux esophagitis (OR 7.1 [2.9-16.6]), longer BE segments (OR 1.3 [1.2-1.4]), and higher BMI (OR 1.1 [1.0-1.2]).

Table 1.

Treatment characteristics and outcomes.

		No PH or PSR N=1,245	PH, no PSR N=67	PSR ± PH N=74	P-value
Treatment characteristics	Treatment duration, months, median (IQR)	8(4-13)	15 (10-20)^*	14 (7-23)^*	<0.01
	Circumferential RFA, n, mean (±SD)	0.6 (0.6)	0.8 (0.8)	1.4 (0.7)^*	<0.01
	Focal RFA, n, mean (±SD)	1.6 (1)	1.9 (1)	1.4 (1)	0.3
	Endoscopic resection endoscopies, n, mean (±SD)	0.7 (0.7)	0.8 (0.9)	1.1 (1)^*	<0.01
	Pop-up lesion, n (%)	61 (5)	7 (10)	16 (22)^*	<0.01
	Esophageal stenosis, n (%)	168 (14)	23 (34)^*	19 (26)^*	<0.01
Treatment outcomes^**	CE-BE, n (%)	1178 (98)	65 (97)	27 (37)^*	<0.01
	Treatment failure, n (%)	29 (2)	2 (3)	47 (63)^*	<0.01
	Progression to advanced cancer, n (%)	6 (<1)	0 (0)	11 (15)^*	<0.01

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^*

Is statistically different from no PH/PSR group after Bonferroni correction.

^**

Overall, in 38 patients treatment was prematurely ended due to unrelated, severe new comorbidity (n=21), or unrelated death (n=17).

Conclusion

PH and/or PSR occurs in 10% of patients after RFA. PH may be managed with additional time and acid suppression. Half of the patients will then have normal squamous regeneration with excellent success rates. On the other side, patients with PSR have a high risk for treatment failure and progression to advanced disease during RFA. Therefore, upon detection of PSR, continuation of ablative therapy should be reconsidered and carefully balanced against alternative treatment options. Endoscop-ic surveillance is a valid alternative in remaining BE with no neoplasia, whereas esophagectomy may be considered at early stages if advanced neoplasia is present.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.115

P0141 Global Prevalence of Barrett's Oesophagus and Oesophageal Cancer in Individuals with Gastro-Oesophageal Reflux: A Systematic Review and Meta-Analysis

LH Eusebi ¹, GG Cirota ^1,^✉, RM Zagari ¹, AC Ford ²

Introduction

Chronic gastro-oesophageal reflux might lead to the development of Barrett's oesophagus (BO), or even oesophageal adenocarcinoma. There has been no definitive systematic review and meta-analysis of data to estimate global prevalence of BO or oesophageal adenocarcinoma in individuals with gastro-oesophageal reflux.

Aims & Methods

We searched MEDLINE, EMBASE, and EMBASE Classic to identify cross-sectional surveys that reported prevalence of BO or oesophageal adenocarcinoma in adults with gastro-oesophageal reflux. We extracted prevalence for all studies, both for endoscopically suspected, and histologically confirmed, cases. We calculated pooled prevalence, according to study location, symptom frequency and sex, as well as odds ratios (ORs), with 95% confidence intervals (CIs).

Results

Of the 4,963 citations evaluated, 44 reported prevalence of endoscopically suspected and/or histologically confirmed BO. Prevalence of BO among individuals with gastro-oesophageal reflux varied according to different geographic regions ranging from 3%-14% for histologically confirmed BO, with a pooled prevalence of 7.2% (95% CI 5.4%-9.3%), whereas pooled prevalence for endoscopically suspected BO was 12.0% (95% CI 5.6%-20.4%). Prevalence of BO was significantly higher in men, both for endoscopically suspected (OR = 2.1; 95% CI 1.6-2.8) and histologically confirmed BO(OR = 2.3; 95% CI 1.7-3.2). Dysplasia was present in 13.9% (95% CI = 8.9%-19.8%) of cases of histologically confirmed BO, 80.7% of which was low-grade. Oesophageal adenocarcinoma was present in 1.2% (95% CI 0.3%-2.9%) of BO cases.

Conclusion

The prevalence of Barrett's oesophagus among individuals with gastro-oesophageal reflux varied strikingly among countries, broadly resembling the geographic distribution of gastro-oesophageal reflux itself. Prevalence of BO was significantly higher in men.

Disclosure

Nothing to disclose

References

Eusebi L.H., Ratnakumaran R., Yuan Y., Solaymani-Dodaran M., Bazzoli F., Ford A.C. Global prevalence of, and risk factors for, gastro-oe-sophageal reflux symptoms: a meta-analysis. Gut 2018; 67: 430–40. [DOI] [PubMed] [Google Scholar]
Zagari R.M., Eusebi L.H., Rabitti S., Cristoferi L., Vestito A., Pagano N. et al. Prevalence of upper gastrointestinal endoscopic findings in the community: A systematic review of studies in unselected samples of subjects. Journal of gastroenterology and hepatology 2016; 31: 1527–38. [DOI] [PubMed] [Google Scholar]

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.116

P0143 Barrett's Esophagus with Dysplasia: Impact of The Referral To A Specialized Center

S Saraiva ^1,^✉, D Conceição ¹, J Castela ¹, S Mão Ferro ¹, P Chaves ¹, A Dias Pereira ¹

Introduction

Barrett's esophagus (BE) is a premalignant condition predisposing to esophageal adenocarcinoma (EAC). Esophageal mucosal lesions in this context are often subtle and challenging to identify. Therefore, any degree of dysplasia in BE should be referred to a BE expert center for confirmation by an expert gastrointestinal (GI) pathologist since the majority of patients will be downstaged.

Aims & Methods

To evaluate the overall change in the diagnosis and degree of dysplasia and the number of patients with visible lesions (VL) in BE patients with flat dysplasia, referred to our institution. We also aimed to evaluate the management and clinical course of these patients. A cohort study was conducted in BE patients with flat dysplasia referred to our centre between January 2016 - February 2020. Histopathological review and endoscopic revaluation were performed. If no VL were found, biopsies were taken according to Seattle protocol.

Results

A total of 24 patients were referred (male: 83.3%; age - 66.5±10.6 years). At the referral, median circumferential (C) extent using Prague criteria was 2.9 cm (range: 0-9cm) and median maximum (M) extent was 4.4cm (range: 1-10cm). Dysplasia grade was as follows: indefinite for dysplasia (IND) - 3; Low grade dysplasia (LGD) - 17 (multifocal-2); multifocal LGD + high grade dysplasia (HGD) - 2; multifocal LGD+HGD+EAC - 1. Following histological review, 54.2% (n=13) of cases were downstaged to non-dysplastic BE (NDBE) or IND. in 12.5% (n=3) there was upstage to HGD. in the remaining cases, initial dysplasia grade was confirmed (IND -3, LGD - 3, HGD - 1, EAC - 1).

After endoscopic revaluations at our institution VL were found in 11 patients (45.8%) (median size: 12.7±7.4mm, Paris classification: 0-Is-4; 0IIa-4; 0-IIb-2; 0-Is+0-IIa-1; 0-IIb+0-IIc-1; not specified-4; histology of the biopsies performed: NDBE - 1, IND - 2, LGD - 7, HGD - 3, LGD+HGD - 1, EAC - 2). From those patients in whom no VL were found, only 2 presented IND and the remaining downstaged to NDBE. in these 2 patients, antireflux medication was optimized and endoscopy repeated 6 months later. VL were once again not found and biopsy samples showed again IND. Patients classified as NDBE after revaluation were put under a surveillance program according to the length of the BE.

The group of patients with VL, 10 were treated by Band Ligation Endoscop-ic Mucosal Resection (L-EMR) and 1 is waiting for endoscopic treatment. L-EMR was technically successful in 90.0% (9/10) of the cases (histology of the specimens: NDBE - 1, LGD - 2, HGD - 2, EAC - 5 [pT1a - 4,pT1b - 1]). One patient underwent esophagectomy after non-curative L-EMR (EAC). Eradication of all remaining Barrett's epithelium using radiofrequency was accomplished in 6 patients, and 1 patient is completing the eradication program. in the other 2 patients, only residual islands remained after L-EMR. During endoscopic follow up (median time: 16.6±14.0 months), recurrence of VL (HGD) occurred in one patient, being endoscopically managed.

Conclusion

Histological revision by expert GI pathologist resulted in the downstage to NDBE or IND in more than half of the patients. Moreover, systematic evaluation of BE segment by BE experienced endoscopist increased the detection of early esophageal lesions, further allowing curative endoscopic treatment in the majority of the cases. Our results are in agreement with ESGE recommendations regarding the referral of BE with dysplasia to specialized centers.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.117

P0144 Genetic Variation From Esophageal Squamous Cell Carcinogenesis To Post-Treatment Regenerated Mucosa

N Akizue ^1,^✉, K Okimoto ¹, Y Hirotsu ², T Matsumura ³, T Ishikawa ¹, W Shiratori ¹, A Nagashima ¹, H Oura ¹, T Kaneko ¹, M Tokunaga ¹, Y Ohta ¹, K Saito ¹, M Arai ⁴, K Amemiya ², H Mochizuki ², J Kato ¹, M Omata ^2,⁵, N Kato ¹

Introduction

Recently genetic mutations in esophageal squamous cell carcinoma (SCC) and also in the background mucosa have been gradually clarified reported. However, genetic characteristics post-treatment regenerated mucosa after endoscopic resection is still not fully understood. in this study, we aimed to elucidate genetic variation in the process from esophageal squamous cell carcinogenesis to post-endoscopic treatment scar.

Aims & Methods

Group A:

As a healthy control, esophageal mucosal tissues were collected from five controls without Lugol voiding lesions in esophagus. Group B:

Tissues from both SCC and background mucosa were collected from 14 patients who underwent endoscopic submucosal discussion (ESD) for esophageal SCC. in 7 of these cases, tissue was collected from the post-ESD scar at the time of upper endoscopic surveillance. We extracted DNA from these tissues and performed next-generation sequencing using a system that targets all exon regions of 70 esophageal cancer-related genes to identify somatic mutations. We also checked whether each mutation was oncogenic or not concerning OncoKB.

Results

Group A:

Out of 5 healthy controls, 2 patients have no somatic mutation, and 3 controls have some somatic mutations without oncogenic mutations. NOTCH1 mutation as detected in that 3 controls and the most frequent somatic mutation between healthy controls.

Group B:

TP53 mutation was the most frequent mutation in SCC (13/14, 93%), on the other hand, NOTCH1 mutation was the most frequent mutation in background mucosa (93% in 13 cases). We confirmed At least one somatic mutation in all specimens of SCC and background mucosa. in only 7 cases in which post-endoscopic resection scar tissue could be obtained, 21 mutations in 11 genes were identified in SCC, 34 mutations in 20 genes in scar, and 66 mutations in 23 genes in background mucosa. The allele frequency (%) of mutations was significantly higher in SCC (33[3-81] vs 23[3-63] vs 8[3-78], p=0.002). 7 mutations in 5 cases in SCC, 1 mutation in 1 case in scar, and 4 mutations in 3 cases in background mucosa were oncogenic. in scar, 4 cases had NOTCH1 mutations, the most frequent mutation, and 3 cases had overlapped somatic mutations in the scar and background mucosa. in contrast, no mutation was found in scar in only 1 case.

Conclusion

Unlike the population with a high risk of esophageal SCC, there were some cases with no somatic mutation in the background mucosa of healthy controls. Judging from these results, it was assumed that exposure to risk factors like smoking or alcohol intake would increase the somatic mutation in the background mucosa. Moreover, these accumulated mutations could cause carcinogenesis.

On the other hand, at the healing phase after endoscopic resection, somatic mutations were partially or fully cancelled in some cases during the process leading to scar. However, almost all of regenerated mucosa had any somatic mutations, which were thought to be caused by the regeneration of cells carrying mutations accumulated in the background mucosa. in the case of esophageal SCC, the regenerated mucosa may also reflect the genetic mutations in the background mucosa.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.118

P0145 Is Local Endoscopic Resection A Viable Therapeutic Option For Early Clinical Stage T1A and T1B Oesophageal Adenocarcinoma? A Propensity-Matched Analysis

S Kamarajah ^1,^✉, A Phillips ¹, G Hanna ², D Low ³, S Markar ⁴

Introduction

The role of endoscopic resection (ER) in the management of subsets of clinical T1N0 oesophageal adenocarcinoma is controversial. The aim of this study was to evaluate the outcome of ER versus oesopha-gectomy in node negative cT1a and cT1b oesophageal adenocarcinoma.

Aims & Methods

Data from the National Cancer Database (2010-2015), was used to identify patients with clinical T1aN0 (n=2,545) and T1bN0 (n=1,281) oesophageal adenocarcinoma that received either ER (cT1a, n=1,581; cT1b, n=335) or oesophagectomy (cT1a, n=964; cT1b, n=946). Propensity score matching (PSM) and Cox multivariable analyses were used to account for treatment selection bias.

Results

ER for cT1a and cT1b disease was performed more commonly over time. The rates of node-positive disease in patients with cT1a and cT1b oesophageal adenocarcinoma were 4% and 15%, respectively. in the matched cohort for cT1a cancers, ER had similar survival to oesophagec-tomy (HR: 0.85, 95% CI: 0.70-1.04, p=0.1). The corresponding 5-year survival for ER and oesophagectomy were 70% and 74% (p=0.1), respectively. For cT1b cancers, there was no statistically significant difference in overall survival between the treatment groups (HR: 0.87, 95% CI: 0.66-1.14, p=0.3). The corresponding 5-year survival for ER and oesophagectomy were 53% vs. 61% (p=0.3), respectively.

Conclusion

This study demonstrates ER has comparable long-term outcomes for clinical T1aN0 and T1bN0 oesophageal adenocarcinoma. However, 15% of patients with cT1b oesophageal cancer were found to have positive nodal disease. Future research should seek to identify the subset of T1b cancers at high risk of nodal metastasis and thus would benefit from oesophagectomy with lymphadenectomy.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.119

P0147 Evaluation of The Relationship Between Superficial Esophageal Squamous Cell Carcinoma and Human Papilloma Virus Together with Genetic Polymorphisms of Adh1B and Aldh2

M Inoue ^1,^✉, Y Shimizu ², M Ishikawa ³, S Abiko ⁴, Y Shimoda ¹, I Tanaka ¹, S Kinowaki ¹, M Ono ², K Yamamoto ², S Ono ⁵, N Sakamoto ¹

Introduction

It is well known that an alcohol consumption habit together with inactive heterozygous ALDH2 is an important risk factor for the development of esophageal squamous cell carcinoma (ESCC). However, some patients with ESCC do not drink or only occasionally drink alcohol. The hypothesis that human papilloma virus (HPV) infection can cause ESCC was proposed more than two decades ago; however, it remains controversial whether HPV infection contributes to the occurrence/development of ESCC. There has been no study in which the relationship between ESCC and HPV in addition to ADH1B/ALDH2 genotype was evaluated.

Aims & Methods

The aim of this study was to clarify the carcinogenic risk of HPV infection for superficial ESCC. in this study, we also evaluated ADH1B/ALDH2 genotype and smoking and alcohol consumption histories. We conducted an exploratory retrospective study using new specimens, and we enrolled 145 patients who underwent endoscopic resection for superficial ESCC and had been observed for more than two years by both physical examination and endoscopic examination in Hokkaido University Hospital. We obtained information on smoking and alcohol consumption histories by using a questionnaire. We also obtained information on the occurrence of metachronous multiple esophageal/head and neck cancer after initial treatment. Buccal mucosa was collected from all patients by using a cotton swab before endoscopic examination to analyze genetic polymorphisms of ADH1B/ALDH2. We performed in situ hybridization for resected specimens to detect HPV by using an HPV type 16/18 probe.

Results

HPV was detected in 15 (10.3%) of the 145 patients with ESCC. HPV-positive rates in inactive ALDH2 *1/*2 and ALDH2 + *2/*2 were 10.8% and 9.8%, respectively (p = 0.83). HPV-positive rates in slow-metabolizing ADH1B and ADH1B *1/*2 + *2/*2 were 12.0% and 10.0%, respectively (p = 0.77). HPV-positive rates in the heavy or moderate alcohol consumption group and the light or rare consumption group were 11.1% and 8.7%, respectively (p = 0.65). HPV-positive rates in the heavy smoking group and the light or no smoking group were 11.8% and 8.3%, respectively (p = 0.50). There were no significant differences in HPV-positive rates according to either ADH1B/ALDH2 genotype or smoking and alcohol consumption histories. The 5-year incidence rates of secondary esophageal/ head and neck cancer after initial treatment in the HPV-positive and HPV-negative groups were 14.4% and 35.0%, respectively (p = 0.22).

Conclusion

In conclusion, our study in which genetic polymorphisms of ADH1B/ALDH2 were considered suggested that HPV did not have an association with ESCC. in the present situation, HPV status is considered to be less important than other risk factors, such as alcohol consumption, smoking habit, and ADH1B/ALDH2 polymorphisms, and HPV status would therefore have no effect on ESCC risk management.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.120

P0149 Endoscopic Reassessment of Ct2N0M0 Esophageal Adenocarcinoma Leads To Downstaging To T1 Tumors and Prevents Unnecessary Adjuvant Treatment: A Multicenter Prospective Cohort Study

SEM van de Ven ^1,^✉, MCW Spaander ¹, RE Pouw ², TJ Tang ³, MHMG Houben ⁴, EJ Schoon ⁵, PJF de Jonge ¹, MJ Bruno ¹, AD Koch ¹

Introduction

The clinical tumor stage in esophageal adenocarcinoma (EAC) is usually based on endoscopic ultrasound (EUS) or CT-scan. Unfortunately, the accuracy of EUS and CT differentiating between T1 and T2 EAC is low (43-55%). A substantial number of patients with pT1 stage are overstaged as cT2. As a result, these patients unnecessarily undergo more invasive treatment, such as chemoradiotherapy and surgery.

Aims & Methods

Our aim was to assess the proportion of cT2 EACs down-staged to cT1 after endoscopic reassessment. We performed a prospective multicenter cohort study in five esophageal cancer expert centers in the Netherlands. All consecutive patients with cT2N0M0 EAC diagnosed between April 2018 and April 2020 were asked to participate. Exclusion criteria were presence of esophageal stenosis limiting endoscopic resection. Patients underwent endoscopic reassessment by an experienced inter-ventional endoscopist who was expert in performing endoscopic resection in the esophagus. If endoscopic reassessment suggested a cT1 tumor, the patient was treated with an endoscopic resection. The primary endpoint was the proportion of cT2 EAC patients in which the tumor was downstaged to cT1 after endoscopic reassessment. Secondary endpoints were the proportion of patients who were successfully treated with endoscopic resection after endoscopic reassessment, and the proportion of curative endoscopic resected pT1 EACs based on the accepted criteria (pT1 EAC with invasion depth limited to 500 |im of the submucosa in combination with good or moderate tumor differentiation, and no lymphovascular invasion).

Results

A total of 25 patients were included. The median diameter of the tumor was 30mm (IQR 20-45). Endoscopic reassessment resulted in down-staging from T2 to T1 EAC in 16/25 (64%) patients whom all underwent an attempt at endoscopic resection. Endoscopic resection was not successful in 4/16 patients due to tumor invasion in the muscle layer. Twelve of sixteen (75%) patients underwent a successful endoscopic resection and all were proven by pathological examination to be pT1 tumors. of these 12 patients, 5/12 (42%) resected pT1 tumors were within the accepted criteria for curative endoscopic resection, 2/12 (17%) patients received adjuvant treatment (definitive chemoradiotherapy in one patient and esophagectomy in another patient), and in 5/12 patients a wait-and-see strategy was chosen based on patients preference. in the remaining 9/25 (36%) patients, endoscopic reassessment confirmed a T2 tumor stage based on the presence of invasive features (e.g. depressed lesion, ulceration). Overall, with a strategy of endoscopic (re-) assessment of suspected tumor stage, 12/25 (48%) cT2 EACs turned out to be histologically proven pT1 EACs. Therapeutic management changed for all 12 patients and 10/25 (40%) patients were treated with endoscopic resection only.

Conclusion

In patients with a cT2 EAC according to CT/EUS assessment, endoscopic reassessment by an experienced interventional endoscopist downstages about half of the cases to a T1 tumor suitable for endoscopic resection. This has a substantial clinical impact on therapeutic management with endoscopic reassessment preventing adjuvant treatment in 40% of patients. Based on these results, we recommend endoscopic reassessment by an experienced interventional endoscopist for all cT2N0M0 staged EAC patients.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.121

P0150 Screening Endoscopy Is Useful For Diagnosis of Early Esophageal Cancer in Asymptomatic Males

Y Nezu ^1,^✉, N Manabe ², M Ohtaka ¹, Y Yoda ¹, K Haruma ³

Introduction

Prognosis of esophageal cancer (EC) is poor, because most EC are diagnosed at advanced stage in clinical practice. Recently, gastric cancer mortality has been decreasing in Japan, but EC mortality has been increasing. Therefore, early detection for EC is required in asymptomatic subjects. EC is characterized by adult males, and history of drinking and smoking are riskfactors. in addition, recent studies indicate that atrophic gastritis is also a risk factor for esophageal squamous cell carcinoma (ESCC).

Aims & Methods

We investigated the prevalence of EC in asymptomatic 53,640 subjects over 50 years old who had the screening esophagogas-troduodenoscopy (EGD) at our Health Care Center during Apr 2016 to Mar 2019. in addition, a case-control study was performed on mean corpuscular volume (MCV), body mass index (BMI), smoking status, alcohol consumption, and the presence of atrophic gastritis. The association between EC and controls was assessed by chi-square test.

Results

Among a total of 53,640 subjects, 25 EC patients (24ESCCand one adenocarcinoma, median age; 66.2 ± 7.3) were detected and the prevalence was 0.05%. All EC patients were diagnosed in the early stage. 24of 25EC patients were male and the prevalence of EC in male subjects was 0.09% (24/27454). Investigating the prevalence by agein male subjects, it was 0.06% in the 50s, 0.07% in 60s, 0.15%, in 70s, and 0.1% in 80s. in the annual trend, it was 0.03% in 2016, 0.02% in 2017, and 0.06% in 2018 and the percentage increased in 2018. Fromthe results of a case-control study of 75healthy male subjects of age-matched EC, significant differences were observed on MCV>100 (p=0.0003), in smoking status (p=0.01) and in alcohol consumption (p=0.001),whereas no difference was found in BMI and the presence of atrophic gastritis between the two groups.

Conclusion

Screening endoscopy for EC is useful in asymptomatic males over 50 years, and MCV in peripheral blood and the history of smoking and drinking is effective to select the subjects. Atrophic gastritis was not associated with ESCC. Prevalence of esophageal adenocarcinoma was still low in Japan.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.122

P0151 Accuracy of Esophageal Cancer Grade On Preoperative Biopsies Compared To Post Resection Pathology

R Shah ^1,^✉, O Alaber ², LK Mejia Perez ¹, N Mehta ³, S Jang ³, J Vargo ³, S Robertson ⁴, A Chak ⁵, A Bhatt ³

Introduction

Endoscopic resection (ER) of early esophageal adenocarci-noma (EAC) is recommended for tumors with a low risk of lymph node metastasis (LNM). High risk histopathologic features of LNM, including poor differentiation, lymphovascular invasion, and deep submucosal invasion, are better treated with esophagectomy. Poorly differentiated pathology on pre-operative esophagogastroduodenoscopy (EGD) biopsies may deter endoscopists from performing ER. Determination of tumor grade can be affected by tissue sample size, which is smaller when obtained from EGD biopsies compared to ER or esophagectomy.

Aims & Methods

We aim to identify the accuracy of EAC grade on EGD mucosal biopsy compared to endoscopically or surgically resected tissue. A multicenter, retrospective analysis included patients with EAC on preoperative EGD biopsies that underwent ER or esophagectomy from 2010-2019. Pathology reports, reviewed by expert gastrointestinal pathologists, were used to compare pathologic differentiation between preoperative EGD biopsies and either EMR, ESD, or esophagectomy specimens.

Results

We identified 262 patients with postresection pathology showing EAC (108 ER, 154 esophagectomy) with preoperative biopsies in our system from 2010-2019. The overall accuracy of tumor grade on preoperative biopsies compared to tissue from ER or esophagectomy was 73.8% (93/126) after excluding marked architectural distortion (MAD), unknown differentiation, or high-grade dysplasia (HGD) on preoperative biopsy. Assuming unknown differentiation or MAD on preoperative biopsies were moderate differentiation4, overall accuracy of preoperative biopsies for tumor grade was 66.5% (145/218).

Of 87 patients with preoperative biopsies showing poor differentiation, postresection pathology was congruent in 78.1% (68/87) and down-staged to moderate differentiation in 21.8% (19/87) of patients. Moderately differentiated tumors were up-staged to poor differentiation in 7 of 34 (20.6%) patients. of 44 pre-operative biopsies showing HGD Barrett's and EAC on postresection pathology, 8 (18.2%) were up-staged to poorly differentiated tumors. in those with unknown differentiation on preoperative EGD, 18.1% (3/16) of patients were found to have poorly differentiated cancer. ESD and EMR had an overall congruence of 77.8% and 37.5%, respectively, when excluding biopsies with MAD, unknown differentiation, or HGD. ESD down-staged 1 of 8 (12.5%) patients from poor to moderate differentiation, and up-staged 1 of 9 (11.1%) patients from HGD to poorly differentiation. EMR upstaged 3 of 30 (10%) patients with HGD on preoperative biopsy to poorly differentiated EAC after resection. EMR down-staged 1 of 2 (50%) poorly differentiated tumors to moderate differentiation. The overall congruence of preoperative EGD biopsies and postresection tissue was 42.9% and 68.8% in T1a and T1b tumors, respectively. in T1a tumors, esophagectomy and EMR down-staged 44.4% (4/9) of poorly differentiated tumors to moderate differentiation. Overall accuracy increases to 11/16 (68.8%) in T1b tumors, and esophagectomy and ESD down-staged 2 of 11 (18.2%) patients from poor to moderate differentiation.

Conclusion

In this study, the overall accuracy of preoperative EGD biopsies compared to ER or esophagectomy is only ∼55%. Poorly differentiated tumors were down-staged to moderate differentiation in 21.8% on overall post-resection pathology, 44.4% of T1a tumors, and 18.2% of T1b tumors. Poorly differentiated EAC pathology on pre-operative biopsies should not preclude endoscopic resection, especially in poor surgical candidates, where staging ESD could be considered.

Disclosure

Nothing to disclose

References

1.ASGE Standards of Practice Committee, Evans J.A., Early D.S. et al. The role of endoscopy in the assessment and treatment of esophageal cancer. Gastrointest Endosc. 2013; 77(3): 328–334. doi: 10.1016/j.gie.2012.10.001 [DOI] [PubMed] [Google Scholar]
2.Pimentel-Nunes P., Dinis-Ribeiro M., Ponchon T. et al. Endoscopic submucosal dissection: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2015; 47(9): 829–854. doi: 10.1055/s-0034-1392882 [DOI] [PubMed] [Google Scholar]
3.Rice T.W., Gress D.M., Patil D.T., Hofstetter W.L., Kelsen D.P., Blackstone E.H. Cancer of the esophagus and esophagogastric junction-Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017; 67(4): 304–317. doi: 10.3322/caac.21399 [DOI] [PubMed] [Google Scholar]
4.Dikken J.L., Coit D.G., Klimstra D.S. et al. Prospective impact of tumor grade assessment in biopsies on tumor stage and prognostic grouping in gastroesophageal adenocarcinoma: relevance of the seventh edition American Joint Committee on Cancer Staging Manual revision. Cancer. 2012; 118(2): 349–357. doi: 10.1002/cncr.26301 [DOI] [PubMed] [Google Scholar]

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.123

P0152 Screening For Synchronous Second Primary Esophageal Tumor in Patients with Head and Neck Cancer

SEM van de Ven ^1,^✉, W de Graaf ¹, O Bugter ², MCW Spaander ¹, S Nikkessen ¹, PJF de Jonge ¹, JA Hardillo ², A Sewnaik ², DA Monserez ², I ten Hove ³, H Mast ³, S Keereweer ², MJ Bruno ¹, RJ Baatenburg de Jong ², AD Koch ¹

Introduction

Patients with head and neck squamous cell carcinoma (HNSCC) have an increased risk of developing a second primary tumor (SPT) in the esophagus. A systematic review of multiple screening studies in mostly Asian populations with HNSCC showed a pooled prevalence of esophageal SPT of 15%. However, the incidence of esophageal SPTs in HNSCC patients in the Western population is still unclear.

Aims & Methods

Our aim was to determine the incidence of synchronous esophageal SPTs in patients with HNSCC in a Western country. We performed a prospective screening study in a tertiary hospital in the Netherlands. All patients diagnosed with HNSCC between February 2019 and February 2020 were eligible.

Inclusion criteria were HNSCC in the oropharynx (HPV negative), hypo-pharynx, or in any other head and neck sub-location in combination with alcohol abuse (male >15 units/week, female >7 units/week). Exclusion criteria were history of esophageal squamous cell carcinoma (ESCC) or contraindications for esophagogastroduodenoscopy (EGD). Included patients underwent endoscopic screening using white light, narrow-band imaging and Lugol chromoendoscopy by an experienced interventional endoscopist during work-up for HNSCC, within two weeks after HNSCC diagnosis. SPT was defined as ESCC or high grade dysplasia, according to the Vienna classification of gastrointestinal epithelial neoplasia.

Results

Out of 123 eligible patients, 30 patients were excluded because of the following reasons: the patient declined to participate (n=22), HNSCC treatment was palliative (n=4), the patient was in poor condition (n=3), or general anesthesia was required for EGD (n=1). Ninety-three patients were included, 81% (n=75) was male, median age was 66 years (IQR 59-70), and 77% used alcohol (median of 21 units/week; IQR 16-40). The majority of HNSCC were located in the oropharynx (33%), hypopharynx (30%) or larynx (20%). in 67/93 (72%) patients no SPT was detected. in 26/93 patients (28%) a lesion was found with a low threshold suspicion for SPT. in 14/26 patients (54%) subsequent biopsy (n=11) or endoscopic mucosal resection (EMR) (n=3) did not confirm an SPT. in 2/26 patients, Lugol voiding lesions suspected for SPT were not found at the subsequent EGD, EMR was therefore not performed. Synchronous SPT was highly suspected in 10 patients. SPT was pathologically confirmed in 6/10 patients. in two of these six patients, radiotherapy field was extended to the esophagus, because of the presence of lymphovascular invasion after endoscopic submucosal dissection (ESD) for T1a ESCC in one patient and T2 ESCC in the other. Four patients had high grade dysplasia or mucosal cancer without adverse criteria, treated with EMR (n=1) or ESD (n=3). in 3/10 patients low grade dysplasia was pathologically confirmed, two were treated with EMR and one patient died due to HNSCC before EMR. in the remaining patient biopsy was not performed to avoid submucosal fibrosis, which might make ESD more difficult. in this patient, ESD and histopathological examination will follow after HNSCC treatment. of 26 lesions suspected for SPT, six are confirmed SPT, three are confirmed low grade dysplasia, histopathological examination will follow after ESD of one lesion, and no SPT was detected in 16 lesions.

Conclusion

Incidence of synchronous esophageal SPT was 6.5% in our cohort of Western HNSCC patients. Most SPTs were detected in an endoscopic curable stage. This SPT incidence is lower than the incidence found in Asian studies.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.124

P0153 Long-Term Clinical Outcomes After Non-Curative Endoscopic Resection For Esophageal Squamous Cell Carcinoma

T Kadota ^1,^✉, D Satou ¹, A Inaba ¹, K Nishihara ¹, K Nakajo ¹, H Yukami ², S Mishima ², K Sawada ², D Kotani ², H Fujiwara ³, M Nakamura ⁴, H Hojo ⁴, Y Yoda ¹, T Kojima ², T Fujita ³, T Yano ¹

Introduction

Recently, endoscopic resection (ER) is performed for early esophageal squamous cell carcinoma (ESCC) world widely. The additional surgical resection or chemoradiotherapy (CRT) were recommended for the patients with pathological non-curative resection after ER. However, the long-term clinical outcomes after non-curative resection according to the additional treatments were unknown.

Aims & Methods

The aim of this study was to clarify the long-term clinical outcomes after non-curative endoscopic resection for ESCC according to the additional treatments. We retrospectively enrolled patients who treated with ER for ESCC between January 2009 and December 2017 and diagnosed pathologically as invading into muscularis mucosae (MM) involving lymphovascular invasion (LVI) or invading into submucosa (SM), and negative for vertical margin. The patients who had the previous treatment for ESCC except curative ER, finally diagnosed as pMM or shallower invasion without LVI, and those who had synchronous or metachronous multiple cancers within the previous 5 years except Stage I were excluded. The enrolled patients were recommended the additional surgery and CRT, and the following treatment or observation was selected. Surgical method was thoracoscopic or open esophagectomy with D3 lymphadenectomy, and CRT consisted of CDDP (70 mg/m2/day, days 1 and 29) and FU (700 mg/m2/day, days 1-4 and 29-32, civ) with concurrent radiotherapy (41.4 Gy/23 fr). After the additional treatment, upper gastrointestinal endoscopy and computed tomography of the neck, chest, and abdomen were basically performed for every 6 months to evaluate the recurrence. We evaluated the cumulative recurrence rate (CRR), progression-free survival (PFS), and overall survival (OS), and accessed them according to the additional treatment. Lymph node and/or distant recurrence were included events in CRR. This study was approved by an institutional review board in our institution.

Results

Totally, we evaluated the eligible 93 patients, consisted of 72 male and 21 female with median age of 70 years (range 46-88). Endoscopic mucosal resection and endoscopic submucosal dissection was performed in 9 and 84 patients. As the pathological findings after ER, the numbers of patients having pMM with LVI, pSM1 without LVI, pSM1 with LVI, pSM2 without LVI, and pSM2 with LVI were 15/9/7/34/28. Twenty-five patients were observed without any additional treatment, 18 were performed with surgery, and 50 were treated with CRT as the additional treatment. During the median follow-up of 51 months (range 1-123 months), locore-gional lymph node recurrences occurred without distant recurrence in 4 patients of observation group and 2 of surgery group. No patients in CRT group developed recurrence. The pathological finding after ER in patients with recurrences were pMM with LVI in one patient, pSM2 without LVI in 2, and pSM2 with LVI in 1 of observation group, and pSM1 with LVI in 2 patients of surgery group. The 3-year CRR, PFS, and OS according to the additional treatment were 9.1%, 81.7%, and 85.4% in observation group, 5.6%, 94.4%, and 94.4% in surgery group, and 0.0%, 98.0%, and 98.0% in CRT group. of six patients with recurrences, 3 had recurrences more than 4 years later from ER.

Conclusion

Additional treatments showed the better long-term outcomes than observation for patients with non-curative endoscopic resection. As recurrence sometimes occur more than 4 years later from ER even if additional treatment was performed, careful long-term follow up is needed for non-curative resection.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.125

P0154 Endoscopic Follow-Up of Radically Resected High-Risk Mucosal Adenocarcinoma and Low- and High-Risk Submucosal Adenocarcinoma Arising in Barrett's Esophagus, Results of 120 Patients From The Dutch Barrett Expert Center Cohort

E Nieuwenhuis ^1,^✉, S van Munster ¹, BLAM Weusten ^2,³, A Alkhalaf ⁴, BE Schenk ⁴, EJ Schoon ⁵, WL Curvers ⁵, AD Koch ⁶, SEM van de Ven ⁶, E Verheij ¹, A Kumcu ¹, WB Nagengast ⁷, M Houben ⁸, JJ Bergman ¹, RE Pouw ¹, on behalf of the Dutch Barrett Expert Centers

Introduction

After radical endoscopic resection (ER) of an esophageal adenocarcinoma (EAC) in Barrett's esophagus with high risk features, optimal management is unclear. This concerns three groups: high-risk (HR) mucosal (T1a) EAC (poorly (G3)/undifferentiated (G4) cancer a/o lympho-vascular invasion (LV+)); low-risk (LR) submucosal (T1b) EAC (submucosal invasion < 500um, well/moderate differentiation, LV-); HR-T1b EAC (invasion >500um, G3/4 cancer a/o LV+). Endoscopic follow-up (FU) to detect lymph node metastases (N+) at a curable stage is considered an option in selected cases, however, optimal FU strategy is unclear. Aim was to evaluate outcomes of endoscopic FU in all patients treated by radical ER for HR-T1a EAC or LR/HR-T1b EAC.

Aims & Methods

Endoscopic therapy for Barrett's neoplasia in the Netherlands is centralized in 9 expert centers with specifically trained endoscopists and pathologists. As part of an ongoing registry, treatment and FU data of all patients treated endoscopically for BE neoplasia in the Netherlands, is collected in a dedicated database. We identified all patients who underwent histologically radical ER for HR-T1a EAC or LR/HR-T1b EAC, followed by endoscopic FU. The decision to follow-up was a shared decision by both patients and the treating physician. Endoscopic FU consisted of gastroduodenoscopy (GDS) ± endoscopic ultrasound (EUS), frequency was determined by the treating physician. Outcome parameters were number of patients with N+, distant metastases (M+) and tumor related death.

Results

From Jan 2008 to Oct 2019, 120 patients (median age 74yrs) underwent radical ER of HR-T1a (n=27), LR-T1b (n=55) or HR-T1b EAC (n=38) and endoscopic FU (median 29 months (IQR 15-48) (see table). Nine patients were diagnosed with N+ (n=4; 3%) and N+M+ (n=5; 4%) after median FU of 27 months (IQR 23-38), of which 6/9 had HR-T1a EAC. N+/M+ was diagnosed by EUS-FNA (n=5), or CT performed for symptoms (n=4). The annual N+/M+ risk was 6,7% in HR-T1a, 0,7% in LR-T1b and 2,1% in HR-T1b patients per year; 4/9 patients with N+ disease were additionally treated with curative intent, of which 1 was cured, 1 is still treated, 2 died of complications. Six patients (5%) died from EAC (of which 2/6 from treatment complications). Non-EAC related mortality was 8,3%.

Conclusion

High-risk mucosal EAC with poor differentiation or lympho-vascular invasion was associated with an unexpected high risk of lymph node metastases. The risk for LR-T1b patients was low. in patients diagnosed with N+ during follow-up, treatment with curative intent was still an option in almost half of patients, and tumor related death was lower than non-tumor related death. Thus, in selected patients with high risk and/or T1b EAC, endoscopic follow-up may be justified, yet the optimal FU regimen to detect N+ at a curable stage is yet to be established.

Disclosure

Nothing to disclose

Follow-up summary per risk group

N=120	Follow-up, months Median (IQR)	Number of GDS, Median (IQR)	Number of EUS, Median (IQR)	N+ / M+during FU, N (%)	Annual risk N+/M+ during FU (95% CI)	Time to N+, M+, months Median (IQR)	Tumor related death, N (%)	Background mortality (non-EAC related death), N (%)
HR-T1a (n=27)	31 (21-49)	6 (3-8)	1 (0-4)	6 (22%)	6,7% (3-15)	29 (19-52)	4 (15%)	2 (7%)
LR-T1b (n=55)	30 (16-48)	4 (2-7)	1 (0-3)	1 (2%)	0,7% (0-4)	22 (NA)	1 (2%)	6 (11%)
HR-T1b (n=38)	23 (13-52)	5 (3-8)	5 (2-7)	2 (5%)	2,1% (0-7)	29 (NA)	1 (2,5%)	2 (5%)

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United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.126

P0156 Organ Preservation After Endoscopic Resection of Early Esophageal Cancer with A High Risk of Lymph Node Involvement

S Dermine ^1,^✉, T Levi-Strauss ², E Abou-Ali ², A Belle ³, S Leblanc ⁴, JE Bibault ⁵, A Barré ², L-J Palmieri ², C Brezault ², M Dhooge ², B Terris ², A Dohan ², P Soyer ², A Berger ⁶, G Rahmi ⁷, R Coriat ⁸, S Chaussade ⁹, M Barret ¹

Introduction

Esophagectomy is recommended after endoscopic resection of an early esophageal cancer in case of pejorative histoprognostic criteria indicating a high risk of lymph node involvement. Our aim was to analyze the clinical outcomes of a non-surgical, organ preserving management in this clinical setting.

Aims & Methods

This retrospective study was performed in two tertiary centers from 2015 to 2019. Patients were included if they had a histologically complete resection of an early esophageal cancer, with, poor differentiation, lymphovascular invasion or deep submucosal invasion. The endoscopic resection was followed by chemoradiotherapy or follow-up in case of surgical contraindications or patient refusal. Outcome measures were the disease-free survival (DFS), overall survival (OS), cancer specific survival (CSS), and the toxicity of chemoradiotherapy.

Results

Forty-one patients (36 with squamous cell carcinomas and 5 with adenocarcinomas) were included. Criteria for non-curative resection were: poor differentiation (n=10), lympho-vascular invasion (n=11), muscularis mucosa invasion (for 5 cases of squamous cell carcinoma) or deep sub-mucosal invasion (n=29. Thirteen patients (32%) were closely monitored, and 20 (49%) and 8 (20%) patients were treated by chemo-radiotherapy and radiotherapy alone, respectively. Disease-free survival, overall survival and cancer specific survival were 80.5%, 83% and 98% respectively.

In the close follow-up group, disease-free, overall and cancer specific survival were 92%, 92% and 100%, respectively, with a median follow-up of 12 months. in the chemo-radiotherapy group, disease-free, overall and cancer specific survival were 75%, 79% and 96%, respectively, with a median follow-up of 28 months. There was no significant difference between the 2 groups in disease-free survival rate at 1 and 2 years. Serious adverse events related to chemo-radiotherapy occurred in 10% of the patients. There were no treatment-related deaths.

Conclusion

Our study shows that close follow-up could be an alternative to systematic esophagectomy after the endoscopic resection of an early esophageal cancer with a predicted high risk of lymph node involvement.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.127

P0157 Tolerability of A Non-Endoscopic Distal Esophageal Sampling Device

O Alaber ^1,^✉, A Chandar ², W Brock ², J Dumot ², A Faulx ², P Thota ³, M Canto ⁴, P Iyer ⁵, J Wang ⁶, NJ Shaheen ⁷, M Anil Kumar ³, H Cosby ⁸, R Lansing ⁹, T Hollander ⁶, Y Ofori-Marfoh ¹⁰, A Watts ¹⁰, R Gawel ¹, H Moinova ², J Lutterbaugh ¹, J Barnholtz-Sloan ¹, J Willis ¹, S Markowitz ¹, A Chak ²

Introduction

Esocheck (Lucid Diagnostics) is an office based, non-endoscopic balloon device for detecting Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). A two-institution pilot study (PMID: 29343623) demonstrated that a two-marker methylated DNA biomarker panel coupled with the device detected BE/EAC with >90% accuracy. A new improved version (Esocheck) is being tested at 8 tertiary care centers, with procedures performed mostly by non-physicians.

Aims & Methods

To assess the tolerability, swallowability, and safety of Esocheck in this multi-institutional research study. Research teams (RN Research coordinators and MDs) were trained through watching a video and performing between 2 and 5 supervised procedures prior to performing the Esocheck test independently. Patient differences between those who successfully swallowed the device and those who were unable to were calculated using t-tests and chi-square tests. Logistic regression was performed to determine which factors played a significant role in successful swallowing.

Results

Between March 2018 and November 2019, a total of 406 patients were approached. of these, ∼84% swallowed the device successfully. The mean age of those who succeeded was significantly higher than those unable to swallow the device (60 vs 55 years, p - value 0.007). Patients who could not swallow were significantly more anxious than those who could. The majority were males, white, and were either overweight or obese (Table 1). The majority who successfully swallowed the sampling device did so the first time and required no local anesthetic spray. The type of provider, (MD or RN) did not affect swallowing. Success in performing the procedure ranged from 68% to 96% among the 9 providers who performed more than 10 procedures. The two providers who had performed more than 100 procedures had a success rate of over 90%.The procedure was well tolerated, 68% preferred it to EGD, and 80% agreed to repeat testing. Gagging and choking scores were significantly lower in the success group (Table 1). Patients who swallowed the device took an average of 2.64 minutes (SD = 1.46 minutes) to get it to the GE junction. in multinomial logistic regression, no one particular factor significantly influenced swallow success. No major adverse events were noted; Grade 1 abrasion was seen in only 1 patient at EGD (< 1%).

Conclusion

Distal esophageal sampling with Esocheck is well tolerated and preferred over EGD by most patients. Younger anxious adults and those with higher gag have greater difficulty in swallowing the device. Providers who performed more than 100 procedures had higher success suggesting performance improves with experience. Esocheck can be quickly and safely performed by trained allied health professionals in an office-based setting.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.128

P0158 Nonphysician Experience with Novel Barrett's Screening Device - Descriptive Study

Y-H Kang ¹, O Alaber ^1,^✉, A Chandar ¹, W Brock ², H Cosby ³, R Lansing ⁴, T Hollander ⁵, H Anthony ⁵, M Anil Kumar ⁶, Y Ofori-Marfoh ⁷, L Moussa ⁷, N Furey ², R Gawel ², A Chak ²

Introduction

Mass endoscopic screening for Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) with EGD is cost-prohibitive and not evidence based. Esocheck is a simple, novel, non-invasive, low-cost, non-endoscopic office-based screening device that can be easily performed by physicians and non-physicians alike and is currently being tested at 8 tertiary care centers across the United States.

Aims & Methods

To describe the experiences of non-physicians (Research Nurse [RN], Research Coordinator [RC]) who are performing the Esocheck procedure in this multi-institution collaborative study. Non-physician coordinators at participating centers were trained over 1-2 days by experienced personnel from the central coordinating site prior to study initiation. An internally tested, novel, 7-part, 50 item survey was created at the main coordinating center and distributed to the recruitment centers after coordinators had gained ∼12 -15 months of experience with the procedure.

Results

Nine non-physician coordinators (2 RNs, 6 RCs and 1 project manager) returned the completed survey. Non-physician coordinators had performed a median of 20 procedures (range, 7-100 procedures). The median years of practice as RN/RC was 10 years (range, 1-20 years). Three out of 9 survey respondents had prior experience administering a swallowed encapsulated sponge screening device. All 9 found in-person training helpful for both patient recruitment and to perform the Esocheck procedure, while 8 found the training video helpful. Coordinators practiced a median of 3 procedures (range, 2-5 procedures) before they started performing Esocheck independently (Table 1), though they said that they felt comfortable doing the procedure on their own after a median of 5 procedures (range, 3-10 procedures).Five out of 9 showed the Esocheck swallowing video to their patients before the procedure. Encouraging deep breaths, explaining the procedure thoroughly, reassurance, and providing encouragement were crucial strategies per RN/RCs to increase procedure success. Performance of procedure in physician office was felt to be easier than doing it in endoscopy suite just prior to EGD.Coordinators used a local anesthetic spray (in the form of a spray or gargle) to decrease gag and enable swallowing. Most RN/RCs said they offered the pharyngeal anesthetic to patients on the 2nd try, whereas one coordinator said they would offer it to their patients only on the 3rd try. Coordinator perceptions of patient factors affecting Esocheck swallowing ability are described in Table 2.

Study Tables

Table 1: Survey responses by non-physician coordinators on their training, preparedness, and level of comfort in performing the Esocheck procedure	Median (Range)	Table 2: Non-physician coordinator perceptions of patient factors possibly affecting Esocheck swallowing ability	Median (Range)
Level of preparedness after training to recruit patients	4 (3-5)	Perceived level of anxiety experienced prior and during the procedure	5 (2-7)
Value of Esocheck training video	4 (2-5)	Perceived level of pain experience during the procedure	1(1-4)
Usefulness of practicing in front of a trainer	5 (3-5)	Perceived level of gagging experienced during the procedure	6 (4-8)
Number of times practiced before performing Esocheck independently	3 (2-5)	Perceived level of choking experienced during the procedure	2 (1-7)
Comfort level at the time of first independently performed Esocheck procedure	3 (2-5)	Perceived overall tolerability of Esocheck procedure	5 (3-7)
Comfort level with independently performing Esocheck at the time of returning survey	5 (4-5)
Overall preparedness after training to independently perform Esocheck procedure	4 (3-5)
Number of procedures before coordinator became comfortable performing Esocheck	5 (4-10)
Reported on a 5-point likert scale, with higher scores being better		Reported on a 10-point likert scale, with higher scores indicating worse tolerability

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Conclusion

Non-physicians can be easily trained to perform distal esophageal sampling with the Esocheck device. Non-physicians quickly become comfortable in the procedure and prefer to perform it in an office-based setting often with the aid of a pharyngeal anesthetic.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.129

P0160 Minimally Invasive Esophagectomies Are More Beneficial in The Treatment of Esophageal Cancer Than Open Surgical Techniques: A Network Meta-Analysis

L Szakó ^1,^✉, D Németh ¹, N Farkas ¹, S Kiss ^1,², ZR Dömötör ^1,³, M Engh ¹, P Hegyi ¹, A Papp ⁴, B Eross ¹

Introduction

Minimally invasive surgical techniques are becoming predominant in all fields of surgery, including oesophageal surgery. Several meta-analyses tried to compare minimally invasive modalities with open techniques, including all types of comparative studies with significant limitations.

Aims & Methods

Our goal is to compare all surgical modalities to each other from results of randomized controlled trials, thus providing objective evidence and a ranking of the different techniques regarding survival, complication rate, operation time, hospital stay, and blood loss. We conducted a systematic search of the PubMed, Embase, and Cochrane databases to identify relevant studies and performed a network meta-analysis (NMA). We used the random effect model. To ensure the interpretability of the NMA results, we will present the geometry of the network, the results with probabilistic statements, and estimates of interventions’ effects along with their corresponding 95 % credible interval (CI), as well as forest plots. For ranking the interventions, we chose to use the surface under the cumulative ranking (SUCRA) curve, which provides a numerical summary of the rank distribution of each treatment.

Results

We included 12 studies in our analysis. A significant difference was found considering pulmonary infection, which favored the laparo-scopic intervention compared to transthoracic surgery (risk ratio 0.49, 95% credible interval 0.23 to 0.99). Operation time was significantly shorter for transhiatal approach compared to transthoracic surgery (mean difference -85 minutes, 95% credible interval -150 to -29), hybrid intervention (mean difference -98 minutes, 95% credible interval -190 to -9.4), laparoscopic technique (mean difference -130 minutes, 95% credible interval -210 to -50), and robot-assisted esophagectomy (mean difference -150 minutes, 95% credible interval -240 to -53). Other comparisons did not yield significant differences.

Conclusion

While individual studies suggest the superiority of the minimally invasive techniques regarding multiple outcomes, the summarized evidence is only conclusive considering the complication rate and operation time. Although the tendency suggests that minimally invasive techniques have better results, more randomized controlled trials are needed to achieve statistical significance and more definite evidence.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.130

P0161 Long-Term Follow-Up After Non-Curative Superficial Scc Endoscopic Resection with Adjuvant Treatment: A Multicenter Western Study

A Berger ^1,^✉, G Perrod ², M Pioche ³, M Barret ⁴, E Cesbron Metivier ⁵, V Lepilliez ⁶, E Perez-Cuadrado-Robles ², F Cholet ⁷, A Daubigny ⁸, C Texier ⁵, E Chabrun ⁹, E Abou Ali ¹⁰, J Jacques ¹¹, T Wallenhorst ¹², J-B Chevaux ¹³, M Schaefer ¹⁴, C Cellier ², G Rahmi ²

Introduction

In case of non-curative endoscopic resection of superficial esophageal squamous cell carcinoma (SCC), adjuvant treatment by chemoradiotherapy (CRT) can be an alternative to surgery.

Aims & Methods

The aim of this study was to assess long-term clinical and oncological outcomes in patients treated with adjuvant CRT or not, after non-curative superficial SCC endoscopic resection. We conducted a retrospective multicenter study in eleven French tertiary care hospitals. Patients treated by endoscopic resection for histologically proven SCC with tumor depth infiltration deeper than the muscularis mucosae were included consecutively. High risk of nodal or/and distal metastasis was defined by tumors with infiltration depth in Sm >200 μm, or positive lym-phovascular invasion, or mild and poor differentiation.

Results

137 endoscopic resections in 132 patients were analyzed. The nodal or distal metastasis recurrence -free survival rate at 5 years was 88%. The death-free survival rate at 5 years was 60.3% for all causes, and 86% due to esophageal cancer. Risk of metastasis strongly increased in patients without adjuvant treatment (P = 0.01). Independent factors for nodal or/and distal metastasis cancer recurrence were age (HR= 1.075(95% CI: 1.007-1.149, P = 0.031), tumor infiltration depth in Sm >200 um, HR = 4.129 (95% CI: 1.067-15.977, P = 0.040), and no adjuvant treatment by CRT or surgery HR = 11.322 (95% CI: 1.281-100.033, P = 0.029). High risk of nodal involvement or metastasis was found in 83 tumors (60.6%), and adjuvant therapy reduced the risk of recurrence (p=0.008). The nodal and distal metastasis recurrence-free survival rate at 5 years was 100% after adjuvant surgery and 97.1% for CRT (P = 0.542).

Conclusion

Combination therapy with endoscopic resection followed by adjuvant CRT reduce the risk of nodal recurrence. This strategy should be considered as an alternative to surgery for patients with severe comorbidities treated endoscopically for superficial SCC with a high risk of lymph node invasion.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.131

P0162 A Novel Approach To Radiotherapy Targeting For Oesophageal Squamous Cell Cancer Using Lugol's Iodine Guided Endoclip Marking

HN Haboubi ^1,^✉, S Lim ¹, S Zeki ¹, J Gossage ², A Qureshi ³, J Dunn ¹

Introduction

Squamous cell carcinoma (SCC) of the oesophagus often presents at a late stage with dysphagia symptoms. Chemoradiation (definitive or neoadjuvant treatment) remains the standard strategy for the treatment of localised SCC. Accurate radiotherapy target delineation is however problematic for very early tumours that cannot be visualised on cross-sectional imaging. We describe a novel technique of endoscopic clip placement to mark the area for targeted radiotherapy, in conjunction with Lugol's iodine chromoendoscopy to delineate the dysplastic field.

Aims & Methods

We aimed to evaluate outcomes in patients receiving Lu-gols iodine chromoendoscopy guided clip deployment to mark radiotherapy field in a tertiary centre. A prospective study of procedures performed using the technique between 2017 and 2020 was undertaken. Unstained lesions (USL) were described and photographed, The proximal and distal extent of USLs were marked with ResolutionTM endoclips (Boston Scientific) which were placed on normal appearing squamous tissue 0.5cm away from the USL. Four operators carried out the procedures with expertise in Endoscopic Eradication therapy and lesion recognition. Endoscopy reports, clinic letters, and imaging modalities were all interrogated to evaluate patient outcomes.

Results

Fifteen patients were enrolled, 4 male, 11 female. Thirteen (86.7%) were for a new diagnosis of SCC, and 2 (13.3%) were for SCC recurrence. All patients were staged as T2N0M0 on CT. Eight patients had prior EUS and 13 had PET-CT scans, but these imaging modalities could only detect the area of abnormality in 3 (20%), and 4 (26.7%) of cases respectively. Lugols Chromoendoscopy was able to clearly delineate the dysplasia in all cases (100%). The mean total length of oesophageal USL marked with clips was 7.3 cm +/- 3.8. The mean length of endoscopic procedure was 9.2 minutes +/- 2.4. All procedures were undertaken with conscious sedation with a median dose of 2.5mg midazolam (2.5-3.0) and 50mcg fentanyl (0-75mcg). All 15 patients scored comfortable on a GRS scale. Mean time from clip deployment to CT radiotherapy planning scan was 7.8 days (+/-5.1). No clips fell off prematurely requiring repeat endoscopy. Median dose of radiotherapy delivered was 50Gy. At 12-months, of those followed up 26.7% had evidence of relapse free survival.

Conclusion

Here we describe a novel technique using Lugols guided clip placement prior to radiotherapy, demonstrating it to be a quick and uncomplicated procedure which can be used in the management of patients with SCC.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.132

P0163 Endoscopic Submucosal Dissection (Esd) of Squamous Neoplasia of The Oesophagus in The West - A Multicentre European Study

S Arndtz ^1,^✉, R Maselli ², S Subramaniam ¹, AA Alkandari ¹, E Hossain ¹, M Abdelrahim ¹, PA Galtieri ², N Pilonis ³, MF Kaminski ³, S Seewald ⁴, A Repici ², P Bhandari ¹

Introduction

The management of squamous cell neoplasia of the oesophagus has been revolutionised by the adoption of endoscopic submu-cosal dissection (ESD). The Japanese Oesophageal Society cancer practice guidelines currently recommend that radical endoscopic treatment can be considered for intra-mucosal lesions confined to the epithelium or lamina propria (pT1a M1 or M2). The reported risk of lymph node metastasis in neoplasia with invasion deeper then M2 is considered unacceptably high and non-curative, however the risk of radical surgery or chemoradiotherapy is not insignificant, especially in an ageing Western population. It is also noteworthy that ESD of squamous oesophageal neoplasia is not as common in the West as it is in the East, as it is considered as a very high risk procedure.

Aims & Methods

Our aim was to evaluate the outcome of ESD for squamous neoplasia of the oesophagus in the hands of Western endoscopists. We performed a retrospective analysis of all oesophageal squamous ESDs performed across 4 tertiary referral centres in Europe (UK, Switzerland, Poland, Italy) between 2011-2020. The primary outcome was sole endo-scopic management at 1 year post resection.

Results

89 squamous ESDs were performed in 81 patients. The mean age was 67 years with 60% being male. Average lesion size was 37mm (range 10-110mm) and commonest location was mid-oesophagus. The en-bloc resection rate was 98%. There were 2 perforations (1 surgery, 1 stent), 1 delayed bleed (managed with blood transfusion) and 25 post -procedural strictures (all managed with dilatation or stent). The R0 resection rate was 95% in lesions ≤M2 and 82% in lesions >M2 (p< 0.001). 1 year follow up data was available on 64 patients (see Table 1). 32/34 (94.1%) of patients meeting curative resection criteria achieved endo-scopic only management at 1 year. This dropped down to 23/30 (76.7%) in those with non-curative resection. Recurrence or metachronous lesions were found in 6 of the curative group and 2 of the non-curative group (all treated endoscopically). 1 patient in the non-curative group developed lymph node metastasis.

Table 1.

Patient status at 1 year post resection in curative (≤M2) vs noncurative resection group (>M2)

Group n = 64	Surgery (n, %)	Chemoradiotherapy (n, %)	Died (n, %)	Recurrence or metachronous lesion (n, %)	Dysplasia free endoscopic follow up (n, %)
≤M2 (n=34)	1 (2.9)	0 (0)	1 (2.9)	6 (17.6)	26 (76.5)
>M2 (n=30)	3 (10.0)	4 (13.3)	0 (0)	3 (10.0)	20 (66.7)

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Conclusion

Our data demonstrates that although the overall numbers of ESD for squamous neoplasia carried out in a Western setting are limited, the complication rates are low and most are managed endoscopically. Almost half of the patients had advanced disease, but this did not increase the complication rates. The overall outcome in those with non curative resection was technically not much different, raising a possibility to consider ESD as a radical treatment for those who are otherwise not fit for surgery or chemoradiotherapy.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.133

P0164 Bisphosphonate Treatment of Osteoporosis Does Not Increase The Risk of Severe Gastrointestinal Side Effects: A Meta-Analysis of Randomized Controlled Trials

ZR Dömötör ^1,^2,^✉, N Vörhendi ¹, L Hanák ¹, P Hegyi ¹, S Kiss ^1,³, L Szakó ¹, E Csiki ¹, A Parniczky ¹, B Eröss ¹

Introduction

Bisphosphonates (BPs) are first-line therapy for severe osteoporosis. BPs-related gastrointestinal (GI) adverse events are primarily responsible for low adherence. Bisphosphonates appear to be effective, however this topic remained conflicting because of the inconsistent results from the studies available so far.

Aims & Methods

Our meta-analysis aims to objectify the risk of severe GI adverse events due to BP therapy in osteoporotic patients. A systematic search was conducted in three databases up to July 2019 for randomized controlled trials (RCTs) detailing gastrointestinal adverse events in adult patients with osteoporosis on the BP and placebo arms. Risk ratios (RRs) 95% with confidence intervals (CI) were calculated for non-severe and severe adverse events with the random-effects model. Statistical heterogeneity was assessed using chi² and I² statistics.

Results

Forty-two RCTs with 39,335 patients with 9,999 non-severe and 1,503 severe GI adverse events were included. The incidence of non-severe and severe adverse events ranged between 0.3-54.9% and 0-10.3%, respectively. There was no difference between BP and control groups in terms of the risk of non-severe or severe side effects: RR=1.05 (CI: 0.98 -1.12), I²=48.1%, and RR=1.01 (CI: 0.92 - 1.12), I²=0.0%, respectively. Subgroup analysis of the most commonly used BP, once-weekly alendronate 70 mg, revealed no association between bisphosphonates and the risk of non-severe and severe GI adverse events [RR=1.16 (CI: 1.00 - 1.36),I²=40.7% and RR=1.20 (CI: 0.83 - 1.74),I²=0.0%].

Conclusion

Our results show that bisphosphonates do not increase the risk of severe GI adverse events, requiring specialist care or endoscopy. However, the marked variability of the screening for side effects in included studies limits the strength of evidence of our result.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.134

P0165 Novel Metal-Free Carbon Monoxide-Releasing Prodrug in Prevention of Gastric Mucosa Against Nsaids-Induced Gastrotoxicity

D Bakalarz ^1,², M Surmiak ^1,³, X Yang ⁴, D Wójcik ¹, E Korbut ¹, Z Sliwowski ¹, G Ginter ¹, G Buszewicz ⁵, T Brzozowski ¹, J Cieszkowski ¹, U Glowacka ¹, K Magierowska ¹, Z Pan ⁴, B Wang ¹, M Magierowski ^1,^✉

Introduction

Carbon monoxide (CO) is produced endogenously in GI tract by the activity of heme oxygenase (HMOX). Additionally, CO-releasing pharmacological tools have been shown in experimental studies to exert anti-inflammatory and anti-oxidative properties maintaining gastric mucosal integrity. But the clinical implementation of these compounds is debatable due to the presence of metals in their chemical structure. We aimed to assess the effectiveness of our novel metal-free CO-based therapeutic, BW-CO-111 administered i.g. against the development of aspirin-induced GI damage.

Aims & Methods

Wistar rats were pretreated with vehicle or BW-CO-111 (0.02-5 mg/kg i.g.) or BW-CP-111, the product after CO release from BW-CO-111. After 30 min, gastrotoxicity was induced by administration of aspirin (125 mg/kg i.g.). Gastric damage area and gastric blood flow (GBF) was determined by planimetry, histology and laser flowmetry, respectively. Gastric mucosal mRNA and/or protein expressions of HMOX-1, HMOX-2, Nrf-2, COX-1, COX-2, iNOS, annexin-A1 and TGF-β1 as well as serum contents of TGF-β1, TGF-β2, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10. IL-12, TNF-a, IFN-y, and GM-CSF were determined by real-time PCR, Western blot or Luminex platform, respectively. CO content in gastric mucosa was assessed by gas chromatography. Gastric mucosal PGE₂ content was determined by ELISA.

Results

Pretreatment with BW-CO-111 (0.1 mg/kg i.g.) increased gastric mucosal content of CO and reduced gastric damage area accompanied by an increased GBF. CO-prodrug decreased and upregulated gastric mucosal mRNA expression for pro-inflammatory iNOS and anti-inflammatory an-nexin-A1, respectively. BW-CO-111 maintained increased by aspirin serum content of anti-inflammatory TGF-b1 and -b1 but did not affect systemic inflammatory response and PGE₂ content alterations in gastric mucosa induced by aspirin. BW-CP-111 did not affect gastric mucosal integrity and molecular pathways expression.

Conclusion

We conclude that BW-CO-111 applied i.g. protected gastric mucosa against aspirin-induced damage due to its ability to release CO, responsible for the gastric microcirculation increase and due to the activation of molecular anti-inflammatory response within gastric mucosa. This novel metal-free CO-prodrug seems to be promising compound for the further development of safer clinical GI pharmacology.

Disclosure

[This study has been partly supported by National Science Centre in Poland (grant no: UMO-2019/33/B/NZ4/00616)]

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.135

P0166 Protective Effect of Ppi Against Gastric Mucosal Injuries in Patients Taking Each Doacs - Comparison Among Individual Doacs

Y Shimada ^1,^✉, Y Kita ¹, Y Ikeda ¹, D Kabemura ¹, S Sato ¹, N Amano ¹, N Yatagai ¹, A Murata ¹, H Tsuzura ¹, S Sato ¹, A Nagahara ², T Genda ¹

Introduction

It has been known that bioavailability and activation rate of drugs in the gastrointestinal tract are very different among individual direct oral anticoagulants (DOACs) Therefore, as in the case of the upper gastrointestinal (GI) bleeding risk, the prevalence of gastric mucosal injury is considered to be different among individual DOACs ⁽²⁾. Since GI bleeding risk can be reduced by concomitant use of proton pump inhibitor (PPI) ⁽³⁾, we recently reported that concomitant use of PPI reduces the prevalence of gastric mucosal injury in DOACs users ⁽⁴⁾. As in previous studies, it is not difficult to image that the effect of PPI to the gastric mucosal injury can be different among individual DOACs.

Aims & Methods

The aim of this study is to explore whether PPI play a protective roll for gastric mucosa in patients taking each DOACs (Dabiga-tran, Edoxaban, Rivaroxaban, Apixaban) or VKA (Warfarin). To reveal the roll of PPI, we compared the severity of gastric mucosal injury between PPI users and no antacid users in the subjects taking each DOACs or VKA, individually. Data were extracted from the records of subjects who underwent upper gastrointestinal endoscopy at our department between April 2015 and June 2019. of the 5,293 subjects analyzed, we focused on 270 subjects who took DOACs or VKA. After excluding subjects who took other type of antacid (histamine 2 receptor blockers or potassium competitive acid blockers), we divided subjects into two subgroups: anticoagulant use with PPI (PPI group), or anticoagulant use without any antacids (no antacid group). Severity of gastric mucosal injury was evaluated endoscopically according to the modified LANZA score (MLS). Statistical analyses were performed by Fisher's exact test.

Results

This study included 101 subjects in PPI group (Dabigatran 12, Edoxaban 18, Rivaroxaban 19, Apixaban 18, Warfarin 34) and 143 subjects in no antacid group (D 20, E 17, R 26, A 21, W 59). in PPI group, average MLS were D: 0.50±1.10, E: 0.41±1.06, R: 0.46±0.95, A: 0.43±0.96 and W: 0.56±1.29, respectively. in no antacid group, average MLS were D: 1.42±1.68, E: 1.06±1.76, R: 0.84±1.42, A: 1.33±1.53 and W: 1.71±2.10, respectively. There was no significant difference of MLS among individual DOACs and VKA in both groups. in the subjects taking Apixaban and warfarin, MLS was significantly lower in PPI group than in no antacid group. However, in the subjects taking Dabigatran, Edoxaban and Rivaroxaban, MLS was tended to be lower in PPI group than in no antacid group but the difference was not significant.

Conclusion

PPI play a protective role in gastric mucosa in patients taking each DOACs, especially in the case of taking Apixaban.

Disclosure

Nothing to disclose

References

1.Vanassche T. et al. Organ-specific bleeding patterns of anticoagulant therapy: lessons from clinical trials. Thromb Haemost. 112(5): 918–23. 2014 [DOI] [PubMed] [Google Scholar]
2. Shimada Y.. et al. Upper gastrointestinal Mucosal Injury in Japanese NOACs Users. UEGW. 2015 [Google Scholar]
3.Ray W.A. et al. Association of Oral Anticoagulants and Proton Pump Inhibitor Cotherapy with Hospitalization for Upper Gastrointestinal Tract Bleeding. JAMA 320(21): 2221–30. 2018 [DOI] [PMC free article] [PubMed] [Google Scholar]
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United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.136

P0168 Predictive Significance of Endosonographic (Eus) Staging in Locally Advanced Gastric (Gc) Or Gastroesophageal-Junction (Aeg) Adenocarcinoma: Analysis of Data From A Perioperative Aio-Cao Phase Ii Study

S Visvakanth ¹, M Stahl ², T Thomaidis ¹, C Utz ³, A Maderer ³, F Lordick ⁴, A Mihaljevic ⁵, T Höhler ⁶, S Kanzler ⁷, P Thuss-Patience ⁸, S Mönig ⁹, S Schroll ¹⁰, V Kunzmann ¹¹, A Tannapfel ¹², H Wilke ², M Moehler ^13,^✉, Arbeitsgemeinschaft Internistische Onkologie (AIO) und Chirurgische Arbeitsgemeinschaft Onkologie

Introduction

This AIO-CAO Phase II Study investigated the additional administration of Panitumumab to a basic ECX therapy (Epirubicin, Cisplatin and Capecitabine) in GC or AEG. This evaluation correlated the preoperative EUS, after neoadjuvant chemotherapy, with the therapy response in addition to the initial examination (baseline EUS).

Aims & Methods

160 patients from 22 german centers were included. Preoperative uT/uN stages were compared with histopathological pT/pN stages. Each reduction in the T-stage from preoperative EUS to baseline EUS was evaluated as downstaging (DS+) and compared with histopathologi-cal regression (grade 1-2 according to Becker) as well as overall survival (OS) of the patient without downstaging (DS-). The preoperative N-stage (positive N+ or negative N-) was correlated with OS too.

Results

In 48% the preoperative EUS T-stage correlated with the pT-stage (sensitivity 48%, specificity 52%) and in 64% the preoperative EUS-N stage correlated with the pN-stage (sensitivity 76%, specific 52%). with DS+, a tendency towards improved OS was detectable (median OS DS+: median OS not reached during observation time (NA), median OS DS-: 38.5 months (M), p=0.18). The OS of the N+ patient (median OS 36.1 M, p = 0.0045) was worse in comparison to the N- patient (median OS NA).

Conclusion

Despite multicenter participation and different EUS devices, this large prospective study showed a restricted diagnostic accuracy (DA) of preoperative EUS, especially in comparison to DA of initial EUS described in prior studies. The preoperative positive EUS-N status is predictive for a worse prognosis.

Therefore, an alternative procedure should be discussed and evaluated in further studies to improve the OS of the subgroup of these patients.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.137

P0171 Platelet Aggregation Test in Patients Who Received Gastric Esd Under Continuous Antiplatelet Agents

S Hirata ^1,^✉, R Takenaka ¹, D Kawai ¹, D Kagawa ¹, T Yamamoto ¹, M Ishida ¹, K Miyamoto ¹, Y Okamoto ¹, K Kumahara ¹, M Takahara ¹, K Hori ¹, H Tsugeno ¹, S Fujiki ¹

Introduction

Bleeding after endoscopic submucosal dissection (ESD) is the most frequent adverse event. Several reports showed that taking antiplatelet agents increase the risk of post-ESD bleeding, especially in the cases of taking thienopyridine or dual antiplatelet therapy. Recently, platelet aggregation test is performed for the assessment of secondary prevention of ischemic heart disease and cerebrovascular disorders, but there is no report on this test for evaluating the risk of post-ESD bleeding taking antiplatelet agents. Therefore, we performed platelet aggregation test in patients who received gastric ESD under continuous antiplatelet agents in our hospital to reveal the relationship between patient characteristics and the levels of platelet aggregometry.

Aims & Methods

Between April 2013 and March 2019, a total of 75 cases were performed gastric ESD and assessed by the aggregometer (PRP313 M, TAIYO Inc.) before procedures under continuous antiplatelet agents such as thienopyridine, aspirin, or cilostazol. Five patients taking anticoagulant agent or only other antiplatelet agent were excluded from this study. Finally, 70 cases were enrolled in this study. Platelet aggregation level was compared according to the grading types (G-type) classified by aggregometer. We retrospectively evaluated the relationship between the platelet aggregation level and the patient characteristics such as age, sex, drugs, comorbidities, the duration and curative rate of the procedure, and the incidence of complications.

Results

The study subjects were 47 men and 23 women at a median age of 79 years (range, 64 - 90 years). Patients taking thienopyridine, aspirin, or cilostazol were 17 cases, 36 cases, 20 cases, respectively, and patients taking dual antiplatelet therapy were 10 cases. En-bloc resection was achieved in all cases with median procedure duration of 70.5 min (25-195 min), and curative resection was achieved in 67 cases. There was no perforation case in this study, but post-ESD bleeding occurred in 8 cases. Median G-type was -1 for the taking thienopyridine group and 0 for the taking no thienopyridine group, and there was a significant difference in the two groups (p= 0.0036). G-type was also significantly lower in the dual antiplatelet therapy group than in the single antiplatelet therapy group (p=0.0031). The median G-type in post-ESD bleeding cases was lower than that in no bleeding cases, but it was not significant (p=0.075).

Conclusion

The levels of platelet aggregometry is low in the cases taking thienopyridine or dual antiplatelet therapy, and the risk of post-ESD bleeding in patients under continuous antiplatelet agents might be assessed by platelet aggregation test.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.138

P0174 Gastric Adenocarcinoma of Fundic-Gland Differentiation

H Ueyama ^1,^✉, T Yao ², Y Akazawa ¹, T Hayashi ², N Utsunomiya ¹, R Uchida ¹, D Abe ¹, S Oki ¹, N Suzuki ¹, A Ikeda ¹, N Yatagai ¹, H Komori ¹, T Takeda ¹, K Matsumoto ¹, K Ueda ¹, K Matsumoto ¹, D Asaoka ¹, M Hojo ¹, A Nagahara ¹

Introduction

We previously proposed gastric adenocarcinoma of fundic-gland type (GA-FG) as a new form of gastric adenocarcinoma with distinct clinicopathological and endoscopic features [1-4]. GA-FG was newly added as a special type cancer in Japanese classification of gastric carcinoma, the 15th Edition, 2017, and also listed as a new and rare gastric neoplasia in WHO Classification of Tumours, 2019. Recently, some cases of an aggressive variant of GA-FG with high cellular atypia have been discovered. This variant exhibited differentiation toward gastric foveolar epithelium in addition to fundic gland differentiation, and it was designated gastric adenocarcinoma of fundic gland mucosa type (GA-FGM). Therefore, gastric adenocarcinoma of fundic-gland differentiation (GA-FGD) can be classified into GA-FG and GA-FGM histopathologically. However, the etiology, classification, and clinicopathological features of GA-FGD has not been well elucidated.

Aims & Methods

We performed a large, multicenter, retrospective study to establish a new classification and clarify the clinicopathological features of GA-FGD. A total of 149 GA-FGD lesions were retrospectively collected from 35 institutions during 2008-2019. of 149 lesions, 100 lesions in 94 patients were enrolled in this study. We designed a new histopathologi-cal classification of GA-FGD using an immunohistochemical analysis and compared them clinicopathologically. To establish molecular pathological concept of GA-FGD, next generation sequencing was employed for 34 GA-FGD lesions.

Results

GA-FGD was classified into 2 major types; GA-FG (Type A: in-tramucosal lesion of GA-FG, n=20 and Type B: submucosal lesion of GA-FG, n=55), and GA-FGM (Type C, n=25). in addition, GA-FGM (Type C) was classified into 3 subtypes; Type C-1 (ordered with exposure type, n=11): the normal architecture or differentiation of fundic gland mucosa (superficial foveolar differentiation and deeper fundic gland differentiation) is preserved, Type C-2 (disordered with exposure type, n=10): its architecture or differentiation is collapsed, and tumor is exposed on the surface, and Type C-3 (disordered with non-exposure type, n=4): its architecture or differentiation is collapsed, and tumor is covered by non-neoplastic mucosa. The average of tumor size (mm, Type A 7.1 vs. Type B 8.4 vs. Type C 20.8, p< 0.01) and depth of submucosal invasion (um, Type B 251.5 vs. Type C 1212.5, p< 0.01) were significantly greater in GA-FGM than in GA-FG. Furthermore, the rates of lymphatic and venous invasion and p53 overexpression were significantly higher in GA-FGM than in GA-FG (Ly: 0% vs. 0% vs. 24%, p< 0.01, V: 0% vs. 1.8% vs. 20%, p< 0.05, p53: 0% vs. 2% vs. 21.1%, p< 0.05). The average of tumor size (mm, Type C-1 11.6 vs. Type C-2 31.8 vs. Type C-3 18.5mm, p< 0.05) was significantly greater and the rates of lymphatic invasion (0% vs. 60% vs. 0%, p< 0.05) was significantly higher in Type C-2 than in Type C-1, C-3. GA-FG had low malignant potential, and GA-FGM should be categorized as an aggressive variant of GA-FGD that has high malignant potential (Type C-2 > Type C-1, C-3). The frequent presence of GNAS mutation was a characteristic genetic feature of GA-FGD (7/34 20.6%; Type A 1/3 33.3%, Type B 3/24 12.5%, Type C 3/7 42.9%).

Conclusion

We established a new histopathological classification of GA-FGD and proposed a new lineage of gastric adenocarcinoma related to GNAS mutation, and this classification is useful to estimate its malignant potential and establish a standard therapeutic approach for GA-FGD.

Disclosure

Nothing to disclose

References

1.Ueyama H et al. Gastric adenocarcinoma of fundic gland type (chief cell predominant type): proposal for a new entity of gastric adenocarcinoma. Am. J. Surg. Pathol. 2010. [DOI] [PubMed] [Google Scholar]
2.Ueyama H et al. Gastric adenocarcinoma of the fundic gland type (chief cell predominant type). Endoscopy. 2014. [DOI] [PubMed] [Google Scholar]
3.Ueyama H et al. Establishment of endoscopic diagnosis for gastric adenocarcinoma of fundic gland type (chief cell predominant type) using magnifying endoscopy with narrow-band imaging. Stomach and intestine. 2015. [Google Scholar]
4.Ueyama H et al. Gastric adenocarcinoma of fundic gland type. Stomach and intestine. 2018. [Google Scholar]

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.139

P0175 P53 Protein Overexpression in Gastric Cancer According To Lauren Histologic Classification: Retrospective Study

KW Kim ^1,^✉, N Kim ^1,², Y Choi ¹, WS Kim ¹, H Yoon ¹, CM Shin ¹, YS Park ¹, DH Lee ^1,²

Introduction

p53 gene is a tumor suppressor gene that inactivates in development of malignancies including gastric cancer (GC) through the alternated role in cell cycle arrest and induction of apoptosis. Several studies have suggested different results about the relationship between p53 protein overexpression and survival in GC. in addition, the effect of p53 overexpression in two types of Lauren classification has not been known, so far.

Aims & Methods

The aim of this study was to evaluate the prognostic significance of p53 overexpression in GC and the effect on Lauren histology. From May 2003 to December 2019, 3314 patients with GC who were treated with endoscopic or surgical treatment at Seoul national university Bun-dang hospital were analyzed retrospectively. Immunohistochemical (IHC) analysis for p53 expression was investigated in endoscopic and surgical gastric specimens. Results were analyzed in difference of clinicopatho-logic characteristics and survival rate according to p53 expression in IHC. Also, subgroup analysis according to Lauren classification was performed.

Results

Among 3314 patients, total 3201 patients were analyzed with IHC stain for presence of p53 protein overexpression. Among 3201 patients, 1175 (36.7%) were p53 protein overexpression positive and 2026 (63.3%) were negative. p53 overexpression was associated with male, presence of atrophic gastritis, intestinal-type, and location of lower third of GC. Other variables including proportion of early GC (EGC) and TNM staging were no significant differences between positive and negative patients. However, in subgroup analysis, p53 overexpression in intestinal-type GC was associated with EGC and lower depth of invasion. in case of diffuse-type GC p53 overexpression was associated with advanced GC (AGC) and advanced TNM stage (Number(proportion) of EGC and AGC, 712:185 (79.4%:20.6%) vs 106:172 (38.1%:61.9%), p-value <0.001, Table).

The overall survival of p53-positive patients was significantly lower than p53-negative patients regardless of histologic subtype. ((A) Total group: p53-negative patients 0.739 vs p53-positive patients 0.626, p <0.001; (B)

Intestinal: 0.714 vs 0.611, p=0.042; (C) Diffuse: 0.765 vs 0.642, p <0.001; Figure 1.) The cumulative GC specific survival (GC-SS) of p53-positive patients had statistical significance in the diffuse-type gastric cancer patients group and not in other groups ((A) Total 0.874 vs 0.860, p=0.282 (B) Intestinal 0.920 vs 0.916, p=0.775 (C) Diffuse 0.828 vs 0.737, p=0.001, Figure 2.).

Conclusion

In conclusion, p53 overexpression was associated with EGC in intestinal type contrast to AGC in diffuse type. in addition, p53 overexpression was associated with poor prognosis in GC, especially in diffuse-type patients, suggesting that p53 overexpression plays a different role in the gastric carcinogenesis depending on tissue type.

Baseline characteristics of gastric cancer patients in different Lauren subtypes depending on p53 overexpression.

		Total GC (n=3201,100%)			Intestinal-type GC (n=2100,100%)			Diffuse-type GC (n=1101,100%)
	p53-(%) (n=2026, 63.3%)	p53+(%) (n=1175, 36.7%)	p-value	p53-(%) (n=1203, 57.3%)	p53+(%) (n=897, 42.7%)	p-value	p53-(%) (n=823, 74.8%)	p53+(%) (n=278, 25.2%)	p-value
EGC vs AGC (EGC)	1406 (69.4)	818 (69.6)	0.905	901 (74.9)	712 (79.4)	0.016	505 (61.4)	106 (38.1)	<0.001
EGC vs AGC (AGC)	620 (30.6)	357 (30.4)		302 (25.1)	185 (20.6)		318 (38.6)	172 (61.9)
T (T1+T2)	1632 (80.7)	967 (82.8)	0.143	1033 (86)	817 (91.2)	<0.001	599 (72.9)	150 (55.1)	<0.001
T (T3+T4)	391 (19.3)	201 (17.2)		168 (14)	79 (8.8)		223 (27.1)	122 (44.9)
N (Negative)	1491 (74.9)	859 (74.6)	0.898	969 (81.8)	729 (82.8)	0.561	522 (64.8)	130 (48)	<0.001
N (Positive)	500 (25.1)	292 (25.4)		216 (18.2)	151 (17.2)		284 (35.2)	141 (52)
M (Negative)	1986 (98.1)	1140 (97.1)	0.085	1189 (98.9)	884 (98.7)	0.685	797 (96.8)	256 (92.1)	0.001
M (Positive)	39 (1.9)	34 (2.9)		13 (1.1)	12 (1.3)		26 (3.2)	22 (7.9)

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Data are presented as number (%) or mean.

p-value was calculated using; Chi-square test for categorical variables.

Bold style indicates statistical significance.

Disclosure

Nothing to disclose

Reference

EGC, Early gastric cancer; AGC, Advanced gastric cancer; GC, Gastric cancer.

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.140

P0177 The Metastatic Pattern of Intestinal and Diffuse Type Gastric Carcinoma - A Dutch National Cohort Study

W Koemans ^1,^✉, J Luijten ², R van der Kaaij ¹, C Grootscholten ³, P Snaebjornsson ⁴, R Verhoeven ², J van Sandick ¹

Introduction

The Lauren classification of gastric adenocarcinoma describes three histological subtypes, the intestinal, the diffuse and the mixed type carcinoma. The metastatic pattern of gastric adenocarcinoma by histological subtype according to the Lauren classification has not yet been studied.

Aims & Methods

Gastric adenocarcinoma patients with metastatic disease at the time of diagnosis between 1999 and 2017 were identified through the Netherlands Cancer Registry (NCR). The Lauren classification was determined based on pathology reports archived in the Dutch Pathology Registry and was linked to individual cases in the NCR. Differences between histological subtypes were analyzed using the Chi-squared test. Overall survival was calculated with the Kaplan-Meier method and was compared between groups with the log-rank test.

Results

Among 8.140 newly diagnosed, metastatic and evaluable gastric adenocarcinoma patients, 57% had an intestinal type carcinoma, 39% patients had a diffuse type carcinoma and 4% had a mixed type carcinoma. Intestinal type carcinomas more often metastasized to the liver (56% versus 20%, p< 0.001) and lungs (13% versus 7%, p< 0.001), whereas diffuse type carcinomas more often metastasized to the peritoneum (58% versus 29%, p< 0.001) and bones (9% versus 6%, p< 0.001). (Table 1) Median overall survival of all patients was 4.1 months and was different for patients with an intestinal type carcinoma than for patients with a diffuse type carcinoma: 4.2 months versus 3.9 months, respectively (p< 0.001). Location specific survival for patients with metastatic disease at a single location differed by histological subtype (diffuse versus intestinal) for peritoneal (median 4.7 versus 5.0 months, p=0.002), liver (median 3.3 versus 3.9 months, p=0.045), lung (median 5.0 versus 6.5 months, p=0.030) and extra-regional lymph node metastases (median 5.0 versus 8.0 months, p< 0.001), respectively.

Table 1.

	Total		Intestinal type		Diffuse type		Mixed type
	(n=8140)		(n=4632)		(n=3149)		(n=359)
Metastatic location	n	(%)	n	(%)	n	(%)	n	(%)	p-value
Peritoneum	2306	(28)	1335	(29)	1840	(58)	184	(51)	<0.001
Liver	3354	(41)	2613	(56)	641	(20)	100	(28)	<0.001
Lung	847	(10)	583	(13)	228	(7)	36	(10)	<0.001
Extra-regional lymph nodes	3359	(41)	1337	(29)	867	(28)	102	(28)	0.44
Bones	579	(7)	255	(6)	294	(9)	30	(8)	<0.001
Adrenal gland	198	(2)	133	(3)	54	(2)	11	(3)	<0.001
Other	480	(6)	223	(5)	229	(7)	28	(8)	<0.001

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Conclusion

In this national cohort study, metastatic gastric adenocarci-noma of the intestinal type had a predilection for the liver and that of the diffuse type for the peritoneum. As holds true for non-metastatic gastric cancer, patients with an intestinal type tumor have a better survival than patients with a diffuse type tumor.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.141

P0179 Long-Term Outcomes After Endoscopic Resection For Late Elderly Patients with Early Gastric Cancer

K Waki ^1,^✉, S Shichijo ¹, N Uedo ¹, R Ishihara ², T Michida ³

Introduction

The incidence of gastric cancer (GC) and the death of GC in the elderly patients are increasing in Japan. and endoscopic resection (ER) is more often performed than surgery for GC in Japan. However, there are few reports on the outcomes of elderly patients with gastric cancer after ER. in this study, we examined the long-term outcomes after ER for elderly patients with gastric cancer in our institute.

Aims & Methods

Among 1,353 early GC patients who underwent ER at our hospital from January 2007 to December 2012, 400 patients who were 75 years or older at the time of ER were included. We investigated the patient's survival and the cause of death at 7 years later from the year of ER by medical records of our hospital, the Osaka Cancer Registry, and contact their primary care doctor. We examined the association between patient and lesion characteristics with the overall survival (OS). We used the en-doscopic curability (eCura) classifications: eCura A is curative resection, B is expanded curative resection, C-1 is non-curative resection only with piecemeal resection or a positive horizontal margin in histologically differentiated cases, C-2 is non-curative resection excluding C-1 (Japanese Gastric Cancer A. Japanese gastric cancer treatment guidelines 2018 (5th edition). Gastric Cancer. 2020).

Results

292 men and 108 women with a mean age of 79.3 years (range 75-93 years) were included. The treatment method was endoscopic submucosal dissection (ESD) in 378 cases and endoscopic mucosal resection (EMR) in 22 cases, and the en bloc resection was obtained in 97.5%. Performance Status (PS) was 0 or 1 in 395 cases and 2 to 4 in 5 cases. Prognostic nutritional index (PNI) was 48.4 on average (range 28.7-63.2). Charlson Risk Index (CCI) was 0 or 1 in 229 cases and 2 or more in 171 cases. Pathological diagnosis revealed that the main histologic type was differentiated type in 378 cases and undifferentiated type in 22 cases, 316 were intramucosal cancer, 26 were submucosal cancer with slight invasion, and 58 were submucosal cancer with massive invasion (more than 500 micrometer[SS1] [kw2]), and lymphatic invasion was observed in 33 cases. 284 were eCura A, while 25 were B, 7 were C-1, and 84 were C-2. The prognosis capture rate was 89% at 5 years and the 5-year OS rate was 80.8%. There were 88 deaths and 7 (8%) caused by GC, all of which were eCura:C-2. As a result of the univariate analysis by the log-rank test, “age 79 or more”, “PS 2 or more”, and “PNI 49 or less” were significant factors with a poor prognosis of OS. Among lesion factors, “lesion size 20mm or more”, “undifferenti-ated type”, “SM2 invasion[SS3] ”, “vertical margin indeterminate or positive”, “lymphatic invasion” and “eCura: C-2” were significant factors with poor prognosis. A multivariate analysis using Cox proportional hazard regression (hazard ratio [95% confidence interval]) for the factors of “age”, “PS”, “PNI”, “CCI”, “eCura”, and ” lymphatic invasion “ showed that “PS 2 or more (10.3 [3.14-34.0]), “PNI _49 (2.63 [1.62-4.28])”, “eCura C-2 (2.00 [1.26-3.18])” were independent risk factor for poor prognosis of OS.

Conclusion

The factors of poor prognosis of OS after ER for late elderly patients with early GC were “PS 2 or more”, “PNI 49 or less”, and “eCura C-2” in this study. Although background factors such as PNI and CCI were only associated with the prognosis for elderly patients according to previous reports, we should also take into consideration about additional surgery in case of non-curative resection (eCura C-2).

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.142

P0180 Helicobacter Pylori Eradication Prevents Metachronous Gastric Cancer in Patients with Mild-To-Moderate Atrophic Gastritis: A Multicenter Retrospective Cohort Study By The Osaka Gut Forum

M Yamamoto ^1,^✉, M Kato ², Y Hayashi ², T Nishida ¹, M Oshita ³, F Nakanishi ⁴, S Yamaguchi ⁵, S Kitamura ⁶, A Nishihara ⁷, T Akasaka ⁸, H Ogiyama ⁹, M Nakahara ¹⁰, T Yamada ¹¹, O Kishida ¹², A Shimayoshi ³, Y Tsujii ², M Kato ¹³, S Shinzaki ², H Iijima ², T Takehara ²

Introduction

The development of metachronous gastric cancer (MGC) remains a major problem for the patients who underwent endoscopic resection (ER) against the early gastric cancer (EGC). Preceding studies have shown controversial conclusions regarding the preventive effect of Helicobacter pylori (H. pylori) eradication on the occurrence of MGC. A reason for the conflicting results may come from the difference of patient characteristics included in each study, especially with regard to the patients’ baseline degree of atrophic gastritis.

Aims & Methods

This multicenter retrospective study, conducted at 12 institutions, aimed to evaluate the long-term effects of H. pylori eradication by stratifying patients’ baseline degrees of atrophic gastritis. A total of 483 H. pylori-positive patients who had undergone curative ER for EGC for the first time between 2003 and 2010 were included, and divided into two groups:

(1) those having undergone successful H. pylori eradication within 1 year after ER (eradicated group, n = 294) and;

(2) those with failed or not attempted H. pylori eradication (non-eradicated group, n = 189).

The cumulative incidences of MGC between the two groups were compared for all patients, for mild-to-moderate atrophic gastritis patients (n = 182), and for severe atrophic gastritis patients (n = 301). The degree of atrophic gastritis at the time of ER was assessed by reviewing the recorded endoscopic images, and classified according to the Kimura-Takemoto classification: it was rated as “mild” for C-1 and C-2, “moderate” for C-3 and O-1, and “severe” for O-2 and O-3. MGC was defined as a new cancer developed more than 1 year after ER.

Results

Median follow-up period was 5.2 years (range, 1.1-14.8). Overall, MGC developed in 52 (17.7%) in the eradicated group and in 35 (18.5%) in the non-eradicated group.

For all patients, the cumulative incidence of MGC was lower in the eradicated group than that in the non-eradicated group (13.9% versus 15.7% at 5 years, P = 0.11). in patients with mild-to-moderate atrophic gastritis, MGC developed in 15 of 111 patients (13.5%) in the eradicated group and in 16 of 71 patients (22.5%) in the non-eradicated group, and the cumulative incidence was significantly lower in the eradicated group than that in the non-eradicated group (8.7% versus 18.8% at 5 years, P = 0.03). in patients with severe atrophic gastritis, MGC developed in 37 of 183 patients (20.2%) in the eradicated group and in 19 of 118 patients (16.1%) in the non-eradicated group, and the cumulative incidences were not significantly different between the two groups (17.1% versus 14.2% at 5 years, P = 0.69).

Conclusion

H. Pylori eradication had a preventive effect on the development of the metachronous gastric cancer in patients with mild to moderate atrophic gastritis.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.143

P0181 Endoscopic Mucosal Resection Vs Endoscopic Submucosal Dissection in The Short-Term Outcomes of Endoscopic Resection For Superficial Non-Ampullary Duodenal Tumors; A Multi-Center Retrospective Study

M Esaki ^1,^2,^✉, K Haraguchi ³, K Akahoshi ⁴, N Tomoeda ⁵, A Aso ³, S Itaba ⁶, H Ogino ¹, Y Kitagawa ⁷, H Fujii ⁸, K Nakamura ⁸, M Kubokawa ⁴, N Harada ⁵, Y Minoda ¹, S Suzuki ², E Ihara ^1,⁹, Y Ogawa ¹

Introduction

The selection of endoscopic treatments for superficial non-ampullary duodenal epithelial tumors (SNADETs) are controversial.

Aims & Methods

We compared the efficacy and safety of endoscopic treatment between endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) for SNADETs.

We conducted a retrospective study by using a database of endoscopic treatment for SNADETs at eight hospitals in Fukuoka, Japan from April 2001 through October 2017. A total of 142 patients with SNADEs treated by EMR or ESD were analyzed. Propensity score matching was applied to adjust for the differences of patients between two groups. We analyzed short-term outcomes including the rates of en-bloc/complete resection, the procedure time, the complication rate and hospital days.

Results

Twenty eight pairs of patients were created. The characteristics of patients among two groups were quite similar after matching. We observed significantly shorter procedure time and hospital days in EMR group than those in ESD group (Median procedure time [interquartile range [IQR]: 8 [6-10.75] vs 11 [8.25-14.75], p = 0.006). Other short-term outcomes were not significantly different between two groups (En-bloc resection rate: 82.1% vs 92.9%, p = 0.42, Complete resection rate: 71.4% vs 89.3%, p = 0.18, complication rate: 3.6% vs 17.9%, p = 0.24). One case in ESD underwent emergent surgery due to intraoperative perforation.

Conclusion

This propensity score matching study suggested that EMR is significantly shorter than ESD in procedure time and hospital days. Curability and safety was not significantly different between both groups. This study suggests that EMR has some advantage in medical cost for the treatment of SNADETs due to shorter procedure time and hospital days.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.144

P0182 Synchronous Occurence of Preneoplastic Lesions in The Upper Gastrointestinal Tract and Cancer in Patients with Lynch Syndrome

R Hüneburg ^1,^2,^✉, D Heling ^1,², T Marwitz ^1,², T Vilz ^2,³, J Kalff ^2,³, C Perne ^2,⁴, S Aretz ^2,⁴, C Strassburg ^1,², J Nattermann ^1,²

Introduction

Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome and accounts for ∼3% of all CRCs. This autosomal dominant disorder is caused by germline mutations in DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2 and EPCAM). Approximately one in 279 individuals of the general population is considered to be a carrier of a pathogenic variant. LS patients are at high CRC risk of up to ∼50% depending on the affected gene, and also at increased risk to develop metachronous CRC. LS also includes a variety of extracolonic malignancies such as gastric carcinoma (life-time risk 13%) or small bowel cancer (life-time risk 8%). So far, prospective endoscopic data on surveillance of the upper gastrointestinal tract is scarce.

Aims & Methods

Patients with a proven pathogenic mutation in a DNA mismatch repair gene were included in a surveillance program at our National Center of Hereditary Tumor Syndromes according to the recommendations of the German Consortium for Familial Intestinal Cancer. Patients were included in the final analysis if they received at least one esophagogastroduodenoscopy (EGD) at our center. Results of endoscopy, histopathology, affected gene and occurrence of other malignancies were compared. Synchronous occurrence of malignancies was defined as cancer being detected six month before or after EGD.

Results

A pathogenic MMR gene variant was detected in all patients (48 MLH1 (38%); 57 MSH2 (46%); 18 MSH6 (14%); 2 PMS2 (2%)). in 6 patients, a prior small bowel cancer was diagnosed (2 MLH1, 2 MSH2, and 2 MSH6). At least one EGD with mucosal biopsy was performed in 125 proven mutation carriers (female 47%) since 2008 (2.5 EGD/patient; range 1-11). An endoscopic follow-up was done with a median time of 36 months, in total a follow-up time of 2948 patient/months.

One esophageal leiomyoma was detected in one patient. Barrett esophagus was detected in 11 patients (9%), one with high-grade dysplasia. Gastritis was histopathological proven in 90 patients (72%), with underlying Helicobacter pylori infection in 16 cases (13%). in 22 patients (18%) intestinal metaplasia was found, in one patient (MLH1) with dysplasia. Overall, gastric or small bowel cancer was diagnosed in 6% of the patients. Two new cases of gastric cancer, two new cases of duodenal cancer and one ampullary cancer were observed (age 50-65 years) during routine en-doscopic surveillance. Two symptomatic patients were diagnosed with small bowel cancer (jejunum and ileum). Three gastric adenomas and five duodenal adenomas were detected (age 32-65 years). The detection of (pre-) neoplastic upper gastrointestinal lesions was often associated with the occurrence of synchronous LS-associated cancer (5/10 patients, 50%).

No difference was noted between MLH1 (5 cases) or MSH2 mutations (5 cases). No lesions were observed in MSH6or PMS2 mutation carriers. Adding prior small bowel cancer, in 10/125 (8%) patients small bowel cancer was observed.

Conclusion

This prospective endoscopic study shows that surveillance of the upper GI tract identifies clinically relevant results in a large proportion of LS patients. Interestingly, the synchronous occurrence of upper GI neoplastic lesions and LS-associated cancers shows the systemic effect of the disease. Further studies are needed to determine surveillance intervals and gene specific tailored approaches.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.145

P0183 Biologic Behaviors of The Early Gastric Signet Ring Cell Cancer and Histology Based Prediction of Lymph Node Metastases

X Wang ^1,^✉, G Zhang ²

Introduction

The behavior of signet ring cell carcinoma (SRCC) in early gastric cancer (EGC) is still controversial. This study aimed to compare clinicopathologic features in different histologic type of Chinese EGC patients and to establish a prognostic nomogram for identifying lymph node metastasis (LNM) in EGCs.

Aims & Methods

We reviewed records of EGCs who undergone surgical resection between 2013 and 2017 in a tertiary hospital in Jiangsu province, China. We divided EGC into pure SRCC, mixed SRCC, and NSRC and reviewed the clinical data, endoscopic features, and pathological data. Then, we built a nomogram based on independent risk factors for LNM prediction.

Results

A total of 1008 EGCs were enrolled. 16.2% patients were classified as SRCC, including 63 cases of pure SRCC and 100 mixed SRCC. The SRCC group was more associated with younger age, male, middle and lower location, mucosa-confined and LNM than NSRC group. Further stratification analyses demonstrated that mixed SRCC were associated with an increased risk of LVI (P = 0.032) and LNM (P < 0.001), in contrast with pure SRCC. By multivariate logistic regression, female, tumor size ≥2cm, flat type, submucosa invasion, LVI, located in middle part and mixed SRCC were independent predictors of LNM in SRCC. No nodal metastases were observed in pure signet ring cell carcinomas ≤1 cm without lymphovascu-lar invasion and confined to the mucosa.

Conclusion

Mixed SRCC in EGCs showed more aggressive behavior. Therefore, more attention should be paid to the purity of the SRCC component in clinical practice.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.146

P0184 The Position of Duodenal Stent Insertion Enhances Stent Patency in Patients with Unresectable Pancreatobiliary Cancers

R Suzuki ^1,^✉, S Ito ¹, T Okuzono ¹

Introduction

Gastric outlet obstructions are common complications associated with pancreatobiliary cancers¹. Gastroenteric bypass surgery is initially used to treat gastric outlet obstructions, but is associated with significant risks of morbidity, mortality and delayed gastric emptying². Therefore, duodenal stent placement is becoming an alternative way to treat gastric outlet obstructions, the position of which is recommended that it does not impose on the papilla of Vater, because it is desirable to keep the route of the biliary stent insertion open³. However, there are few reports available that emphasize the impact of stent positioning.

Aims & Methods

The purpose of this study is to assess the effectiveness of stent positioning by evaluating stent patency with a particular focus on the positional relationship between the oral-site end of the duodenal stent and the pylorus. We defined stent obstructions as follows: (a) when the stent dysfunctions were proven by endoscopy, and (b) when the patient would vomit. This retrospective and single-center study included patients with unresectable pancreatobiliary cacers treated with duodenal stents between March 2013 and March 2020, and they were assessed until April 2020. The study protocol was approved by Sendai Kousei Hospital, and we obtained patient acceptability of opt-out consent for this study. The patients were divided into two groups based on where the stent was inserted: the proximal group, in which the oral-site end of the duodenal stent was placed in an area proximal to the pylorus; and the distal group, in which the stent was placed in an area distal to the pylorus. The rate of stent patency was assessed by Kaplan-Meier analysis, and at 30, 60, 90, and 120 days after the stent insertion by chi-square test. A P-value < .05 was considered to indicate statistical significance.

Results

36 patients were enrolled in this study, with 12 patients in the proximal group and 24 patients in the distal group. The patient demographics and clinical characteristics are summarized in Table 1. The period of stent patency is significantly longer in distal group than in proximal group in Kaplan-Meier analysis (P=0.019), especially at 30 days after insertion by chi-square test (30 days: P=0.018, 60 days: P=0.068, 90 days: P=0.10, 120 days: P=0.14).

Conclusion

Duodenal stent patency could be enhanced in patients with unresectable pancreatobiliary cancers by placing the stent in a position distal to the pylorus. We presume that the appropriate position of the duodenal stent is beneficial for the patients of unresectable pancreatobiliary cancers.

Table 1.

Patient demographics and characteristics

	Proximal group	Distal group
Patients, n	12	24
Age, median (range), years	74 (49-89)	75 (56-90)
Sex, male, n (%)	9 (75.0)	11 (45.8)
Underlying disease
Biliary tract cancer, n (%)	4 (33.3)	3 (12.5)
Pancreatic cancer, n (%)	8 (66.7)	20 (83.3)
Gallbladder cancer, n (%)	0 (0)	1 (4.2)
Obstruction, n (%)	8 (66.7)	7 (29.2)

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Disclosure

Nothing to disclose

References

1.Shah A., Fehmi A., Savides T.J. et al. Increased rates of duodenal obstruction in pancreatic cancer patients receiving modern medical management. Dig Dis Sci. 2014; 59(9): 2294–8. [DOI] [PubMed] [Google Scholar]
2.van Hooft J.E., Uitde-haag M.J., Bruno M.J. et al. Efficacy and safety of the new WallFlex enteral stent in palliative treatment of malignant gastric outlet obstruction (DUOFLEX study): a prospective multicenter study. Gastrointest Endosc. 2009; 69(6): 1059–66. [DOI] [PubMed] [Google Scholar]
3.Jung G.S., Song H.Y., Kang S.G. et al. Malignant gastro-duodenal obstructions: treatment by means of a covered expandable metallic stent-initial experience. Radiology. 2000; 216(3): 758–63. [DOI] [PubMed] [Google Scholar]

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.147

P0185 Analysis of Volatile Organic Compounds Emitted By Gastric Juice

P Mochalski ^1,², L Mezmale ^3,^4,^✉, I Polaka ³, I Kikuste ^3,^4,⁵, A Vanags ⁵, I Tolmanis ⁵, V Veliks ³, M Leja ^3,^4,⁵

Introduction

Currently, volatile constituents of human volatolome are considered to be a reliable and rapid source of information on normal and abnormal physiological processes occurring in the body and have thereby, a great potential for medical diagnosis and therapy. Breath analysis holds in this context a distinguished status as it is non-invasive, real-time and some breath constituents have already been linked to various disease processes including cancer.

However, the main unresolved issue is the poor understanding of the sources and metabolic fate of volatile organic compounds (VOCs) in the human organism. This problem can be addressed via comparing volatile patterns obtained from different sources (fluids, or tissues).

Aims & Methods

The primary goal of this pilot study was to identify volatiles being emitted by gastric juice (GJ) as an alternative source of information on potential gastric cancer markers. A cohort of 10 healthy volunteers were enrolled. For VOCs analysis GJ were collected during gastroscopy.

After collection, all samples were frozen. Gas chromatography with mass spectrometric detection coupled with head-space needle trap extraction as the pre-concentration technique was used to identify and quantify VOCs emitted by GJ.

Results

A total number of 62 compounds have been identified in the headspace of the GJ samples. However, only 33 species exhibited occurrence above 20%. Amongst, them there were several hospital environment related species (propofol, 1-propanol and 2-propanol). The predominant chemical classes were aldehydes and alcohols with fourteen and nine species, respectively. Apart from these, there were six ketones, seven esters, six organic acids, six hydrocarbons, three aromatics and three heterocy-clics. Only one compound (acetone) was found in all samples and further three (2 methyl-propanal, 2-butanone and cyclohexanone) in all samples but one. The number of VOCs found in the GJ samples ranged from 14 to 26 (median 23).

Conclusion

Analysis of VOCs emitted by GJ samples provides an opportunity to identify compounds associated with a gastric cancer state. These components in turn could be targeted in breath of gastric cancer patients and thereby assist the non-invasive diagnosis of gastric cancer based on simply in use, portable breath analyzers.

Further studies involving GJ samples obtained from gastric cancer patients and healthy controls are required to detect volatile biomarkers of this disease and to understand their origin and fate in human organism.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.148

P0186 Addition of Linked Color Imaging To White Light Endoscopy Improves Delineation Performance of Early Gastric Cancer Lesions By Non-Expert Endoscopists

K Fockens ^1,^✉, J de Groof ¹, M Struyvenberg ¹, T Khurelbaatar ², N Mostafavi ³, H Fukuda ², Y Miura ², T Takezawa ², WL Curvers ⁴, H Osawa ⁵, JJ Bergman ¹, H Yamamoto ²

Introduction

Early gastric cancer lesions are subtle, focally distributed, and poorly visible endoscopically. Therefore, endoscopists have difficulties evaluating these subtle early gastric cancer lesions.

Aims & Methods

The aim of this study was to evaluate the role of linked color imaging (LCI) for the visualization of early gastric cancer in comparison to white light endoscopy (WLE) alone, when assessed by non-expert endoscopists. 40 unique cases of early gastric cancer, visualized in both WLE and LCI, were collected for this study. To establish ground truth, all cases were delineated by three expert endoscopists from Japan. Using a web based module, these cases were delineated by 48 non-expert endoscopist assessors of four different countries (Japan, Netherlands, Portugal and Sweden). Endoscopic expertise was divided into different levels: fellow in training, junior endoscopist and senior endoscopist. The module consists of three assessment phases, with a wash-out period of 2 weeks in between each phase. Assessment 1: WLE alone; Assessment 2: LCI alone; Assessment 3: WLE+LCI in a side-to-side display. The outcomes of this study were: 1) overlap between assessors’ delineation and expert ground truth; 2) assessors’ delineation performance in terms of differentiating between neoplastic tissue and normal tissue; 3) ability to delineate the lesions (VAS-scores 1-10); 4) assessors’ preferred imaging modality (WLE, LCI or no preference).

Results

Linear mixed-effect models showed a significant increase in assessors’ delineation performance from 77% (SD 26%) in WLE alone and 75% (SD 28%) in LCI alone to 81% (SD 24%) when combining both imaging modalities (P < 0.001). When differentiating neoplastic from non-dysplas-tic tissue, the combination WLE+LCI also caused increased performance scores (49% in WLE and 49% in LCI to 53% in WLE+LCI; P < 0.001). Japanese assessors performed significantly better than Dutch, Portuguese and Swedish assessors when delineating early gastric cancer lesions, regardless of imaging modality (87% vs. 71%, 72% and 73% respectively; P < 0.001). There was no distinction between the different levels of endoscopic expertise. Median VAS scores were higher for phase 2 (6; IQR 5-8) and 3 (7; IQR 5-8) compared with phase 1 (5; IQR 3-7) for the ability to delineate the lesion (P < 0.001). Assessors preferred LCI over WLE (72.4% vs. 5.2%, 22.4% no preference) for the appreciation of early gastric cancer lesions.

Conclusion

The combined use of WLE and LCI resulted in enhanced delineation of early gastric cancer lesions by non-expert endoscopists. Although assessors appreciated the ability of LCI for delineation better than WLE, there was no difference in separate delineation scores for LCI and WLE.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.149

P0187 Genetic Counseling For Gastric and Pancreatic Cancer Based On Suspicion Criteria Is An Effective Strategy For Detecting High-Risk Groups

J Llach ^1,^✉, L Moreno ¹, T Ocaña ¹, A Sánchez ¹, M Cuatrecasas ², L Rivero-Sánchez ¹, C Herrera ¹, R Moreira ¹, M Díaz ¹, G Jung ¹, M Pellisé ¹, A Castells ¹, F Balaguer ¹, L Moreira ¹, S Carballal ¹

Introduction

Gastric adenocarcinoma (GC) and pancreatic adenocarci-noma (PC) are in an increasing incidence and entail high mortality, mainly due to their late diagnosis. The identification of high risk groups of GC/PC (hereditary or familial cancers) could imply a benefit in the affected families, by allowing their inclusion in prevention programs adapted to their risk (genetic counseling).

Aims & Methods

To assess the diagnostic yield of hereditary and familial syndromes GC/PC in individuals evaluated in a high-risk cancer clinic based on 3 suspicion criteria: 1) personal history (PH) of GC/PC < 60 years, 2) PH of GC/PC (at any age) and other malignancy and 3) family history (FH): ≥ 2 relatives with GC or PC. Immunohistochemical analysis of DNA mismatch repair proteins (IHC-MMR) was performed in available tumors. A germline genetic analysis was performed if clinical criteria of hereditary syndrome were fulfilled, according to current guidelines^1,2. Familial GC (FGC) was defined as ≥3 first or second degree relatives (FDR or SDR) with GC or ≥2 FDR/SDR with GC (at least one < 50 years). Familial PC(FPC) was defined as ≥2 FDR with PC or ≥3 relatives with PC, regardless of the degree and age of the relative. Hereditary CG/PC was defined if known causative mutation was detected. The remaining cases were classified as sporadic. Multivariate logistic regression analysis was performed for identifying variables associated with hereditary basis of GC/PC. We included OR with 95% CIs to quantify the magnitude of the association.

Results

From May 2014 to October 2019, 77 families (45 from GC group and 32 from PC group) were recruited due to pre-selected suspicion criteria fulfillment: 51(66.2%) due to cancer diagnosis < 60 years, 3 (4%) due to CG/PC and PH of other cancer and 23 (29.8%) due to FH. Median age at cancer diagnosis was 49 (interquartile range: 41.5-58) and 46 (59.7%) were female. Nine (11.7%) had PH of other malignancy. IHQ-MMR was performed in 38 (49.3%) tumors being pathological in 1(2%) GC. Causative gene mutations were found in 10/22(45.5%) families analyzed [7/16(43.7%) from GC group and 3/6(50%) from PC group (Table 1)] and 19 (24.7%) families fulfilled criteria of familial cancer. The remaining 48 (62.5%) cases were classified as sporadic cancers. Diagnosis of cancer ≤40 years and PH of other cancers were independent risk factors of hereditary origin [OR:11.3 (95%IC 1.9-67); p=0.007 and OR: 17.4 (95% IC 2.5-119.9); p=0.004; respectively].

Conclusion

Almost 40% of the families with GC or PC evaluated based on suspicious criteria belonged to a high-risk group of cancer. Alteration of the DNA MMR system is infrequent in this setting; however, the selection of patients based on specific clinical criteria leads to high diagnostic yield, detecting a causative germline mutation in the 45.5% of cases. Given the wide variability of cancer syndromes observed, both meticulous genetic counseling and use of multi-gen panels seems crucial in this ambit. Factors such as young age at diagnosis and previous history of other malignancies may be able to identify patients with hereditary syndromes.

Characteristics of the hereditary syndromes detected in the total cohort (77 families)

Patient	Group	Age^*	Gender	Referral criteria	Other cancer (age)	IHC-MMR	Genetics technique	Mutation	Hereditary Syndrome
1	GC	75	Female	GC+other tumor	Endometrium (53)	MSH2/ MSH6 -	Single-gene test	MSH 2	Lynch syndrome
2 and 3	GC	55^* and 35^*	Both Female	Both Family history	2 - Breast (58)and 3 -Endometrium (58)	Undone	Multigen panel	ATM	ATM-associated hereditarian cancer
4 and 5	GC	41 and 38	Both Male	Both GC<60 years	No	Undone	Multigen panel	CDH1	Hereditary diffuse GC syndrome
6	GC	49	Female	GC<60 years	Breast (44)	MMR+	Single-gene test	BRCA 2	Breast and ovarian cancer syndrome
7	GC	34	Male	GC<60 years	No	MMR+	Multigen panel	P53	Li-Fraumeni syndrome
8	PC	45^*	Female	Family history	No	Undone	Single-gene test	BRCA 2	Breast and ovarian cancer syndrome
9	PC	33	Male	PC<60 years	No	Undone	Multigen panel	ATM	ATM-associated hereditarian cancer
10	PC	33	Male	PC<60 years	No	Undone	Multigen panel	PALB 2	Breast and ovarian cancer syndrome

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^*

If no personal history of GC or PC, the age corresponds to the youngest relative. IHC-MMR: immunohistochemical anaysis of DNA mismatch repair proteins; GC gastric cancer, PC: pancreatic cancer.

Disclosure

Nothing to disclose

References

1.Syngal S., Brand R.E., Church J.M. et al. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015; 110(2): 223–263. doi: 10.1038/ajg.2014.435 [DOI] [PMC free article] [PubMed] [Google Scholar]
2.Vangala D.B., Cauchin E., Balmaña J. et al. Screening and surveillance in hereditary gastrointestinal cancers: Recommendations from the European Society of Digestive Oncology (ESDO) expert discussion at the 20th European Society for Medical Oncology (ESMO)/ World Congress on Gastrointestinal Cancer, Barcelona, June 2018. Eur J Cancer. 2018; 104: 91–103. doi: 10.1016/j.ejca.2018.09.004 [DOI] [PubMed] [Google Scholar]

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.150

P0188 The Surveillance Strategy After Endoscopic Or Surgical Treatment of Early Gastric Cancer

S Kang ^1,^✉, Y Kim ¹, Y Park ¹, C Shin ¹, H Yoon ¹, N Kim ¹, D Lee ¹

Introduction

With the increasing detection of early gastric cancer(EGC), minimally invasive treatment methods have been investigated to improve quality of life in patients with EGC, while maintaining survival rates comparable to those with conventional radical gastrectomy. Endoscopic resection, a representative minimally invasive treatment for EGC, is currently recognized as the standard treatment method for this disease in selected case. As the number of patients diagnosed with EGC has been increasing as a result of improved surveillance, it is becoming more important to detect recurrence. However, the surveillance strategy for EGC after the treatment has not yet been well established.

Aims & Methods

To investigate the role of regular endoscopy and computed tomography (CT) scan surveillance after treatment of EGC. Consecutive clinical data of 1,615 patients with 1,692 lesions who had undergone endoscopic or surgical treatment for EGC between 2007 and 2012 were retrospectively reviewed. All the gastric lesions were completely resected and all of them had one or more endoscopy and CT scan examination during the follow-up.

Results

In endoscopic resection group (434 lesions in 415 patients), 14 revealed metachronous gastric adenocarcinoma, all of which could be detected by endoscopy with biopsy. in surgical resection group (1258 lesions in 1200 patients), 15 patients revealed tumor recurrence, including 6 cases with metachronous gastric adenocarcinoma, 5 with loco-regional recurrence, 1 with regional lymph node metastasis without distant metastasis, and 3 with both lymph node and distant metastases. All metachronous gastric adenocarcinoma and loco-regional recurrent tumors could be detected by endoscopy with biopsy. All the metastasis cases (n = 4) were diagnosed by abdominal CT, and their initial EGC pathologies were all submucosal invasive early gastric cancers with lymph node involvement.

Conclusion

Regular follow-up of both endoscopy and CT scan is necessary after the surgical treatment of EGC; CT scan seems to be more valuable in case of submucosal invasive early gastric cancers and/or lymph node involvement. CT scan might have a limited role for the surveillance after endoscopic resection of EGCs which meet the expended criteria as well as absolute criteria. in view of cost-effectiveness, tailored surveillance strategy might be necessary after treatment of EGCs.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.151

P0189 Association Between Long-Term Use of Proton Pump Inhibitors and The Risk of Gastric Cancer: A Systematic Review and Meta-Analysis

D Segna ^1,^✉, N Brusselaers ², D Glaus ³, N Krupka ⁴, B Misselwitz ^1,⁵

Introduction

Current evidence suggests that long-term proton pump inhibitor (PPI) use may be associated with an increased risk of gastric cancer (GC).

Aims & Methods

We conducted a systematic literature review and metaanalysis on the association between PPI long-term use and GC risk. Three independent reviewers systematically searched Ovid MEDLINE and EMBASE (inception-November 2019) according to a predefined protocol in PROSPERO (CRD42018102536) and assessed study quality using the Newcastle Ottawa Quality Assessment Scale.

Reviewers independently extracted data, meta-analyzed available and newly calculated Odds ratios (OR) using a random effects model and stratified for GC site (cardia vs non-cardia) and PPI duration (< 1 year, 1-3 years, >3 years).

Results

We screened 1,734 records and included four retrospective cohort and seven case-control studies of good quality comprising 1,191,285 individuals in our meta-analysis.

We found an increased GC risk in long-term PPI users (OR 2.05, 95% confidence interval [95%CI] 1.49-2.82) in random effect models. Stratified analyses indicated a significant risk increase in non-cardia (OR 2.19, 95%CI 1.27-3.76), but not cardia regions (OR 1.85, 95%CI 0.53-6.45). There was no GC increase with longer durations of PPI exposure (< 1 year: OR 2.29, 95%CI 2.13-2.47; 1-3 years: OR 1.46, 95%CI 0.53-4.01; >3 years: OR 2.08, 95%CI 0.56-7.77).

Conclusion

We found a twofold increased GC risk among long-term PPI users, but this association does not confirm causation and studies are highly heterogeneous.

Long-term PPI therapy should only be prescribed when strictly indicated, and dedicated prospective research is urgently needed.

Disclosure

DS has received traveling fees from AbbVie and a research grant from the Novartis Foundation for medical-biological research unrelated to this work. BM has served at an advisory board for Gilead and Novigenix. He has received speaking fees from Vifor, MSD and Takeda and traveling fees from Vifor, Novartis, MSD and Takeda. He has received a research grant from MSD unrelated to this work. NB and DG have nothing to disclose.

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.152

P0190 Clinical Characterization and Screening Strategies in Familial Gastric Cancer: Preliminary Results of The First Spanish Multicenter Study

J Llach ^1,^✉, A Pocurull Aparicio ¹, M Diaz Centeno ¹, I Salces ², J Cubiella ³, V Piñol ⁴, L Peries ⁴, A Guerra ⁵, P Diez Redondo ⁶, MD Pico Sala ⁷, O Murcia Pomares ⁸, D Rodríguez-Alcalde ⁹, J Reyes ¹⁰, M Escalante ¹¹, A Sánchez ¹, C Herrera-Pariente ¹, T Ocaña ¹, L Moreno ¹, R Moreira ¹, L Rivero Sánchez ¹, M Pellisé Urquiza ¹, F Balaguer ¹, S Carballal ¹, L Moreira Ruiz ¹

Introduction

Approximately 10% of gastric adenocarcinomas (GC) show familial aggregation, and a hereditary cause is determined in up to 5% (hereditary GC). Familial GC (FGC) is characterized by an autosomal dominant inheritance pattern of GC, without a responsible germline mutation. The clinical characteristics of FGC, the prevalence of GC and GC-Precursor Lesions (GCPL) and the effectiveness of preventive strategies, have been poorly studied.

Aims & Methods: Objective

To describe the clinical and pathological characteristics of FGC, the screening strategies used and estimate the risk of GC and GCPL in this scenario.

Methodology

a multicenter nationwide study with retrospective inclusion of individuals with FGC was performed. FGC was defined as: a) Criterion A: ≥ 2 first-degree relatives (FDR) or second-degree relatives (SDR) affected by GC (≥ 1 diagnosed < 50 years), or b) Criterion B: ≥ 3 FDR or SDR with GC at any age. Clinical data, oncological personal and family history (FH), endoscopic and pathological reports, were collected.

Results

A total of 69 patients (50 families) were included from 11 Spanish centers: the median age was 59 years (range 46-71) and 37 (53.6%) were women. The criterion A of inclusion was fulfilled by 37,7% of the cases and criterion B was present in the remaining 62.3% individuals. Prevalence of smoking history and chronic alcohol consumption was 38% and 9.4%, respectively. in 14 (20%) cases, personal history of extra-gastric malignancies was reported (3 breast, 2 colorectal, 2 prostate, 2 melanoma, 2 leukemia, 3 other cancers).

Twenty-one (30.4%) patients, corresponding to 18 families, developed GC at a median age of 63 years (range 47-73) and 2 (9.5%) of them were diagnosed during screening endoscopy. Diffuse histology was reported in 10

(47.6%) cases and 13 (62%) tumors were detected in advanced stages (III/ IV). Gastrectomy was performed in 14 (66.6%) patients: 9 (64%) total and 5 (36%) partial gastrectomy. Eight (38%) patients died due to this neoplasia. Regarding screening, gastroscopy was performed in 47 (68.1%) individuals, with a total of 176 explorations: in 42 (89.3%) cases random biopsies were taken [(Sydney protocol in 7 (14.9%) and Cambridge protocol in 4 (8.5%)], in 31 (66%) helicobacter pylori (HP) infection was tested and no biopsies were taken in the remaining 5 (10.7%) cases. Median age at first screening endoscopy was 50.5 (range 36-56) years, with a median of 3 (range 1-5) procedures and a median surveillance of 4 (range 1-12) years. Overall, HP was investigated in 39 (56.5%) individuals, being positive in 24 (61.5%).

During endoscopic screening, 19/47 (40.4%) GCPL were detected (if more than one in the same patient, the most advanced lesion is specified): complete or incomplete intestinal metaplasia in 6 (12.7%) and 5 (10.6%), respectively; extensive atrophic gastritis in 4 (8.5%), low and high-grade dysplasia in 3 (6.3%) and 1 (2.1%), respectively. Moreover, invasive GC was detected by screening gastroscopy in 2 (4.2%) patients, both in an early stage (I and II).

Conclusion

Despite previous family history, the majority of GC within a cohort of individuals of FGC, were diagnosed at advanced stage. Whereas endoscopic screening was performed in nearly 70% of individuals with FGC, HP infection was investigated in just over half.

Up to 45% individuals of FGC

under endoscopic screening were diagnosed with GC-precursor lesions and early stages GC. Definitive results of our study could improve the characterization of FGC in order to determine the best prevention measures for these patients.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.153

P0193 Serologically Determined Gastric Atrophy Associated with Lifestyle, Dietary Factors and Helicobacter Pylori Status

D Razuka-Ebela ^1,^✉, I Polaka ¹, S Parshutin ¹, I Daugule ², I Ebela ^2,^✉, D Santare ¹, O Sjomina ¹, R Herrero ³, JY Park ³, M Leja ¹

Introduction

Serum pepsinogen (Pg) is regarded the best non-invasive method of assessing gastric mucosal status and has a moderate diagnostic yield in detecting precancerous changes with substantial heterogeinity between studies, possibly due to unacounted population factors [1]. Although there is strong evidence implicating H. pylori (HP) and genetics in the development of gastric atrophy and cancer, data on the role of lifestyle and dietary factors, especially pertaining to atrophic gastritis, remains controversial.

Aims & Methods

A total of 2055 participants aged 40-64 years from the “Helicobacter pylori eradication and pepsinogen testing for prevention of gastric cancer mortality (GISTAR) study” in Latvia were tested for PgI and PgII by latex-agglutination (Eiken Chemical, Japan). HP presence was detected by ¹³C-urea breath test. Data on gender, age, education, employment, dietary intake including alcohol, exercise, smoking, BMI, and proton pump inhibitor use (PPI) was obtained by survey and compared for those with and without serologically detected gastric atrophy (sGA) (cutoff values Pg I/Pg II ≤2and Pg I ≤30ng/mL as determined previously) [2]. A supplementary analysis with a second group of participants (1578) of the GISTAR study with HP determined by serum IgG antibodies (>30ng/ml) instead of UBT was performed as described above to assess for differences based on the method used to identify HP infection.

Results

Almost half of the participants included (mean age 52.2 years SD±6.8, 42.5% male) were HP positive (48.7%) and 7.3% had sGA. Multivariate analysis included age, gender, employment, HP, consumption of salted, pickled products, onion, fruit/vegetables and instant coffee, daily meals and PPI use. Smoking and alcohol were additionally included based on the evidence from previous studies.

In multivariate analysis sGA was significantly associated with age (OR 1.1 per year increase; 95% CI 1.0, 1.1), frequent consumption of salted products (1.6; 1.0, 2.6), onion (3.0; 1.4, 6.8), and instant coffee (1.5; 1.0, 2.1), but inversely with current smoking (OR 0.6; CI 0.4, 0.9), HP detected by UBT (0.4; 0.3, 0.6), frequent consumption of pickled products (0.2; 0.1, 0.7) and PPI use in the past month (0.5; 0.2, 0.9). in the second group, sGA was associated with age (OR 1.0 per year increase, 95% CI 1.0, 1.1), male gender (1.8; 1.2, 2.9), frequent consumption of salted products (3.1; 1.3, 7.2), instant coffee (1.6; 1.1, 2.4), and having five or more vs. two to three meals per day (2.3; 1.5, 3.4), but inversely with being employed (0.5; 0.3, 0.8), current smoking (0.6; 0.3, 1.0), and frequent consumption of pickled products (0.3; 0.1, 1.2). in the second group, there was a tendency towards an association between sGA and HP seropositivity, but was not statistically significant (OR 1.5; CI 1.0, 2.3; p = 0.06).

Conclusion

Serologically determined gastric atrophy was positively associated with several dietary factors which have also been linked to the risk of gastric cancer, and inversely with smoking. The nature of the association with H. pylori seemed to depend on the method used to detect HP. Further analysis to determine if these factors are linked to the diagnostic yield of Pg, and whether their effects are modified by H. pylori presence, could be useful in improving the detection of individuals at increased risk of gastric cancer.

Disclosure

The study was funded by project nr. lzp-2018/1-0135 “Research on implementation of a set of measures for prevention of gastric cancer mortality by eradication of H. pylori and timely recognition of precancerous lesions” of the Latvian Council of Science. The authors declare no conflict of interest.

References

1.Bang C.S. et al. Prediction of Chronic Atrophic Gastritis and Gastric Neoplasms by Serum Pepsinogen Assay: A Systematic Review and Meta-Analysis. J Clin Med. 2019; 8(5): 657. [DOI] [PMC free article] [PubMed] [Google Scholar]
2.Leja M et al. Detection of gastric atrophy by circulating pepsinogens: A comparison of three assays. Helicobacter 2017; 22: e12393. [DOI] [PMC free article] [PubMed] [Google Scholar]

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.154

P0194 Evaluation of Ki67 Index For The Assessment of Malignancy Risk in Gastric Gastrointestinal Stromal Tumors

G Seven ^1,^✉, K Kochan ¹, AT Ince ¹, IH Koker ¹, H Senturk ¹

Introduction

The risk of malignancy in gastrointestinal stromal tumors (GISTs) is determined by assessing the resected tumors according to the risk classification systems, that are based on tumor size, location, and mitotic index. Recent studies has focused on assessing other prognostic factors to precisely predict the prognosis. Ki67, a cell cycle marker, index in resected samples has been reported to have a prognostic value in GISTs and furthering the ascertainment of proliferation rate in addition to mitotic index. The feasibiliy of the classification systems using EUS-guided fine needle aspiration (FNA) samples is not accepted, because mitotic index can not be assessed on FNA samples, even in high-risk tumors. However, Ki67 can be assessed on FNA samples. in this study we aimed to analyse the accuracy of EUS-FNA of later resected GISTs in reference to Ki67 index as taking surgical samples gold standard.

Aims & Methods

We retrospectively analyzed 55 patients who underwent EUS followed by surgical resection for gastric GIST between October 2010 and December 2019 at a single tertiary center. Data investigated in this study included age, sex, tumor size, location, mitotic index, cell type (spindle, epithelioid, or mixed), cellularity (mild, moderate or high), pleo-morphism, presence of ulceration, hemorrhage, necrosis, and invasion, growth pattern (expansile or infiltrative), and Ki67 index.

Results

The median age was 56 years (range 22-78), there were 35 female and 20 male pateints. Localization of GISTs were cardia 10, fundus 9, gastric body 22, and antrum 14. The median tumor size was 40 (range: 20-200) mm. We coalesced the patients into a low-risk (very low-risk was considered low-risk) and a high-risk groups (intermediate-risk group was considered high-risk) for further analysis according to Armed Forces Institute of Pathology (AFIP) risk classification. in univariate analysis, excluding tumour size and mitotoic index that are already features determining classification, fundus location (P = .019), ulceration (P = .022), hemorrhage (P = .016), mucosal invasion (P = .026), and Ki67 index (P = .020) were higher in high-risk group, but in the multivariate analysis, only presence of bleeding and Ki67 index were only significant factors (P = .034 and P = .018) in surgical samples. The best cut off level of Ki67 between low-risk and high-risk groups was 5%, with a sensitivity of 88.2%, specificity of 52.8%, PPV of 46.9%, and NPV of 90.5% (P = .021). in addition, a level of Ki67 index over 5% was correlated with high mitotic index, with a sensitivity of 87.5%, specificity of 51.4%, PPV of 43.8%, and NPV of 90.5% (P = .032). The mean Ki67 index was lower on EUS-FNA samples than on surgical specimens [2% (1-15) vs. 10% (1-70), P = .001). in addition, the intra-class correlation coefficient value of Ki67 that was .199 (P = .362) between FNA and surgical samples showed no reliability of FNA samples.

Conclusion

Expression of Ki67 on resected samples was correlated with high-risk GISTs, although it has no additive value and Ki67 index on FNA samples was not correlated with surgical results.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.155

P0196 Elastography in Upper Gastrointestinal Tract Subepithelial Tumors

P Uhrík ^1,^✉, L Nosáková ¹, P Banovcin ¹, M Schnierer ¹, M Kalman ², R Hyrdel ¹

Introduction

Subepithelial tumors (SETs) are lesions growing under the intact epithelium. Endoscopic ultrasonography (EUS) is a standard in SET diagnostics. The possibility of increasing the accuracy of the EUS is elas-tography (EG). EG is an ultrasonographic modality that allows to assessed tissue elasticity. in the study, we focused on the possibilities of using EG in EUS examinations in order to differentiate malignant SETs and specify their diagnosis.

Aims & Methods

22 patients aged 18 to 73 were enrolled in the study. 12 gastric tumors, 5 duodenal tumors and 4 esophageal lesions were evaluated. The EG image was evaluated qualitatively by a 4 and 5 grade classification system for endoscopic EG and semi-quantitatively using strain ratio (SR) and strain histogram (SH).

Characteristics of patients,localization and size of subepithelial lesions.

	Gender (male/ female)	Age (in yr.) median	esophagus/ stomach/ duodenum	Layer (1/2/3/4)	Dimensions (mm) median
Leiomyoma	3/0	62 (61 - 67)	3/0/0	0/2/1/0	14,5 (14.5 -21,4)
Lipoma	0/1	27	0/1/0	0/0/1/0	10
Inflammatory fibroid polyp	1/0	45	0/1/0	0/1/0/0	4,1
Neuroendocrine tumor	4/3	59 (29 - 74)	0/5/2	0/2/5/0	9,2 (7 - 13,2)
Adenoma	1/2	56 (49 - 64)	0/0/3	3/0/0/0	13 (10,8 - 18,7)
Gastrointestinal stromal tumor	1/1	56,5 (56 - 57)	0/2/1	0/0/0/2	19 (15 - 23,1)
Aberrant pancreas	0/2	45 (30 - 60)	0/2/0	0/0/2/1	12 (10,6 - 13,5)
B-lymphoma	1/0	56	0/1/0	1/1/1/1	12,6
Spinocellular carcinoma	1/0	65	1/0/0	1/0/0/0	31,2

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Results

Using a 5-grade classification system, a value of 1, 2 in 80% and a value of 3, 4, 5 in 20% were assigned to benign tumors. Malignant lesions grade 3, 4, 5 was assigned in 87.5% and 1, 2 in 12.5%. in the 4-grade classification system, the values of 1, 2 were observed in 80% and 3, 4 in 20% of the benign lesions. in contrast, malignant tumors were assigned values of 3, 4 in 87.5% and 1, 2 in 12.5%. The median SR for benign tumors was 6.51 (0.64-15) and the median SH 71 (16-185). in the group of malignant tumors, the median SR was 6.195 (1.5-33), SH 40.19 (14-98).

Conclusion

A high sensitivity and specificity of the 5 and 4-grade classification to distinguish pancreatic malignant lesions is reported in the published literature. SR values above 6.04 and SH below 175 are typical of pancreatic malignant lesions. Significantly different SR and SH values from other lesions in the group were seen in inflammatory polyp and neuroendocrine tumors. According to our observations, the use of a 5-grade scale for evaluating the EG image in combinations with semi-quantitative methods of SR and SH appears to distinguish malignant SETs as the most promising. Further studies with a larger number of patients will show the utility of elastography in differential SET diagnosis.

Disclosure

Nothing to disclose

References

This work was supported by Ministry of Health of the Slovak Republic under the project registration number 2019/44-UKMT-7.

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.156

P0197 Factors Associated with Gastric Atrophy “Missed” By Serologic Testing

D Razuka-Ebela ^1,^2,^✉, I Polaka ¹, S Parshutin ¹, I Daugule ², I Ebela ^2,^✉, D Santare ¹, R Herrero ³, JY Park ³, M Leja ^1,²

Introduction

Serum pepsinogen (Pg) is regarded as the best non-invasive method of assessing gastric mucosal status and has a moderate diagnostic yield in the detection of precancerous lesions and gastric cancer with substantial heterogeinity between studies, possibly due to unnacounted population factors [1].

Identifying factors that may substantially impact Pg values and adjusting Pg cut off values accordingly could potentially improve the diagnostic yield of Pg in detecting gastric atrophy.

Aims & Methods

Participants aged 40-64 years from “Helicobacter pylori eradication and pepsinogen testing for prevention of gastric cancer mortality (GISTAR) study” in Latvia with moderate to severe gastric atrophy confirmed by biopsy were tested for blood PgI, PgII by latex-agglutination (Eiken Chemical) and H. pylori (HP) IgG antibodies (Biohit). They were then divided into two groups based on whether gastric atrophy was also identified serologically (where Pg I/Pg II ≤2and Pg I ≤30ng/mL) [2]. Those with gastric atrophy on biopsy and by serology were placed in the serologically determined gastric atrophy group (sGA), while those not identified by serologic testing were placed in the “missed” gastric atrophy group (mGA). Factors associated with decreased Pg were compared between sGA and mGA- gender, age, employment, consumption of ≥400g fruit/vegetables daily, frequency of having salted, pickled products, coffee and allium vegetables, daily meals, smoking, proton pump inhibitor use (PPI), as well as having alcohol and fish, exercise, BMI and self-reported history of peptic ulcer disease based on previous studies.

Results

Out of 1196 participants, 138 (11.5%) had moderate to severe gastric atrophy. A total of 108 cases which had data on H. pylori were included in the analysis - 59.3% were male and 79.6% were HP positive. of these, gastric atrophy was “missed” by Pg testing in 37 (34.3%). The median age for mGA was slightly lower than sGA (54.0, IQR 11 vs. 57.0, IQR 10 respectively, p = 0.03). Based on univariate analysis, factors with p < 0.10 (age, H. pylori, peptic ulcer disease and daily meals) were included in multivariate analysis with gender, employment, smoking and PPI use included additionally based on previous studies. in multivariate analysis, mGA was significantly associated with male gender (OR 4.27, 95% CI 1.11, 16.40), current smoking (OR 5.9; CI 1.4, 24.4), and inversely with HP (OR 0.3; CI 0.1, 0.8) and having five or more versus three to four meals per day (OR 0.07; CI 0.01, 0.7) when compared to sGA. This means that gastric atrophy was more likely to be “missed” by serologic Pg testing in men, current smokers, those seronegative for HP, and those having 3-4 meals per day.

Conclusion

The likelihood of gastric atrophy being missed by serologic pepsinogen testing was increased by several factors, suggesting that adjusted Pg cut-off values for specific subsets of the population (by gender, HP seropositivity, smoking status) might improve the diagnostic yield of Pg testing. A more detailed analysis in a larger population sample is necessary to determine the significance of the application thereof.

Disclosure

The study was funded by project nr. lzp-2018/1-0135 “Research on implementation of a set of measures for prevention of gastric cancer mortality by eradication of H. pylori and timely recognition of precancerous lesions” of the Latvian Council of Science. The authors declare no conflict of interest.

References

1.Bang C.S. et al. Prediction of Chronic Atrophic Gastritis and Gastric Neoplasms by Serum Pepsinogen Assay: A Systematic Review and Meta-Analysis. J Clin Med. 2019; 8(5): 657. 2. Leja M et al. Detection of gastric atrophy by circulating pepsinogens: A comparison of three assays. Helicobacter 2017;22:e12393. [DOI] [PMC free article] [PubMed] [Google Scholar]

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.157

P0198 Prognostic and Survival Factors of Gastroduodenal Neuroendocrine Tumors: Our Center's Experience

MJ Mascarenhas Saraiva ^1,^✉, L Brozzi ², MG Macedo ³

Introduction

Gastroduonenal neuroendocrine tumors represent a rare group of neoplasms, with an incidence of approximately 0.5 in 100000 inhabitants, constituting a small percentage of the gastroduodenal neoplasms. This study evaluated the location, type of primary tumor, degree of systemic attainment as well as other relevant clinical-pathological aspects with an impact on overall survival and disease-free survival

Aims & Methods

We retrospectively evaluated 38 patients with gastric and and duodenal neuroendocrine tumors with anatomopathological diagnosis confirmed by biopsies as well as resected specimens in a tertiary referral center between 2008 and 2020.

Patients with MEN-1 (Type 1 Multiple Endocrine Neoplasia) or Von Hippel-Lindau Syndrome were excluded.

Results

There were 20 resected specimens and 18 biopsies. The most frequent primary location was the duodenum with 31 patients (82%), with just 7 patients with primary location in the stomach (18%). The most patients were female (21 patients; 55%). Mean age at diagnosis was 51.2 years (range 19-87 years). The median survival was 156 months. Regarding the existence of metastasis in the time of diagnosis (synchronous or metachronous), were present in 13 patients (34%). Regarding the therapeutic approach, patients underwent surgery (68% - 26 patients), surgery + chemotherapy (24% - 9 patients) or chemotherapy alone (8% - 3 patients). Survival was higher in patients undergoing surgery (P < 0.001). Spearman correlation was used to correlate Ki67, tumor grade and mitotic count. There was a strong correlation between Ki67 and mitotic count and also between ki67 and tumor grade. We found only a moderate correlation between mitotic rate and tumor grade.

It should be noted that the patient's age over 65 years at diagnosis (P < 0.001), the size of the primary tumor greater than 25 mm (P = 0.04), the presence of synchronous metastasis (P = 0.04) and the presence of a Ki67> 5% (P = 0.02) proved to be independent factors of adverse prognosis.

Conclusion

The clinical presentation and biological behavior of gastroduodenal neoplasms varies considerably. in line with previously published case series, the patient's age less than 65 years, the size of the primary tumor and the absence of locoregional disease, angioinvasion and metastasis are associated with a better prognosis.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.158

P0199 Predictors To Resistant To Quit Smoking After Diagnosis of Gastrointestinal Cancer Among Gastrointestinal Cancer Survivors: Nation Wide Study

YI Choi ^1,^✉, DK Park ²

Introduction

Cessation of smoking is essential to improve cancer related outcomes among gastrointestinal cancers (GIC) survivors. However, few studies have assessed the determinant factors to resistant to quit smoking after diagnosis of GIC.

Aims & Methods

We aimed to investigate the predictors to resistant to quit smoking after diagnosis of GIC.

Total of 625 GIC survivors (age≥40 years, median 7.1 years of follow up) from the HEXA Study (2004-2016) were included in this study. Smoking status at diagnosis of GIC cancer was investigated. After exclusion of never smoker, GIC survivors were classified in to quitters and non-quitters according to the smoking status at the diagnosis of GIC. To evaluate the determinant factors to quit smoking after diagnosis of GIC, we used a univari-ate and multivariate regression analyses between two groups (quitter vs non quitter).

Results

The overall smoking cessation rate was 60.3% (n=226 of 375) among current smoker at the time of diagnosis of GIC. in univariate analysis, female gender (7.7% vs 1.7%, p=0.006), current high risk drinking (72.9% vs 41.4%, p=< 0.001), obesity (23.3 ±3.0 vs 22.6 ±2.6, p=0.02) were more prevalent in non-quitter group than quitter group with statistical significance. in multivariate analysis, low household income(Odds ratio(OR) 1.2, 95% confidence interval(CI): 1.1-2.0), current high risk drinking(OR1.4, 95%CI: 1.1-1.9), no regular exercise(OR 1.6, 95%CI:1.3-2.9) smoking duration more than 30 years(OR 1.3, 95%CI:1.1-1.9), and heavy smoker (≥25 cigarrettes /day) (OR 1.5, 95%CI:1.1-2.5) were the independent risk factors to resistant to quit smoking after diagnosis of cancer even after adjusting after adjusting cancer type, treatment status, age at diagnosis of GIC, the smoking age, education status, income status, work type, cancer related factors.

Conclusion

Given that smoking cessation is important for GIC survivors’ prognosis, it is necessary for physicians to pay attention to survivors who have determinant factors to resistant to quit smoking with monitoring and educating carefully.

Disclosure

Nothing to disclose

References

1.Choi S., Chang J., Kim K. et al. Effect of Smoking Cessation and Reduction on the Risk of Cancer in Korean Men: A Population Based Study. Cancer Res Treat 2018; 50: 1114–1120. [DOI] [PMC free article] [PubMed] [Google Scholar]
2.Parsons A., Daley A., Begh R. et al. Influence of smoking cessation after diagnosis of early stage lung cancer on prognosis: systematic review of observational studies with meta-analysis. Bmj 2010; 340: b5569. [DOI] [PMC free article] [PubMed] [Google Scholar]
3.Ramaswamy A.T., Toll B.A., Chagpar A.B. et al. Smoking, cessation, and cessation counseling in patients with cancer: A population-based analysis. Cancer 2016; 122: 1247–53. [DOI] [PubMed] [Google Scholar]
4.Sitas F., Weber M.F., Egger S. et al. Smoking cessation after cancer. J Clin Oncol 2014; 32: 3593–5. [DOI] [PubMed] [Google Scholar]

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.159

P0200 Comprehensive Evaluation of Five Recq Dna-Helicase Family Members Expression and Its Prognosis Value in Human Gastric Cancer

Y Xie ^1,^✉, J Wen ²

Introduction

The RecQ DNA helicase families including five members -RECQL, Bloom (BLM), Werner (WRN), RECQL4, and RECQL5, play an important role in maintaining genome integrity. Although several studies have reported that RecQ DNA helicase families was closely correlated with the susceptibility to liver cancer and breast cancer, the effect on prognosis in gastric cancer was not yet clarified. Here, we analyzed the expression, prognostic values and clinical characteristics of RecQ family members in gastric cancer.

Aims & Methods

mRNA-expression levels of RecQ members were analyzed via the Tumor Immune Estimation Resource (TIMER) and Oncomine database site. We evaluated the influence of RecQ members on clinical characteristics and prognosis using Gene Expression Profiling Interactive Analysis (GEPIA), MEXPRESS(https://mexpress.be/index.html), and Kaplan-Meier plotter. The functionsof the five RecQ family members at the gene and protein levels were explored by the tool of GeneMANIA. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) services provided the Gene ontology enrichment analysis and KEGG pathway analysis.

Results

All members of the RecQ family were highly expressed in most tumors tissues compared to normal tissues. The expression levels of the RecQ family members were correlated with tumor stage, family history of stomach cancer, barrette's esophagus, sample type, histological type, gender, and sample type. High mRNA expression of RECQL was significantly related with poor overall survival (OS), first progression (FP), and post progression survival (PPS) in all gastric cancers. in contrast, high mRNA expression of BLM, RECQL4, and RECQL5 was associated with better OS, FP, and PPS in gastric patients. in addition, Survival analysis revealed that high transcription levels of RecQ members were associated with OS, FP, and PPS in patients with HER2 status, different treatment, stage, differentiation, and lauren classification gastric cancer.

Conclusion

Taken together, these data indicate that RECQL may become a new potential therapeutic target for patients with gastric cancer and that BLM, RECQL4, and RECQL5 may be useful as prognostic biomarkers for gastric cancer. Further research is required to better understand the role of the RecQ genes.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.160

P0201 Identification of New Genes Involved in Germline Predisposition To Early-Onset Gastric Cancer

C Herrera-Pariente ^1,^✉, R Capó-García ¹, S Carballal ¹, J Muñoz ¹, J Llach ¹, M Díaz-Gay ¹, A Sánchez ¹, L Bonjoch ¹, C Arnau-Collell ¹, Y Soares de Lima ¹, J Lozano ², A Castells ¹, F Balaguer ¹, L Bujanda ³, S Castellvi-Bel ¹, L Moreira ¹

Introduction

Gastric cancer is the fifth most common cancer worldwide, showing a high mortality rate. Although the majority of gastric cancers cases are sporadic, 10% of them show familial aggregation and a genetic cause is present in up to 5% of all cases. The main associated inherited syndrome is hereditary diffuse gastric cancer, which is mainly caused by CDH1 mutations. However, the genetic cause for a high number of families with gastric cancer aggregation is unclear, especially in early-onset patients.

Aims & Methods

The aim of the present study was to identify new candidate genes involved in germline predisposition to gastric cancer. For this reason, whole-exome sequencing (WES) of germline samples was performed in 20 patients with gastric cancer before the age of 50 and without CDH1 mutations at germline level. Nine tumor samples were also available, and WES was also performed. Sequencing data of germline samples were filtered by a pipeline to select those variants with plausible pathogenicity, rare frequency in the general population and previously involved in cancer. After that, a manual filtering was performed in order to prioritize genes previously involved in germline predisposition to any type of cancer and other genes according to current knowledge and gene function. These genetic variants were prevalidated with Integrative Genomics Viewer (IGV). in addition, data of tumor samples was used to analyze its tumor profile using SigProfilerWeb. Subsequently, a selection step was performed according to gene function and information obtained from analysis of tumor samples. Selected variants were validated by Sanger sequencing.

Results

After manual filtering, 274 genetic variants located on 205 different genes were prioritized. Using IGV, 86 genetic variants in 41 genes were discarded. Among the remaining genetic variants, 60 of them corresponding to 54 genes were selected and Sanger sequencing was performed. Finally, 58 final genetic variants in 52 different candidate genes were validated (Table 1).

Table 1.

Final candidate genes to gastric cancer predisposition.

Function	Genes
Germline cancer predisposition	APC, ATM, SDHC, COL7A1, GPC3, RNF43, EXT2, POLD1, EXT1, POT1, PTCH1, POLH, GATA2, BAP1, ERCC2 and FANCA
Cell adhesion	FAT1, FAT2, FAT4 and CTNND1
Tumor suppression genes	PHF2, LARP7, LRP1B, WWOX, ADAMTS9, LATS1, BCL6B, ITIH5, NEO1, MAD1L1, GPX7, IQGAP2, DACT2, SIRT3, RCC1 and EPHB2
Helicobacter pylori recognition	IL12A, TLR1, TLR2, TLR5, TLR10, A4GNTand MUC1
DNA repair	UNG, KAT5, RAD23A, HBP1 and LIG3
Other related functions	ARID4A, ARID1B, ATP4A and ROBO1

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Conclusion

Among 52 candidate genes, APC, FAT4, CTNND1 and TLR2 seem to be the most promising ones because of their involvement in germline predisposition to hereditary cancer syndromes or in important functions such as tumor suppression, cell adhesion and Helicobacter pylori recognition, respectively. Although replication in a different cohort and functional studies will be needed, this project will be helpful to increase the knowledge of predisposition to early-onset gastric cancer.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.161

P0202 Long Non-Coding Rna Polymorphisms and Risk of Gastric Cancer and Atrophic Gastritis

V Petkevicius ^1,^✉, K Balciute ², A Link ³, M Leja ⁴, L Jonaitis ¹, L Kupcinskas ¹, J Skieceviciene ², P Malfertheiner ³, J Kupcinskas ¹

Introduction

Long noncoding RNAs (lncRNAs) are greater than 200 nu-cleotides in length and do not encode functional proteins. They regulate gene expression through various processes, such as chromatin modification, transcription and post-transcription processing. Accumulating evidence shows that lncRNA single nucleotide polymorphisms (SNPs) play an important role in the carcinogenesis of various tumours.

Aims & Methods

The aim of this study was to assess the associations of lncRNA rs217727, rs3200401, rs17840857, rs1054000, rs17694493, rs1333045, rs1011970 polymorphisms with gastric cancer (GC) and atro-phic gastritis (AG). SNPs were analyzed in 613 GC patients, 118 patients with AG and 476 controls from 3 tertiary centres in Germany, Lithuania and Latvia. All patients were of European descent. Genomic DNA was extracted from peripheral blood leukocytes using the salting-out method. SNPs were genotyped by the real-time polymerase chain reaction. Associations between gene polymorphism, GC and AG were evaluated using multiple logistic regression analysis with adjustment for sex, age and country.

Results

The prevalence of several genotypes differs between AG patients and controls. CT genotype of rs3200401 was more prevalent in AG patients than in controls (39.3% and 25.5% respectively, p=0,014). The same association was found for TG genotype of rs17840857 (48.3% in AG patients and 38.7% in controls, p=0.029). The frequency of T allele was 36.0% in AG patients and 27.4% in controls (p<0.009). CG genotype of rs17694493 was less prevalent in AG patients than in controls (16.9% and 26.9% respectively, p=0.005). Lower prevalence of CT genotype of rs1333045 was also observed in AG patients compared to controls (39.7% and 51.7% respectively, p=0.019). No statistically significant differences in the distribution of genotypes and alleles were found between GC patients and controls. Logistic regression analysis revealed that only one polymorphism (rs17694493) was associated with an increased risk of GC. Carriers of GG genotype had higher odds of GC when compared to CC genotype (OR - 4.93; 95% PI 1.28 - 19.00, P=0.02). More associations were found between analyzed genotypes and AG. Carriers of CT genotype of rs3200401 had higher odds of AG than those with CC genotypes (OR - 1.81; 95% PI 1.17-2.80, p=0.007). OR for AG was 1.61 (95% PI 1.04-2.50, p=0.034), when TG genotype was compared with TT genotype of rs17840857. GG genotype of rs17694493 as associated with higher odds of AG than CC genotype (OR 5.11; 95% PI 1.10-23.80, p=0.038). Higher odds were found for a recessive model for rs1333045, where comparison of CC vs TT+CT genotypes showed an increased risk of AG (OR 1.88; 95% PI 1.19-2.95, p=0.007).

Conclusion

rs17694493 SNP is associated with increased risk of GC and AG, while polymorphisms of rs3200401, rs17840857, and rs1333045 are linked with risk of AG.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.162

P0203 Introducing Mental Health Into Gi Clinics - Integrating The Brain and The Gut

S Mole ^1,^✉, BT Theron ², C Calvert ³

Introduction

Anxiety and Depression are highly prevalent in the Gastroenterology patients. Even with this knowledge, patients are not routinely screened for their psychological health. We sought to introduce regular mental health screening to all gastroenterology outpatient clinics at Royal Devon and Exeter (RD&E) and North Devon District hospital (NDDH) using the General Anxiety Disorder- 2 (GAD-2) and Patient Health Question-naire-2 (PHQ-2).

Aims & Methods

Using QI methodology with Plan Do Study Act cycles (PDSA), a screening questionnaire was first trialled in gastroenterological outpatient clinics. Functionality and effectiveness of this screening tool was assessed and the GAD-2 and PHQ-2 scores of >2 were used to trigger referrals to talking therapy service called TalkWorks. Throughout each cycle data was collected on age, diagnosis and GAD-2, PHQ-2 scoring. PDSA cycle 1: (24/8/18 - 19/9/18). At RD&E the questionnaire was handed out in the clinic waiting room. The ease and functionality of the questionnaire was assessed. Feedback was obtained from patients and service providers. PDSA cycle 2: (24/9/18- 6/11/18). The 2^nd updated version was trialled again and no further alterations were made.

PDSA cycle 3: (11/3/19- 24/04/19). The 3^rd version was sent out alongside a clinic appointment letter to every patient.

PDSA cycle 4: (08/11/2019- 27/11/2019). The questionnaire was trialled in a different hospital (NDDH) before being sent out to patients alongside clinic appointment letters.

Results

Across 4 cycles, data was collected from 287 (78:82:95:32) patient questionnaires. The mean age is 50.72. 55.4% (159/287) were female, 44.6% (128/287) were male. The rates of anxiety and depression were 20.6% (59/287) and 23.7% (68/287) respectively. 31.7% (91/287) had anxiety and/ or depression. Higher scores were seen in females, with 37.7% (60/139) scoring for anxiety and/or depression than males 24.2% (31/128), P = .02. Patients with ulcerative colitis (77) and Crohn's disease (79) had similar rates of anxiety and/or depression, 26.0% (20/77) and 26.6% (21/79) respectively. Rates were non-significantly higher in the irritable bowel syndrome cohort (40), at 37.5% (15/40), P = .51.

Conclusion

In keeping with previous studies, we found a high prevalence of anxiety and depression in the gastroenterology clinic. A questionnaire incorporating GAD-2 and PHQ-2 is an effective and easy to administer tool to screen for psychological comorbidity amenable to talking therapies. Across RD&E and NDDH all gastroenterology patients are now being screened for anxiety and depression. Those identified are referred to an integrated psychological health service if appropriate. We aim to gather referral and outcome data from Talkworks to assess if the introduction of this screening has an impact on quality of life.

Disclosure

Nothing to disclose Poster presentations H. pylori

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.163

P0204 Prevalence of Helicobacter Pylori Decreased Significantly During The Last 25 Years Among Lithuanian Medical Students

H. pylori H. pylori 09:00-19:00 / Poster Exhibition

IR Jonaityte ¹, E Ciupkeviciene ¹, L Jonaitis ^1,^✉, L Kupcinskas ², P Jonaitis ^1,^✉, J Kupcinskas ¹

Introduction

The prevalence of Helicobacter pylori infection is decreasing in the modern Western world while remaining high in developing countries. There is limited up-to-date information about the prevalence of H. pylori in Eastern Europe.

Aims & Methods

The study was approved by the Bioethics Center of LUHS (no. BEC-MF-164). The groups of students from the 1^st to the 4^th study year were randomly selected in the Medical and Nursing Faculties. The students were tested for the presence of antibodies against H. pylori performing serological test from finger blood. Similar studies on the prevalence of H. pylori among LUHS students were performed in 1995, 2012 and 2016 by other authors. in 1995, the “Helisal” test was used, in 2012, 2016 and 2020 the “SureScreen Diagnostics Ltd” test was used.

Results

In the present study, 148 students of LUHS were examined. There were 120 female (81.1%) and 28 male (19.9%) students. The mean age of study participants was 20.4±1.7 years (min. 18 years, max. 33 years). The serological test for the presence of antibodies against H. pylori was positive in 21 (14.2%) students, negative in 125 (84.4%) students and 2 (1.4%) tests were non-informative. Non-informative tests were eliminated in further statistical analysis. H. pylori were found in 19 (16.1%) female students and in 2 (7.1%) male students. No significant difference between genders was observed (p>0.05).

The number of students who participated in the previous studies were: 120 in the year 1995 (mean age - 21.3±1.0 years), 187 in the year 2012 (mean age - 22.4±0.7 years), and 262 in the year 2016 (mean age - 20.4±1.0 years). H. pylori test was positive in 62 students (51.7%) in 1995, in 57 students (30.4%) in 2012, and in 69 students (26.3%) in 2016. The statistically significant difference in the prevalence of H. pylori was found between all study years, except between 2012 and 2016.

Conclusion

1. in our study, Helicobacter pylori were established in 14.2% of students of Lithuanian University of Health Sciences. 2. Over the last 25 years, the prevalence of H. pylori among students of Lithuanian University of Health Sciences has decreased significantly.

Disclosure

Nothing to disclose

References

1.Roberts S.E., Morrison-Rees S., Samuel D.G., Thorne K., Ak-bari A., Williams J.G. Review article: the prevalence of Helicobacter pylori and the incidence of gastric cancer across Europe. Aliment Pharmacol Ther. 2016. Feb 1; 43(3): 334–45. [DOI] [PubMed] [Google Scholar]
2.Leja M., Grinberga-Derica I., Bilgilier C., Steininger C. Review: Epidemiology of Helicobacter pylori infection. Helicobacter. 2019. Sep 4; 24(S1). [DOI] [PubMed] [Google Scholar]

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.164

P0205 Stable Rate of Helicobacter Pylori Infection in Patients with Peptic Ulcer Disease in A Tertiary Referral Hospital Over The Last Decade

T Matthews ^1,^✉, N Afzal ¹, J Mahon ¹, A O'Connor ², N Breslin ¹, B Ryan ¹, D McNamara ¹, S O'Donnell ¹

Introduction

Helicobacter pylori is a gastric luminal dwelling gram-negative bacterium associated with an increased risk of peptic ulcer disease and gastric cancer. A systematic review over two time periods (1970-1999 and 2000-2016) demonstrated declining trends in Europe (48.8% to 39.8%), Northern American (42.7% to 26.6%) and Oceania (26.6% to 18.7%) and static rates in Asia, Latin America and the Caribbean. Declining prevalence of infection in Europe is thought to have resulted from rising standards of living and improved sanitation. Proportionally more gastric and duodenal ulcers have been attributed to other causes such as medication and ischaemia.

Aims & Methods

Our aim was to assess year on year the proportion of patients diagnosed with gastric and duodenal ulcer in whom H. pylori was present. We interrogated our endoscopy database, for the period 01/01/2011 to 12/04/2020, returning a total of 999 oesophagogastroduo-denoscopies (OGDs) coded with a finding of gastric (522) and duodenal (477) ulcer. Presence of H. pylori was detected by observation on histology.

Helicobacter positivity rates over time were depicted graphically and a line of best fit was applied.

A “split point” year, following Hooi et al (2017), was selected which divided the timeline into two periods. An odds ratio for helicobacter positivity in the later period, relative to the earlier, was calculated. This process was repeated with each of the years 2012 to 2020 serving as a split point. Similar analysis was conducted using a probit regression model. Heli-cobacter positivity was the binary dependent variable. An independent dummy variable was constructed which took the value of 1 for investigations occurring in the later period.

Results

21% (range 13% to 29% by year) of gastric ulcers and 31% (range 20% to 45% by year) of duodenal ulcers identified on endoscopy were helicobacter positive. Graphical analysis of positivity rates over time show stable rates of H. pylori among patients with gastric ulcer and a small trend towards decreased prevalence in duodenal ulcer not meeting statistical significance. The odds ratio of helicobacter pylori positivity in later periods, relative to earlier, was not significantly different from one for any of the analysed permutations.

Multiple probit regressions failed to demonstrate a significant relationship between time period and the probability of helicobacter positivity.

Conclusion

This study fails to demonstrate a significant declining trend in helicobacter infection associated with upper GI ulcers. H. pylori is still a very significant aetiology of upper GI ulcers with a significant associated morbidity and mortality.

Disclosure

Nothing to disclose

References

Hooi J. K. Y. et al. 2017, ‘Global Prevalence of Helicobacter pylori Infection: Systematic Review and Meta-Analysis’, Gastroenterology, vol. 153, no. 2, pp. 420–429. [DOI] [PubMed] [Google Scholar]

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.165

P0206 Helicobacter Pylori Screening in Patients with Acute Myocardial Infarction

R Hofmann ^1,^✉, J Wärme ¹, M Sundqvist ¹, K Mars ¹, L Aladellie ², M Bäck ²

Introduction

Potent antithrombotic therapy has significantly improved prognosis for patients with acute myocardial infarction (MI), however, at a price of increased bleeding risk. Chronic gastric infection with Heli-cobacter pylori (HP) commonly causes upper gastrointestinal bleeding (UGIB) and is proposed as a risk factor for MI. The prevalence of Hp in a current MI population and the feasibility of Hp screening as part of routine clinical care are unclear.

Aims & Methods

In this multicenter, open-label, clinical trial, all patients admitted for acute MI during the study period were eligible for enrollment. After written informed consent patients were tested for Hp infection with a bedside urea breath test (UBT [Mayoly Spindler]) incorporated into routine care during the hospitalization period.

Results

274 consecutive MI patients (median age 67 years, 24% women) were enrolled. Overall, the HP prevalence was 20% (95% CI, 15.5-25.3). The proportion of proton pump inhibitors (PPi) users was significantly higher in Hp negative compared to Hp positive patients (38% vs. 16%; P=0.003). After censoring of the 93 subjects with PPi exposure preceding the UBT, the HP prevalence was 25%. After adjusting for age and sex, smoking was found to be significantly associated with testing positive compared with negative for HP (33% vs 20%, P=0.03).

Conclusion

Hp is highly prevalent in a contemporary MI population. Hp screening in the setting of acute MI was found to be feasible. A future randomized trial is needed to determine if routine Hp screening and subsequent eradication therapy improves bleeding complications, cardiovascular outcomes, and ultimately, prognosis.

Disclosure

Mayoly Spindler generously supported the diagnostics in this study, but had no role in the design of this study, data collection or interpretation of results.

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.166

P0207 Clarithromycin Resistance Is More Common Among Less Virulent Helicobacter Pylori Strains - Data From An Irish Centre

C Sinha ¹, R FitzGerald ^1,^✉, A Whelan ², L O'Reilly ³, N Curran ³, AR Douglas ¹, D Brennan ¹, C O'Morain ¹, D McNamara ¹, S Smith ¹

Introduction

H. pylori can cause a range of pathologies, including chronic gastritis, peptic ulcers, gastric carcinoma and mucosa-associated lym-phoid tissue lymphoma. Eradication is recommended in symptomatic patients, but increasing antibiotic resistance is making eradication progressively difficult. Patients are often treated with a first-line triple therapy containing a proton pump inhibitor, clarithromycin and amoxicillin. If first-line treatment fails, patients are frequently treated with a levofloxa-cin-based second-line therapy.

There is a high level of genetic diversity among H. pylori strains. Virulence factor genotypes are known to play a role in determining the severity of disease. The vacuolating cytotoxin A (VacA), which induces vacuole formation and the cytotoxin-associated gene A (CagA), which is injected into the host cells by a type IV secretion system and influences cell signalling, are two of the most studied virulence factors. Others include the adherence protein outer inflammatory protein A (OipA) and cytotoxin-associated gene E (CagE).

Aims & Methods

To evaluate correlations between H. pylori clarithromycin and fluoroquinolone resistance and virulence factor genotype. DNA was isolated from combined antral and corpus biopsies of rapid urease test-positive endoscopy patients attending Tallaght University Hospital, Dublin. The GenoType HelicoDR assay (Hain Lifesciences) was used to detect resistance-mediating mutations. Genotyping for virulence factors was done by PCR. SPSS Statistics software (version 26) was used to perform chi-squared tests to analyse the correlations between the H. pylori virulence factor genotypes and antibiotic resistance. A p-value of < 0.05 was considered statistically significant.

Results

In all, 127 patients (mean age 48.3 ± 15.7 years; 59% (n=75/127) male) were included in the study, regardless of H. pylori treatment history. The most common histological finding was chronic gastritis (74%; n=94/127). Overall resistance to clarithromycin was 54.3% (n=69/127) and overall resistance to fluoroquinolones was 11.8% (n=15/127). 30.7% (n=39/127) of strains were cagA-positive. 60.6% (77/127) of strains had the S1/M2 vacA allele combination while 23.6% (n=30/127) had S1/M1, 15% (n=19/127) had S2/M2 and 0.8% (n=1/127) had S2/M1. 52.7% (n=67/127) of strains were cagE-positive and 56.7% (n=72/127) were oipA-positive.

Clarithromycin resistance was significantly lower in cagA-positive than cagA-negative strains (38.5% vs 61.4%, respectively: x² = 5.7, p = 0.02). Similarly, fewer cagE-positive strains were clarithromycin resistant than cagE-negative strains (44.8% vs 65%, respectively: x² = 5.2, p = 0.02). Clar-ithromycin resistance was also lower among more virulent vacA S1 genotypes compared to S2 (49.5% vs 80%, respectively: x² = 6.3, p = 0.01). No significant associations were found between oipA genotype and clarithromycin resistance or any of the virulence factor genotypes and fluroquino-lone resistance.

Conclusion

The absence of cagA, cagE and the presence of less virulent vacA genotypes are associated with clarithromycin resistance in this cohort. Although antibiotic resistance is increasing, clarithromycin resistance appears to be associated with less virulent strains of H. pylori.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.167

P0208 Genotypic Primary Resistance To Clarithromycin and Levofloxacin Detected in Stool Samples Within A Three Year Period

G Losurdo ¹, F Giorgio ^2,^✉, A Iannone ¹, F Russo ³, G Riezzo ³, E Ierardi ¹, A Di Leo ¹

Introduction

Clarithromycin and levofloxacin are two antibiotics that are commonly used to treat Helicobacter pylori (H. pylori) infection. However, the rate of antibiotic resistance is the main reason for therapy failure, and depends on point mutations in bacterial DNA. Bacterial DNA in stools may be used to detect such mutations in a non invasive way. We aimed to report the trend of H. pylori antimicrobial genotypic resistance in a three-year period, detected in fecal samples.

Aims & Methods

We enrolled consecutive people ≥18 years without previous diagnosis of H. pylori infection, referred for dyspepsia in the period 2017-19. Diagnosis of infection was achieved by concordance of histology and at least one non invasive test (either urea breath test or stool antigen).

Participants collected stool samples shortly after enrollment to be examined using a new fecal investigation (THD fecal test). A2142C, A2142G and A2143G point mutations in the 23S rRNA subunit gene for clarithromycin resistance, and C261A, C261G, G271A, A272G, G271T and A270T point mutations in the A-subunit of gyrase gene for levofloxacin resistance were assessed in stools by real time polymerase chain reaction (RT-PCR).

Results

Ninety-nine consecutive, H. pylori positive patients were enrolled (40 in 2017, 30 in 2018 and 29 in 2019). Resistance to clarithromycin was 30% in 2017, 30% in 2018 and 24.1% in 2019. Resistance to levofloxacin got ahead of 10% in 2017, 3.3% in 2018 and 34.5% in 2019. Double resistance was 5% in 2017, 3.3% in 2018 and 10.3% in 2019.

Conclusion

In the 3-year period in object, resistance to clarithromycin remained stable but above the critical threshold of 20%. On the other hand, we found a relevant peak in levofloxacin resistance in 2019 presumably due to the cross resistances among fluoroquinolones.

Disclosure

A. Di Leo served as consultant for T.H.D. spa

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.168

P0209 Impact of Helicobacter Pylori Infection On Severity of Metabolic Syndrome-Related Nonalcoholic Fatty Liver Disease

M Doulberis ^1,^2,³, S Srivastava ⁴, S Polyzos ⁵, A Papaefthymiou ^5,^6,^✉, J Klukowska-Rötzler ³, A Blank ⁷, A Exadaktylos ³, DS Srivastava ³, J Kountouras ⁸

Introduction

Nonalcoholic fatty liver disease (NAFLD) consists a novel major global burden, especially in West, and Helicobacter pylori infection (Hp-I) has been suggested as a risk factor for NAFLD, through insulin resistance (IR) and metabolic syndrome (MetS), although discrepancy exists.

This study aimed to investigate retrospectively any potential effect of active Hp-I on NAFLD severity in morbidly obese patients, subjected to bar-iatric surgery and gastric biopsy for documentation of Hp-I.

Aims & Methods

A total of 94304 patient-cases presented to the emergency department (ED) of Inselspital Bern from 1 January 2017 to 30 November 2018 were evaluated retrospectively for eligibility. Eligible were morbidly obese, adult patients underwent bariatric surgery and liver and gastric biopsy for documentation of NAFLD and active Hp-I, respectively. Grading and staging of NAFLD was based on NASH Clinical Research Network scoring systems; for the discrimination between NAFL and NASH, both NAFLD, Activity Score and Fatty Liver Inhibition of Progression were used, the latter introduced in morbidly obese populations. Histologically severe disease was defined, as steatosis, activity and fibrosis (SAF) scoring system ≥3 and/or F ≥3. Statistical analysis was performed with SPSS and significance was set at p< 0.05 (two tailed).

Results

Sixty-four patients were finally enrolled, with 15 having active Hp-I (23.4%). Higher rates of nonalcoholic steatohepatitis (NASH) were revealed to them than those without Hp-I (86.7% vs. 26.5%, respectively; p< 0.001). Histologically, steatosis grade (p=0.027), ballooning (p< 0.001), lobular inflammation (p=0.003) and fibrosis stage (p< 0.001) were also more severe in Hp infected patients. Likewise, liver function tests, and Mets parameters, like IR, dyslipidemia and arterial hypertension were significantly higher in Hp positive patients.

Conclusion

This study favors a potential impact of active Hp-I connected with Mets on NAFLD severity in morbidly obese patients underwent bariatric surgery and thus, further research is required.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.169

P0210 H.Pylori Infection and Nutritional Status in End-Stage Renal Disease Patients

M Mitrovié ^1,^✉, S Markovié ¹, D Vrinic-Kalem ¹, A Jankovié ², P Svorcan ¹

Introduction

End Stage Renal Disease (ESRD) patients have a high prevalence of malnutrition due to a protein-energy wasting. The pathogenic mechanism of this process is not completely defined, but it is possible that chronic H.pylori infection plays important role in it, possibly by causing dyspeptic symptoms, or even by decreasing the plasma levels of anabolic hormone, ghrelin.

Aims & Methods

The aim of this cross- sectional, single-center study is to investigate the prevalence of H.pylori infection in a population of ESRD patients, and it's possible influence on malnutrition development. in a period between April 1, 2016 and March 1, 2020, a total of 178 ESRD patients without previous history of verified H.pylori infection, underwent upper endoscopy with multiple mucosal biopsies as a part of pre-kidney-transplantation assessment. Before endoscopic procedures, patients were interviewed for their dyspeptic symptoms using Gastrointestinal Symptom Rating Scale (GSRS), underwent body composition measurement, and their blood levels of pepsinogen I and II, as well as acyl-ghrelin were determined. Multiple regression analysis was used to study possible impact of H.pylori infection on development of dyspepsia, histological features of gastric atrophy, plasma levels of pepsinogen and ghrelin and clinical features of malnutrition.

Results

The prevalence of H.pylori infection in our ESRD patient population was 38.2% (68/178), significantly lower than predicted by our national H.pylori prevalence (88.3%). By using GSRS, we found that H.pylori positive patients did not complain on dyspeptic symptoms more often, even though histological analysis showed that the presence of infection significantly increased the risk of atrophic body gastritis (OR 2.4, CI 1.3-4.8, p=0.037). We also found that the presence of histological features of gastric atrophy negatively correlated with acyl-ghrelin levels (29.6 vs 34.1 fmol/L; P = 0.021) as well as nutritional markers, such as pre-dialysis albumin levels (32.7 vs 39.2 g/L; P = 0.028) and body cell mass (33.0 vs 38.7%; P = 0.035).

Conclusion

Our population of ESRD patients had lower prevalence of H.pylori infection, but it significantly increased the risk of atrophic gastritis development. The possible clinical implication is that we must think of H.pylori eradication before progression to gastric atrophy in population of ESRD patients, in order to improve their prognosis and possibly quality of life.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.170

P0211 Application of Olga and Olgim Staging Systems in Hp Gastritis

F Ben Farhat ^1,^✉, M Sabbah ², B Nawel ², Z Benzarti ², D Trad ², F Khanchel ³, N Bibani ², A Kchaou Ouakaa ¹, D Gargouri ²

Introduction

H. pylori infection is strongly associated with chronic gastritis and is probably the main course of chronic inflammation in the gastric mucosa. Gradually, HP gastritis will result in gastric atrophy (GA) and intestinal metaplasia (IM), the two detectable precursor lesions in gastric carcinomas. Early endoscopic examination is of paramount importance in the early detection and treatment of advanced precursor lesions and cancer.

Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) are adopted to individualize the case with high evolutionary risk.

Aims & Methods

The aim of our study was to evaluate OLGA and OLGIM staging system in HP gastritis and to determine any correlations between these classifications.

One hundred and forty nine patients who underwent upper-endoscopy were enrolled into our study retprospectively from January 2019 to June 2019. The diagnosis of HP gastritis was confirmed by histologic examination. Epidemiological, endoscopic and anathomopathological data were collected. OLGA and OLGIM systems were applied to classify our patients according to cancer risk (stages 0-II are associated with low risk, while stages III and IV with high risk).

Results

Mean age was 51,27 years, the sex ratio 0.88. Upper endoscopy was epigastric pain in 60%, anemia in 18%, vomiting in 10,5 % and diarrhea in 6%. Endoscopic findings included antral gastropathy in 63%, fundic gastropathy in 20% and ulcers in 22%. According to histologic examination, HP density was mild in 28,8%, moderate in 34,2% and marked in 36%. Gastric atrophia was noted in 20,7%. It was mild in 64,5% and moderate in 22,5%. Six patients had severe GA and according to OLGA staging system low risk gastritis represented 95,2% and high risk gastritis were 4,8%. Intestinal metaplasia was noted in 16,7%. It was mild in 52%, moderate in 24% and six patients had severe IM.

According to OLGIM stagin system, low risk gastritis represented 94,6% and high risk represented 5,4%. There was no significant association between the OLGA and OLGIM stages and the HP density (p=0,2 and p=0,42 respectively). However, low risk gastritis in OLGA staging system were significantly associated with marked HP density (p=0,017) and high risk gastritis were associated with mild HP density (p=0,016). The association between OLGA staging system and the degree of intestinal metaplasia was significant (p< 0,001) as well as the association between OLGIM staging system and the degree of gastric atrophia (p< 0,001). According to both OLGIM and OLGA staging system, 91,5% patients had low risk gastritis and 5,2% had high risk gastritis with a positive correlation between the two systems (p< 0,001). Discrepancies were noted in five cases.

Conclusion

OLGA and OLGIM staging systems can be very useful in evaluating gastric cancer risk. This correlation implies that close and frequent monitoring of high-risk patients is necessary to facilitate early diagnosis of gastric cancer.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.171

P0212 Endoscopic Yield of Chronic Epigastric Pain Syndrome in Outpatients

F Ben Farhat ^1,^✉, M Sabbah ², B Nawel ², Z Benzarti ², D Trad ², N Bibani ², A Kchaou Ouakaa ¹, D Gargouri ²

Introduction

The diagnostic evaluation and management of patients with chronic epigastric pain syndrom may differ geographically according to patient age, prevalence of Helicobacter pylori, and risk of gastric cancer. Guidelines recommend early endoscopy in dyspeptic patients who are older than 45 years, or present alarm features.

Aims & Methods

The aim of our study was to determine the prevalence of H. pylori and the performance characteristics of alarm features in predicting organic lesions.

A retrospective study of 91 patients with chronic epigastric pain who underwent upper endoscopy from January To June 2020 was conducted. Clinical characteristics, H. pylori prevalence, endoscopic and histological findings of patients with functional or organic causes of dyspepsia were compared. Organic lesions are defined by the presence of ulcers (defined as mucosal break of 3 mm or greater) or cancer (confirmed by histology). Alarm features are recent onset dyspepsia in a person > 45 years, odyno-phagia, progressive dysphagia, upper gastrointestinal bleeding, recurrent vomiting, unexplained weight loss. SPSS version 22.0 was used for the descriptive and comparative analyses.

Results

Mean age was 49.71 (±16.5) years, 43.9% were male. Common alarm features were recent onset dyspepsia in a patient over 45 years in 62%, recurrent vomiting in 10.9% and anemia in 6.5%. The most frequent endoscopic finding was antral gastropathy in 59.8%. The major organic lesions were gastric or duodenal ulcers (21,7%). No malignancies were noted. Twenty one patients had normal esophagogastroduodenoscopy (EGD)(23,07%). The prevalence of H.Pylori was 64%. of patients with organic lesions, 70% were H. pylori- positive.

In univariate analysis, only age older than 45years was associated with organic lesions (p=0,05). The pooled sensitivity and specificity of any alarm feature for organic lesions were 80% and 63%, the PPV and NPV were 26,2% and 86,7% respectively.

Conclusion

In our experience, most of chronic epigastric pain syndrome were diagnosed with functional or H. pylori-associated syndrome. The presence of alarm features was not sensitive or specific for differentiating organic and functional dyspepsia.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.172

P0213 Nrf2 Role and Targeting in Helicobacter Pylori-Induced Gastric Carcinogenesis

O Martin ^1,^✉, S Bacon ¹, E Sifre ¹, P Lehours ^1,², C Varon ¹

Introduction

Gastric cancer (GC) is the third leading cause of cancer death worldwide and is responsible of many relapse cases. Chronic infection with Helicobacter pylori is the major risk factor of GC through induction of chronic inflammation and oxidative stress. Our team has participated to the demonstration that H. pylori infection leads to the emergence of cells having cancer stem cells (CSC) properties through an epithelial to mesenchymal transition (EMT). The transcription factor Nrf2 is the major driver of cellular antioxidant response activated after a high oxidative stress. in addition, Nrf2 expression has been correlated to gastric cancer progression and is higher in cancer stem cells.

Aims & Methods

The aims of the project are: (i) to check the activation of Nrf2 signaling pathway after H. pylori infection, (ii) to decipher the role of Nrf2 in EMT and CSC emergence and (iii) to target the pathway using polyphenols which are natural modulators of Nrf2.

Results

Kinetic infection of AGS and MKN74 cells with H. pylori induces an early activation of Nrf2 signaling pathway shown by increase of nuclear translocation of Nrf2, by activation of the antioxidant responsive element (ARE) sequence and by increase expression of target genes and proteins such as GSH, HO-1, SOD, catalase, TRX. Inhibition of Nrf2 by CRISPR-Cas9 strategy leads to an increase of EMT-related gene expression and to cells with CSC properties shown by tumorsphere assays. Transcriptomic analyses of patient-derived xenograft (PDX) cells, FACS-sorted for the CSC marker CD44, showed that CD44+ cells exhibit a higher Nrf2 signature than CD44^- cells. Moreover, polyphenols can be used to target Nrf2 and can be combined with classical chemotherapy agents to decrease the number of tumorsphere-forming cells.

Conclusion

In conclusion, infection with H. pylori induces an early activation of the Nrf2 signaling pathway. Our results demonstrate that Nrf2 is important for the maintenance of the epithelium integrity and the control of CSC emergence and is overactivated in CD44+ gastric PDX cells. Finally, it is possible to modulate Nrf2 using natural polyphenols to specifically target CSC.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.173

P0214 Luminal Nitric Oxide Is Increased in Helicobacter Pylori-Induced Gastric Inflammation and Related To Virulence Factors of The Bacterium

H Saaed ^1,^✉, A-S Rehnberg ², D-L Webb ³, C Rubio ², R Befrits ², PM Hellström ⁴

Introduction

Helicobacter pylori (H. pylori)categorized as the major risk factor in the development of chronic gastritis, peptic ulcer disease and gastric cancer, is considered a major health threat worldwide. Nitric oxide (NO)has been shown to protect the gastric mucosa against damage and to stimulate repair and healing of mucosal inflammation, erosions and ulcerations. in line with this, NO produced via inducible nitric oxide syn-thase might be elaborated in response to Helicobacter pylori-associated inflammation.

Aims & Methods

The present study was conducted to investigate the relationship between H. pyloriinfection, and gastric luminal NO levesl with inflammatory-associated immunological and histopathological findings and the possible usefulness of NO measurements in the diagnostic setting.

In 96 consecutive adult patients (56 women, 40 men), who were referred to routine diagnostic upper gastrointestinal endoscopy after being diagnosed with H. pylori infection by the urea breath test (UBT). Immediately during upper endoscopy, luminal NO was measured by chemilumines-cence, and two biopsies were obtained for culture, one from the gastric antrum and one from corpus. in addition, ELISA and immunoblot tests performed on blood samples.

Later, measured NO levels were correlated with the presence of H. pylori, the immune response to virulence factors of the bacteria, e.g. CagA, VacA, the ELISA optical density and histopathological grades for acute and chronic inflammation, atrophy, intestinal metaplasia and pseudopylo-ral metaplasia. in a subset of patients and controls a 40-plex cytokine/ chemokine electrochemiluminescence assay was carried out in order to reveal possible inflammatory mediators in Helicobacterinfection and NO release.

Results

H. pylori-positive patients had significantly higher luminal NO levels (336 ±26 ppb) than H. pylori-negative(128 ±47 ppb) (p< 0.0001). The H. pylori-positive with CagA-negativeinfection had slightly higher NO levels (390 ±56 ppb) than the CagA-positive(321 ±30 ppb) patients. No correlation was seen between the NO level and presence of VacA. Histopathological changes of the mucosa were found in almost all (99%) H. pylori-positive patients.

However, 37% of the H. pylori-negative patients displayed histopathological changes. High percentage 78-100% of histopathological concordance were found between the paired biopsies from the corpus and antrum, which displayed the same histological grade. A positive trend was found between the gastric luminal NO levels and the degree of acute inflammation. Similarly, a positive trend was noted between mean serum lgG ELISA optical density (OD) readings and degree of chronic inflammation. The grading of atrophy, intestinal metaplasia or pseudopyloral metaplasia did not correlate with the measured gastric NO levels.

Conclusion

Our study results show that luminal gastric NO is increased in H. pylori-infected patients due to the inflammatory response in the mu-cosa. Positive trends were found between the gastric luminal NO levels and the degree of acute inflammation in the mucosa, as well as the serum levels of anti-H. pylori IgG and CagA-positivity in the bacterial strains.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.174

P0215 “Test-And-Treat” Strategy with Urea Breath Test: A Cost-Effective Approach For The Management of Helicobacter Pylori-Related Dyspepsia and The Prevention of Peptic Ulcer in The United Kingdom - Results of The Hp-Breath Initiative

DM Pritchard ^1,^✉, J Bornschein ², ILP Beales ³, H Salhi ⁴, A Beresniak ⁵, P Malfertheiner ^6,⁷

Introduction

Clinical data comparing strategies used for the management of H. pylori-associated diseases are limited. in the UK, Stool Antigen Test (SAT) seems to be the most frequently used non-invasive test for H. pylori detection. Cost-effectiveness studies might help to identify optimal strategies.

Aims & Methods

To assess cost-effectiveness of the “Test-and-Treat” strategy with Urea Breath Test (UBT) versus other strategies, in patients with H. pylori-associated dyspepsia and peptic ulcer in the UK. Cost-effectiveness models compared four strategies: “Test-and-Treat” including either UBT or SAT, “Endoscopy and Treat” and “Symptomatic Treatment”. Advanced simulations were performed over a 4 week time horizon for the endpoint “Probability of dyspepsia symptoms relief” and over 10 years for the “Probability of peptic ulcer avoided”. Models were developed according to UK routine medical practice and costs.

Results

For the “Probability of dyspepsia symptoms relief” endpoint, “Test-and-Treat” strategies with either UBT or SAT were the most cost-effective (respectively 526€ and 518€/success) versus “Endoscopy and Treat” and “Symptomatic Treatment” (respectively 1,280€ and 1,029€/success). For the “Probability of peptic ulcer avoided” endpoint, “Test-and-Treat” strategies with either UBT or SAT were also the most cost-effective (respectively 208€ and 191€/peptic ulcer avoided/year) versus “Endoscopy and Treat” and “Symptomatic Treatment” (respectively 717€ and 651€/peptic ulcer avoided/year); (1 EUR = 0,871487 GBP).

Conclusion

“Test-and-Treat” strategies with either UBT or SAT are the most cost-effective medical approaches for the management of H. pylori-associated dyspepsia and the prevention of peptic ulcer in the UK. “Test-and-Treat” strategy with UBT has comparable cost-effectiveness outcomes to the strategy utilising SAT.

Disclosure

This study was funded by Mayoly Spindler Laboratories. DMP, JB, ILPB, PM have received honoraria from Mayoly Spindler Laboratories for their contribution to the study; HS is an employee of Mayoly Spindler Laboratories; AB has received honoraria from Mayoly Spindler Laboratories for data management and data analyses; PM has received honoraria for consultancy from Bayer, Danone and speaker honoraria from Alfasig-ma, Bayer, Dr Falk, Malesci.

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.175

P0216 Personalised Medicine: Is This The Way To Combat Helicobacter Pylori (Hp) Eradication Failure?

CK Tai ¹, S hwang ^1,^✉, J Klein ², K Woods ³, A Jepson ³, V Kulhalli ¹, G Tritto ⁴, L Marelli ⁵

Introduction

Antibiotic-resistant HP varies in different geographical areas. A recent review of international guidelines suggest evidence-based locally relevant treatment strategies. Within the United Kingdom, hospitals develop local antibiotic guidelines as per local resistance rates. However, Public Health England (PHE) recommendation for treatment regimes in primary care remains to be clarithromycin and metronidazole-based regimes for patients with dyspepsia who are HP positive. The Gastrointestinal Bacteria Reference Unit (GBRU), PHE is the national reference laboratory which tests all HP cultures in England. We aimed to look local HP secondary resistance data from 3 different units in London and compared whether variation in specimen collection practice impacted on rates of HP culture positivity.

Aims & Methods

We compared culture data from 3 different units in London. Due to differences in the local databases used, the date ranges of data collected was varied.

We obtained 34 months data between March 2016 and December 2018 from Homerton University Hospital (HUH). There were no local guidelines at HUH regarding number of biopsy samples taken and samples were transported to the lab routinely.

Culture data from Guys & St Thomas’ Hospital (GST) was for 10 months between January to October 2019. At least 4 to 6 samples were taken on Monday to Thursday morning lists to ensure samples are sent to reference lab urgently.

Culture data from Newham University Hospital (NUH) was for 12 months from October 2018 to October 2019. At least 6 gastric biopsy samples were taken on a dedicated endoscopist's list on a weekday morning and samples were urgently transported by taxi to the laboratory.

Results

122 gastric biopsy samples were sent in HUH and 36 isolated HP, giving a 29.5% positive culture rate.

112 gastric biopsy samples were sent in GST and 72 isolated HP, giving a 64.2% positive culture rate.

34 gastric biopsy samples were sent in NUH and 15 isolated HP, giving a 44.1% positive culture rate.

Phenotypic HP sensitivities by hospital:

Amoxicillin: HUH 100%, GST 100%, NUH 100%

Tetracycline: HUH 97%, GST 100%, NUH 100%

Levofloxacin: HUH 72%, GST 77%, NUH 53%

Metronidazole: HUH 4%, GST 20%, NUH 7%

Clarithromycin: HUH 28%, GST 39%, NUH 7%

Percentage of antibiotic resistance by hospital:

HUH - 22% single resistance, 56% dual resistance, 22% triple resistance

GST - 19% fully sensitive, 23% single resistance, 39% dual resistance, 19% triple resistance

NUH - 7% single resistance, 53% dual resistance, 40% triple resistance.

Conclusion

38% of UK's foreign born population live in London. Variation in concentrations of migrant communities within a city can lead to variations in antimicrobial resistance. Our results are skewed towards resistant isolates as patients having gastroscopy and cultures taken for HP sensitivity would have had multiple courses of antibiotics. They suggest a benefit in tailoring local second line antimicrobial guidelines to local resistance rates. Given the lack of amoxicillin resistance, we recommend penicillin allergy testing for patients who report allergy.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.176

P0217 Accuracy of The Helicobacter Pylori Diagnostic Tests in Patients with Peptic Ulcer Bleeding- The Results of A Network Meta-Analysis

N Vörhendi ^1,^✉, P Hegyi ², B Tinusz ³, P Sarlós ⁴, Z Szakács ⁵, A Miko ⁵, D Pécsi ³, B Eross ⁵

Introduction

Peptic ulcer (PU) being the most frequent source of gastrointestinal bleeding and Helicobacter pylori is a main etiologic factor for it. Some studies suggest accuracy of the diagnostic tests is decreased in PU bleeding. The international guidelines are vague on the method of testing in the setting of acute PU bleeding. However, detection of H. pylori would be essential as it reduces the risks of untoward outcomes.

Aims & Methods

Our aim was to update the most recent meta-analysis [1] which included studies until 2004 and to asses the accuracy of one or a combination of more diagnostic tests for H. pylori in patients with bleeding peptic ulcer.

A comprehensive literature search was carried out from inception to November 2019 to perform a network meta-analysis. We collected the raw data of diagnostic tests such as true positive, true negative, false positive and false negative values. All statistical calculations performed by R programming language using anova arm-based model by Nyaga et al., 2018. We ranked the methods index tests according to the superiority index and calculated pooled sensitivity and specificity.

Results

We analyzed 7 arbitrary gold standards in 7 networks against a single or a combination of diagnostic index tests. None of the calculated superiority indices proved that any of the tests have better diagnostic accuracy than the individual index tests.

Conclusion

The results from the network meta analysis showed that none of the current diagnostic tests for H. plyori are better or worse in the diagnosis of the infection in the context of PU bleeding.

Disclosure

Nothing to disclose

References

Gisbert J.P., and Abraira V. Accuracy of Helicobacter pylori diagnostic tests in patients with bleeding peptic ulcer: a systematic review and meta-analysis. Am J Gastroenterol, 2006. 101(4): p. 848–63. [DOI] [PubMed] [Google Scholar]

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.177

P0218 Management of Helicobacter Pylori Infection At The Primary Care Level: Evaluation Ofdifferent Strategies To Improve Its Approach

E Alfaro ^1,^✉, V Laredo De La Torre ¹, C Sostres Homedes ^1,², T Arroyo Villarino ¹, A Lanas ^1,^2,³

Introduction

Helicobacter pylori (Hp) infection is now mainly managed at primary care level. Previously, our group showed that the strategy of sending specific counselling (SC) to primary care physicians (PCP), (a personal letter with accepted indications and treatment issued by their referent Gastroenterologist) has significantly improved treatment regimens and eradication rates, but not indications (1). New strategies in order to improve Helicobacter Pylori infection management are still needed.

Aims & Methods

To evaluate and compare the effect of formative lessons (FL) in primary care centers (PCC) in addition to sending specific counselling in urea breath test (UBT) indications, treatment regimens and eradication rates.

Firstly, we prospectively included 399 consecutive UBT indicated by PCP after sending a SC

(Phase I). Then, formative lessons were given in four PCC from our health area with high number of UBT requests. After that period, 400 consecutive UBT were prospectively included, 100 from PCC with FL and 300 from PCC without FL (Phase II). Specific counselling has been previously sent to both groups of PCC.

Appropriate UBT indications and treatment regimens were considered according to national guidelines and consensus documents.

Results

We have analyzed 799 UBT, 399 after sending SC and 400 after FL period (100 from PCC with FL and 300 from PCC without FL). The mean age was 47.33±15.68 years old, 64.7% were women. An improved trend is observed in appropriate indication between phase I group (SC sent) and PCC with FL (57.5% vs 67%; p=0.06). No differences were observed in appropriate indications between PCC with FL and without FL (67% vs 62.9% p=0.45). Appropriate treatment regimens were significantly higher in PCC with FL compared to phase I group (94% vs 75.3%; p=0.01). Also they were significantly higher in PCC with FL compared to PCC without FL (94% vs 85.6%; p=0.03). However, no differences in eradication rates were observed among groups.

Conclusion

The strategy of sending specific counselling to PCP has significantly improved treatment regimens and eradication rates but not indications. Formative lessons after sending a specific counselling improve indications and treatment regimens but no eradiation rates.

Disclosure

Nothing to disclose

References

1.Laredo V., Sostres C., Alfaro E., Arroyo M.T., Lanas Á. Management of Helicobacter pylori infection at the primary care level. The implementation of specific counseling improves eradication rates. Helicobacter. 2019; e12586. 10.1111/hel.12586 [DOI] [PubMed] [Google Scholar]

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.178

P0220 Efficacy and Safety of Modified Bismuth Quadruple Therapy and Concomitant Therapy For Helicobacter Pylori Infection in Rajavithi Hospital: A Randomized Controlled Trial

K Chanpiwat ^1,^✉, K Lohkittivanich ¹, C Bunchorntavakul ¹

Introduction

The failure rate of the standard triple therapy for H. pylori infection has been increasing due to the rising prevalence of antimicrobial resistance. Concomitant therapy has been recommended to replace the standard triple therapy in regions with high rate of clarithromycin resistance. Since bismuth has shown its effectiveness to increase the eradication rate of H. pyroli infection with lower treatment-related side effects, this study was, therefore, conducted to compare the efficacy and safety of H. pyroli eradication using the triple bismuth therapy and standard concomitant therapy.

Aims & Methods

This study was conducted to i) compare the H. pylori eradication rates in patients treated with different treatment interventions (10-day modified triple bismuth therapy and 10-day standard concomitant therapy) and ii) assess the treatment-related side effects between the treatment regimens.

Materials and methods

A total of 205 patients who underwent upper gastrointestinal endoscopy at Rajavithi Hospital, Bangkok between January 2018 and November 2018 and were diagnosed with H. pylori infection were included. Considering the exclusion criteria of severe comorbidities, previous H. pylori treatment, history of antibiotic ingestion, and penicillin allergy, 173 active H. pylori infected patients were randomized (1:1) and allocated into either the 10-day modified triple bismuth therapy (omeprazole 20 mg b.i.d., amoxicillin 1000 mg b.i.d., clarithromycin 500 mg b.i.d. and bismuth subsalicylate 1048 mg b.i.d.) or the 10-day standard concomitant therapy (omeprazole 20 mg b.i.d., amoxicillin 1000 mg b.i.d., clarithromycin 500 mg b.i.d. and metronidazole 400 mg t.i.d.). Four weeks after the completion of treatment, the ¹⁴C-urea breath test was performed to evaluate the H. pylori eradication rate. The efficacies of treatments were analyzed using the intention-to-treat (ITT) and per-protocol (PP) analyses. The safety of treatment was evaluated by using the records of the treatment-related symptoms and side effects and patients’ compliance.

Results

A total of 86 and 87 H. pylori infected patients were randomly allocated into the 10-day modified triple bismuth therapy and standard concomitant therapy, respectively. The eradication rates of the modified triple bismuth therapy were 87.2% for ITT and 92.6% for PP. While the eradication rates of the standard concomitant therapy were 87.4% for ITT and 92.7% for PP. The common mild side effects of both regimens which were bitter taste, nausea, dizziness, and vomiting were less commonly reported in the modified triple bismuth group. Bitter taste was the most common side effect of both treatment regimens with the incidence of 13.6% in the modified triple bismuth group and 25.6% in the standard concomitant group. Two patients of the standard concomitant group experienced severe nausea/vomiting, headache and dizziness after the treatment.

Conclusion

The H. pylori treatment using the 10-day modified triple bismuth therapy achieved the acceptable eradication rate with fewer side effects, as compared to the standard 10-day concomitant therapy. This regimen can be considered as a good alternative H. pylori treatment in Thailand.

Disclosure

Nothing to disclose

References

1.Hooi J.K.Y., Lai W.Y., Ng W.K., Seun M.M.Y., Underwood F.E., Tany-ingoh D., Malfertheiner P., Graham D.Y., Wond V.W.S., Wu J.C.Y., Chan F.K.L., Sung J.J.Y., Kaplan G.G., Ng S.C. Global prevalence of Helicobacter pylori infection: Systematic review and meta-analysis. Gastroenterology. 2017; 153: 420–429. [DOI] [PubMed] [Google Scholar]
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3.Uchida T., Miftahussurur M., Pittayanon R., Vilaichone R., Wisedopas N., Ratanachu-ek T., Kishida T., Moriyama M., Yamaoka Y., Mahachai V. He-licobacter pylori infection in Thailand: A nationawide study of the CagA phenotype. PLOS ONE. 2015; 1–13. DOI: 10.1374/journal.pone.0136775. [DOI] [PMC free article] [PubMed] [Google Scholar]
4.Mahachai V., Vilaichone R., Pittayanon R., Rojborwonwitaya J., Leelakuso-lvong S., Kositchaiwat C., Mairiang P., Praisontarangkul O., Ovartlarnporn B., Sottisuporn J., Pisespongsa P., Maneerattanaporn M., Sony R., Sirinthornpu-nya S., Chaiyamahapurk O., Wiwattanachange O., Sansak I., Harnsomboon P., Chitapanarux T., Chuenrattanakul S. Thailand consensus on Helicobacter pylori treatment 2015. Asian Pacific Journal of Cancer Prevention. 2016; 17: 2351–2560. [PubMed] [Google Scholar]
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United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.179

P0221 Randomized Clinical Trial Comparing Triple Therapy Versus Non-Bismuth Based Quadruple Therapy For Eradication of Helicobacter Pylori in Kuwait

A Dangi ¹, A Alfadhli ¹, M Afifi ², M Alboraie ^3,^✉

Introduction

Helicobacter pylori (H. pylori) induced chronic infection is associated with peptic ulcer, chronic gastritis, gastric cancer, and increasing antibiotic resistance. Eradication of H. pylori reduces morbidity in patients with chronic gastritis and can prevent gastric cancer in the high-risk population.

Aims & Methods

We aimed to evaluate the efficacy of clarithromycin-based triple therapy and non-bismuth based quadruple therapy for eradicating H. pylori in patients with chronic gastritis in Kuwait. We enrolled a total of 606 treatment-naive dyspeptic patients with gastric biopsy-proven chronic gastritis secondary to H. pylori in a prospective, open-label, randomized study conducted at the gastroenterology outpatient clinics of Haya Al-Habeeb gastroenterology center in Kuwait. Patients were randomized into two groups: the first group received the standard triple therapy (omeprazole, amoxicillin, and clarithromycin) for 14 days; and the second group received quadruple therapy (omeprazole, amoxicillin, clarithromycin, and metronidazole) for 14 days. All patients were tested for the eradication of H. pylori by carbon-13 urea breath test (13 C- UBT) one month after completion of eradication therapy.

Results

The overall eradication rate in both groups was 63.18%. The eradication rates in intention to treat (ITT) and per protocol (PP) population were 58.4% and 64.6%, respectively in triple therapy group. While in the quadruple therapy group, the eradication rates in ITT and PP population were 68% and 78.5%, respectively with a statistically significant higher eradication rate in patients treated by quadruple therapy than the triple therapy (P>0.01). Multivariate logistic regression analysis showed that treatment regimen was the only significant predictor for successful H. pylori eradication (OR 1.98, 95% CI [1.3 to 2.9]); P=0.001). The most common adverse events were abnormal taste, headache, dizziness, and abdominal pain.

Conclusion

Non-bismuth based quadruple therapy is more effective than slandered clarithromycin-based triple therapy for eradicating H. pylori in patients with chronic gastritis in Kuwait.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.180

P0222 Rifabutin Triple Therapy For First-Line and Rescue Treatment of Helicobacter Pylori Infection: A Systematic Review and Meta-Analysis

R Gingold - Belfer ¹, Y Niv ¹, Z Levi ², D Boltin ^2,^✉

Introduction

Due to the increasing resistance of H. pylori there is a need for novel antibiotic treatment protocols.

Aims & Methods

We aimed to perform a meta-analysis of clinical trials in order to determine the effectiveness and safety of rifabutin triple therapy for H. pylori infection. We selected prospective clinical trials with a treatment arm consisting of proton pump inhibitor, amoxicillin and rifabutin, and a recorded outcome measure.

Results

Thirty-three studies including 44 data sets were included. The pooled eradication success for rifabutin triple therapy was 73.2% (95% CI 0.710-0.753) and the pooled OR for rifabutin triple therapy vs control was 1.40 (95% CI 1.103-1.775, I²=73.55, p=0.006). Treatment was more likely to be successful when given first line vs rescue (82.4% vs 71.3%, p=0.0001), in Asian vs non-Asian populations (81.0% vs 72.4% p=0.001) and when drug dose or duration were augmented (80.6% vs 66.0% p=0.0001). The overall event rate for adverse effects was 25.3% (95% CI 0.23-0.28) and the pooled OR for adverse effects in the treatment vs control group was 0.79 (95% CI 0.57-1.09, I²=61.58, p=0.15).

Conclusion

Rifabutin is a relatively safe and effective option for first-line and rescue treatment for H. pylori infection in adults.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.181

P0223 Pcab-Based Helicobacter Pylori Eradication in Patients with Penicillin Allergy

S Sue ^1,^✉, T Sasaki ¹, H Kaneko ¹, K Irie ¹, M Kondo ¹, S Maeda ¹

Introduction

Recently, the potassium-Competitive Acid Blocker, Vono-prazan, has been increasingly used for Helicobacter pylori eradication in Japan, and a meta-analysis has demonstrated a higher eradication rate using a vonoprazan-containing regimen combined with amoxicillin and clarithromycin than PPI based regimen. of all patients, 3-7% are allergic to penicillin. in cases of penicillin allergy, it is necessary to develop a new regimen without amoxicillin, and clarithromycin, metronidazole, and sita-floxacin currently represent the major antibiotics for H. pylori eradication therapy in Japan.

Aims & Methods

To reveal the effectiveness and safety of first-line therapy with vonoprazan, clarithromycin, and metronidazole, and second-line therapy with vonoprazan, metronidazole, and sitafloxacin for H. pylori infected patients with penicillin allergy. This interventional single arm study was registered as jRCTs031180133. The treatment regimens were vono-prazan 20mg bid, clarithromycin 200mg or 400mg bid, and metronidazole 250mg bid 7days for first-line therapy, and vonoprazan 20mg bid, metronidazole 250mg bid, and sitafloxacin 100mg bid 7days for second-line. Eradication success was assessed by the urea breath test.

Results

Sixty cases were enrolled. The average age of the patients was 65 years old. Seventeen males and 43 females were included. The first patient was included in March 2015, and about 15 patients per year were included thereafter. The last patient was included in August 2019. Forty-three and 17 cases underwent first-line or second-line eradication therapy, respectively. The eradication rate of first-line therapy with vono-prazan, clarithromycin and metronidazole for 7-days was 92.9% (95%CI: 80.5-98.5%, n=42), and the eradication rate of second-line therapy with vonoprazan, metronidazole and sitafloxacin for 7-days was 88.2% (95%CI: 63.6-98.5%, n=17). One patient in whom H. pylori was eradicated with first-line therapy was excluded from analysis, because the urea breath test was not performed after the eradication. in all 60 cases, drug compliance was good, and no serious adverse events were reported.

Conclusion

First-line 7-day therapy with vonoprazan, clarithromycin and metronidazole, and second-line 7-day therapy with vonoprazan, metronidazole and sitafloxacin showed sufficient efficacy and safety for H. pylori infected patients with penicillin allergy.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.182

P0224 Phase 3 Study Evaluating The Efficacy and Safety of Vonoprazan 20 Mg Versus Lansoprazole 30 Mg in The Treatment of Endoscopically Confirmed Duodenal Ulcers in Asian Subjects with Or Without Helicobacter Pylori Infection

X Hou ^1,^✉, F Meng ², J Wang ³, W Sha ⁴, CT Chiu ⁵, WC Chung ⁶, L Gu ⁷, K Kudou ⁸, CF Chong ⁹, S Zhang ²

Introduction

Duodenal ulcers (DU) are a growing health concern in Asia. Proton-pump inhibitors such as lansoprazole are the first-line therapy for DU. Vonoprazan, a potassium-competitive acid blocker, has shown superior healing compared with lansoprazole in Japanese patients with erosive esophagitis; however, lack of sufficient clinical data for use of vonoprazan in Asian patients with DU.

Aims & Methods

This study, evaluated the efficacy and safety of vonoprazan versus lansoprazole in the treatment of DU in Asian patients. in this phase 3, multicentre, double-blind, double-dummy, non-inferiority, randomised study, Asian adults with endoscopic evidence of active DU ≥5 mm received oral vonoprazan 20 mg or lansoprazole 30 mg. The study drugs were given once daily, but Helicobacter pylori (Hp) + patients received the study drugs twice daily for the first 2 weeks as part of bismuth-containing quadruple Hp eradication therapy.

Primary end point was percentage of patients with endoscopically confirmed healing of DU, defined as disappearance of all white coats associated with DU, at week 4 or 6. Secondary end points included successful Hp eradication after 4 or 6 weeks, as determined by ¹³C urea breath test 4 weeks post-treatment and resolution of gastrointestinal (GI) symptoms associated with DU at weeks 2 to 6. The non-inferiority margins were -6% and -10% for the primary and Hp eradication end points using a 2-sided 95% confidence interval (CI).

Results

In total, 533 patients were randomised to receive either vonoprazan (n = 265) or lansoprazole (n = 268). Baseline characteristics were comparable between the groups. Majority (85.4%) of the patients were Hp+. The primary outcome of endoscopically confirmed healing of DU was observed in 96.9% and 96.5% of patients in the vonoprazan and lansoprazole groups, respectively (difference: 0.4%; 95% CI: -3.00%, 3.79%), thus meeting the primary end point of non-inferiority of vonoprazan versus lansoprazole. The lower limit of CI was above the non-inferiority margin of -6%. The secondary outcome of Hp eradication was seen in 91.5% and 86.8% of patients in the vonoprazan and lansoprazole groups, respectively (difference: 4.7%; 95% CI: -1.28%, 10.69%), showing non-inferiority of vonoprazan versus lansoprazole. No significant difference was observed in the percentage of subjects with post-treatment resolution of GI symptoms between the 2 groups. Treatment-emergent adverse event (TEAE) rates were 74.1% and 64.9% for vonoprazan and lansoprazole, respectively. The difference in TEAE rates was largely due to higher incidences of pepsinogen test positive (47.1% vs. 10.4%), pepsinogen I increased (35.0% vs. 13.8%) and abnormal gastrin test (36.9% vs. 7.5%) in the vonoprazan group compared with lansoprazole group, respectively. Treatment discontinuation rates due to TEAE were 1.5% (n = 4) and 2.2% (n = 6) in the vonoprazan and lansoprazole groups, respectively. Serious TEAE rates were similar between the groups (vonoprazan, 0.4%, n = 1; lansoprazole, 1.1%, n = 3), with no deaths reported in both the groups.

Conclusion

Vonoprazan was non-inferior to lansoprazole in healing DU and eradicating Hp in Asian patients. Vonoprazan was well tolerated and had a similar safety profile to lansoprazole.

Disclosure

The study was funded by Takeda Pharmaceutical Company Ltd. Liqun Gu and Chui Fung Chong are employees of Takeda Development Center Asia, Pte, Ltd, and Chui Fung Chong is the stock shareholder in Air Liquide and Abbott Laboratories. Ltd. Kentarou Kudou is an employee of Takeda Pharmaceutical Company Limited, Japan. Shutian Zhang, Xiaohua Hou, Fandong Meng, Jiangbin Wang, Weihong Sha, Cheng-Tang Chiu and Chung Woo Chul have no disclosures.

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.183

P0225 First-Line H. Pylori Eradication Therapy in Europe: Results From 24,882 Cases of The European Registry On H. Pylori Management (Hp-Eureg)

OP Nyssen ¹, DS Bordin ², B Tepeš ³, MÁ Perez Aisa ⁴, M Caldas Álvarez ^1,^✉, L Bujanda Fernández de Piérola ⁵, M Pabon Carrasco ⁶, M Castro Fernandez ⁶, F Lerang ⁷, M Leja ⁸, T Rokkas ⁹, L Kupcinskas ¹⁰, L Jonaitis ¹¹, O Shvets ¹², A Gasbarrini ¹³, A Axon ¹⁴, H Şimşek ¹⁵, GM Buzás ¹⁶, JCL Machado ¹⁷, Y Niv ¹⁸, L Boyanova ¹⁹, L Rodrigo ²⁰, J Perez-Lasala ²¹, E-A Goldis ²², V Lamy ²³, A Tonkic ²⁴, K Przytulski ²⁵, C Beglinger ²⁶, M Venerito ²⁷, P Bytzer ²⁸, L Capelle ²⁹, V Milivojevic ³⁰, L Veijola ³¹, J Molina Infante ³², L Vologzhanina ³³, V Dino ³⁴, G Fadeenko ³⁵, I Ariño Pérez ³⁶, G Fiorini ³⁷, A Garre ¹, A Keko-Huerga ⁶, F Heluwaert ³⁸, J Garrido ³⁹, C Fernandez Perez ⁴⁰, I Puig ⁴¹, F Megraud ⁴², C O'Morain ⁴³, JP Gisbert ¹, On behalf of the Hp-EuReg Investigators.

¹Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Gastroenterology Unit, Madrid, Spain

²A.S. Loginov Moscow Clinical Scientific Center, Department of pancreatic, biliary and upper GI diseases, Moscow, Russian Federation

³Abakus Medico d.o.o., Gastroenterology, Rogaska Slatina, Slovenia

⁴Agencia Sanitaria Costa del Sol, Red de Investigación en Servicios de Salud en Enfermedades Crónicas (REDISSEC), Servicio de Gastroenterologia, Marbella, Spain

⁵Hospital Donostia/Instituto Biodonostia, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Universidad del Pais Vasco (UPV/EHU), Department of Gastroenterology, San Sebastian, Spain

⁶Hospital de Valme, Digestive Unit, Sevilla, Spain

⁷Central Hospital Ostfold, Medicine, Fredrikstad, Norway

⁸University of Latvia, Institute of Clinical and Preventive Medicine & Faculty of Medicine, Digestive Diseases Centre GASTRO, Riga, Latvia

⁹Henry Dunant Hospital, Department of Gastroenterology, Athens, Greece

¹⁰Lithuanian University of Health Sciences Inst. for Digestive Research, Gastroenterology Department, Kaunas, Lithuania

¹¹Lithuanian University of Health Sciences, Gastroenterology, Kaunas, Lithuania

¹²National Medical University named after O.O. Bogomolets, Internal Medicine No.1, Kyiv, Ukraine

¹³Gastroenterology Area, Fondazione Policlinico Universitario A. Gemelli, Internal Medicine, Gastroenterology and Liver Diseases, Rome, Italy

¹⁴Gastroenterology Unit, University of Leeds, Department of Medicine, Leeds, United Kingdom

¹⁵Hacettepe University Faculty of Medicine, Internal Medicine/ Gastroenterology Department, Ankara, Turkey

¹⁶Ferencváros Policlinic, Gastroenterology Unit, Budapest, Hungary

¹⁷Instituto de Investigaçao e Inovaçao em Saúde, Universidade do Porto, and Ipatimup - Institute of Molecular Pathology and Immunology of the University of Porto, Diagnostics, Porto, Portugal

¹⁸Rabin Medical Center, Tel Aviv University, Department of Gastroenterology, Petach Tikva, Israel

¹⁹Medical University of Sofia, Department of Medical Microbiology, Sofia, Bulgaria

²⁰Hospital Universitario Central de Asturias, Gastroenterology Unit, Oviedo, Spain

²¹HM Sanchinarro, Digestive Service, Madrid, Spain

²²Gastroenterology Unit, Timisoara Hospital, Department of Gastroenterology, Timisoara, Romania

²³CHU Charleroi, Department of Gastroenterology, Hepatology & Nutrition, Charleroi, Belgium

²⁴University Hospital of Split, School of Medicine, University of Split, Department of Gastroenterology, Split, Croatia

²⁵Gastroenterology Unit, Medical Centre for Postgraduate Education, Endoscopy, Warszawa, Poland

²⁶Gastroenterology Unit, Hospital de Basel, Division of Gastroenterology, Basel, Switzerland

²⁷Otto-von-Guericke University Hospital, Department of Gastroenterology Hepatology and Infectious Diseases, Magdeburg, Germany

²⁸Zealand University Hospital, Copenhagen University, Clinical Medicine, Copenhagen, Denmark

²⁹Erasmus MC University, Department of Gastroenterology and Hepatology, Rotterdam, Netherlands

³⁰Medical Department, Clinical Center of Serbia Clinic for Gastroenterology and Hepatology, University of Belgrade, Belgrade, Serbia

³¹Herttoniemi Hospital, Department of Internal Medicine, Helsinki, Finland

³²Hospital San Pedro de Alcantara, Caceres and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Gastroenterology, Madrid, Spain

³³Gastroenterology Unit, Gastrocentr, Moscow, Russian Federation

³⁴University of Bologna, Department of Clinical Medicine, Bologna, Italy

³⁵Digestive Ukrainian Academy of Medical Sciences, Kyiv, Ukraine

³⁶Hospital Clínico Universitario Lozano Blesa, Gastroenterology Unit, Zaragoza, Spain

³⁷University of Bologna, Department of Surgical and Medical Sciences, Bologna, Italy

³⁸Centre Hospitalier Annecy Genvois, Pringy, France

³⁹UniversidadAutónoma de Madrid, Departamento de Psicología Aplicada, Madrid, Spain

⁴⁰Hospital Clínico San Carlos, Facultad de Enfermería, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Servicio de Medicina Preventiva, Madrid, Spain

⁴¹Althaia Xarxa Assistencial Universitaria de Manresa and Universitat de Vic-Universitat Central de Catalunya (UVicUCC), Digestive Diseases Department, Manresa, Spain

⁴²Laboratoire de Bactériologie, HôpitalPellegrin, Inserm U1053, Bordeaux, France

⁴³Trinity College Dublin, Faculty of Health Sciences, Department of Clinical Medicine, Dublin, Ireland

^✉

Contact E-Mail Address: m.caldas.a@gmail.com

Introduction

The best approach for Helicobacter pylori management remains unclear. An audit process is essential to ensure clinical practice is aligned with best standards of care.

Aims & Methods

International multicentre prospective non-intervention-al registry starting in 2013 aimed to evaluate the decisions and outcomes in H. pylori management by European gastroenterologists. Patients were registered in an e-CRF by AEG-REDCap up to April 2020. Variables included: demographics, previous eradication attempts, prescribed treatment, adverse events, and outcomes. Modified intention-to-treat (mITT) and per-protocol (PP) analyses were performed and data were subject to quality review to ensure information reliability.

Results

In total 36,319 patients from 29 European countries were evaluated and 24,882 (70%) first-line empirical H. pylori treatments were included for analysis. Triple therapy with amoxicillin and clarithromycin was most commonly prescribed (40%), followed by concomitant treatment (19%) and bismuth quadruple (Pylera®) (10%) achieving 83%, 91% and 95% mITT eradication rate, respectively.

Over 90% effectiveness was obtained only with 10 and 14-day bismuth quadruple or 14-day concomitant treatment (Table). Longer treatment duration, higher acid inhibition and compliance were associated with higher eradication rates.

Conclusion

Management of H. pylori infection by European gastroenter-ologists is heterogeneous. Only quadruple therapies lasting at least ten days are able to achieve over 90% eradication rates.

Disclosure

Dr. Nyssen has received research funding from Mayoly, Allergan. Dr. Gisbert has served as a speaker, a consultant and advisory member for or has received research funding from Mayoly, Allergan, Diasorin.

Table 1.

Effectiveness (by modified intention-to-treat and per-protocol analyses) of first-line empirical treatments in Europe.

First-line treatment	Length (days)	mITT, N (%)	(95% CI)	PP, N (%)	(95% CI)
Triple-C+A	7/10 / 14	1,903 (83) / 3,057 (83) / 72,264 (89)	(81-84) / (82-85) / (88-90)	1,886 (83) / 3,015 (84) / 2,238 (89)	(81-85) / (82-85) / (88-91)
Triple-A+M	7 / 10	118 (81) / 163 (85)	(74-89) / (79-90)	117 (81) / 161 (85)	(74-89) / (79-91)
Triple-C+M	7 / 10 / 14	724(84) / 114(65) / 80 (70)	(82-87) / (56-74) / (59-81)	721 (85) / 112(66) / 80 (70)	(82-87) / (57-75) / (59-81)
Triple-A+L	7 / 10	178(79)/ 142 (85)	(72-85) / (79-91)	176(78)/ 136 (86)	(72-85) / (80-92)
Sequential-C+A+M/T	10	596 (83)	(80-86)	556 (85)	(82-88)
Quadruple-C+A+M/T	10 / 14	2,378 (88) / 2,228 (93)	(87-90) / (92-94)	2,316 (89) / 2,180 (93)	(88-90) / (92-94)
Quadruple-C+A+B	10 / 14	394 (86) / 1,194 (91)	(82-89) / (89-93)	390 (86) / 1,178 (91)	(83-90) / (90-93)
Quadruple-M+Tc+B	10	130 (94)	(89-98)	130 (94)	(89-98)
Pylera® (M+Tc+B)	10	2,267 (95)	(94-96)	2,223 (95.5)	(95-96)

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mITT: modified intention-to-treat; PP: per-protocol; A - amoxicillin, C - clarithromycin; M - metronidazole; T - tinidazole; L - levofloxacin B; -bismuth salts; Tc - tetracycline.

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.184

P0226 European Registry On H. Pylori Management (Hp-Eureg): Analysis of Empirical Second-Line Treatments in Europe

OP Nyssen ¹, A Perez Arisa ², B Tepeš ³, DS Bordin ⁴, D Vaira ⁵, O Shvets ⁶, L Kupcinskas ⁷, R Marcos-Pinto ⁸, M Leja ⁹, N Fernandez Moreno ², I Santaella ², G Fiorini ⁵, L Vologzhanina ⁴, G Fadeenko ¹⁰, L Jonaitis ⁷, A Lucendo ¹¹, L Bujanda ¹², S Sarsenbaeva ¹³, M Areia ¹⁴, M Caldas Álvarez ^1,^✉, A Garre ¹⁵, I Puig ¹⁶, F Megraud ¹⁷, C O'Morain ¹⁸, JP Gisbert ¹, On behalf of the Hp-EuReg Investigators

¹Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain

²Servicio de Gastroenterologia, Agencia Sanitaria Costa del Sol, Red de Investigación en Servicios de Salud en Enfermedades Crónicas (REDISSEC), Marbella, Spain

³Gastroenterology Unit, AM DC Rogaska, Rogaska Slatina, Slovenia

⁴Department of Pancreatobiliary and Upper GI Diseases, Moscow Clinical Scientific Center, and A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow, Russian Federation

⁵Department of Surgical and Medical Sciences, University of Bologna, Bologna, Italy

⁶Internal Diseases Department No.1, National Medical University named after O.O. Bogomolets, Kyiv, Ukraine

⁷Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania

⁸Centro Hospitalar do Porto, Institute of Biomedical Sciences Abel Salazar, University of Porto and CINTESIS, University of Porto, Porto, Portugal

⁹Faculty of Medicine, University of Latvia, Riga, Latvia

¹⁰National Academy of Medical Sciences, Kyiv, Ukraine

¹¹Hospital de Tomelloso, Ciudad Real, Spain

¹²Department of Gastroenterology. Hospital Donostia/Instituto Biodonostia. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd). Universidad del Pais Vasco (UPV/EHU), Donostia, Spain

¹³Gastroenterological Center Chelyabinsk, Chelyabinsk, Russian Federation

¹⁴Portuguese Oncology Institute of Coimbra, Coimbra, Portugal

¹⁵Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain

¹⁶Althaia Xarxa Assistencial Universitaria de Manresa and Universitat de Vic-Universitat Central de Catalunya (UVicUCC), Manresa, Spain

¹⁷Laboratoire de Bactériologie, Hôpital Pellegrin, Bordeaux, France

¹⁸Department of Clinical Medicine, Trinity College Dublin, Dublin, Spain

^✉

Contact E-Mail Address: m.caldas.a@gmail.com

Introduction

Even with the currently most effective treatment regimens, approximately 10-20% of patients will fail to obtain H. pylori eradication.

Aims & Methods

To evaluate the effectiveness and safety of second-line empirical treatments in Europe.

A systematic prospective registry of the clinical practice of European gas-troenterologists regarding H. pylori infection and treatment was established. All infected adult patients were systematically registered at AEG-REDCap e-CRF from June 2013 to April 2020. Variables included: Patient's demographics, previous eradication attempts, prescribed treatment, adverse events, and outcomes. Modified intention-to-treat (mITT) and per-protocol (PP) analyses were performed and data were subject to quality review.

Results

Overall, 5,516 patients from 29 countries were given a second-line therapy; from those, 4,862 (88%) were treated empirically and were therefore included for analysis. Mean age was of 49 (±15) years, 64% were women and 5% had penicillin allergy. Most frequent treatment indications were dyspepsia (54%) and gastroduodenal ulcer (17%). Endoscopy was performed in 48% of the cases and ¹³C-UBT was used in 45% to diagnose the infection. Overall effectiveness was 83.7% (by mITT) and 84% (by PP). Over 97% of patients were compliant. AEs were reported in 28% of the cases and tolerance was similar among therapies. Most frequent second-line prescriptions and effectiveness per antibiotic combination is shown in Table 1. After failure of first-line clarithromycin-containing treatment, optimal eradication (>90%) was obtained with moxifloxacin-containing triple therapy, the single capsule (Pylera”) or quadruple therapy with le-vofloxacin and bismuth. in patients receiving triple regimens containing levofloxacin or the standard bismuth quadruple regimen, cure rates were optimized with 14-day regimens using high doses of proton pump inhibitors (PPIs). However, Pylera” or quadruple therapy with levofloxacin and bismuth achieved reliable eradication rates regardless of the PPI dose, duration of therapy, or previous first-line treatment regimen.

Conclusion

Empirical second-line triple therapies generally provided low eradication rates unless they included 14 days of levofloxacin or moxiflox-acin. However, high effectiveness was obtained with second-line bismuth-containing quadruple therapies.

Table 1.

Frequency of second-line empirical treatment prescriptions and effectiveness by modified intention-to-treat and per-protocol analyses

Treatment	N	% Use	mITT, N (%)	(95% CI)	PP, N (%)	(95% CI)
Triple-A+L	1,522	33.2	1,341 (81)	(79-83)	1,320 (81)	(79-83)
Pylera (single capsule	692	15.1	622 (90)	(87-92)	607 (90)	(88-93)
Quadruple-A+L+B	529	11.5	478 (89)	(86-92)	462 (89)	(86-92)
Triple-C+A	477	10.4	231 (81)	(76-86)	226 (81)	(76-86)
Quadruple-M+Tc+B	204	4.4	183 (83)	(77-89)	177 (84)	(78-90)
Quadruple-C+A+M	179	3.9	169 (85)	(79-90)	167 (84)	(79-90)
Triple-A+Mx	143	3.1	135 (91)	(86-96)	135 (91)	(86-96)
Triple-A+M	93	2.0	76 (60.5)	(49-72)	76 (60.5)	(49-72)
Total*	4,862	100%	3,966 (84)	(82-85)	3,966 (84)	(81-83)

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mITT - modified intention-to-treat, PP - per-protocol, 95%CI - 95% confidence interval, C - clarithromycin, M - metronidazole, T - tinidazole, A - amoxicillin, L - levofloxacin, B - bismuth salts, Tc - tetracycline, Mx - moxifloxacin, N - Total of patients receiving an empirical treatment, Total* - accounted also 1,023 (21%) second-line empirical treatments with less than 100 patients treated in each category, that are not reported in the table.

Disclosure

Dr. Nyssen has received research funding from Mayoly, Allergan. Dr. Gisbert has served as a speaker, a consultant and advisory member for or has received research funding from Mayoly, Allergan, Diasorin.

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.185

P0227 Bismuth Quadruple Three-In-One Single Capsule: 3 Or 4 Times Daily? Sub-Analysis of The Spanish Data of The European Registry On H. Pylori Management (Hp-Eureg)

OP Nyssen ¹, J Gomez Rodriguez ², J Barrio ³, M Castro-Fernández ⁴, M Pabón-Carrasco ⁴, A Keko-Huerga ⁴, M Mego ⁵, Á Perez-Aisa ⁶, N Fernandez Moreno ⁶, B Gómez ⁷, L Tito ⁷, E Iyo ⁸, JM Huguet ⁹, AJ Lucendo ¹⁰, T Di Maira ¹¹, FJ Martinez Cerezo ¹², O Núñez Martínez ¹³, M Barenys ¹⁴, M Perona ¹⁵, A Campillo ¹⁶, P Mata Moreno ¹⁷, J Santos-Fernández ¹⁸, A Cerezo Ruiz ¹⁹, S Lario ²⁰, MJ Ramirez ²⁰, M Caldas ^1,^✉, I Puig ²¹, F Megraud ²², C O'Morain ²³, JP Gisbert ¹, X Calvet ²⁰, On behalf of the Hp-EuReg Investigators

Introduction

Bismuth quadruple with the single capsule Pylera” (PPI, bismuth, tetracycline and metronidazole) includes the intake of 3 capsules four times a day (3c/6h), according to the technical sheet. This scheme may not be suitable for Spanish eating habits; therefore, some physicians prescribe the treatment in the form of 4 capsules three times a day (4c/8h).

Aims & Methods

To assess the effectiveness and safety of quadruple single capsule bismuth therapy (Pylera^®) administered three times a day (4c/8h) in the European Registry on the management of Helicobacter pylori (Hp-EuReg).

Methods

Systematic prospective registry of the clinical practice of European gastroenterologists (27 countries) on the management of H. pylori infection and its treatment. All infected adult patients were systematically registered at AEG-REDCap e-CRF from June 2013 to June 2019. Extraction and analysis of all cases treated with Pylera” were subject to quality control. Effectiveness was provided for both the modified intention-to-treat and per-protocol sets.

Results

Of the 2,326 Spanish patients treated with Pylera^® in the Hp-EuReg, 1,140 (74%) were treated with 3c/6h and 403 (17%) with the 4c/8h scheme. The average age was 48 years, 63% were women, and 11% had a peptic ulcer. Most of the cases (72%) were naïve to treatment. The dose of PPI did not influence eradication rates. Both treatment schedules showed equivalent compliance, adverse events, and eradication rates (Table 1). One patient suffered a serious adverse event (C. difficile infection), in the group 3c/6h.

Conclusion

The prescription of quadruple therapy with single capsule bismuth (Pylera”) given as four capsules three times a day seems to have the same compliance, tolerance and effectiveness as the scheme included in the data sheet (three capsules four times a day).

Table 1.

Effectiveness,compliance and safety of treatment with Pylera® in first-,second-,and third-line.

			Modified intention-to-treat (%)			Per-protocol (%)
Pylera®	Compliance (%)	AEs (%)	Pylera®	Overall	91	Pylera®	Overall	93
4c/8h	97	22	4c/8h	1st line	95	4c/8h	1st line	96
				2nd line	92		2nd line	94
				3rd line	86		3rd line	92
Pylera®	Compliance (%)	AEs (%)	Pylera®	Overall	86	Pylera®	Overall	90
3c/6h	98	24	3c/6h	1st line	93	3c/6h	1st line	95
				2nd line	83		2nd line	87
				3rd line	84		3rd line	86

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AEs: adverse events. 4c/8h: four capsules three times a day (every 8 hours); 3c/6h: three capsules four times a day (every 6 hours).

Disclosure

Dr. Nyssen has received research funding from Mayoly, Allergan. Dr. Gisbert has served as a speaker, a consultant and advisory member for or has received research funding from Mayoly, Allergan, Diasorin. Xavier Calvet has received grants for research from Abbott, MSD, Vifor fees for advisory boards form Abbott, MSD, Takeda, Pfizer, Janssen AND VIFOR and has given lectures for Abbott, MSD, Janssen, Pfizer,Takeda, Shire and Allergan.

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.186

P0228 European Registry On H. Pylori Management (Hp-Eureg): Experience with Single Capsule Bismuth Quadruple Therapy in 3,439 Patients

OP Nyssen ¹, A Perez-Aisa ², M Castro-Fernandez ³, R Pellicano ⁴, JM Huguet ⁵, L Rodrigo ⁶, J Ortuño ⁷, BJ Gomez-Rodriguez ⁸, R Marcos Pinto ⁹, M Areia ¹⁰, M Perona ¹¹, O Nuñez ¹², M Romano ¹³, AG Gravina ¹³, L Pozzati ¹⁴, M Fernandez-Bermejo ¹⁵, M Venerito ¹⁶, P Malfertheiner ¹⁶, L Fernandez-Salazar ¹⁷, A Gasbarrini ¹⁸, D Vaira ¹⁹, M Dominguez-Cajal ²⁰, M Jimenez-Moreno ²¹, E Iyo ²², J Perez-Lasala ²³, J Molina Infante ²⁴, J Barrio ²⁵, B Tepeš ²⁶, F Bermejo ²⁷, D Burgos ²⁸, P Almela Notari P ²⁹, L Bujanda ³⁰, AJ Lucendo ³¹, F Heluwaert ³², DS Bordin ³³, T Rokkas ³⁴, L Kupcinskas ³⁵, M Caldas ^1,^✉, I Puig ³⁶, F Megraud ³⁷, C O’ Morain ³⁸, JP Gisbert ¹

¹Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain

²Servicio de Gastroenterologia, Agencia Sanitaria Costa del Sol, Red de Investigación en Servicios de Salud en Enfermedades Crónicas (REDISSEC), Marbella, Malaga, Spain

³Hospital de Valme, Sevilla, Spain

⁴Molinette Hospital, Turin, Italy

⁵Consorcio Hospital General Universitario, Valencia, Spain

⁶Hospital Universitario Central de Asturias, Oviedo, Spain

⁷Hospital Universitari i Politècnic La Fe, Valencia, Spain

⁸Hospital Quiron Sagrado Corazon, Sevilla, Spain

⁹Centro Hospitalar do Porto, Institute of Biomedical Sciences Abel Salazar, University of Porto and CINTESIS, University of Porto, Porto, Portugal

¹⁰Oncology Institute Coimbra, Coimbra, Portugal

¹¹Hospital Quiron, Marbella, Spain

¹²Hospital Universitario Sanitas La Moraleja, Madrid, Spain

¹³Università degli Studi della Campania ‘Luigi Vanvitelli, Napoli, Italy

¹⁴Hospital, Merida, Spain

¹⁵Clinica San Francisco, Caceres, Spain

¹⁶Otto-von-Guericke University Hospital, Magdeburg, Germany

¹⁷Hospital Clinico Universitario, Valladolid, Spain

¹⁸Fondazione Policlinico Universitario A. Gemelli, Rome, Italy

¹⁹Department of Surgical and Medical Sciences, University of Bologna, Bologna, Italy

²⁰Hospital San Jorge, Huesca, Spain

²¹Hospital Universitario de Burgos, Burgos, Spain

²²Hospital Comarcal de Inca, Mallorca, Spain

²³HM Sanchinarro, Madrid, Spain

²⁴Hospital San Pedro de Alcantara, Caceres and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Caceres, Spain

²⁵Hospital Rio Hortega, Valladolid, Spain

²⁶AM DC Rogaska, Gastroenterology, Rogaska Slatina, Slovenia

²⁷Hospital Universitario de Fuenlabrada, Madrid, Spain

²⁸Hospital Ramon y Cajal, Madrid, Spain

²⁹Hospital General Universitario de Castellón, Castellon, Spain

³⁰Hospital Donostia, Instituto Biodonostia. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Universidad del Pais Vasco (UPV/EHU), Donostia, Spain

³¹Hospital de Tomelloso, Ciudad Real, Spain

³²Centre Hospitalier Annecy Genvois, Pringy, France

³³Gastroenterolgy Unit, A. S. Loginov Moscow Clinical Scientific Center, Department of Outpatient Therapy and Family Medicine, Tver State Medical University and Department of Propaedeutic of Internal Diseases and Gastroenterology, Moscow, Russian Federation

³⁴Henry Dunant Hospital, Athens, Greece

³⁵Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania

³⁶Althaia, Xarxa Assistencial Universitaria de Manresa, Digestive Diseases Department, Manresa, Spain

³⁷Hopital Pellegrin, Laboratoire de Bacteriologie, Inserm U1053, Bordeaux Cedex, France

³⁸Trinity College Dublin, Faculty of Health Sciences, Dublin, Ireland

^✉

Contact E-Mail Address: m.caldas.a@gmail.com

Introduction

There has been a resurgence in the use of bismuth-quadruple therapy (PPI, bismuth, tetracycline and metronidazole) in Europe with the commercialization of a single-capsule formulation (Pylera”), but the experience with this regimen is still limited.

Aims & Methods

To evaluate the effectiveness and safety of Pylera” in the European Registry on Helicobacter pylori management (Hp-EuReg). International multicenter prospective non-interventional registry aimed to evaluate the decisions and outcomes of H. pylori management by European gastroenterologists. All infected adult patients treated with Pylera” according to data sheet (3 capsules/6h) were systematically registered at AEG-REDCap e-CRF until December 2019. Variables included: Patient's demographics, previous eradication attempts, prescribed treatment, adverse events, and outcomes. Modified intention-to-treat (mITT) analyses were performed and data were subject to quality review.

Results

Of the 34,460 patients in the Hp-EuReg, 2,100 (6.1%) were prescribed single-capsule bismuth-quadruple therapy (10 days, 3 capsules q.i.d.). The majority of these patients were naïve (63%), with an average age of 50 years, 64% female and 16% with peptic ulcer. Pylera” achieved a high eradication rate based on the mITT (91.9%). Effectiveness was higher when using Pylera” as a first-line treatment (94.6%) but it had also high effectiveness as a rescue therapy, both in second-line (89.3%) or subsequent lines of therapy (3rd-6th line: 91.9%) (Table1). Compliance was the factor most closely associated with the effectiveness of treatment. Adverse events (AEs) were generally mild-to-moderate and transient, only 3% of patients reporting a severe AE, leading to discontinuation of treatment in 1.7% of patients.

Table 1.

Pylera® effectiveness (by modified intention-to-treat) in first-,and consecutive rescue treatment lines.

	Use, N (%)	mITT, N (%)	95% CI	PP, N (%)	95% CI
Overall	2,100 (6*)	1,777 (92)	(91-93)	1,761 (92-94)	(92-94)
Naïve	1.335(63)	1,166 (95)	(93-96)	1,158 (94-97)	(94-97)
2nd line	465 (22)	375 (89)	(86-92)	370 (87-93)	(87-93)
3rd line	212(10)	174 (89)	(84-93)	177 (83-93)	(83-93)

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Conclusion

The 10-day treatment with single-capsule bismuth-quadruple therapy (Pylera”) achieves H. pylori eradication in approximately 90% of patients by mITT in real-world clinical practice, both as a first-line and rescue treatment, with a favourable safety profile.

Disclosure

Dr. Nyssen has received research funding from Mayoly, Allergan. Dr. Gisbert has served as a speaker, a consultant and advisory member for or has received research funding from Mayoly, Allergan, Diasorin.

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.187

P0229 Safety of The Treatment of H. Pylori Infection: Experience From The European Registry On H. Pylori Management (Hp-Eureg) On 22,000 Patients

OP Nyssen ¹, L Kupcinskas ², B Tepeš ³, O Shvets ⁴, D Bordin ⁵, M Leja ⁶, JCL Machado ⁷, T Rokkas ⁸, GM Buzás ⁹, I Simsek ¹⁰, T Axon ¹¹, F Lerang ¹², L Jonaitis ², R Muñoz ¹, E Resinas ¹, M Espada ¹, I Puig ¹³, F Megraud ¹⁴, C O'Morain ¹⁵, JP Gisbert ^1,^✉, On behalf of the Hp-EuReg Investigators.

Introduction

The safety of Helicobacter pylori eradication treatments and to what extent adverse events (AEs) may influence therapeutic compliance is unknown.

Aims & Methods

To assess the frequency, type, intensity and duration of AEs, and their impact on compliance, for the most frequently used treatments in the European Registry on Helicobacter pylori management (Hp-EuReg). Systematic prospective non-interventional registry of the clinical practice of European gastroenterologists (27 countries, 300 investigators) on the management of H. pylori infection in routine clinical practice, promoted by the EHMSG. All prescribed eradication treatments and their corresponding safety profile were recorded in an e-CRF in AEG-REDCap until June 2019. AEs were classified depending on the intensity of symptoms as mild/moderate/severe, and as serious AEs (death, hospitalisation, disability, congenial anomaly and/or requires intervention to prevent permanent damage). All data were subject to quality control.

Results

The different treatments prescribed to a total of 22,492 naïve and non-naïve patients caused at least one AE in 22% of the cases (Table 1), the classic bismuth-based quadruple therapy being the worst tolerated (37% of AEs). Taste disturbance (7%), diarrhoea (7%), nausea (6%) and abdominal pain (3%) were the most frequent AEs. The majority of AEs were mild (57%), 6% were severe, and only 0.08% were serious, with an average duration of 7 days. The treatment compliance rate was 97%. Only 1.3% of the patients discontinued treatment due to AEs.

Conclusion

H. pylori eradication treatment frequently induces AEs, although they are usually mild and of limited duration. Its appearance does not interfere significantly with the compliance of treatment.

Table 1.

Safety in naïve and non-naïve patients

Adverse events	Yes	%	95%CI
Triple-C+A	1,037	15	(14-16)
Quadruple-C+A+M	926	25	(23-26)
Pylera®	642	28	(26-30)
Quadruple -C+A+B	627	34	(34-37)
Triple-A+L	339	21	(19-23)
Triple-C+M	184	20	(18-23)
Quadruple -A+L+B	180	32	(28-36)
Quadruple -M+Tc+B	84	37	(30-43)
TOTAL	4,298	22	(22-23)

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CI- confidence interval; A - amoxicillin, C - clarithromycin; M -metronidazole; L - levofloxacin; B; - bismuth; Tc - tetracycline.

Disclosure

Dr. Nyssen has received research funding from Mayoly, Allergan. Dr. Gisbert has served as a speaker, a consultant and advisory member for or has received research funding from Mayoly, Allergan, Diasorin.

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.188

P0230 Vonoprazan-Amoxicillin Dual Therapy For H. Pylori Infection: A Systematic Review and Meta-Analysis

L Gatta ^1,^✉, C Scarpignato ^2,³

Introduction

H. pylori infection is associated with several gastrointestinal and extra-gastrointestinal conditions and is the leading cause of gastric cancer. Its eradication is therefore performed worldwide to improve or prevent these conditions¹. Unfortunately, the eradication rate of the currently available regimens is declining, mostly owing to the increase its resistance to antimicrobials^1,2. Several studies have shown the importance of profound and long-lasting acid suppression for H. pylori eradication³. Vonoprazan, a novel potassium-competitive acid blocker, provides a stronger and longer-lasting antisecretory effect than proton pump inhibitors. A dual therapy, combining vonoprazan with amoxicillin, could be a simple regimen for H. pylori infection and, because it contains a single antibiotic, could allow antimicrobial stewardship compared with triple or quadruple regimens. in addition, since - even after multiple treatments -H. pylori resistance to amoxicillin is very low², this dual regimen has the potential to overcome the ever-lower eradication rate of regimens employing clarithromycin, imidazole or/and quinolone antimicrobial agents, toward which resistance is constantly increasing².

Aims & Methods

Performing a systematic review and meta-analysis to evaluate the effectiveness and the safety (adverse events - AEs) of vono-prazan-amoxicillin dual therapy for H. pylori eradication. MEDLINE, EM-BASE, and Cochrane Central Register of Controlled Trials were searched from inception to April 2020. Furthermore, abstract books of major European, American and Asian gastroenterological meetings were also examined. Data for primary and secondary outcomes were pooled using a random effects model.

Results

The search strategy identified 4 studies, all performed in Asia: 2 studies where dual therapy lasted 7 days, and 2 studies where dual therapy lasted 14 days. According to the ITT analysis, the pooled eradication rate was 85.6% (95%CI: 74.8 to 94.0), with evidence of significant heterogeneity (Cochrane Q: p = 0.036; I² = 64.8%). According to the PP analysis, the pooled eradication rate was 89.1% (95%CI: 76.9 to 97.5), with evidence of significant heterogeneity (Cochrane Q: p = 0.008; I² = 74.7%). One study showed an outlier eradication rate, and after its removal, the pooled eradication rate was 88.6% (95%CI: 82.4 to 93.8 - Cochrane Q: p = 0.264; I² = 24.9%) and 92.8% (95%CI: 85.0 to 98.1 - Cochrane Q: p = 0.128; I² = 51.3%), according to ITT and PP analysis, respectively. The eradication rate in patients harboring strains resistant to clarithromycin was 95.4% (95% CI: 86.6 to 100). Finally, the overall AEs were 26.5% (95% CI: 20.0 to 33.5), without any severe event.

Conclusion

Vonoprazan-amoxicillin dual therapy provided clinically relevant H. pylori eradication rates, even in patients harboring strains resistant to clarithromycin. Further European and North American studies are needed to confirm these results.

Disclosure

Nothing to disclose

References

1.Fallone C.A., Moss S.F., Malfertheiner P. Reconciliation of Recent Helicobacter pylori Treatment Guidelines in a Time of Increasing Resistance to Antibiotics. Gastroenterology 2019; 157: 44–53. [DOI] [PubMed] [Google Scholar]
2.Gatta L., Scarpignato C., Fiorini G. et al. Impact of primary antibiotic resistance on the effectiveness of sequential therapy for Helicobacter pylori infection: lessons from a 5-year study on a large number of strains. Alimentary Pharmacology & Therapeutics 2018; 47: 1261–9. [DOI] [PubMed] [Google Scholar]
3.Scarpignato C., Gatta L., Zullo A. et al. Effective and safe proton pump inhibitor therapy in acid-related diseases - A position paper addressing benefits and potential harms of acid suppression. BMC Med 2016; 14: 179. [DOI] [PMC free article] [PubMed] [Google Scholar]

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.189

P0231 Empirical Versus Susceptibility-Guided Treatment of Helicobacter Pylori Infection: A Meta-Analysis

M Espada ¹, OP Nyssen ¹, JP Gisbert ^1,^✉

Introduction

Treating patients according to antibiotic resistances has frequently been recommended. However, the information on its real effectiveness is scarce.

Aims & Methods

To perform a meta-analysis comparing empirical versus susceptibility-guided treatment of H. pylori. Selection of studies: comparing empirical versus susceptibility-guided treatment. Search strategy: electronic&manual. Data synthesis: by intention-to-treat (random effects model).

Results

Overall, 38 studies were included (6,525 patients in the empirical and 5,124 in the susceptibility-guided group). H. pylori eradication was achieved in 87% versus 77% respectively (RR:1.13; 95%CI:1.09-1.17; I²:77%). Similar results were found when only RCTs were evaluated (22 studies; RR:1.16; 95%CI:1.10-1.22; I²:72%). Similar results were also observed when susceptibility testing was assessed by culture (RR:1.13; 95%CI:1.07-1.19) or PCR (RR:1.14; 95%CI:1.05-1.23). When assessing first-line treatments (naïve patients) only (28 studies), better efficacy results were obtained with the susceptibility-guided strategy (RR:1.16; 95%CI:1.11-1.21; I²:79%). However, when prescribing empirical first-line quadruple regimens only (both with and without bismuth, excluding the suboptimal triple therapies), no differences in efficacy were found versus the susceptibility-guided group (RR:1.02; 95%CI:0.95-1.09); this lack of difference was confirmed in RCTs not based on CYP2C19 gene polymorphism (RR:1.07; 95%CI:0.98-1.17). For rescue-therapies (13 studies, most as 2^nd-line), similar results were demonstrated with both strategies, both including all studies (RR:1.09; 95%CI:0.97-1.22; I²:82%) and also when only RCTs were considered (RR:1.15; 95%CI:0.97-1.36).

Conclusion

The benefit of susceptibility-guided treatment over empirical treatment of H. pylori infection could not be demonstrated, either in first-line (if the most updated quadruple regimens are prescribed) or in rescue therapies.

Disclosure

Marta Espada has no conflicts of interest to declare. Dr. Nyssen has received research funding from Allergan and Mayoly. Dr. Gisbert has served as a speaker, a consultant and advisory member for or has received research funding from Mayoly, Allergan and Diasorin.

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.190

P0232 European Registry On H. Pylori Management (Hp-Eureg): Clinical Phenotypes Through Machine Learning of First-Line Treated Patients in Spain During The Period 2013-2018

OP Nyssen ¹, A Sanz-García ², GJ Ortega ², JP Gisbert ^1,^✉, On behalf of the Hp-EuReg Investigators.

Introduction

The segmentation of patients in homogeneous groups, according to their clinical variables and treatments, could help to improve the effectiveness of current eradication therapy.

Aims & Methods

1) To group patients from the European Registry on Helicobacter. pylori management (Hp-EuReg) according to their demographic and clinical characteristics as well as to the different treatment types by means of a multivariate categorical analysis and, subsequently, a cluster decomposition. 2) To evaluate the treatments’ effectiveness in the resulting patients’ clusters.

Systematic prospective registry of the routine clinical practice of European gastroenterologists on the management of H. pylori infection. First-line empirical treatments were included. The following categorical variables were used: sex, ethnicity, diagnosis, symptoms, therapeutic indication, treatment scheme, duration of treatment, proton-pump inhibitor (PPI) dose, compliance, adverse events, and region of the prescribing center.

Results

In total, 8,322 patients from Spanish centers were analysed from June 2013 to December 2018. Table 1 shows the upward average effectiveness trend of treatments, ranging from 78.4% in 2013 to 92.2% in 2018. The lowest effectiveness, for clusters with more than 100 patients, was obtained in cluster 1 in 2015, with an eradication rate of 82.8%. This cluster was composed by two first-line treatments: triple therapy with PPI-clar-ithromycin-amoxicillin and concomitant therapy with PPI-clarithromycin-amoxicillin-metronidazole/tinidazole, lasting both 10 days in the vast majority of cases. Pylera” treatment administered together with high PPI doses during 10 days obtained over 95% effectiveness (cluster 3, in 2018), uniformly distributed among Malaga, Valencia, Ciudad Real, Sevilla, Madrid, and Valladolid’ cities. Concomitant therapy with high PPI dose given for 14 days achieved an effectiveness of 90.7% during the 2018 year (94% of patients in cluster 1), distributed mainly between Malaga, Ciudad Real and Madrid’ cities.

Conclusion

The cluster analysis allows both identifying homogeneous groups of patients as well as assessing the effectiveness of the different first-line treatments evaluated.

Table 1.

Trends in the overall effectiveness (by modified intention-to-treat,per cluster) between 2013 and 2018 in Spain

Effectiveness % (number of patients) per cluster
Year	Number of clusters	1	2	3	4	5
2013	3	89.6 (280)	83.2 (619)	80.0 (80)
2014	3	88.2 (1685)	69.6 (46)	83.3 (6)
2015	5	91.6 (83)	89.4 (839)	82.9 (615)	70.8 (24)	88.2 (17)
2016	3	94.7 (359)	86.1 (853)	92.6 (296)
2017	3	94.3 (630)	90.6 (636)	91.6 (153)
2018	3	91.8 (122)	90.7 (161)	96.5 (338)

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Simple underlining highlights the lowest effectiveness for groups of more than 100 patients and double underlining the highest effectiveness.

Disclosure

Dr. Nyssen has received research funding from Mayoly, Allergan. Dr. Gisbert has served as a speaker, a consultant and advisory member for or has received research funding from Mayoly, Allergan, Diasorin.

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.191

P0233 Real-World Comparative Effects of Three-In-One Single Capsule Bismuth Quadruple Therapy Vs. Non-Bismuth Quadruple Concomitant Therapy: Interim Analysis of The European Registry On H. Pylori Management (Hp-Eureg)

I Puig ^1,^✉, M Serra ², OP Nyssen ³, G Fiorini ⁴, V Dino ⁴, A Perez Arisa ⁵, N Fernandez-Moreno ⁵, I Santaella ⁵, M Castro Fernandez ⁶, AJ Lucendo ⁷, L Bujanda ⁸, M Areia ⁹, A Gasbarrini ¹⁰, M Romano ¹¹, AG Gravina ¹¹, R Marcos-Pinto ¹², F Megraud ¹³, C O'Morain ¹⁴, JP Gisbert ³, On behalf of the Hp-EuReg Investigators

Introduction

RCTs have strict selection criteria that render results not fully transferable to the clinical practice.

Aims & Methods

To assess the comparative effects of first-line bismuth-single-capsule (PPI-bismuth-tetracycline-metronidazole) vs. non-bismuth quadruple concomitant therapy (PPI-amoxicillin-clarithromycin-nitro-imidazole). The European Registry on H. pylori management (Hp-EuReg) data from Spain, Italy and Portugal was used to emulate a target trial with prospective observational data, comparing the relative effectiveness (modified intention-to-treat, mITT; and per-protocol, PP) and safety (adverse events, AEs) of first-line bismuth-single-capsule [10 days,3 PPI dosages] and concomitant therapy [10/14 days; 3 PPI dosages], rendering 9 prescription strategies. Regression analysis controlling for confounders was used to estimate the relative effects of each strategy.

Results

Overall, 2,340 individuals were included. Compared to 10-day concomitant therapy at low PPI doses (n=484), all bismuth-single-capsule combinations presented an eradication incremental benefit by mITT ranging from 7.3% (95%CI:1.1-13%;p=0.024) with low dose PPI to 12.1% (95%CI:5.1-19%;p< 0.001) with standard PPI dose. High PPI dosages in the concomitant therapy resulted in an eradication incremental benefit by mITT ranging from 7.7% (95%CI:2.5-12.8;p=0.003) to 8.8% (95%CI:1.1-16.5;p=0.025) when administered for 14 and 10 days, respectively (Table 1). No differences were found with respect to AEs or severe AEs in any of the assessed strategies.

Conclusion

Single-capsule bismuth quadruple therapy and non-bismuth quadruple concomitant therapy appear to have similar risk-benefit ratios when prescribed with high PPI doses.

Adjusted estimates* for eradication with respect to non-bismuth quadruple concomitant therapy during 10 days and low dose PPI

Strategies	mITT absolute risk difference (95% CI)	P value	PP absolute risk difference (95% CI)	P value
Bismuth-single-capsule, 10 days, low dose PPI	7.4 (1.8-13.1)	0.010	8.9 (3.4-13.5)	0.002
Bismuth-single-capsule, 10 days, standard dose PPI	12.1 (5.1-19.0)	<0.001	12.6 (5.8-9.4)	<0.001
Bismuth-single-capsule, 10 days, high dose PPI	7.3 (0.9-13.6)	0.025	8.3 (2.0-14.5)	0.009
Non-bismuth quadruple concomitant therapy, 10 days, standard dose PPI	8.2 (2.1-14.2)	0.008	8.0 (2.2-13.9)	0.007
Non-bismuth quadruple concomitant therapy, 10 days, high dose PPI	8.8 (1.1-16.5)	0.025	10.0 (2.5-17.6)	0.009
Non-bismuth quadruple concomitant therapy, 14 days, low dose PPI	4.5 (-1.8-10.8)	0.166	4.6 (-1.6-10.8)	0.145
Non-bismuth quadruple concomitant therapy, 14 days, standard dose PPI	7.5 (-0.6-15.5)	0.069	6.8 (-1.0-14.6)	0.088
Non-bismuth quadruple concomitant therapy, 14 days, high dose PPI	7.7 (2.5-12.8)	0.003	7.5 (2.4-12.5)	0.004

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Low dose PPI: ranging from 4.5 to 27 mg omeprazole equivalents, b.i.d. Standard dose PPI: ranging from 32 to 40 mg omeprazole equivalents, b.i.d. High dose PPI: ranging from 54 to 128 mg omeprazole equivalents, b.i.d. Bismuth-single-capsule (PPI-bismuth-tetracycline-metronidazole). Non-bismuth quadruple concomitant therapy (PPI-amoxicillin-clarithro-mycin-nitroimidazole). ‘Estimates controlling for: age, sex, ethnicity, indication, concomitant allergy drug, hospital fixed effects and year fixed effects.

Disclosure

Dr. Ignasi Puig has no conflicts of interest to declare. Dr. Gisbert has served as a speaker, a consultant and advisory member for or has received research funding from Mayoly, Allergan, Diasorin.

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.192

P0234 Antibiotic Resistance Trends of Helicobacter Pylori Nave Patients in The Period 2013-2019: Analysis of The European Registry On H. Pylori Management (Hp-Eureg)

L Bujanda ^1,^✉, OP Nyssen ², A Cosme ¹, DS Bordin ³, B Tepeš ⁴, A Pere-Aisa ⁵, D Vaira ⁶, M Caldas Álvarez ², M Castro-Fernandez ⁷, F Lerang ⁸, M Leja ⁹, L Rodrigo ¹⁰, T Rokkas ¹¹, L Kupcinskas ¹², J Perez-Lasala ¹³, L Jonaitis ¹², O Shvets ¹⁴, A Gasbarrini ¹⁵, H Simsek ¹⁶, ATR Axon ¹⁷, GM Buzas ¹⁸, JC Machado ¹⁹, Y Niv ²⁰, L Boyanova ²¹, A Goldis ²², V Lamy ²³, A Tonkic ²⁴, W Marlicz ²⁵, C Beglinger ²⁶, M Venerito ²⁷, P Bytzer ²⁸, LG Capelle ²⁹, T Milosavljevic ³⁰, LI Veijola ³¹, J Molina Infante ³², L Vologhzanina ³³, G Fadeenko ³⁴, I Ariño ³⁵, G Fiorini ⁶, E Resinas ², R Muñoz ², I Puig ³⁶, F Megraud ³⁷, C O’ Morain ³⁸, JP Gisbert ², On behalf of the Hp-EuReg Investigators

¹Hospital Donostia/Instituto Biodonostia, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Universidad del Pais Vasco (UPV/EHU), Department of Gastroenterology, Donostia, Spain

²Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Gastroenterology Unit, Madrid, Spain

³A.S. Loginov Moscow Clinical Scientific Center, Department of Pancreatic, Biliary and Upper GI Diseases, Moscow, Russian Federation

⁴AM DC Rogaska, Gastroenterology, Rogaska Slatina, Slovenia

⁵Agencia Sanitaria Costa del Sol, Red de Investigación en Servicios de Salud en Enfermedades Crónicas (REDISSEC), Servicio de Gastroenterologia, Marbella, Spain

⁶University of Bologna, Department of Surgical and Medical Sciences, Bologna, Italy

⁷Hospital de Valme, Digestive Unit, Sevilla, Spain

⁸Central Hosspital of Ostfold, Medicine, Fredrikstad, Norway

⁹Institute of Clinical and Preventive Medicine & Faculty of Medicine, University of Latvia, Riga, Latvia

¹⁰Hospital Universitario Central de Asturias, Gastroenterology Unit, Oviedo, Spain

¹¹Henry Dunant Hospital, Department of Gastroenterology, Athens, Greece

¹²Lithuanian University of Health Sciences, Department of Gastroenterology, Kaunas, Lithuania

¹³HM Sanchinarro, Digestive Service, Madrid, Spain

¹⁴National Medical University named after O.O. Bogomolets, Internal Diseases Department No.1, Kyiv, Ukraine

¹⁵Fondazione Policlinico Universitario A. Gemelli, Gastronterology Area, Rome, Italy

¹⁶Hacettepe University Faculty of Medicine, Internal Medicine/ Gastroenterology Department, Ankara, Turkey

¹⁷University of Leeds, Gastroenterology Unit, Leeds, United Kingdom

¹⁸Ferencváros Policlinic, Gastroenterology Unit, Budapest, Hungary

¹⁹Instituto de Investigaçao e Inovaçao em Saúde, Universidade do Porto, and Ipatimup - Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal

²⁰Rabin Medical Center, Tel Aviv University, Department of Gastroenterology, Tel Aviv, Israel

²¹Medical University of Sofia, Department of Medical Microbiology, Sofia, Bulgaria

²²Timisoara Hospital, Gastroenterology Unit, Timisoara, Romania

²³CHU Charleroi, Department of Gastroenterology, Hepatology & Nutrition, Charleroi, Belgium

²⁴University Hospital Centre Split, Split, Croatia

²⁵Pomeranian Medical University, Gastroenterology Unit, Szczecin, Poland

²⁶Hospital de Basel, Gastroenterology Unit, Basel, Switzerland

²⁷Otto-von-Guericke University Hospital, Department of Gastroenterology, Hepatology and Infectious Diseases, Magdeburg, Germany

²⁸Zealand University Hospital, Copenhagen University, Department of Medicine, Copenhagen, Denmark

²⁹Erasmus MC University, Gastroenterology and Hepatology, Rotterdam, Netherlands

³⁰Clinical Center of Serbia, Clinic for Gastroenterology and Hepatology, University of Belgrade, Medical Department, Belgrade, Serbia

³¹Herttoniemi Hospital, Internal Medicine, Helsinki, Finland

³²Hospital San Pedro de Alcántara, Gastroenterology Unit, Caceres, Spain

³³Gastrocentre, Gastroenterology Unit, Perm, Russian Federation

³⁴Digestive Ukrainian Academy of Medical Sciences, Kyiv, Ukraine

³⁵Hospital Clínico Universitario Lozano Blesa, Gastroenterology Unit, Zaragoza, Spain

³⁶Althaia Xarxa Assistencial Universitaria de Manresa and Universitat de Vic-Universitat Central de Catalunya (UVicUCC), Manresa, Spain

³⁷Laboratoire de Bactériologie, Hôpital Pellegrin, Bordeaux Cedex, France

³⁸Trinity College Dublin - Faculty of Health Sciences, Trinity College Dublin; Dublin/IE, Faculty of Health Sciences, Dublin, Ireland

^✉

Contact E-Mail Address: luis.bujanda@osakidetza.eus

Introduction

Bacterial antibiotic resistance changes over time based on multiple factors. It is essential to study these trends to apply preventive strategies to help reducing such resistances.

Aims & Methods

To conduct a time-trend analysis of the antibiotic resistance to H. pylori infection in the European Registry on H. pylori (Hp-EuReg). International multicenter prospective non-interventional European Registry on H. pylori Management (Hp-EuReg) aiming to evaluate the decisions and outcomes of H. pylori infection by European gastroenterolo-gists. All infected adult patients diagnosed with culture and with a result of the antibiotic resistance test were registered at AEG-REDCap e-CRF from 2013 to 2019.

Results

A total of 32,447 patients were included, and culture was performed in 3,474 (11%), where 2,483 näive patients were included for analysis. Resistance to at least one antibiotic was described in 57% of the patients. Resistance to metronidazole (27%) was most frequent, whereas resistance to tetracycline and amoxicillin was below 1%. Clarithromycin resistance remained above 15% throughout the studied years (Table 1). A significant decrease in the metronidazole resistance rate was observed between 2013 (38%) and 2018 (21%).

Conclusion

In naïve patients, resistance to clarithromycin remained above 15% in the period 2013-2019. A progressive decrease in metroni-dazole resistance was observed. No increasing or decreasing trend was observed in the bacterial resistance to other antibiotics.

Table 1.

Antibiotic resistance trends (2013-2019) of Helicobacter pylori naïve patients in Europe. C: clarithromycin; M: metronidazole; L: lefloxacin

N(%)	2013	2014	2015	2016	2017	2018	2019	Variation range
N° Cultures	435	522	469	286	355	282	310	282-522
No resistance	210 (48)	259(50)	197 (42)	93 (33)	162 (46)	106 (38)	104 (33.5)	33-50
Clarithromycin (C)	86 (20)	120(23)	117 (25)	59 (21)	68 (19)	65 (23)	57 (18)	18-25
Metronidazole (M)	165(38)	156(30)	140(30)	72 (25)	64 (18)	60 (21)	66 (21)	18-38
Levofloxacin (L)	58 (13	100 (19)	103(22)	46 (16)	59 (17)	55 (20)	41 (13)	13-22
Amoxicillin	6 (1)	0 (0)	0 (0)	0 (0)	10 (3)	1 (0.4)	0 (0)	<1
Tetracyclin	3 (0.7)	1 (0.2)	0 (0)	1 (0.3)	5 (1.4)	0 (0)	1 (0.3)	<1.4
Dual (C+M)	56 (13)	65 (13)	62 (13)	33 (12)	30 (9)	28 (10)	29 (9)	9-13
Triple (C+M+L)	22 (5)	31 (6)	32 (7)	16 (6)	12 (3)	12 (4)	8 (3)	3-7

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C: clarithromycin; M: metronidazole; L: lefloxacin

Disclosure

Dr Luis Bujanda has no conflicts of interest to declare. Dr. Gisbert has served as a speaker, a consultant and advisory member for or has received research funding from Mayoly, Allergan, Diasorin.

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.193

P0235 The Long-Term Effect of The Eradication of Helicobacter Pylori in T2Dm Or Predm Patients

WS Kim ^1,^✉, N Kim ^1,², G Noh ¹, KW Kim ¹, H Yoon ¹, CM Shin ¹, YS Park ¹, DH Lee ^1,²

Introduction

The positive relationship between Helicobacter pylori (H. pylori) infection and extra-gastrointestinal disease has been revealed in several studies. However, the long-term effect of H. pylori eradication on the metabolic syndrome or diabetes mellitus (DM) have not been established, yet.

Aims & Methods

The aim of this study was to evaluate the effect of H. pylori eradication on glycemic control in type 2 DM (T2DM) or preDM patients. From Dec 2006 to Feb. 2019, 3,608 subjects were enrolled at Seoul National University Bundang Hospital who received esophagogastroduo-denoscopy. 147 subjects with T2DM or preDM were selected and were divided in three groups, H. pylori-negative (n=40), H. pylori-positive with non-eradicated (n=57) and eradicated group (n=50). H. pylori was diagnosed by culture, histology, CLOtest and Anti-H. pylori IgG antibodies. HbA1c was measured before an eradication therapy or an enroll date in case of H. pylori-negative and non-eradicated group. The follow-up points were 1 year and 5 years after enrollment. For the statistical significance of HbA1c changes according to follow up period in three groups, a linear mixed model was used. P-value < 0.05 was regarded as statistically significant.

Results

There were no significant baseline differences of HbA1c among H. pylori-negative, H. pylori-positive with non-eradicated and eradicated group. in H. pylori-eradicated group, the values of HbA1c were significantly decreased after the eradication compared to H. pylori-negative and H. pylori-positive with non-eradicated groups in each 1 and 5 year points. in subgroup analysis, HbA1c values decreased in the patients who are male and/or age under 65 in the eradicated group compared to other groups. in contrast, HbA1c changes were not different among three groups in female or aged group over 65. We also proved the interaction between follow up period and group difference adjusted for age, sex, smoke, alcohol (Table 1). The eradication of H. pylori had significant effect on improvement of HbA1c values through follow up period compared to non-eradicated group at 1 and 5 year follow-up. However, TG and HDL has no statistically significant difference between three groups.

Multivariate analysis regarding changes in HbA1c according to H. pylori status

	Estimate	P value
Age<65 vs ≥ 65	0.34 (0.15)	0.021
Male vs female	0.05 (0.22)	0.811
Non vs Current/ex-smoker	0.06 (0.22)	0.782
Non vs Current/ex-drinker	-0.25 (0.16)	0.130
H. pylori negative * 1 years^‡	0.04 (0.14)	0.778
Eradicated * 1 years^‡	-0.31 (0.13)	0.016
H. pylori negative * 5 years^‡	-0.06 (0.16)	0.735
Eradicated * 5 years^‡	-0.48 (0.15)	0.001

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Data are presented as mean (standard error). Adjusted variables: age, sex, smoke, alcohol.

^‡

The interaction between H. pylori status and follow up period (1 and 5 years). P value: adjusted P value; compared to Non-eradicated group.

Conclusion

H. pylori eradication decreased HbA1c level in T2DM or DM patients for long term follow up period, especially in male subjects and age under 65, which support the rationale for recommendation of H. pylori eradication therapy in male or young patients with T2DM or preDM.

Disclosure

Nothing to disclose

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.194

P0236 Room For Improvement in The Treatment of Helicobacter Pylori Infection: Lessons From The European Registry On H. Pylori Management (Hp-Eureg)

OP Nyssen ¹, D Vaira ², B Tepeš ³, L Kupcinskas ⁴, D Bordin ⁵, Á Pérez-Aisa ⁶, A Gasbarrini ⁷, M Castro-Fernández ⁸, L Bujanda ⁹, A Garre ¹, A Lucendo ¹⁰, L Vologzhanina ¹¹, N Brglez Jurecic ¹², L Rodrigo-Sáez ¹³, JM Huguet Malavés ¹⁴, I Voynovan ⁵, J Perez-Lasala ¹⁵, P Mata Moreno ¹⁶, M Vujasinovic ¹⁷, R Abdulkhakov ¹⁸, J Barrio ¹⁹, L Fernandez-Salazar ²⁰, L Jonaitis ⁴, M Espada ¹, F Mégraud ²¹, C O'Morain ²², JP Gisbert ^1,^✉, On behalf of the Hp-EuReg Investigators

¹Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain

²Department of Surgical and Clinical Sciences, University of Bologna, Bologna, Italy

³Gastroenterology Unit, AM DC Rogaska, Rogaska Slatina, Slovenia

⁴Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania

⁵Department of Pancreatobiliary and Upper GI Diseases, Moscow Clinical Scientific Center, and A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow, Russian Federation

⁶Servicio de Gastroenterologia, Agencia Sanitaria Costa del Sol, Red de Investigación en Servicios de Salud en Enfermedades Crónicas (REDISSEC), Marbella, Spain

⁷Gastronterology Area, Fondazione Policlinico Universitario A. Gemelli, Rome, Italy

⁸Digestive Unit, Hospital de Valme, Sevilla, Spain

⁹Department of Gastroenterology, Hospital Donostia/Instituto Biodonostia. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd). Universidad del Pais Vasco (UPV/EHU), Donostia, Spain

¹⁰Hospital de Tomelloso, Ciudad Real, Spain

¹¹Gastrocentre Perm, Perm, Russian Federation

¹²DC, Bled, Slovakia

¹³Gastroenterology Unit, Hospital Universitario Central de Asturias, Oviedo, Spain

¹⁴Hospital General Universitario de Valencia, Valencia, Spain

¹⁵Digestive Service, HM Sanchinarro, Madrid, Spain

¹⁶Hospital San Pedro de Alcántara, Cáceres, Spain

¹⁷General Hospital, Slovenj Gradec, Gradec, Slovenia

¹⁸Kazan State Medical University, Kazan, Russian Federation

¹⁹Hospital Río Hortega, Valladolid, Spain

²⁰Hospital Clínico Universitario, Valladolid, Spain

²¹Laboratoire de Bactériologie, Hôpital Pellegrin, Bordeaux, France

²²Trinity College Dublin, Faculty of Health Sciences, Dublin, Ireland

^✉

Contact E-Mail Address: javier.p.gisbert@gmail.com

Introduction

Managing Helicobacter pylori infection requires constant decision-making, and each decision is open to possible errors.

Aims & Methods

To evaluate common mistakes in the eradication of H. pylori, based on the European Registry on Helicobacter pylori management (Hp-EuReg). Hp-EuReg is an international multicentre prospective non-interventional registry evaluating the decisions and outcomes of H. pylori management by European gastroenterologists in routine clinical practice.

Results

Countries recruiting more than 1,000 patients were included (26,340 patients). The most common mistakes (percentages) were: 1) To use the standard triple therapy where it is ineffective (46%). 2) To prescribe eradication therapy for only 7-10 days (69%) (Table 1). 3) To use a low dose of proton pump inhibitors (48%). 4) in patients allergic to penicillin, to prescribe always a triple therapy with clarithromycin and met-ronidazole (38%). 5) To repeat certain antibiotics after eradication failure (>15%). 6) To ignore the importance of compliance with treatment (2%). 7) Not to check the eradication success (6%). Time-trend analyses showed progressive greater compliance with current clinical guidelines.

Conclusion

The management of H. pylori infection by European gastroen-terologists is heterogeneous, frequently suboptimal and discrepant with current recommendations. Clinical practice is constantly adapting to updated recommendations, although this shift is delayed and slow.

Table 1.

Use and effectiveness of 7,10 and 14-day triple regimens in Europe.

	7 or 10 days			14 days
	Mistake (%) ¹	mITT (%)	14-days use, N (%)	mITT, N (%)	95%CI
Spain	71	71	1,429 (29)	1,297 (86)	(83-87)
Russia	63	77	984 (37)	790 (90)	(88-92)
Slovenia	62	85	1,070 (38)	722 (91)	(89-93)
Italy	93	84	28 (7)	21 (67)	(43-85)
Lithuania	84	75	182 (16)	1 (100)	(1.3-99)
Total	69	81	3,693 (31)	2,831 (88)	(87-89)

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N: total number of patients, mITT: modified intention-to-treat,

PP: per-protocol, CI: confidence interval 1% of mistake accounted for 7 or 10 day-treatment durations.

Disclosure

Dr. Nyssen has received research funding from Mayoly, Allergan. Dr. Gisbert has served as a speaker, a consultant and advisory member for or has received research funding from Mayoly, Allergan, Diasorin.

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.195

P0238 Bismuth Quadruple Regimen with Tetracycline Or Doxycycline Versus Pylera” As Third-Line Rescue Therapy For H. Pylori Infection: A Prospective Multicenter Analysis of The European Registry On Helicobacter Pylori Management (Hp-Eureg)

OP Nyssen ¹, A Perez-Aisa ², L Rodrigo-Saez ³, M Castro-Fernandez ⁴, M Pabón-Carrasco ⁴, A Keko-Huerga ⁴, P Mata Romero ⁵, J Ortuño ⁶, J Barrio ⁷, J Huguet ⁸, I Modollel ⁹, N Alcaide ¹⁰, A Lucendo ¹¹, X Calvet ¹², M Perona ¹³, B Gomez ¹⁴, B Gomez Rodriguez ¹⁵, P Varela ¹⁶, M Jimenez-Moreno ¹⁷, M Dominguez-Cajal ¹⁸, L Pozzati ¹⁹, D Burgos ²⁰, L Bujanda ²¹, J Hinojosa ², J Molina Infante ⁵, T Di Maira ⁶, L Ferrer ⁸, L Fernández-Salaza ¹⁰, A Figuerola ¹², L Tito ¹⁴, C de la Coba ¹⁶, J Gomez-Camarero ¹⁷, N Fernandez ², M Caldas ^1,^✉, A Garre ¹, E Resinas ¹, M Espada ¹, I Puig ²², F Megraud ²³, C O'Morain ²⁴, JP Gisbert ¹, On behalf of the Hp-EuReg Investigators.

Introduction

Different bismuth-quadruple therapies containing proton pump inhibitors, bismuth, metronidazole, and a tetracycline have been recommended as third-line Helicobacter pylori eradication treatment after failure with clarithromycin and levofloxacin.

Aims & Methods

To evaluate the efficacy and safety of third-line treatments with bismuth, metronidazole and either tetracycline or doxycy-cline. Sub-study of the European Registry on H. pylori Management (Hp-EuReg), an international multicenter prospective non-interventional registry of the routine clinical practice of European gastroenterologists. After previous failure with clarithromycin- and levofloxacin-containing therapies, patients receiving a third-line regimen with 10/14-day of PPI, bismuth, metronidazole and either tetracycline (T) or doxycycline (D), or 10-day Pylera” (P). Data were registered at AEG-REDCap online database.

Results

Four-hundred and fifty-four patients have been treated so far: 85 with T, 94 with D, and 275 with P. Average age was 53 years, 68% were women. Overall modified intention-to-treat and per-protocol eradication rates were 81% (D: 65%, T: 76%, P: 88%) and 82% (D: 66%, T: 77%, P: 88%), respectively. Further details on the effectiveness and compliance of each treatment group according to the length are presented in Table 1. By logistic regression, higher eradication rates were associated with compliance (OR=2.96; 95%CI=1.01-8.84) and no prior metronidazole use (OR=1.96; 95%CI=1.15-3.33); P was superior to D (OR=4.46; 95%CI=2.51-8.27), and T marginally superior to D (OR= 1.67; 95%CI=0.85-3.29).

Conclusion

Third-line (after failure with clarithromycin and levofloxacin) H. pylori eradication with bismuth quadruple treatment offers acceptable efficacy and safety. Highest efficacy was found in compliant patients and in those taking 10-day Pylera” or 14-day tetracycline. Doxycycline seems to be less effective and therefore should not be recommended.

Table 1.

Effectiveness (by modified intention-to-treat and per-protocol) and compliance according to the treatment regimen and length

Effectiveness, N (%)		Compliance	mITT, N	mITT	(95%CI)	PP, N	PP	(95%CI)
Group T	Overall	82 (97%)	64	76%	(66-86)	63	77%	(67-86)
	10 days*	29 (97%)	19	66%	(47-85)	19	66%	(47-85)
	14 days	45 (96%)	45	82%	(71-93)	44	83%	(72-94)
Group D	Overall	85 (93%)	58	65%	(55-76)	56	66%	(55-77)
	10 days*	37 (90%)	25	63%	(46-79)	23	63%	(45-79)
	14 days	53 (96%)	32	70%	(55-84)	32	71%	(57-85)
Group P	10 days*	249 (96%)	222	88%	(83-92)	216	88%	(84-92)

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Group T - tetracycline containing bismuth quadruple therapy, Group D - doxycycline containing bismuth quadruple therapy, Group P - single capsule bismuth quadruple therapy (Pylera”), 95%CI - 95% confidence interval. ITT: intention-to-treat, mITT: modified intention-to-treat; PP: per-protocol. The Chi² test showed statistically significant differences of treatment length in the mITT set between treatment groups (T, D and P) as reported in the table: *p < 0.001.

Disclosure

Dr. Nyssen has received research funding from Mayoly and Allergan. Dr. Gisbert has served as a speaker, a consultant and advisory member for or has received research funding from Mayoly, Allergan and Diasorin.

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.196

P0239 Impact of Helicobacter Pylori Clarithromycin Resistance On The Treatment Effectiveness: Data of The European Registry On H. Pylori Management (Hp-Eureg)

L Bujanda ^1,^✉, OP Nyssen ², A Cosme ¹, DS Bordin ³, B Tepeš ⁴, A Perez-Aisa ⁵, D Vaira ⁶, M Caldas ², M Castro-Fernandez ⁷, F Lerang ⁸, M Leja ⁹, L Rodrigo ¹⁰, T Rokkas ¹¹, L Kupcinskas ¹², J Perez-Lasala ¹³, L Jonaitis ¹², O Shvets ¹⁴, A Gasbarrini ¹⁵, H Simsek ¹⁶, ATR Axon ¹⁷, GM Buzas ¹⁸, JC Machado ¹⁹, Y Niv ²⁰, L Boyanova ²¹, A Goldis ²², V Lamy ²³, A Tonkic ²⁴, W Marlicz ²⁵, C Beglinger ²⁶, M Venerito ²⁷, P Bytzer ²⁸, LG Capelle ²⁹, T Milosavljevic ³⁰, L Veijola ³¹, J Molina Infante ³², L Vologzhanina ³³, G Fadeenko ³⁴, I Ariño ³⁵, G Fiorini ³⁶, E Resina ², R Muñoz ², I Puig ³⁷, F Megraud ³⁸, C O'Morain ³⁹, JP Gisbert ², On behalf of the Hp-EuReg Investigators.

¹Hospital Donostia/Instituto Biodonostia, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Universidad del País Vasco (UPV/EHU), Department of Gastroenterology, San Sebastian, Spain

²Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Gastroenterology Unit, Madrid, Spain

³A. S. Loginov Moscow Clinical Scientific Center, Department of Outpatient Therapy and Family Medicine, Tver State Medical University, Tver and Department of Propaedeutic of Internal Diseases and Gastroenterology, Gastroenterolgy Unit, Moscow, Russian Federation

⁴AM DC Rogaska, Gastroenterology Unit, Rogaska Slatina, Slovenia

⁵Agencia Sanitaria Costa del Sol, Red de Investigación en Servicios de Salud en Enfermedades Crónicas (REDISSEC), Servicio de Gastroenterología, Marbella, Spain

⁶University of Bologna, Department of Surgical and Medical Sciences, Bologna, Italy

⁷Hospital de Valme, Digestive Unit, Sevilla, Spain

⁸Central Hospital Ostfold, Medical Department, Fredrikstad, Norway

⁹Institute of Clinical and Preventive Medicine & Faculty of Medicine, University of Latvia, Riga, Latvia

¹⁰Hospital Universitario Central de Asturias, Gastroenterology Unit, Oviedo, Spain

¹¹Henry Dunant Hospital, Gastroenterology Unit, Athens, Greece

¹²Lithuanian University of Health Sciences, Department of Gastroenterology, Kaunas, Lithuania

¹³HM Sanchinarro, Digestive Service, Madrid, Spain

¹⁴National Medical University n. a. O.O. Bogomolets, Internal Diseases Department No.1, Kyiv, Ukraine

¹⁵Fondazione Policlinico Universitario A. Gemelli, Gastronterology Area, Rome, Italy

¹⁶Hacettepe University Faculty of Medicine, Internal Medicine/Gastroenterology Department, Ankara, Turkey

¹⁷University of Leeds, Gastroenterology Unit, Leeds, United Kingdom

¹⁸Ferencváros Policlinic, Gastroenterology Unit, Budapest, Hungary

¹⁹Instituto de Investigaçao e Inovaçao em Saúde, Universidade do Porto, and Ipatimup - Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal

²⁰Rabin Medical Center, Tel Aviv University, Department of Gastroenterology, Tel Aviv, Israel

²¹Medical University of Sofia, Department of Medical Microbiology, Sofia, Bulgaria

²²Timisoara Hospital, Gastroenterology Unit, Timisoara, Romania

²³CHU Charleroi, Gastroenterology, Hepatology & Nutrition, Charleroi, Belgium

²⁴University Hospital Centre Split, Split, Croatia

²⁵Pomeranian Medical University, Gastroenterology Unit, Szczecin, Poland

²⁶Hospital de Basel, Gastroenterology Unit, Basel, Switzerland

²⁷Otto-von-Guericke University Hospital, Gastroenterology, Hepatology and Infectious Diseases, Magdeburg, Germany

²⁸Zealand University Hospital, Copenhagen University, Medicine, Copenhagen, Denmark

²⁹Erasmus MC University, Gastroenterology and Hepatology, Rotterdam, Netherlands

³⁰Clinical Center of Serbia Clinic for Gastroenterology and Hepatology, University of Belgrade, Medical, Belgrade, Serbia

³¹Internal Medicine, Herttoniemi Hospital, Helsinki, Finland

³²Hospital San Pedro de Alcántara, Gastroenterology Unit, Caceres, Spain

³³Gastrocentre, Gastroenterology Unit, Perm, Russian Federation

³⁴Digestive Ukrainian Academy of Medical Sciences, Kyiv, Ukraine

³⁵Hospital Clínico Universitario Lozano Blesa, Gastroenterology Unit, Zaragoza, Spain

³⁶University of Bologna, Surgical and Medical Sciences, Bologna, Italy

³⁷Althaia Xarxa Assistencial Universitària de Manresa and Universitat de Vic-Universitat Central de Catalunya (UVicUCC), Manresa, Spain

³⁸Hôpital Pellegrin, Laboratoire de Bactériologie, Bordeaux, France

³⁹Trinity College Dublin - Faculty of Health Sciences, Dublin, Ireland

^✉

Contact E-Mail Address: luis.bujanda@osakidetza.net

Introduction

Antibiotic resistance is the major factor affecting our ability to cure Helicobacter pylori infection. Quadruple therapy is currently recommended; however, triple therapy with two antibiotics may be sufficient in those patients without clarithromycin resistance.

Aims & Methods

To evaluate the effectiveness of the treatments according to the clarithromycin H. pylori resistance in Europe. International multicenter prospective non-interventional European Registry on H. pylori Management (Hp-EuReg) aiming to evaluate the decisions and outcomes of H. pylori infection. Infected adult patients diagnosed with culture registered at AEG-REDCap e-CRF from 2013 to 2019. Per-protocol (PP) analysis was performed based on the presence or absence of clarithromycin bacterial resistance.

Results

Overall, 5,036 patients were included: 1,747 (35%) were resistant and 3,289 (65%) sensitive to clarithromycin. The overall eradication rate was higher in clarithromycin-susceptible patients (91% vs. 84%; p< 0.001). Triple therapy with a PPI, clarithromycin and amoxicillin achieved over 90% eradication rates in clarithromycin-susceptible patients. However, in those with clarithromycin-resistance, optimal effectiveness was only achieved when treated with quadruple therapy with a PPI, clarithromycin, amoxicillin and bismuth (Table 1).

Conclusion

Classic triple therapy with a PPI, clarithromycin and amoxicillin achieves optimal results (>90%) in patients susceptible to clarithromycin. However, when clarithromycin resistance is unknown, quadruple therapy with a PPI, clarithromycin, amoxicillin and bismuth may be a better treatment option.

Table 1.

Effect of the clarithromycin Helicobacter pylori resistance on the effectiveness of treatments in Europe

Treatment schemes	Clarithromycin resistant (E/N,%)			Clarithromycin susceptible (E/N,%)
Triple-C+A	11	14	79%	392	431	91%
Triple-A+L	165	191	86%	47	55	85%
Triple-A+M	46	55	84%	147	166	89%
Triple-A+R	91	102	89%	9	11	82%
Quadruple-C+A+M/T	43	54	80%	88	100	88%
Quadruple-C+A+B	10	11	91%	36	40	90%
Sequential-C+A+T	242	286	85%	627	664	94%
Sequential-C+A+M	17	23	74%	41	53	77%
Single capsule	66	80	83%	53	54	98%

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E: number of eradicated patients N: total number of patients analysed; %: per-protocol effectiveness; C: clarithromycin; M: metronidazole; B: bismuth; A: amoxicillin; T: tinidazole; Single capsule: three-in-one single capsule containing bismuth, tetracycline and metronidazole (marketed as Pylera”)

Disclosure

Dr Luis Bujanda has no conflicts of interest to declare. Dr. Gisbert has served as a speaker, a consultant and advisory member for or has received research funding from Mayoly, Allergan, Diasorin.

United European Gastroenterol J. 2020 Oct 10;8(8 Suppl):144–887. doi: 10.1177/2050640620927345.197

P0240 Helicobacter Pylori Antibiotic Resistance: Data From The European Registry On H. Pylori Management (Hp-Eureg)

L Bujanda ^1,^✉, OP Nyssen ², A Cosme ¹, DS Bordin ³, B Tepeš ⁴, A Perez-Aisa ⁵, D Vaira ⁶, M Caldas ², M Castro-Fernandez ⁷, F Lerang ⁸, M Leja ⁹, L Rodrigo ¹⁰, T Rokkas ¹¹, L Kupcinskas ¹², J Perez-Lasala ¹³, L Jonaitis ¹², O Shvets ¹⁴, A Gasbarrini ¹⁵, H Simsek ¹⁶, ATR Axon ¹⁷, GM Buzas ¹⁸, JC Machado ¹⁹, Y Niv ²⁰, L Boyanova ²¹, A Goldis ²², V Lamy ²³, A Tonkic ²⁴, W Marlicz ²⁵, C Beglinger ²⁶, M Venerito ²⁷, P Bytzer ²⁸, LG Capelle ²⁹, T Milosavljevic ³⁰, L Veijola ³¹, J Molina Infante ³², L Vologhzanina ³³, G Fadeenko ³⁴, I Ariño ³⁵, G Fiorini ⁶, E Resina ², R Muñoz ², I Puig ³⁶, F Megraud ³⁷, C O'Morain ³⁸, JP Gisbert ², On behalf of the Hp-EuReg Investigators.

¹Hospital Donostia/Instituto Biodonostia, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Universidad del Pais Vasco (UPV/EHU), Gastroenterology, San Sebastian, Spain

²Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Gastroenterology Unit, Madrid, Spain

³A. S. Loginov Moscow Clinical Scientific Center, Dept of Outpatient Therapy and Family Medicine, Tver State Medical University, Dept of Propaedeutic of Internal Diseases and Gastroenterology, Gastroenterolgy Unit, Moscow, Russian Federation

⁴AM DC Rogaska, Gastroenterology Unit, Rogaska Slatina, Slovenia

⁵Agencia Sanitaria Costa del Sol, Red de Investigación en Servicios de Salud en Enfermedades Crónicas (REDISSEC), Servicio de Gastroenterologia, Marbella, Spain

⁶University of Bologna, Surgical and Medical Sciences, Bologna, Italy

⁷Hospital de Valme, Digestive Unit, Sevilla, Spain

⁸Central Hospital Ostfold, Medical, Fredrikstad, Norway

⁹Institute of Clinical and Preventive Medicine & Faculty of Medicine, University of Latvia, Riga, Latvia

¹⁰Hospital Universitario Central de Asturias, Gastroenterology Unit, Oviedo, Spain

¹¹Henry Dunant Hospital, Gastroenterology Unit, Athens, Greece

¹²Lithuanian University of Health Sciences, Gastroenterology, Kaunas, Lithuania

¹³HM Sanchinarro, Digestive Service, Madrid, Spain

¹⁴National Medical University n. a. O. O. Bogomolets, Internal Diseases Dept No.1, Kyiv, Ukraine

¹⁵Fondazione Policlinico Universitario A. Gemelli, GastronterologyArea, Rome, Italy

¹⁶Hacettepe University Faculty of Medicine, Internal Medicine/Gastroenterology, Ankara, Turkey

¹⁷University of Leeds, Gastroenterology Unit, Leeds, United Kingdom

¹⁸Ferencváros Policlinic, Gastroenterology Unit, Budapest, Hungary

¹⁹Instituto de Investigaçao e Inovaçao em Saúde, Universidade do Porto, and Ipatimup - Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal

²⁰Rabin Medical Center, Tel Aviv University, Gastroenterology, Tel Aviv, Israel

²¹Medical University of Sofia, Medical Microbiology, Sofia, Bulgaria

²²Timisoara Hospital, Gastroenterology Unit, Timisoara, Romania

²³CHU Charleroi, Gastroenterology, Hepatology & Nutrition, Charleroi, Belgium

²⁴University Hospital Centre Split, Split, Croatia

²⁵Pomeranian Medical University, Gastroenterology Unit, Szczecin, Poland

²⁶Hospital de Basel, Gastroenterology Unit, Basel, Switzerland,