Abstract
INTRODUCTION:
Although proton-pump inhibitor (PPI) is often prescribed for reducing delayed bleeding in upper gastrointestinal endoscopic treatments, no studies with a sufficient sample size evaluated its reduced effect compared with the absence of acid-suppressive agents. The aim of this study was to investigate the effect of oral PPI on reducing delayed bleeding in 5 upper gastrointestinal endoscopic treatments.
METHODS:
This population-based cohort study collected data from patients who were either prescribed with PPIs or received no acid-suppressive therapy and who underwent esophageal endoscopic mucosal resection (E-EMR), esophageal endoscopic submucosal dissection (E-ESD), gastric endoscopic mucosal resection (G-EMR), gastric endoscopic submucosal dissection (G-ESD), or percutaneous endoscopic gastrostomy (PEG) in Japan between 2012 and 2022 from the Diagnosis Procedure Combination database. The primary outcome was delayed bleeding in each procedure. We conducted propensity score matching to balance 2 comparison groups and performed logistic regression analyses to compare bleeding outcomes.
RESULTS:
This study included data on 172,635 patients. After propensity score matching, the delayed bleeding risk with PPI use was significantly lower in G-EMR (odds ratio [OR], 0.66; 95% confidence interval [CI], 0.52–0.84) and G-ESD (OR, 0.39; 95% CI, 0.30–0.50). By contrast, a lower delayed bleeding risk of PPI was not observed in E-EMR (OR, 1.05; 95% CI, 0.56–1.99), E-ESD (OR, 1.09; 95% CI, 0.86–1.38), and PEG (OR, 1.03; 95% CI, 0.93–1.13). The subgroup and sensitivity analyses almost consistently confirmed the main results.
DISCUSSION:
Oral PPI administration contributed to reducing delayed bleeding risk in G-EMR and G-ESD but not in E-EMR, E-ESD, and PEG.
KEYWORDS: proton-pump inhibitor, delayed bleeding, upper gastrointestinal endoscopic treatment
INTRODUCTION
Delayed bleeding is a major complication in upper gastrointestinal (GI) endoscopic treatments, and several studies have focused on this notion (1–5). In particular, the delayed bleeding risk is higher in gastric endoscopic submucosal dissection (G-ESD), accounting for 3.2%–8.7% (6). Several methods for preventing delayed bleeding, such as ulcer closure (7) and polyglycolic acid sheet (8), were proposed; however, prospective or large-scale retrospective studies did not exhibit marked efficacy of these techniques (9).
Acid-suppressive agents are extensively used for reducing delayed bleeding in G-ESD (10,11), and proton-pump inhibitor (PPI) plays a central role globally. This is based on the advantageous effects of oral PPI over histamine-2-receptor antagonist (H2RA), which is a weaker acid-suppressive agent than PPI, according to a previous randomized controlled trial (12). The European and Japanese guidelines strongly recommended PPI administration in G-ESD (13,14). However, no studies have compared the delayed bleeding risk between oral PPI administration and no acid-suppressive therapy in G-ESD; thus, the authentic effectiveness of oral PPI on reducing delayed bleeding in G-ESD remains unclear.
Furthermore, PPI is often prescribed conventionally in upper GI endoscopic treatments other than G-ESD because of its convenience. However, considering the potential risk of adverse events associated with PPI, including Clostridioides difficile infection (15) , PPI administration should be avoided when it is not effective for reducing delayed bleeding in upper GI endoscopic treatments. In the context of esophageal endoscopic resection, there was only one randomized controlled trial with a small sample size (16), based on which conclusive determination of the effectiveness of PPI administration on reducing delayed bleeding is challenging. Moreover, no studies have evaluated the effect of PPI in gastric endoscopic mucosal resection (G-EMR) and percutaneous endoscopic gastrostomy (PEG).
To accurately determine the effectiveness of oral PPI administration in each upper GI endoscopic treatment, the analysis comprising a large cohort is warranted. However, the sample size was not adequate even in a multicenter study (16). The Diagnosis Procedure Combination (DPC) database includes a large number of patients according to the Japanese health system, and several studies have evaluated delayed bleeding outcomes, especially in G-ESD (17,18). We aimed to identify the efficacy of oral PPI administration compared with no acid-suppressive therapy on reducing delayed bleeding in 5 upper GI endoscopic treatments, including esophageal endoscopic mucosal resection (E-EMR), esophageal endoscopic submucosal dissection (E-ESD), G-EMR, G-ESD, and PEG.
METHODS
Study design and data source
This retrospective population-based cohort study extracted patient data from the DPC database (19), which is one of the reimbursement systems in the Japanese health insurance system. This database includes data from over 1,700 acute-care hospitals throughout Japan. For this analysis, data from over 1,100 hospitals and more than 7 million cases annually were used, thereby making it highly representative of acute care inpatient services in Japan. The database comprises patient data, including diagnosis, comorbidities, age, sex, height, weight, medication, medical history, complication during hospitalization, admission and discharge dates, treatment date, and records of all medical procedures in each patient. Records were coded according to the International Classification of Diseases and Related Health Problems, 10th Revision codes (20), supplemented by text data in Japanese. Procedures were coded with the Medical Intervention Classification master code (19).
The Ethics Committee of Tohoku University Graduate School of Medicine approved this study. Informed consent was waived considering data anonymity.
Study population
We enrolled patients aged 20 years or older who underwent one of the 5 upper GI endoscopic treatments (E-EMR, E-ESD, G-EMR, G-ESD, and PEG) between April 2012 and March 2022. To accurately compare the delayed bleeding risk between oral PPI use and no acid-suppressive therapy, the following patients were excluded: (i) those prescribed with vonoprazan, (ii) those prescribed with oral PPI only on the day after the procedure or thereafter, (iii) those who received intravenous PPI before delayed bleeding, (iv) those prescribed or injected with H2RA before delayed bleeding, and (v) those with missing data.
PPI dose
Four types of oral PPIs (lansoprazole, rabeprazole, esomeprazole, and omeprazole) can be prescribed in Japan, with standard daily doses of 30, 10, 20, and 20 mg, respectively. However, oral PPIs are not available over the counter in Japan. The PPI doses were categorized into 2 groups: (i) the standard-dose PPI, defined as the standard or higher dose of each PPI, and (ii) the reduced-dose PPI, defined as less than the standard dose of each PPI.
Data collection and variables
We accessed data on age, sex, body mass index, comorbidities, hemodialysis, concurrent medication, upper GI endoscopic treatment type (E-EMR, E-ESD, G-EMR, G-ESD, and PEG), indication for endoscopic mucosal resection (EMR)/endoscopic submucosal dissection (ESD), indication for PPI, bleeding outcome, annual hospital volume, admission and discharge dates, upper GI endoscopic treatment date, and treatment year. Furthermore, information on postdischarge bleeding outcomes within 30 days of upper GI endoscopic treatments was collected. Comorbidities were measured with the Charlson Comorbidity Index (21). G-ESD and duodenal ESD were identical to gastroduodenal ESD on the DPC database code until March 2022; thus, G-ESD was defined as gastroduodenal ESD for gastric tumors in this study. The annual hospital volume was categorized into quartiles by the number of upper GI endoscopic treatments for a month as low (≤7 cases/mo), intermediate (8–12 cases/mo), high (13–19 cases/mo), and very high (≥20 cases/mo). The concurrent medications included antiplatelet agents (aspirin, P2Y12 receptor antagonist [P2Y12RA], cilostazol, and others), anticoagulants (warfarin, direct oral anticoagulants, heparin, and others), nonsteroidal anti-inflammatory drugs, corticosteroids, and mucosal protective agents. The treatment year was categorized into 2012–2013, 2014–2015, 2016–2017, 2018–2019, and 2020–2021.
Exposures and outcomes
The primary exposure was oral PPI administration (PPI group) or no acid-suppressive therapy (non-PPI group). The primary outcome was delayed bleeding in each upper GI endoscopic treatment. Delayed bleeding was defined as endoscopic hemostasis and/or blood transfusion from 2 to 30 days after the treatment, according to previous studies (22–24). Endoscopic hemostasis included contact thermal therapy, clipping, and other methods.
Statistical analysis
We conducted propensity score matching (PSM) to reduce bias between the 2 comparison groups. Based on previous studies (25–27) and the potential risk for delayed bleeding, 19–20 variables were selected for estimating each propensity score as follows: age, sex, body mass index, comorbidities, hemodialysis, concurrent medications (aspirin, cilostazol, P2Y12RA, other antiplatelet agents, warfarin, direct oral anticoagulants, heparin, other anticoagulants, nonsteroidal anti-inflammatory drugs, corticosteroids, and mucosal protective agents), annual hospital volume, treatment year, indication for EMR/ESD, and indication for PPI. We conducted 1:1 PSM using the nearest neighbor with a 0.2 caliper width of the pooled SD of the logit of the propensity score. We also calculated the standardized difference (SD). An SD of ≤ 10% indicated a good balance and an SD of ≤ 20% represented an acceptable balance of covariates between the 2 comparison groups before and after PSM (28). After each PSM, we compared the bleeding outcome in each upper GI endoscopic treatment using a logistic regression analysis. A P value of < 0.05 indicated statistical significance.
Categorical variables were presented as the frequency and proportion, and continuous variables were expressed as the median and interquartile range. All statistical data were analyzed with SPSS version 28.0 for Windows software (IBM, Armonk, NY) and R software version 4.1.2 (The R Foundation for Statistical Computing, Vienna, Austria).
Subgroup analyses
We conducted subgroup analyses based on age, sex, hemodialysis, antithrombotic agents, and indication for EMR/ESD to investigate the consistency of the acquired odds ratios (ORs) across the subgroups by the significance of an interaction term between the 2 comparison groups. A P value for the interaction of <0.10 indicated statistical significance in the subgroup analyses.
Sensitivity analyses
Two predefined and 2 post hoc sensitivity analyses were conducted to confirm the robustness of the acquired findings. First, inverse probability of treatment weighting (IPTW) analyses, which is another statistical method using propensity score (29), was performed with the same covariates instead of PSM. Second, we conducted additional PSMs for each upper GI endoscopic treatment between the following groups to minimize the dose-selection bias for the outcome: (i) the standard-dose PPI group vs the non-PPI group and (ii) the reduced-dose PPI group vs the non-PPI group.
In the post hoc sensitivity analyses, additional PSMs combining E-EMR and E-ESD cases were conducted to complement the unsatisfactory sample power for detecting differences in bleeding outcomes in these procedures because of lower bleeding rates or a smaller sample size. To investigate the effect of cases with missing data, we further performed multiple imputation of missing variables, followed by IPTW for each upper GI endoscopic treatment.
RESULTS
Patient characteristics
Among the 776,948 patients who underwent one of the 5 upper GI endoscopic treatments, this study included data on 172,635 patients who either received PPI prescription or did not receive acid-suppressive therapy (Figure 1). After PSMs, 915 pairs of E-EMR, 5,380 pairs of E-ESD, 3,025 pairs of G-EMR, 1,591 pairs of G-ESD, and 30,854 pairs of PEG were analyzed. All SDs after PSMs were <10% for G-EMR and PEG, indicating a good balance between the 2 groups (see Supplementary Tables 1 and 2, Supplementary Digital Contents 1 and 2, http://links.lww.com/AJG/D766, http://links.lww.com/AJG/D767). For G-ESD, E-EMR, and E-ESD, the balance between the 2 groups after PSMs was good or acceptable with the maximal SDs being 12.3%, 13.1%, and 13.7%, respectively (Table 1) (see Supplementary Tables 3 and 4, Supplementary Digital Contents 3 and 4, http://links.lww.com/AJG/D768, http://links.lww.com/AJG/D769).
Figure 1.
Flow diagram of the patient enrollment. E-EMR, esophageal endoscopic mucosal resection; E-ESD, esophageal endoscopic submucosal dissection; EMR, endoscopic mucosal resection; ESD, endoscopic submucosal dissection; G-EMR, gastric endoscopic mucosal resection; G-ESD, gastric endoscopic submucosal dissection; GI, gastrointestinal; H2RA, histamine-2 receptor antagonist; PEG, percutaneous endoscopic gastrostomy; PPI, proton-pump inhibitor; PSM, propensity score matching.
Table 1.
Baseline characteristics of the PPI and non-PPI groups before and after PSM in G-ESD
Incidence rate and risk of delayed bleeding in the PPI group in upper GI endoscopic treatments
The incidence rates of delayed bleeding in the 5 upper GI endoscopic treatments are presented in Figure 2. The incidence rates of delayed bleeding in G-EMR in the PPI and non-PPI groups were 3.9% and 5.9%, respectively, with a significantly lower risk observed in the PPI group (OR, 0.66; 95% confidence interval [CI], 0.52–0.84) (Figure 3). The incidence rates of delayed bleeding in G-ESD were 5.7% and 13.3% in the PPI and non-PPI groups, respectively. Logistic regression analysis in G-ESD revealed a further lower risk in the PPI group (OR, 0.39; 95% CI, 0.30–0.50) (Figure 3).
Figure 2.
Incidence rates of delayed bleeding in the 5 upper GI endoscopic treatments in the PPI and non-PPI groups. E-EMR, esophageal endoscopic mucosal resection; E-ESD, esophageal endoscopic submucosal dissection; G-EMR, gastric endoscopic mucosal resection; G-ESD, gastric endoscopic submucosal dissection; GI gastrointestinal; PEG, percutaneous endoscopic gastrostomy; PPI, proton-pump inhibitor.
Figure 3.
Delayed bleeding risk of PPI administration after PSM for each upper GI endoscopic treatment. CI, confidence interval; E-EMR, esophageal endoscopic mucosal resection; E-ESD, esophageal endoscopic submucosal dissection; G-EMR, gastric endoscopic mucosal resection; G-ESD, gastric endoscopic submucosal dissection; GI, gastrointestinal; OR, odds ratio; PEG, percutaneous endoscopic gastrostomy; PPI, proton-pump inhibitor; PSM, propensity score matching.
By contrast, the PPI and non-PPI groups exhibited comparable incidence rates of delayed bleeding in E-EMR, E-ESD, and PEG (Figure 2). Logistic regression analyses indicated no significant delayed bleeding risk in the PPI group in E-EMR (OR, 1.05; 95% CI, 0.56–1.99), E-ESD (OR, 1.09; 95% CI, 0.86–1.38), and PEG (OR, 1.03; 95% CI, 0.93–1.13) (Figure 3).
Subgroup analyses
No significant interaction was observed in most subgroup analyses; however, 2 significant interactions were identified in G-EMR: the indication for EMR/ESD and sex (P for interaction < 0.001 and = 0.096, respectively) (Table 2). In particular, the ORs differed markedly between gastric cancer and others in the indication for EMR/ESD (0.42 vs 1.05).
Table 2.
Subgroup analyses for the comparison of delayed bleeding risk between the PPI and non-PPI groups, according to age, sex, hemodialysis, use of AT agents, and indication for EMR/ESD
Sensitivity analyses
In the predefined sensitivity analyses, the balance between the 2 groups after IPTWs was good or acceptable with the maximum SD being 13.5%. The delayed bleeding risk in the PPI groups after IPTW was similar to that after PSM, and significant results were consistently observed for the upper GI endoscopic treatments (see Supplementary Figure 1, Supplementary Digital Contents 5, http://links.lww.com/AJG/D770). Furthermore, in the analyses investigating the effect of the standard-dose PPI or reduced-dose PPI, the balance between the 2 groups after PSMs was good or acceptable with the maximum SD being 13.4%. The comparison between the standard-dose PPI and non-PPI groups revealed results similar to those of the original PSM (Figure 4). Identical results were obtained in the comparison between the reduced-dose PPI and non-PPI groups after PSM (Figure 5).
Figure 4.
Delayed bleeding risk of the standard-dose PPI administration after PSM for each upper GI endoscopic treatment. CI, confidence interval; E-EMR, esophageal endoscopic mucosal resection; E-ESD, esophageal endoscopic submucosal dissection; G-EMR, gastric endoscopic mucosal resection; G-ESD, gastric endoscopic submucosal dissection; GI, gastrointestinal; OR, odds ratio; PEG, percutaneous endoscopic gastrostomy; PPI, proton-pump inhibitor; PSM, propensity score matching.
Figure 5.
Delayed bleeding risk of the reduced-dose PPI administration after PSM for each upper GI endoscopic treatment. CI, confidence interval; E-EMR, esophageal endoscopic mucosal resection; E-ESD, esophageal endoscopic submucosal dissection; G-EMR, gastric endoscopic mucosal resection; G-ESD, gastric endoscopic submucosal dissection; GI, gastrointestinal; OR, odds ratio; PEG, percutaneous endoscopic gastrostomy; PPI, proton-pump inhibitor; PSM, propensity score matching.
We further performed 2 post hoc sensitivity analyses. In PSMs combining E-EMR and E-ESD cases, the balance between the 2 groups was good or acceptable with the maximum SD being 11.9%. No significant results were obtained in each analysis (see Supplementary Figure 2, Supplementary Digital Content 6, http://links.lww.com/AJG/D771). In IPTWs after multiple imputation, the balance between the 2 groups was good or acceptable with the maximum SD being 12.9%. Significant results were consistent for the upper GI endoscopic treatments (see Supplementary Figure 3, Supplementary Digital Contents 7, http://links.lww.com/AJG/D772).
DISCUSSION
Despite the current recommendation of the European and Japanese guidelines on PPI administration in G-ESD (13,14), no studies have directly compared the delayed bleeding risk between oral PPI administration and no acid-suppressive therapy in G-ESD. Furthermore, the efficacy of oral PPI for delayed bleeding in E-EMR, E-ESD, G-EMR, and PEG remains unknown. Our large-scale population-based study revealed the reduced effect of oral PPI on delayed bleeding in G-ESD and G-EMR but not in E-ESD, E-EMR, and PEG. The subgroup and sensitivity analyses almost consistently confirmed the acquired results.
This study includes clinical insights on each upper GI endoscopic treatment. In G-ESD, we first found that oral PPI administration reduced delayed bleeding risk (OR, 0.39). Most patients currently receive acid-suppressive agents for G-ESD in clinical practice, based on the results of a previous randomized trial comparing oral PPI with H2RA (12). However, no studies reported the actual reduction in the effect of PPI for delayed bleeding because very few patients currently undergo G-ESD without the administration of acid-suppressive agents. Indeed, only 0.48% of patients (1,591/331,011) who underwent G-ESD did not receive acid-suppressive agents. However, a large database enabled us to compare the bleeding outcomes between oral PPI administration and no acid-suppressive therapy in G-ESD. Our results could provide additional evidence on the use of PPI in G-ESD. Furthermore, PPI was useful, regardless of whether the standard- or reduced-dose PPI was administered.
To the best of our knowledge, we first demonstrated the efficacy of oral PPI administration on reducing delayed bleeding in G-EMR. Although the OR of PPI use in G-EMR (0.66) was lower than that in G-ESD (0.39), the ORs were similar between G-EMR and G-ESD when the indication for EMR/ESD was limited to gastric cancer (0.42 vs 0.38). Meanwhile, in cases wherein the indication for EMR/ESD was “others” (i.e., neither gastric cancer nor neuroendocrine tumor), the OR in G-EMR was 1.05, indicating no reduced effect of PPI on delayed bleeding in this category. Unlike G-ESD, many cases in G-EMR were categorized as others in the indication for EMR/ESD (1.0%–1.3% vs 68.5%–69.6%), and most cases (96.7%–97.6%) under this category of G-EMR involved gastric polyps. G-EMR included gastric polypectomy in this database; thus, our results suggest that oral PPI administration may be effective in reducing delayed bleeding in true G-EMR but not in gastric polypectomy. Moreover, in the subgroup analysis, there was also a significant interaction between sex and the effect of PPI on the delayed bleeding risk in G-EMR. Based on this result, the effect of PPI on reducing delayed bleeding might be lower in female than that in male. However, the reason for this finding is unclear.
By contrast, oral PPI administration did not significantly reduce the delayed bleeding risk in E-EMR and E-ESD, with ORs of 1.05 and 1.09, respectively, after PSM. Based on a previous randomized controlled trial, the incidence rates of delayed bleeding after esophageal endoscopic resection in patients with and without PPI administration were 0% and 3%, respectively (16). However, this randomized trial focused on gastroesophageal reflux disease-like symptoms and its sample size (n = 229) and the number of events (n = 3) were inadequate for evaluating the delayed bleeding risk. Our study compared outcomes between patients who received oral PPI and those who did not receive acid-suppressive therapy using 915 pairs of E-EMR and 5,380 pairs of E-ESD after PSM. Thus, our results provided novel insights on the effect of PPI regarding delayed bleeding in esophageal endoscopic resection. PPI may not be required to reduce the delayed bleeding risk in E-ESD and E-EMR.
Oral PPI administration did not exhibit reduced effects on delayed bleeding in PEG. Although the Japanese guidelines (30,31) classify PEG as a high-risk procedure for bleeding with delayed bleeding rates of 2.0%–2.5% (32–34), few studies have investigated the role of PPI in preventing such adverse events. This study first investigated the effectiveness of oral PPI in preventing delayed bleeding after PEG. Based on our results, PPI administration may not be required for PEG.
This study has several limitations. First, this was a retrospective study and randomization between the 2 groups was not conducted. Although propensity score methods were performed, which enabled adjustment for the measured covariates, unmeasured confounders might have existed. In particular, higher ORs (1.20–1.57) in some sensitivity analyses of E-EMR might be attributed to unmeasured confounders. Second, collecting data on the continuation or discontinuation of antithrombotic agents was challenging because of the database characteristics. Furthermore, we could not include endoscopic methods, such as ESD ulcer closure, for preventing delayed bleeding in G-ESD as covariates. However, previous studies revealed that these methods did not significantly reduce delayed bleeding in G-ESD (9). Third, we used the data on the initially prescribed dose of PPI; however, the changes in PPI doses were not considered. Fourth, type II error might have occurred in the endoscopic procedures with lower events and smaller sample sizes, such as E-EMR. Fifth, data from a Japanese database were used; thus, our findings may not be generalizable to other populations or healthcare systems with different practices or patient characteristics. Sixth, many patients were excluded because of various reasons. In the comparison of baseline characteristics between patients who were enrolled and those who were excluded, the balance was good or acceptable in most variables, but there was an imbalance for 3 variables (mucosal protective agents, G-ESD, and PEG) (data not shown). Last, we could not account for coding errors, although the DPC database is generally considered highly reliable (35). Moreover, it could have inaccuracies in diagnosis codes or procedure records.
In conclusion, this large-scale, population-based retrospective cohort study demonstrated the reduced effect of oral PPI administration on delayed bleeding in G-EMR and G-ESD by direct comparison between oral PPI treatment and no acid-suppressive therapy, whereas reduced effects were not observed in E-EMR, E-ESD, and PEG. These results indicated that PPI should be administered in G-EMR and G-ESD among the 5 upper GI endoscopic treatments.
CONFLICTS OF INTEREST
Guarantor of the article: Waku Hatta, MD, PhD.
Specific author contributions: H.A., W.H.: planning and conducting the study; H.A., K.T.: collecting data; H.A., W.H.: interpreting data; H.A., W.H.: drafting the manuscript; T.K., Y.H., Y.O., M.S., X.J., T.K., A.I., S.H., K.F., K.F., A.M.: critical revision of the manuscript; H.A.: statistical analysis; K.F., K.F., A.M.: study supervision. All authors approved the final version of the manuscript.
Financial support: This work was supported by the Ministry of Health, Labor, and Welfare (Grant number, 22AA2003).
Potential competing interests: None to report.
Study Highlights.
WHAT IS KNOWN
✓ Delayed bleeding is a major complication in upper gastrointestinal endoscopic treatments.
✓ Proton-pump inhibitor (PPI) is often prescribed for reducing delayed bleeding in upper gastrointestinal endoscopic treatments, despite that no studies with a sufficient sample size have evaluated its reduced effect compared with no acid-suppressive therapy.
WHAT IS NEW HERE
✓ The delayed bleeding risk was lower in PPI use compared with no acid-suppressive therapy in gastric endoscopic mucosal resection and gastric endoscopic submucosal dissection.
✓ The delayed bleeding risk was similar between PPI use and no acid-suppressive therapy in esophageal endoscopic mucosal resection, esophageal endoscopic submucosal dissection, and percutaneous endoscopic gastrostomy.
✓ Our nationwide population-based study showed that oral PPI should be administered in gastric endoscopic mucosal resection and gastric endoscopic submucosal dissection; however, it may not be required in esophageal endoscopic mucosal resection, esophageal endoscopic submucosal dissection, and percutaneous endoscopic gastrostomy.
Supplementary Material
ACKNOWLEDGEMENT
The authors thank Enago (www.enago.jp) for their professional English language editing of the manuscript.
ABBREVIATIONS:
- AT
antithrombotic
- BMI
body mass index
- CCI
Charlson Comorbidity Index
- CI
confidence interval
- DOAC
direct oral anticoagulant
- DPC
Diagnosis Procedure Combination
- E-EMR
esophageal endoscopic mucosal resection
- E-ESD
esophageal endoscopic submucosal dissection
- ESD
endoscopic submucosal dissection
- EMR
endoscopic mucosal resection
- G-EMR
gastric endoscopic mucosal resection
- GERD
gastroesophageal reflux disease
- G-ESD
gastric endoscopic submucosal dissection
- GI
gastrointestinal
- H2RA
histamine-2-receptor antagonist
- IPTW
inverse probability of treatment weighting
- IQR
interquartile range
- NSAIDs
nonsteroidal anti-inflammatory drugs
- NET
neuroendocrine tumor
- OR
odds ratio
- PEG
percutaneous endoscopic gastrostomy
- PSM
propensity score matching
- P2Y12RA
P2Y12 receptor antagonist
- PPI
proton-pump inhibitor
- SD
standardized difference
Footnotes
SUPPLEMENTARY MATERIAL accompanies this paper at http://links.lww.com/AJG/D766, http://links.lww.com/AJG/D767, http://links.lww.com/AJG/D768, http://links.lww.com/AJG/D769, http://links.lww.com/AJG/D70, http://links.lww.com/AJG/D771, http://links.lww.com/AJG/D772
Contributor Information
Hiroko Abe, Email: abehiroco@gmail.com.
Kunio Tarasawa, Email: tarasawa@med.tohoku.ac.jp.
Yutaka Hatayama, Email: yutaka.hatayama.e4@tohoku.ac.jp.
Yohei Ogata, Email: gmaps177@gmail.com.
Masahiro Saito, Email: sitmshr@gmail.com.
Xiaoyi Jin, Email: kim_x_y@med.tohoku.ac.jp.
Tomoyuki Koike, Email: tkoike@rd5.so-net.ne.jp.
Akira Imatani, Email: aimatani@med.tohoku.ac.jp.
Shin Hamada, Email: hamadas@med.tohoku.ac.jp.
Kenji Fujimori, Email: fujimori@med.tohoku.ac.jp.
Kiyohide Fushimi, Email: kfushimi.hci@tmd.ac.jp.
Atsushi Masamune, Email: atsushi.masamune.d2@tohoku.ac.jp.
REFERENCES
- 1.Tomizawa Y, Iyer PG, Wong Kee Song LM, et al. Safety of endoscopic mucosal resection for Barrett's esophagus. Am J Gastroenterol 2013;108:1440–7. quiz 1448. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Minamide T, Kawata N, Maeda Y, et al. Clinical outcomes of endoscopic submucosal dissection for superficial circumferential esophageal squamous cell carcinoma. Gastrointest Endosc 2023;97(2):232–40.e4. [DOI] [PubMed] [Google Scholar]
- 3.Nagami Y, Hatta W, Tsuji Y, et al. Antithrombotics increase bleeding after endoscopic submucosal dissection for gastric cancer: Nationwide propensity score analysis. Dig Endosc 2022;34(5):974–83. [DOI] [PubMed] [Google Scholar]
- 4.Oka S, Tanaka S, Kaneko I, et al. Advantage of endoscopic submucosal dissection compared with EMR for early gastric cancer. Gastrointest Endosc 2006;64(6):877–83. [DOI] [PubMed] [Google Scholar]
- 5.Lucendo AJ, Sanchez-Casanueva T, Redondo O, et al. Risk of bleeding in patients undergoing percutaneous endoscopic gastrotrostomy (PEG) tube insertion under antiplatelet therapy: A systematic review with a meta-analysis. Rev Esp Enferm Dig 2015;107(3):128–36. [PubMed] [Google Scholar]
- 6.Shiroma S, Hatta W, Tsuji Y, et al. Timing of bleeding and thromboembolism associated with endoscopic submucosal dissection for gastric cancer in Japan. J Gastroenterol Hepatol 2021;36(10):2769–77. [DOI] [PubMed] [Google Scholar]
- 7.Ego M, Abe S, Nonaka S, et al. Endoscopic closure utilizing endoloop and endoclips after gastric endoscopic submucosal dissection for patients on antithrombotic therapy. Dig Dis Sci 2021;66(7):2336–44. [DOI] [PubMed] [Google Scholar]
- 8.Kataoka Y, Tsuji Y, Hirasawa K, et al. Endoscopic tissue shielding to prevent bleeding after endoscopic submucosal dissection: A prospective multicenter randomized controlled trial. Endoscopy 2019;51(7):619–27. [DOI] [PubMed] [Google Scholar]
- 9.Hatta W, Koike T, Abe H, et al. Recent approach for preventing complications in upper gastrointestinal endoscopic submucosal dissection. DEN Open 2022;2(1):e60. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Yamamoto Y, Kikuchi D, Nagami Y, et al. Management of adverse events related to endoscopic resection of upper gastrointestinal neoplasms: Review of the literature and recommendations from experts. Dig Endosc 2019;31(Suppl 1):4–20. [DOI] [PubMed] [Google Scholar]
- 11.Repici A, Hassan C, Carlino A, et al. Endoscopic submucosal dissection in patients with early esophageal squamous cell carcinoma: Results from a prospective Western series. Gastrointest Endosc 2010;71(4):715–21. [DOI] [PubMed] [Google Scholar]
- 12.Uedo N, Takeuchi Y, Yamada T, et al. Effect of a proton pump inhibitor or an H2-receptor antagonist on prevention of bleeding from ulcer after endoscopic submucosal dissection of early gastric cancer: A prospective randomized controlled trial. Am J Gastroenterol 2007;102(8):1610–6. [DOI] [PubMed] [Google Scholar]
- 13.Libanio D, Pimentel-Nunes P, Bastiaansen B, et al. Endoscopic submucosal dissection techniques and technology: European Society of Gastrointestinal Endoscopy (ESGE) Technical Review. Endoscopy 2023;55(4):361–89. [DOI] [PubMed] [Google Scholar]
- 14.Ono H, Yao K, Fujishiro M, et al. Guidelines for endoscopic submucosal dissection and endoscopic mucosal resection for early gastric cancer (second edition). Dig Endosc 2021;33(1):4–20. [DOI] [PubMed] [Google Scholar]
- 15.Janarthanan S, Ditah I, Adler DG, et al. Clostridium difficile-associated diarrhea and proton pump inhibitor therapy: A meta-analysis. Am J Gastroenterol 2012;107(7):1001–10. [DOI] [PubMed] [Google Scholar]
- 16.Kakushima N, Hori K, Ono H, et al. Proton pump inhibitor after endoscopic resection for esophageal squamous cell cancer: Multicenter prospective randomized controlled trial. J Gastroenterol 2016;51(2):104–11. [DOI] [PubMed] [Google Scholar]
- 17.Ono Y, Hatta W, Tarasawa K, et al. Optimal direct oral anticoagulant for upper gastrointestinal endoscopic submucosal dissection. J Gastroenterol 2025;60(1):66–76. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Shiratori Y, Niikura R, Ishii N, et al. Vonoprazan versus proton pump inhibitors for postendoscopic submucosal dissection bleeding in the stomach: A multicenter population-based comparative study. Gastrointest Endosc 2022;95(1):72–9.e3. [DOI] [PubMed] [Google Scholar]
- 19.Ministry of Health, Labour and Welfare. Accessed December 25, 2024. https://shinryohoshu.mhlw.go.jp/shinryohoshu/.
- 20.Bramer GR. International statistical classification of diseases and related health problems. Tenth revision. World Health Stat Q 1988;41(1):32–6. [PubMed] [Google Scholar]
- 21.Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation. J Chronic Dis 1987;40(5):373–83. [DOI] [PubMed] [Google Scholar]
- 22.Takeuchi T, Ota K, Harada S, et al. The postoperative bleeding rate and its risk factors in patients on antithrombotic therapy who undergo gastric endoscopic submucosal dissection. BMC Gastroenterol 2013;13:136. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Abe H, Hatta W, Ogata Y, et al. Prevention of delayed bleeding with vonoprazan in upper gastrointestinal endoscopic treatment. J Gastroenterol 2021;56(7):640–50. [DOI] [PubMed] [Google Scholar]
- 24.Schumacher B, Charton JP, Nordmann T, et al. Endoscopic submucosal dissection of early gastric neoplasia with a water jet-assisted knife: A Western, single-center experience. Gastrointest Endosc 2012;75(6):1166–74. [DOI] [PubMed] [Google Scholar]
- 25.Libanio D, Costa MN, Pimentel-Nunes P, et al. Risk factors for bleeding after gastric endoscopic submucosal dissection: A systematic review and meta-analysis. Gastrointest Endosc 2016;84(4):572–86. [DOI] [PubMed] [Google Scholar]
- 26.Yano T, Tanabe S, Ishido K, et al. Different clinical characteristics associated with acute bleeding and delayed bleeding after endoscopic submucosal dissection in patients with early gastric cancer. Surg Endosc 2017;31(11):4542–50. [DOI] [PubMed] [Google Scholar]
- 27.Hatta W, Tsuji Y, Yoshio T, et al. Prediction model of bleeding after endoscopic submucosal dissection for early gastric cancer: BEST-J score. Gut 2021;70(3):476–84. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Austin PC. Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples. Stat Med 2009;28(25):3083–107. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Austin PC, Stuart EA. Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies. Stat Med 2015;34(28):3661–79. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Fujimoto K, Fujishiro M, Kato M, et al. Guidelines for gastroenterological endoscopy in patients undergoing antithrombotic treatment. Dig Endosc 2014;26:1–14. [DOI] [PubMed] [Google Scholar]
- 31.Kato M, Uedo N, Hokimoto S, et al. Guidelines for gastroenterological endoscopy in patients undergoing antithrombotic treatment: 2017 appendix on anticoagulants including direct oral anticoagulants. Dig Endosc 2018;30(4):433–40. [DOI] [PubMed] [Google Scholar]
- 32.Schapiro GD, Edmundowicz SA. Complications of percutaneous endoscopic gastrostomy. Gastrointest Endosc Clin N Am 1996;6(2):409–22. [PubMed] [Google Scholar]
- 33.Anderson MA, Ben-Menachem T, Gan SI, et al. Management of antithrombotic agents for endoscopic procedures. Gastrointest Endosc 2009;70(6):1060–70. [DOI] [PubMed] [Google Scholar]
- 34.Larson DE, Burton DD, Schroeder KW, et al. Percutaneous endoscopic gastrostomy. Indications, success, complications, and mortality in 314 consecutive patients. Gastroenterology 1987;93(1):48–52. [PubMed] [Google Scholar]
- 35.Yamana H, Moriwaki M, Horiguchi H, et al. Validity of diagnoses, procedures, and laboratory data in Japanese administrative data. J Epidemiol 2017;27(10):476–82. [DOI] [PMC free article] [PubMed] [Google Scholar]