Predictors of abnormal functional luminal impedance planimetry findings in non-mechanical esophagogastric junction outflow obstruction

Abstract

Background

Esophagogastric junction outflow obstruction (EGJOO) is a common but non-specific motility pattern identified by esophageal high-resolution manometry (HRM). Functional luminal impedance planimetry (FLIP) provides information regarding lower esophageal sphincter (LES) mechanics, which can identify achalasia-spectrum disorders and is useful in evaluating EGJOO. However, the relationship between HRM and FLIP parameters in EGJOO is not clearly defined.

Aims

To identify predictors of abnormal FLIP findings in patients with non-mechanical EGJOO.

Methods

This is a retrospective cohort study of patients with non-mechanical EGJOO who underwent FLIP between 10/1/16 and 7/1/19. Demographic data including age and gender, exam indication, concomitant medications, HRM parameters, symptom burden, and FLIP metrics of diameter and distensibility index (DI) were collected. DI was categorized as not low (DI>2.8), borderline low (DI 1.1–2.8), and definitely low (DI≤1). Kruskal-Wallis and Fisher exact tests were used to assess the relationship between HRM and FLIP parameters and to identify predictors of abnormal FLIP.

Results

Among the 44 patients studied, most were female (n=33, 75%) and the median age was 63. The median IRP was 18.2 and 10 (23%) patients used chronic narcotics. Lower total heartburn and regurgitation scores, and LES diameter by FLIP are associated with definitely low DI.

Conclusions

In patients with non-mechanical EGJOO, reflux burden scores and FLIP diameters can aid in predicting DI. These results may provide useful adjunctive data to help in differentiating which patients have meaningful outflow obstruction.

INTRODUCTION

The widespread use of esophageal high-resolution manometry (HRM) has improved diagnostic sensitivity and specificity for numerous disorders(1, 2). The Chicago Classification (CC) provides a hierarchical approach to HRM diagnosis, with primacy placed on disorders of the lower esophageal sphincter (LES), including achalasia subtypes and esophagogastric junction outflow obstruction (EGJOO)(3).

Although defined by HRM parameters of elevated median integral relaxation pressure (IRP) greater than 15 mmHg with peristaltic findings not consistent with achalasia subtypes I-III, EGJOO can occur in several distinct disorders or as procedural artefact. The potential causes encompass both mechanical obstruction and variant or incipient achalasia. As a result, and particularly in non-mechanical EGJOO, there is a variable course with resulting therapeutic uncertainty(4–6). Indeed, as many as 50% of patients may have spontaneous resolution of EGJOO(6). Also, many prior studies have not included standardized symptom assessments in their analysis of outcomes so their value as a prognostic tool assessing and counselling patients with EGJOO is not well characterized(5, 7, 8). Therefore, additional testing can add complementary information to the HRM and may provide added prognostic value.

Endoscopic functional luminal impedance planimetry (FLIP), which utilizes impedance planimetry to determine distensibility across the LES, has been increasingly utilized for these purposes(9, 10). Existing data support the ability of FLIP to discriminate between major motility disorders(11, 12). Measurement of LES distensibility through the distensibility index (DI) is also useful to differentiate between controls and patients with gastro-esophageal reflux disease (GORD)(13). Additionally, DI measurements are important markers of treatment success when disrupting the LES for achalasia(14). However, FLIP parameters among patients with EGJOO vary(11). It is unknown if factors aside from HRM diagnoses are associated with abnormal FLIP findings in patients with EGJOO, which could have meaningful implications for treatment outcomes. Therefore, we aimed to evaluate factors predictive of abnormal FLIP distensibility in patients with EGJOO.

METHODS

Study design

We performed a retrospective study of patients diagnosed with EGJOO by esophageal HRM between 10/1/2016 and 7/1/2019, corresponding to the use of FLIP version 1.0 at our institution. All adult patients (≥18 years of age) were eligible for inclusion if they underwent FLIP and were excluded if there was evidence of vascular artefact on HRM or mechanical obstruction on either upper endoscopy (EGD) or barium swallow (BaS).

Demographic data were collected on age, gender, race, and medication usage. Data also were collected on HRM and FLIP parameters as well as BaS findings if performed. Indication for HRM and FLIP were recorded. Data were extracted in accordance with best practices using a standardized form with quality assurance performed. The study was approved by the Duke University Institutional Review Board and conformed to the recognized standards of the US Federal Policy for the Protection of Human Subjects.

Esophageal function testing

All patients underwent HRM after an overnight fast per institutional protocol(15, 16). Medications that potentially affect esophageal smooth motor function (calcium channel blockers, nitrates, narcotic medications, benzodiazepines, tricyclic antidepressants, and promotility agents such as metoclopramide) were discontinued 24 hours prior to testing. HRM tests were performed with a 36-channel solid state catheter (Medtronic, Minneapolis, MN) with recording sites at 1 cm intervals. The catheter was placed through an anaesthetized nasal canal followed by a 5-minute acclimatization period. Recordings of 10 supine swallows of 5 mL ambient temperature water spaced 30 seconds apart were obtained. Studies were interpreted on a dedicated display (Manoview, Medtronic, Minneapolis, MN) by one of three esophagologists (DAL, RKW, RAS). Results were interpreted according to CCv3.0 and a final diagnosis and report were compiled in a standard note; patients with a median IRP ≥15mmHg with evidence of peristalsis not meeting criteria for achalasia subtypes I-III were diagnosed with EGJOO(3). Data extracted from the report included IRP, distal contractile integral (DCI), distal latency (DL), and basal respiratory pressure. Although not universally performed, additional manometry maneuvers, such as upright swallows, were utilized to screen for vascular or other artefact that could confound the diagnosis of EGJOO. Patients with previous esophago-gastric surgery, peptic stricture, and eosinophilic esophagitis were excluded.

Functional luminal impedance planimetry (FLIP)

Patients underwent FLIP during sedated EGDs, all of which were performed with monitored anesthesia care (MAC) using propofol sedation and infrequently additional agents such as fentanyl and midazolam per anesthesia discretion which would not be expected to affect findings, performed after an overnight fast, and medications potentially affecting esophageal function (such as narcotics) were discontinued at least 24 hours prior to the exam(11). An 8cm EndoFLIP catheter (FLIP 1.0, Crospon Ltd, Galway, Ireland) was placed per orally and measurements were performed in accordance with recommended practice for the clinical evaluation of esophageal motility disorders based on the EF-325 protocol(17, 18).

The FLIP probe was positioned with the distal 7–9 impedance sensors beyond the esophagogastric junction so that the center of the balloon was at the esophagogastric junction. The endoscope was withdrawn prior to the initiation of the FLIP study protocol. The FLIP probe was adjusted by the gastroenterologist to maintain placement relative to the esophagogastric junction as visualized on real-time output. FLIP measurements were obtained at volumes ranging from 20 mL to 50 mL in a step-wise manner with appropriate acclimatization periods of 30 seconds between volumes. Statistical analysis was performed on data collected using a balloon volume of 40 mL, which is the optimal volume for LES assessment(19). The simultaneous measurements of DI and LES diameter were recorded in a standard EGD report by one of three esophagologists (DAL, RKW, RAS). The measurements obtained at a 40 mL volume required at least 30 seconds of observation at maximum diameter with the average of three real-time measurements used for reporting purposes. The diameter was recorded as a continuous variable and DI was categorized. Although the evidence base for precise cutoffs in the context of EGJOO is evolving, we considered DI in three categories: definitely low (<1), borderline low (1–2.8), and not low (>2.8)(11).

Patient reported outcomes (PROs)

Symptoms were recorded on patients prior to performance of esophageal function testing during their motility lab encounter. Patient reported symptoms were obtained using the Eckardt score, Brief Esophageal Dysphagia Questionnaire (BEDQ), and the reflux disease questionnaire (RDQ). Responses were extracted from standard clinical intake forms(20–22).

The Eckardt score is comprised of a sum of patients’ reported dysphagia, chest pain, regurgitation, and weight loss for a potential maximum of 12. The sum Eckardt score was analyzed as a continuous variable and as a binary variable with a value <3 considered normal. The BEDQ uses dysphagia, odynophagia, and cough to determine the severity of esophageal motor dysfunction for a potential maximum score of 40. Scores were grouped by questions pertaining to frequency and severity, and were analyzed as sum and average scores for each category with a combined value >10 suggesting major motor dysfunction. The RDQ is a 12-item survey that uses heartburn, chest pain, and regurgitation symptoms to quantify the severity of gastro-esophageal reflux disease via a Likert-type scale ranging from 0 to 5. Scores from the RDQ were grouped by questions pertaining to frequency and severity, and were analyzed as sum and average scores for each category.

Statistical analysis

Continuous variables are presented as mean (standard deviation), median, and Q1, Q3. Categorical variables are presented as a frequency and percent. The number of missing data are presented for each characteristic. Patient characteristics and outcome associations with DI are assessed using the Fisher exact test for categorical variables and the Kruskal-Wallis test for continuous variables. All tests are evaluated at a type 1 error of alpha=0.05. Analyses were done using SAS 9.4 (Cary, NC).

RESULTS

A total of 44 patients met study criteria. The median age of patients was 63 (range 24–81), most were women (n=33, 75%), and the majority of included patients self-identified as white race (n=28, 63.6%). The most common indications for manometry were dysphagia and evaluation of esophageal motility (n= 23, 52.3% for both), and the most common indication for EGD with FLIP was dysphagia (n=38, 86.4%). BaS was performed in 33 people (75%) and the presence of tertiary contractions was the most common finding (n=8, 18.2%). A total of 10 patients (22.7%) used narcotic medications (Table 1), which included oxycodone, hydrocodone, tramadol, long-acting morphine, and buprenorphine-naloxone.

Table 1.

Demographic and clinical data of study cohort by distensibility index (DI).

	DI≤1 (Definitely low) (N=17)	DI 1.1–2.8 (Borderline low) (N=14)	D>2.8 (Not low) (N=13)	Total (N=44)	p-value
Age (median, Q1, Q3)	62.0 (54.0, 66.0)	64.5 (59.0, 67.0)	62.0 (56.0, 74.0)	63.0 (55.0, 70.5)	0.83
Gender (female, %)	11 (64.7%)	12 (85.7%)	10 (76.9%)	33 (75.0%)	0.42
Race (white, %)	14 (82.4%)	7 (50.0%)	7 (53.8%)	28 (63.6%)	0.14
Narcotics use (%)	1 (5.9%)	4 (28.6%)	5 (38.5%)	10 (22.7%)	0.09
Indication for manometry
Dysphagia (%)	10 (58.8%)	9 (64.3%)	4 (30.8%)	23 (52.3%)	0.20
Esophageal motility (%)	8 (47.1%)	5 (35.7%)	10 (76.9%)	23 (52.3%)	0.09
Indication for EGD w/FLIP: Dysphagia (%)	16 (94.1%)	13 (92.9%)	9 (69.2%)	38 (86.4%)	0.13
Abnormal BaS:
Tertiary contractions (%)	4 (23.5%)	3 (21.4%)	1 (7.7%)	8 (18.2%)	0.62
Tablet delayed (%)	2 (11.8%)	3 (21.4%)	1 (7.7%)	6 (13.6%)	0.64
Tablet not passed (%)	1 (5.9%)	1 (7.1%)	0 (0.0%)	2 (4.5%)	1.00
Hiatal hernia (%)	0 (0.0%)	3 (21.4%)	1 (7.7%)	4 (9.1%)	0.10
Moderate dysmotility (%)	4 (23.5%)	3 (21.4%)	0 (0.0%)	7 (15.9%)	0.16
HRM Parameters
Basal respiratory pressure (mean, SD)	49.1 (19.0)	46.9 (8.7)	35.1 (9.2)	44.1 (14.6)	0.01
IRP, median, (Q1, Q3)	23.4 (17.4, 24.3)	17.0 (15.9, 19.6)	17.7 (16.0, 20.5)	19.7 (4.0)	0.06
DCI (mean, SD)	2483.6 (2047.0)	3231.1 (4367.3)	2443.3 (1815.1)	2697.4 (2848.5)	0.95
DL (mean, SD)	6.5 (1.6)	7.6 (1.4)	7.5 (1.6)	7.1 (1.6)	0.06
LES diameter† (mean, SD)	6.3 (1.3)	8.7 (1.7)	12.7 (2.0)	9.0 (3.1)	<0.001

Q1, first quartile; Q3, third quartile

SD, Standard Deviation

EGD, esophagogastroduodenoscopy; FLIP, functional luminal impedance planimetry

BaS, Barium Swallow

IRP, Integrated Relaxation Pressure (mmHg); DCI, Distal Contractile Integral (mmHg.s.cm); DL, Distal Latency (seconds)

LES, lower esophageal sphincter, diameter (mm)

^†measured by EndoFLIP

Esophageal testing

HRM findings demonstrated an overall median IRP of 18.2 mmHg, mean DCI of 2697.4 mmHg-cm-sec, and mean DL of 7.1 seconds. The mean LES diameter was 9.0mm as measured by FLIP. The basal LES pressure and FLIP diameter differed significantly between patients according to DI (Table 1) (p=0.01 and p<0.001, respectively). Although it does not reach statistical significance, we found a trend toward lower DI with higher IRP (p=0.06) (Figure 1). A lower diameter measured with FLIP was significantly associated with simultaneously obtained DI (p<0.001). A minority of patients had concurrent reflux testing, which was not randomly distributed. As only two patients with low DI had pH testing, formal statistical analyses of these results were not performed.

Figure 1.

There is a trend toward significant (p=0.06) association between integrated relaxation pressure (IRP) and distensibility index (DI). When DI is categorized as definitely low (DI≤1), borderline line (DI 1.1–2.8), and not low (DI≥2.8), the median IRP is numerically higher in patients with a lower DI.

Patient Symptoms

A total of 21 (47.7%) of patients completed all PRO survey instruments in their entirety, and therefore summary measures were used as endpoints. Regarding dysphagia symptom burden, the mean Eckardt sum score was 3.8 (n=24) and 16 patient scores were considered abnormal (≥3).

For the BEDQ, the mean frequency sum score and severity sum score were 5.2 and 3.8, respectively (n=24, 21). When summarized, the BEDQ scores are considered low and therefore do not suggest the presence of major motor dysfunction. Overall, there was no significant relationship between markers of dysphagia symptom burden and FLIP outcomes (Table 2).

Table 2.

Patient reported outcomes (PROs) separated by distensibility index (DI).

	DI≤1 (Definitely low)	DI 1.1–2.8 (Borderline low)	DI>2.8 (Not low)	Total	p-value
Eckardt Score
Sum Score, n=24 (mean, SD)	3.1 (1.6)	4.1 (2.0)	4.0 (2.6)	3.8 (2.0)	0.67
Binary Score, n=24 (N abnormal, %)	5 (71.4%)	7 (70.0%)	4 (57.1%)	16 (66.7%)	0.87
BEDQ
Frequency Sum Score, n=24 (mean, SD)	5.3 (2.2)	5.8 (2.1)	4.3 (4.2)	5.2 (2.8)	0.57
Frequency Average Score, n=24 (mean, SD)	2.3 (1.4)	2.1 (1.2)	1.6 (1.5)	2.0 (1.3)	0.57
Severity Sum Score, n=21 (mean, SD)	3.7 (2.3)	3.9 (3.1)	3.7 (3.9)	3.8 (3.0)	0.93
Severity Average Score, n=21 (mean, SD)	1.7 (1.2)	1.7 (1.4)	1.7 (1.7)	1.7 (1.4)	0.96
RDQ
Frequency Sum Score, n=22 (mean, SD)	2.2 (2.5)	2.5 (1.7)	7.0 (3.5)	3.6 (3.2)	0.03
Frequency Average Score, n=24 (mean, SD)	0.9 (0.5)	1.6 (0.9)	3.4 (1.3)	1.9 (1.4)	0.01
Severity Sum Score, n=22 (mean, SD)	1.7 (1.9)	2.8 (1.9)	6.2 (2.4)	3.4 (2.6)	0.01
Severity Average Score, n=24 (mean, SD)	0.9 (0.7)	1.5 (0.8)	3.0 (1.1)	1.7 (1.2)	0.002

SD, Standard Deviation; BEDQ, Brief Esophageal Dysphagia Questionnaire; RDQ, Reflux Disease Questionnaire

In contrast, there was a significant difference in reflux burden between groups as defined by DI. Specifically, patients who did not have low DI measurements had a significantly higher reflux burden compared to those with both borderline and definitely low DI (Table 2). For questions related to symptom frequency, mean RDQ sum score was 1.5 in definitely low DI patients, 3.0 in borderline low DI patients, and 7.5 in not low DI patients (n=22, p=0.03) with an average score per question of 0.8, 1.6, and 3.3 for each group respectively (n=24, p=0.01). For questions related to symptom severity, the mean RDQ sum score was 1.5 among patients with definitely low DI, 3.5 for borderline low DI, and 5.5 for not low DI (n=22, p=0.01) with an average score per question of 0.5, 1.4, and 3.2 for each group respectively (n=24, p<0.01).

DISCUSSION

The treatment approach for patients with non-mechanical EGJOO identified on HRM remains controversial and FLIP is increasingly used to adjudicate the severity and clinical relevance of this diagnosis. Our findings indicate that the presence of a lower reflux symptom burden as well as specific HRM metrics can aid in predicting patients with abnormal FLIP findings. Although there was no significant association between IRP and DI in our cohort, patients with a definitely low DI had a trend toward having a higher IRP. These findings together may be useful in differentiating patients with more meaningful outflow obstruction that warrants intervention.

Patients with EGJOO have been identified to have a variable clinical course(4). In those with non-mechanical EGJOO, as many as 50% may resolve spontaneously(6). A prior systematic review of the literature indicated the lack of methodically captured patient symptom data as a limitation in predicting the significance of EGJOO identified on HRM, particularly as this can occur incidentally or as artefact(23, 24). In contrast, EGJOO patients with low DI found during FLIP have been shown to respond well to achalasia-type treatment, while those with a normal DI often improve with conservative management alone(25). As a result, FLIP is utilized as an adjunct in the evaluation of EGJOO when available(9).

In our study, there was no significant difference in dysphagia burden as measured by both Eckardt and BEDQ scores. The majority of patients underwent HRM or FLIP to further evaluate the presenting symptom of dysphagia, and these patients were referred to the esophageal clinic due to their symptom burden. Nonetheless, the severity of dysphagia reported on PRO questionnaires was relatively low with a mean Eckardt score of 3.8 and a mean BEDQ severity score of 1.7. Therefore, while the presence of dysphagia was frequently present in the cohort, we likely did not have enough variability in symptom severity between patients to discern a statistical difference across either the Eckardt or BEDQ scores. However, we did find that the presence of higher reflux burden was a negative predictor for abnormal DI. This is particularly relevant to help clinical decision-making as esophageal symptoms may be non-specific and many patients with achalasia are initially treated for refractory reflux(26, 27). Others have suggested refining the criteria for EGJOO based on symptoms, which would be consistent with our findings(28). Our results may be especially important given their significance even with a relatively small population.

Further, symptoms typically motivate diagnostic evaluation and for this reason the association we found between indication for procedures (i.e., HRM and EGD) and DI is expected. Patients referred for these procedures to further investigate dysphagia or esophageal motility would have a higher pre-test probability for a low DI. However, our finding of a significant relationship between DI and diameter, measured simultaneously with FLIP, is a useful additional metric to consider in EGJOO patients. It is acknowledged that there is a direct relationship between DI and diameter measurements through calculation of cross-sectional area. However, in some instances, discordance exists between the measured diameter and the DI. For example, a small measured diameter and not low DI may be reasonably attributed to subtle strictures requiring dilation or other findings(12). Our findings indicate that the presence of both abnormal DI and diameter further solidify the relevance of the HRM finding of EGJOO. Additionally, we found that a higher IRP trended towards a finding of low DI, though our sample size likely limits our power to identify a significant difference. Additionally, we found that higher basal respiratory pressure is associated with a low DI. However, this finding is of uncertain clinical significance. According to past criteria, a high baseline LES pressure might have suggested a diagnosis of “hypertensive LES” but such a diagnosis does not appear in the Chicago Classification. As such, and particularly because this finding does not often influence clinical decision-making, broader conclusions about its implications are limited and are of uncertain utility in clinical practice(29).

In contrast to prior studies, we did not find the use of chronic narcotic medications to be significantly associated with DI. It has been frequently shown that narcotics can impact esophageal motility, and oxycodone and fentanyl in particular are associated with a diagnosis of EGJOO(30–32). We caution interpreting our findings as a refutation of these data for several reasons. Firstly, although medication data were obtained from review of the electronic health record, we acknowledge that this list may not always accurately reflect a current medication regimen. Also, our sample size may not be sufficient to identify such an association, though we did find a higher proportion of patients used narcotics in the not low DI category. This itself may represent unmeasured confounding, though likely also is related to the fact we routinely discontinue narcotic medications prior to both HRM and endoscopy with FLIP, which should minimize the impact of these medications on observed physiology during FLIP.

An important aspect of EGJOO evaluation is excluding mechanical etiologies, as this HRM finding has been attributed to strictures, vascular anomalies, eosinophilic esophagitis and malignancies(33). Although their use in EGJOO is advocated for in the Chicago Classification, endoscopic ultrasound and computed tomography scans were not utilized in this patient population given their previously demonstrated low utility and our own institutional experience (34–36).

As a result, many patients in our cohort underwent BaS prior to endoscopy as the finding of a structural esophageal abnormality would obviate the need for FLIP. In addition to luminal findings, a radiographic motility assessment was reported, and among the studied group there were no findings associated with low DI. Recognizing the uncertain relationship between BaS findings and esophageal motility, we acknowledge that timed barium swallow (TBS) is a more useful adjunctive test than a BaS in EGJOO to identify meaningful LES dysfunction(7, 37). Indeed, even as it is possible that IRP is falsely elevated it can also occur that EndoFLIP findings are “falsely negative.” A normal DI does not always eliminate the clinical relevance of a high IRP. Because EndoFLIP is not a “gold standard” for outflow obstruction, but rather data that should be incorporated into clinical decision-making, in instances of high clinical suspicion for meaningful outflow obstruction additional testing such as TBS and symptom burden can be useful adjuncts. Our study specifically evaluated the utility of FLIP parameters, though future work could be done to clarify the relationship between HRM, FLIP, and TBS findings. In addition, future studies could incorporate data gathered via FLIP 2.0 to further assess contractility patterns in EGJOO.

Our study is not without limitations, primarily those inherent to its retrospective design. Both HRM and FLIP measurements were obtained from 3 practitioners, potentially leading to variability in results. Although many patients were evaluated prior to publications that have attempted to standardize the method in which FLIP measurements are obtained, efforts were made to ensure consistency across providers in documenting real-time measurements through prospective consensus agreement. We adhered to a standard HRM acquisition and reporting protocol as well as utilized a single FLIP balloon size and volume to obtain measurements to minimize this variability. Furthermore, several published studies have relied on complex post-processing analysis to determine FLIP metrics(17, 25). In contrast, it has been shown that intra-procedural assessment with FLIP can be reliable(12). Our current results, though not utilizing post-processing data, provide further support for the use of FLIP in making real-time clinical decisions.

Patients in our cohort were strictly defined and evaluated for alternative causes of EGJOO. Note is made of some missing data, particularly with respect to symptoms, and therefore these findings should be considered hypothesis-generating and offer important directions for future study in this challenging clinical entity. The lack of association detected between dysphagia symptom scores and DI is unexpected, which could represent selection bias. Furthermore, not all patients with EGJOO underwent FLIP testing. This could lead to selection bias and therefore we limit our conclusions to identifying potential predictive factors rather than assessing formal performance characteristics for FLIP testing such as positive and negative predictive values. Although it is among the largest studies to date in assessing EGJOO, our cohort size is small, which limits the statistical power and ability to conduct extensive multivariable modelling. The small sample size further limits the overall conclusions we can draw from our findings and suggests larger studies will be needed in the future to further evaluate our findings.

In addition to limitations imposed by our sample size, the reliance on medication reconciliation and patient self-report to verify narcotic use as it pertains to the peri-procedural period could bias our results. While efforts were made to reconcile medication usage with patients and explicit instructions to withhold narcotics were provided per protocol, the lack of verification with objective testing is a potential source of confounding. Specifically, patient non-adherence and a potential dose-response effect could meaningfully impact our results in ways that we are unable to assess and remain limitations of the study. Finally, while we do identify important patient symptoms that could aid in the prediction of clinically meaningful EGJOO, we did not attempt to report patient outcomes given the lack of standardization in management approach.

In conclusion, we found patient symptoms and luminal diameter are associated with abnormally low DI during FLIP performed in patients with functional EGJOO. These data identify novel associations that may be used to aid in the prediction or stratification of clinically relevant outflow obstruction. We suggest utilizing FLIP parameters and patient symptoms to help arbitrate when the clinical relevance of the manometric finding of EGJOO is uncertain. The lack of outcome data in the studied population indicate further studies are warranted to further refine the role of FLIP in the management of EGJOO.