A Combined DNA/RNA-based Next-Generation Sequencing Platform to Improve the Classification of Pancreatic Cysts and Early Detection of Pancreatic Cancer Arising From Pancreatic Cysts.

OBJECTIVE: We report the development and validation of a combined DNA/RNA next-generation sequencing (NGS) platform to improve the evaluation of pancreatic cysts. BACKGROUND AND AIMS: Despite a multidisciplinary approach, pancreatic cyst classification, such as a cystic precursor neoplasm, and the detection of high-grade dysplasia and early adenocarcinoma (advanced neoplasia) can be challenging. NGS of preoperative pancreatic cyst fluid improves the clinical evaluation of pancreatic cysts, but the recent identification of novel genomic alterations necessitates the creation of a comprehensive panel and the development of a genomic classifier to integrate the complex molecular results. METHODS: An updated and unique 74-gene DNA/RNA-targeted NGS panel (PancreaSeq Genomic Classifier) was created to evaluate 5 classes of genomic alterations to include gene mutations (e.g., KRAS, GNAS, etc.), gene fusions and gene expression. Further, CEA mRNA ( CEACAM5 ) was integrated into the assay using RT-qPCR. Separate multi-institutional cohorts for training (n=108) and validation (n=77) were tested, and diagnostic performance was compared to clinical, imaging, cytopathologic, and guideline data. RESULTS: Upon creation of a genomic classifier system, PancreaSeq GC yielded a 95% sensitivity and 100% specificity for a cystic precursor neoplasm, and the sensitivity and specificity for advanced neoplasia were 82% and 100%, respectively. Associated symptoms, cyst size, duct dilatation, a mural nodule, increasing cyst size, and malignant cytopathology had lower sensitivities (41-59%) and lower specificities (56-96%) for advanced neoplasia. This test also increased the sensitivity of current pancreatic cyst guidelines (IAP/Fukuoka and AGA) by >10% and maintained their inherent specificity. CONCLUSIONS: PancreaSeq GC was not only accurate in predicting pancreatic cyst type and advanced neoplasia but also improved the sensitivity of current pancreatic cyst guidelines.

Endoscopic Ultrasound-Guided Gallbladder Drainage Versus Percutaneous Drainage in Patients With Acute Cholecystitis Undergoing Elective Cholecystectomy.

INTRODUCTION: Cholecystectomy (CCY) is the gold standard treatment of acute cholecystitis (AC). Nonsurgical management of AC includes percutaneous transhepatic gallbladder drainage (PT-GBD) and endoscopic ultrasound-guided gallbladder drainage (EUS-GBD). This study aims to compare outcomes of patients who undergo CCY after having received EUS-GBD vs PT-GBD. METHODS: A multicenter international study was conducted in patients with AC who underwent EUS-GBD or PT-GBD, followed by an attempted CCY, between January 2018 and October 2021. Demographics, clinical characteristics, procedural details, postprocedure outcomes, and surgical details and outcomes were compared. RESULTS: One hundred thirty-nine patients were included: EUS-GBD in 46 patients (27% male, mean age 74 years) and PT-GBD in 93 patients (50% male, mean age 72 years). Surgical technical success was not significantly different between the 2 groups. In the EUS-GBD group, there was decreased operative time (84.2 vs 165.4 minutes, P < 0.00001), time to symptom resolution (4.2 vs 6.3 days, P = 0.005), and length of stay (5.4 vs 12.3 days, P = 0.001) compared with the PT-GBD group. There was no difference in the rate of conversion from laparoscopic to open CCY: 5 of 46 (11%) in the EUS-GBD arm and 18 of 93 (19%) in the PT-GBD group ( P value 0.2324). DISCUSSION: Patients who received EUS-GBD had a significantly shorter interval between gallbladder drainage and CCY, shorter surgical procedure times, and shorter length of stay for the CCY compared with those who received PT-GBD. EUS-GBD should be considered an acceptable modality for gallbladder drainage and should not preclude patients from eventual CCY.

Endoscopic ultrasound-directed transgastric ERCP (EDGE): A multicenter US study on long-term follow-up and fistula closure.

Background and study aims Endoscopic ultrasound-directed transgastric ERCP (EDGE) is a safe and efficacious procedure to treat pancreaticobiliary diseases in Roux-en-Y gastric bypass (RYGB). This multicenter study aimed to determine the long-term outcomes of EDGE focusing on fistula persistence rates and post-procedure weight change. Patients and methods Information about patients with Roux-en-Y gastric bypass anatomy who underwent EDGE between 2015 and 2021 from 10 institutions was captured in a registry. Patient demographics, procedural details, and clinical outcomes were analyzed. Results One hundred seventy-two patients were included in the study (mean age 60, 25 % male). Technical success of lumen-apposing metal stent (LAMS) placement was 171 of 172 (99.4 %) while clinical success of intervention was 95%. The mean procedure time was 65 minutes. The most commonly reported complication was stent dislodgement/migration (n = 29, 17). Mean length of time of LAMS duration was 69 days. Mean follow-up time was 6 months. Endoscopic fistula closure was performed in 40 % of patients (69/172) at the time of LAMS removal. Persistence of fistula was observed in 19 of 62 patients (31 %) assessed. Length of LAMS indwell time (days) was a predictor of persistent fistula. The average weight gain while the LAMS was in place was 12 lb in 63 patients (36.6 %); 59.4 % of patients gained < 5 lb. Conclusions EDGE is a safe and efficacious procedure for RYGB patients requiring ERCP. Post-procedure evaluation and management of the enteral fistula varies widely among centers currently and would benefit from further standardization. Fistula persistence appears to be uncommon and can be managed endoscopically but may be related to length of indwell times of the LAMS.

Prospective, Multi-Institutional, Real-Time Next-Generation Sequencing of Pancreatic Cyst Fluid Reveals Diverse Genomic Alterations That Improve the Clinical Management of Pancreatic Cysts.

BACKGROUND & AIMS: Next-generation sequencing (NGS) of pancreatic cyst fluid is a useful adjunct in the assessment of patients with pancreatic cyst. However, previous studies have been retrospective or single institutional experiences. The aim of this study was to prospectively evaluate NGS on a multi-institutional cohort of patients with pancreatic cyst in real time. METHODS: The performance of a 22-gene NGS panel (PancreaSeq) was first retrospectively confirmed and then within a 2-year timeframe, PancreaSeq testing was prospectively used to evaluate endoscopic ultrasound-guided fine-needle aspiration pancreatic cyst fluid from 31 institutions. PancreaSeq results were correlated with endoscopic ultrasound findings, ancillary studies, current pancreatic cyst guidelines, follow-up, and expanded testing (Oncomine) of postoperative specimens. RESULTS: Among 1933 PCs prospectively tested, 1887 (98%) specimens from 1832 patients were satisfactory for PancreaSeq testing. Follow-up was available for 1216 (66%) patients (median, 23 months). Based on 251 (21%) patients with surgical pathology, mitogen-activated protein kinase/GNAS mutations had 90% sensitivity and 100% specificity for a mucinous cyst (positive predictive value [PPV], 100%; negative predictive value [NPV], 77%). On exclusion of low-level variants, the combination of mitogen-activated protein kinase/GNAS and TP53/SMAD4/CTNNB1/mammalian target of rapamycin alterations had 88% sensitivity and 98% specificity for advanced neoplasia (PPV, 97%; NPV, 93%). Inclusion of cytopathologic evaluation to PancreaSeq testing improved the sensitivity to 93% and maintained a high specificity of 95% (PPV, 92%; NPV, 95%). In comparison, other modalities and current pancreatic cyst guidelines, such as the American Gastroenterology Association and International Association of Pancreatology/Fukuoka guidelines, show inferior diagnostic performance. The sensitivities and specificities of VHL and MEN1/loss of heterozygosity alterations were 71% and 100% for serous cystadenomas (PPV, 100%; NPV, 98%), and 68% and 98% for pancreatic neuroendocrine tumors (PPV, 85%; NPV, 95%), respectively. On follow-up, serous cystadenomas with TP53/TERT mutations exhibited interval growth, whereas pancreatic neuroendocrine tumors with loss of heterozygosity of ≥3 genes tended to have distant metastasis. None of the 965 patients who did not undergo surgery developed malignancy. Postoperative Oncomine testing identified mucinous cysts with BRAF fusions and ERBB2 amplification, and advanced neoplasia with CDKN2A alterations. CONCLUSIONS: PancreaSeq was not only sensitive and specific for various pancreatic cyst types and advanced neoplasia arising from mucinous cysts, but also reveals the diversity of genomic alterations seen in pancreatic cysts and their clinical significance.

Tumour-induced osteomalacia: a rare cause of chronic pain and weakness.

Tumor-induced osteomalacia is a rare and often misdiagnosed condition that presents with progressively worsening unexplained chronic pain and proximal muscle weakness. The osteomalacia leads to multiple stress fractures which do not heal properly, leading to progressive disability. It is caused by chronic hypophosphatemia due to inappropriate urinary phosphate wasting. This is due to a typically benign mesenchymal tumor that over-secretes a phospaturic hormone. Neurologists need to appreciate the relevance of chronic hypophosphatemia in people with chronic unexplained pain, as timely diagnosis and treatment of tumour-induced osteomalacia can be curative.

Laparoscopic-assisted ERCP following RYGB: a 12-year assessment of outcomes and learning curve at a high-volume pancreatobiliary center.

INTRODUCTION: Treatment of pancreaticobiliary pathology following Roux-en-Y gastric bypass (RYGB) poses significant technical challenges. Laparoscopic-assisted endoscopic retrograde cholangiopancreatography (LA-ERCP) can overcome those anatomical hurdles, allowing access to the papilla. Our aims were to analyze our 12-year institutional outcomes and determine the learning curve for LA-ERCP. METHODS: A retrospective review of cases between 2007 and 2019 at a high-volume pancreatobiliary unit was performed. Logistic regression was used to identify predictors of specific outcomes. To identify the learning curve, CUSUM analyses and innovative methods for standardizing the surgeon's timelines were performed. RESULTS: 131 patients underwent LA-ERCP (median age 60, 81% females) by 17 surgeons and 10 gastroenterologists. Cannulation of the papilla was achieved in all cases. Indications were choledocholithiasis (78%), Sphincter of Oddi dysfunction/Papillary stenosis (18%), management of bile leak (2%) and stenting/biopsy of malignant strictures (2%). Median total, surgical and ERCP times were 180, 128 and 48 min, respectively, and 47% underwent concomitant cholecystectomy. Surgical site infection developed in 9.2% and post-ERCP pancreatitis in 3.8%. Logistic regression revealed multiple abdominal operations and magnitude of BMI decrease (between RYGB and LA-ERCP) to be predictive of conversion to open approach. CUSUM analysis of operative time demonstrated a learning curve at case 27 for the surgical team and case 9 for the gastroenterology team. On binary cut analysis, 3-5 cases per surgeon were needed to optimize operative metrics. CONCLUSION: LA-ERCP is associated with high success rates and low adverse events. We identify outcome benchmarks and a learning curve for new adopters of this increasingly performed procedure.

"Innocent as a LAMS": Does Spontaneous Fistula Closure (Secondary Intention), After EUS-Directed Transgastric ERCP (EDGE) via 20-mm Lumen-Apposing Metal Stent, Confer an Increased Risk of Persistent Fistula and Unintentional Weight Gain?

BACKGROUND AND AIMS: Persistent gastrogastric or jejunogastric fistula is theoretically a concerning sequela of EUS-directed transgastric ERCP/EUS (EDGE), as it may functionally reverse the malabsorptive mechanism of Roux-en-Y gastric bypass (RYGB). Prior EDGE studies, using predominantly 15-mm (diameter) lumen-apposing metal stents (LAMS) and fistula closure by primary intent, collectively report 9% persistent fistula rate, without a clear weight gain association. Our study determines the incidence of persistent fistula, and its association with unintentional weight gain, among recipients of EDGE via 20-mm LAMS followed by spontaneous fistula closure (secondary intent). METHODS: We conducted a dual-center prospective cohort study of 22 RYGB patients who underwent EDGE using 20-mm between 3/2018 and 10/2019. After LAMS extraction, all GGFs/JGFs were allowed to heal spontaneously. Objective testing for persistent fistula and total body weight (TBW) occurred a minimum of 8 weeks after LAMS extraction. RESULTS: Persistent fistula was identified in 9 patients (41%). Longer LAMS dwell time (median 77-days) was observed in the persistent fistula group, compared to those with durable spontaneous fistula closure (median 35-days) (p = 0.03). Weight gain of ≥ 5% TBW occurred in 56% (n = 5) of patients with persistent fistula, compared to 15% (n = 2) of patients with spontaneous fistula closure (p = 0.128). Four patients with symptomatic persistent fistulas underwent attempted endoscopic fistula closure a median 7.5 months after LAMS extraction. Durable fistula closure occurred in the single patient who received argon plasma coagulation plus endoscopic suturing, whereas fistula dehiscence occurred in 3/3 (100%) patients with endoscopic suturing monotherapy. CONCLUSIONS: Larger LAMS diameter (20-mm), longer LAMS dwell time, and spontaneous fistula closure may be technical factors that increase the likelihood of post-EDGE persistent fistula. Post-EDGE persistent fistula has not been shown by ours or other studies to be significantly associated with unintentional weight gain; however, this may be due to small sample size. We question the utility of routine fistula closure by primary intent and suggest a personalized approach to post-EDGE fistula management.

EUS-guided choledochoduodenostomy creation using a biliary fully covered self-expanding metal stent after maldeployment of lumen-apposing metal stent.

Video 1Video depicts EUS-guided choledochoduodenostomy creation using a biliary fully covered self-expanding metal stent after maldeployment of a lumen-apposing metal stent.

Endoscopic ultrasound-directed transgastric ERCP (EDGE): a retrospective multicenter study.

BACKGROUND: Endoscopic ultrasound-directed transgastric endoscopic retrograde cholangiopancreatography (ERCP; EDGE) is an alternative to enteroscopy- and laparoscopy-assisted ERCP in patients with Roux-en-Y gastric bypass anatomy. Although short-term results are promising, the long-term outcomes are not known. The aims of this study were: (1) to determine the rates of long-term adverse events after EDGE, with a focus on rates of persistent gastrogastric or jejunogastric fistula; (2) to identify predictors of persistent fistula; (3) to assess the outcomes of endoscopic closure when persistent fistula is encountered. METHODS: This was a multicenter retrospective study involving 13 centers between February 2015 and March 2019. Adverse events were defined according to the ASGE lexicon. Persistent fistula was defined as an upper gastrointestinal series or esophagogastroduodenoscopy showing evidence of fistula. RESULTS: 178 patients (mean age 58 years, 79 % women) underwent EDGE. Technical success was achieved in 98 % of cases (175/178), with a mean procedure time of 92 minutes. Periprocedural adverse events occurred in 28 patients (15.7 %; mild 10.1 %, moderate 3.4 %, severe 2.2 %). The four severe adverse events were managed laparoscopically. Persistent fistula was diagnosed in 10 % of those sent for objective testing (9/90). Following identification of a fistula, 5 /9 patients underwent endoscopic closure procedures, which were successful in all cases. CONCLUSIONS: The EDGE procedure is associated with high clinical success rates and an acceptable risk profile. Persistent fistulas after lumen-apposing stent removal are uncommon, but objective testing is recommended to identify their presence. When persistent fistulas are identified, endoscopic treatment is warranted, and should be successful in closing the fistula.

Shortened-Interval Dual-Session EDGE Reduces the Risk of LAMS Dislodgement While Facilitating Timely ERCP.

BACKGROUND AND AIMS: EUS-directed transgastric ERCP (EDGE) is an endoscopic modality for treating pancreaticobiliary disorders after Roux-en-Y gastric bypass. EDGE consists of EUS-directed gastrogastrostomy/jejunogastrostomy creation (EUS-GG; step 1), followed by transgastric ERCP (step 2). The two steps can be performed in the same or separate endoscopic session(s). Single-session EDGE is immediately therapeutic but risks perforation via LAMS dislodgement. Dual-session EDGE does not risk perforation, but the clinical malady festers during the 10-14-day interval required for fistula maturation. A "shortened-interval dual-session" EDGE (2-4 day interval) may resolve this dilemma. Our study compares 20-mm LAMS dislodgement risk between single-session and shortened-interval dual-session EDGE. METHODS: We conducted a single-center retrospective study of 21 RYGB patients who underwent EDGE using 20-mm LAMS by one advanced endoscopist between 3/2018 and 2/2020. Given the small sample size, a permutation of regressor residuals test was conducted to investigate the association between EDGE interval type and LAMS dislodgement, controlling for the effect of fistula type. RESULTS: Eleven patients (six female; mean age 55 years old) underwent single-session EDGE; LAMS dislodgement occurred in five cases (45%). Ten patients (eight female; mean age 60 years old) underwent shortened-interval dual-session EDGE (median interval 2 days); LAMS dislodgement occurred in one case (10%). The odds of LAMS dislodgement during single-session EDGE was 817% that of shortened-interval dual-session EDGE (OR 8.17; p = 0.05), after controlling for the effect of fistula type. CONCLUSIONS: Shortened-interval dual-session EDGE decreases the risk of intraprocedural 20-mm LAMS dislodgement while allowing for timely transgastric ERCP.

Endoscopic endgame for obstructive pancreatopathy: outcomes of anterograde EUS-guided pancreatic duct drainage. A dual-center study.

BACKGROUND AND AIMS: Anterograde endoscopic ultrasound-guided pancreatic duct drainage (EUS-PDD) refers to transmural drainage of the main pancreatic duct via an endoprosthesis passed anterograde through the gastric (or intestinal) wall. Anterograde EUS-PDD is a rescue procedure for recalcitrant cases of benign obstructive pancreatopathy. METHODS: We conducted a dual-center retrospective chart review of 28 patients (mean age, 59 years; 50% female) who underwent attempted anterograde EUS-PDD between April 2016 and September 2019 for chronic pancreatitis (CP) (93%) or pancreaticojejunostomy stenosis (PJS) after Whipple resection (7%). The study endpoint was achievement of transpapillary/transanastomotic drainage (definitive therapy). RESULTS: Gastropancreaticoenterostomy (ring drainage, definitive therapy) was successfully performed during the index procedure in the 2 patients with PJS (technical success, 100%). Clinical success was 100% in the 2 ring drainage recipients during a mean 18-month follow-up period. The remaining 26 patients with CP underwent attempted pancreaticogastrostomy (PG) with 81% technical success, 75% clinical success, and 15% adverse events (AEs). Repeat endoscopic transmural interventions were performed in the 15 patients with clinical success after PG creation. Definitive therapy transpired in all 15 patients after a median 1 repeat procedure per patient. Clinical success after definitive therapy was maintained in all 15 patients (100%) during a median 4.5-month follow-up. CONCLUSIONS: In agreement with previous studies, our study showed mild to moderately high rates of technical failure (19%), clinical failure (25%), and AEs (15%) during index drainage (PG creation). Among patients with CP with both technical and clinical success after index PG creation (n = 15), 100% definitive therapy was achieved and clinical outcomes were excellent (100% clinical success, 0% AEs).

Reduced risk of post ERCP pancreatitis in statin users.

BACKGROUND: One of the most feared complications of endoscopic retrograde cholangiopancreatography (ERCP), with an incidence of 3.5 to 15%, is post ERCP pancreatitis (PEP). Given the role of statins in the reduction of systemic and pancreatic intraluminal inflammation, we hypothesized that the use of statins may lower the risk of PEP. METHODS: A retrospective cohort study of all patients undergoing ERCP at West Virginia University during the years 2016 and 2017 was performed. Possible association of collected variables with PEP was assessed with Univariate tests and multivariable logistic regression analyses. RESULTS: A total of 1162 ERCPs were included. Mean age was 60.12 years (SD: 17.5). 51.3% of the participants were female. Two hundred and sixty-three participants underwent more than one ERCP during the study period. Seven hundred and ninety-nine ERCPs (78.8%) were conducted in participants who were not taking a statin medication at the time of ERCP, while 363 participants were on statin medications at the time of ERCP; 118 and 245 participants were taking high dose statins (atorvastatin 40-80 mg or rosuvastatin 20 mg), and low/medium dose statins (all other statin regimens) at the time of the procedure, respectively. The overall incidence of PEP in the cohort was 7.3%. In the non-statin and statin groups, 9.5 and 3.4% of participants developed PEP, respectively. On univariate analysis, young age, no statin use, history of PEP, and endoscopic sphincterotomy were found to be significantly associated with the development of PEP. In a binary logistic regression model, young age (P = 0.033), history of PEP (P = 0.0001, OR 2.41, 95% CI: 1.05-5.51) and endoscopic sphincterotomy (P = 0.038, OR 2.85, 95% CI: 1.7-4.78) were found to be associated with increased risk of PEP. Statin usage was found to be protective against PEP, (OR 0.35, 95% CI: 0.18-0.69). CONCLUSION: Chronic statin usage is protective against post ERCP pancreatitis, and our findings suggest a potential role of these drugs as prophylactic agents. Randomized controlled trials are needed to establish any potential clinical application.

Beta-sitosterol-induced Acute Pancreatitis: A Case Report and Review of the Literature.

While drug-induced pancreatitis from corticosteroids has been well described in the medical literature, the exact mechanism is unclear. We present the first reported case of drug-induced pancreatitis from beta-sitosterol, a naturally occurring plant sterol structurally similar to cholesterol, obtained primarily through Western diet and supplementation. A 57-year-old male with a history of situs inversus and benign prostatic hyperplasia presented from an outside facility with a two-day history of worsening epigastric pain radiating to the right upper quadrant. Lipase was markedly elevated at 572 U/L. CT scan and ultrasound of the abdomen were remarkable for acute pancreatitis with acute necrotic collections and normal appearing gallbladder and bile ducts without the presence of gallstones. The patient was managed with aggressive intravenous hydration and supportive management and had resolution of symptoms. At his follow-up appointment, the patient disclosed that he had started a new herbal supplement, beta-sitosterol, on the morning after his symptoms began. Abdominal magnetic resonance cholangiopancreatography obtained at follow-up appointment showed interval resolution of pancreatitis and normal biliary anatomy. In the absence of classical risk factors for acute pancreatitis, a diagnosis of drug-induced pancreatitis secondary to beta-sitosterol was made. The patient was advised to avoid beta-sitosterol, and thus continued to remain asymptomatic. We describe the first reported case of drug-induced pancreatitis from beta-sitosterol, a common phytosterol found in many over the counter supplements worldwide. After a thorough workup to exclude other causes, our case demonstrates consistent resolution of symptoms and pancreatic enzymes along with normal imaging following discontinuation of the offending agent.

EUS-directed transenteric ERCP in non-Roux-en-Y gastric bypass surgical anatomy patients (with video).

BACKGROUND AND AIMS: Enteroscopy-assisted ERCP is challenging in patients with surgically altered upper GI anatomy. This study evaluated a novel procedure, EUS-directed transenteric ERCP (EDEE), in the de novo creation of an enteroenteric anastomosis for the performance of ERCP in non-Roux-en Y gastric bypass (RYGB) patients. METHODS: This was a multicenter retrospective study involving 7 centers between January 2014 and October 2018. Primary outcome was clinical success (completion of EDEE and ERCP with intended interventions), and secondary outcomes were technical success and rate/severity of adverse events. RESULTS: Eighteen patients (mean age, 63 years; 13 women) were included. The most common type of surgical anatomy was Whipple (10/18) and Roux-en-Y hepaticojejunostomy (6/18). Technical success rate of EUS-guided lumen-apposing metal stent (LAMS) placement was 100% and of ERCP was 94.44% (17/18). Fourteen patients underwent separate-session EDEE with a median of 21 days (interquartile range [IQR], 11.5-36) between the 2 procedures. Median total procedure time was 111 minutes (IQR, 81-192). Clinical success and adverse events occurred in 17 (94.4%) and 1 (5.6%; abdominal pain) patients, respectively, during a median follow-up of 88 days (IQR, 54-142). CONCLUSIONS: This study suggests that EDEE using LAMSs is feasible and safe in patients with non-RYGB surgical anatomy and complex pancreaticobiliary pathologies.

Endoscopic ultrasound-guided drainage of pancreatic walled-off necrosis using 20-mm versus 15-mm lumen-apposing metal stents: an international, multicenter, case-matched study.

BACKGROUNDS: Endoscopic ultrasound (EUS)-guided placement of lumen-apposing metal stents (LAMSs) has gained popularity for the treatment of pancreatic walled-off necrosis (WON). We compared the 20-mm and 15-mm LAMSs for the treatment of symptomatic WON in terms of clinical success and adverse events. METHODS: We conducted a retrospective, case-matched study of 306 adults at 22 tertiary centers from 04/2014 to 10/2018. A total of 102 patients with symptomatic WON who underwent drainage with 20-mm LAMS (cases) and 204 patients who underwent drainage with 15-mm LAMS (controls) were matched by age, sex, and drainage approach. Conditional logistic regression analysis was performed to compare clinical success (resolution of WON on follow-up imaging without reintervention) and adverse events (according to American Society for Gastrointestinal Endoscopy criteria). RESULTS: Clinical success was achieved in 92.2 % of patients with 20-mm LAMS and 91.7 % of patients with 15-mm LAMS (odds ratio 0.92; P = 0.91). Patients with 20-mm LAMS underwent fewer direct endoscopic necrosectomy (DEN) sessions (mean 1.3 vs. 2.1; P < 0.001), despite having larger WON collections (transverse axis 118.2 vs. 101.9 mm, P = 0.003; anteroposterior axis 95.9 vs. 80.1 mm, P = 0.01). There was no difference in overall adverse events (21.6 % vs. 15.2 %; P = 0.72) and bleeding events (4.9 % vs. 3.4 %; P = 0.54) between the 20-mm and 15-mm LAMS groups, respectively. CONCLUSIONS: The 20-mm LAMS showed comparable clinical success and safety profile to the 15-mm LAMS, with the need for fewer DEN sessions for WON resolution.