Restorative proctocolectomy with ileal pouch–anal anastomosis (IPAA) is the reference standard surgical procedure for patients with Ulcerative Colitis (UC). Conflicting data exist regarding the relationship between pre-operative advanced therapy use and development of pouchitis, even though in pouchitis rates after IPAA has been recorded over time [1]. We aimed to evaluate long-term pouchitis-free survival in a large cohort of UC patients who underwent IPAA. We conducted a retrospective multicenter study involving 15 centers from the Latium Net and affiliated with IG-IBD. Patients with UC who underwent IPAA and had ileostomy closure between January 1980 and December 2024 were included. Relevant variables were collected, including clinical and demographic data, pre-colectomy treatments, centre and type of surgery, and follow-up data of at least one year. For the analysis, using the date of ileostomy closure as baseline, the entire cohort was divided into three temporal subgroups, defined according to the years advanced therapies for UC became commercially available in Italy: Infliximab in 2006 and Vedolizumab in 2016. A total of 237 patients were enrolled: 67 underwent surgery before 2006 (cohort 1), 76 between 2006 and 2016 (cohort 2), and 94 after 2016 (cohort 3). At colectomy 19.4% had at least one extra-intestinal manifestation, and the prevalence increased significantly over time (from 10.4% to 28.7%, p = 0.01). Pre-operative exposure to corticosteroids also increased across periods (from 85,1% to 92,6%, p = 0.025). Conversely, the proportion of patients naïve to advanced therapies decreased (from 94% to 17%, p < 0.001). The rate of elective surgical procedures rose from 52.2% to 70.2% (p < 0.001) and the approach with a three-stage procedure increased over time (p = 0.002). After a median follow-up of 3.1 years, up to 50% of patients experienced at least one episode of pouchitis. Pouchitis-free survival at one year declined from 92.54% in cohort 1 to 64.65% in cohort 3, p < 0001. Overall, 98 patients (41.3%) developed chronic pouchitis; of these 22.3% with antibiotic-dependent and 11% exhibited a Crohn-like phenotype, yielding an incidence rate of 3.49 per 100 person-years. Among patients with chronic pouchitis, 81 patients (82.7%) required an advanced therapy, with a significant increase in the later cohorts (p < 0.001). Finally, 10.1% of the entire cohort required a definitive ileostomy and 0.8% underwent surgical pouch revision. Over time, we observed a reduced probability of pouchitis-free survival, a progressive shortening of the time to the first pouchitis episode and an increased need for advanced therapy to manage chronic pouchitis in recent years. Reference: 1. Fischman M, Godny L, Friedenberg A, et al. Factors Associated With Biologic Therapy After Ileal Pouch-Anal Anastomosis in Patients With Ulcerative Colitis. Inflamm Bowel Dis. 2024 Nov 14:izae272. doi: 10.1093/ibd/izae272. Epub ahead of print. PMID: 39540419. Conflict of interest: Cuccia, Giuseppe: none Aratari, Annalisa: Consultant or Advisory board member (in the last two years) for Takeda,Abbvie,Pfizer,Galapagos Zerboni, Giulia: none Festa, Stefano: Personal Fees: Consultant and/or Advisory board member for: Takeda, Johnson & Johnson, Pfizer, Galapagos, Abbvie, Ferring, Eli Lilly Del Gaudio, Angelo: none Marafini, Irene: Irene Marafini served as advisory board member for Abbvie, Eli Lilly, Galapagos and received speaker honoraria from Abbvie and Eli Lilly Bracci, Fiametta: none Falasco, Giuliano: none Di Cola, Simone: None Pagnini, Cristiano: none Laterza, Lucrezia: Employment full time / part time None Research Grant (P.I., collaborator or consultant pending and received grants) None Other research support None Speakers Bureau / Honoraria Company name/Lecturer Abivax, Biocure Ownership interest (stock, stock-options, patent or intellectual property None Consultant / advisory board Actial Farmaceutica, Abbvie, Lilly, J & J Baccini, Flavia: None Zampaletta, Costantino: none Mancone, Roberto: none Vincoli, Giuseppina: none Parisio, Laura: None Caldaro, Tamara: None Monterubbianesi, Rita: none Merli, Manuela: None Di Paolo, Maria Carla: None Magiotta, Ambra: none Giovannone, Maurizio: None Scarozza, Patrizio: No Conflict of Interest to declare Bragazzi, Maria Consiglia: none Cesarini, Monica: none D’Arcangelo, Giulia: None Scaldaferri, Franco: Consultancy fee/board for Janseen, Takeda, Pfizer, MSD, Sandoz, Galapagos, Celltrion, Ferring, Abbvie, Lilly, Alfasigma, Abivax Fiorino, Gionata: Personal Fees: Takeda, Johnson&Johnson, Alfasigma, AbbVie, Celltrion, Pfizer, Sandoz, Abivax, Lilly, STADA Pugliese, Daniela: Consultant/Lectures fees from: AbbVie, Takeda, Johnson, Pfizer, Alfasigma, MSD, Lilly, Celltrion.

Tumor necrosis factor-alpha (TNF-α) inhibitors, including infliximab, have redefined the treatment of inflammatory bowel diseases (IBD) such as ulcerative colitis (UC). Despite their efficacy, these agents are associated with rare but serious adverse events, including drug-induced interstitial lung disease (D-ILD). We report a case of infliximab-induced ILD in a 63-year-old male undergoing treatment for UC. The patient presented with fever, dyspnea, and a miliary hypersensitivity pattern on imaging. Infectious causes were excluded, and drug-induced pulmonary toxicity was diagnosed. Discontinuation of infliximab and appropriate management led to gradual clinical improvement. This case highlights the importance of early recognition and management of pulmonary complications associated with TNF-α inhibitors. Given that UC itself and other autoimmune diseases can predispose patients to ILD, we also explore the role of disease activity and additional risk factors, including prior exposure to 5-aminosalicylic acid-based medications. Endoscopic disease activity, fecal calprotectin levels, autoimmune markers (ANA, ENA, ANCA), and bronchoalveolar lavage results are provided to further elucidate the diagnostic process.

BACKGROUND:Guidelines recommend leaving in situ rectosigmoid polyps diagnosed during colonoscopy that are 5 mm or smaller if the endoscopist optically predicts them to be non-neoplastic. However, no randomised controlled trial has been done to examine the efficacy and safety of this strategy. METHODS:This open-label, multicentre, non-inferiority, randomised controlled trial enrolled adults age 18 years or older undergoing colonoscopy for screening, surveillance, or clinical indications across four Italian centres. Eligible patients were randomised 1:1 (with stratification by patient sex, age, and previous adenoma removal) via a central web-based system, to either the leave-in-situ group, in which endoscopists could leave non-neoplastic lesions in place after optical diagnosis, or the resect-all group, in which all detected polyps were systematically removed, regardless of optical diagnosis. Patients and endoscopists were not masked to group allocation but pathologists and investigators assessing outcomes were masked. All procedures in both groups were done with the assistance of a computer-aided detection and diagnosis system. Endoscopists optically diagnosed lesions through a combination of white light, blue light, and computer-aided detection. The primary outcome was the adenoma detection rate (ADR), defined as the proportion of participants with at least one adenoma detected (per-patient analysis), assessed by intention-to-treat, to determine whether the leave-in-situ strategy was non-inferior to the resect-all approach, with an absolute 10% non-inferiority margin. This trial was registered with ClinicalTrials.gov (NCT05500248) and is completed. FINDINGS:Between Oct 1, 2022, and April 30, 2024, 1147 patients were recruited and 895 patients (507 [57%] females, 388 [43%] males, mean age 61·1 years [SD 9·8]) were randomly assigned to either the leave-in-situ group (n=441) or resect-all group (n=454). 197 adenomas or colorectal cancers were detected in the leave-in-situ group and 211 in the resect-all group; the ADR was 44·7% (95% CI 40·4 to 49·5) in the leave-in-situ group and 46·5% (41·8 to 51·2) in the resect-all group (absolute difference -1·8 percentage points, 95% CI -8·9 to 4·9; pnon-inferiority=0·013). No colonoscopy-related complications, including perforation and bleeding, were reported in either group. INTERPRETATION:The leave-in-situ strategy through optical diagnosis with computer-assisted diagnosis support does not reduce oncological safety of colonoscopy, as measured by ADR. By reducing unnecessary polypectomies, this strategy could be considered as an attractive option in colonoscopy practice. FUNDING:European Society of Gastrointestinal Endoscopy.

Infliximab, a monoclonal antibody targeting tumor necrosis factor-alpha (TNF-α), is widely used in treating inflammatory bowel diseases (IBD), including ulcerative colitis (UC). While generally well-tolerated, infliximab is associated with rare but significant adverse effects, including autoimmune hemolytic anemia (AIHA). This report describes the case of a 54-year-old male diagnosed with UC, who developed hemolytic anemia secondary to infliximab therapy after 1 year of treatment. During the infusion preceding the onset of anemia, the patient experienced a severe infusion reaction characterized by urticaria, bronchospasm, chills, fever, and pulsating headache. Laboratory findings confirmed hemolytic anemia with a positive direct and negative indirect Coombs tests. The patient responded well to corticosteroid therapy (prednisone at 1 mg/kg/day for 30 days) and stopping anti-TNF-α, with hemoglobin levels improving from 7.2 g/dL at presentation to 14.6 g/dL after 1 month. AIHA should be considered an uncommon but serious complication of infliximab therapy, necessitating careful monitoring, especially in patients treated for gastrointestinal indications. This case underscores the importance of recognizing and managing infusion-related complications of biologic therapies.

Background Texture and color enhancement imaging (TXI) was recently proposed as a substitute for standard high definition white-light imaging (WLI) to increase lesion detection during colonoscopy. This international, multicenter randomized trial assessed the efficacy of TXI in detection of colorectal neoplasia. Methods Consecutive patients aged ≥ 40 years undergoing screening, surveillance, or diagnostic colonoscopies at five centers (Italy, Germany, Japan) between September 2021 and May 2022 were enrolled. Patients were randomly assigned (1:1) to TXI or WLI. Primary outcome was adenoma detection rate (ADR). Secondary outcomes were adenomas per colonoscopy (APC) and withdrawal time. Relative risks (RRs) adjusted for age, sex, and colonoscopy indication were calculated. Results We enrolled 747 patients (mean age 62.3 [SD 9.5] years, 50.2 % male). ADR was significantly higher with TXI (221/375, 58.9 %) vs. WLI (159/372, 42.7 %; adjusted RR 1.38 [95 %CI 1.20–1.59]). This was significant for ≤ 5 mm (RR 1.42 [1.16–1.73]) and 6–9 mm (RR 1.36 [1.01–1.83]) adenomas. A higher proportion of polypoid (151/375 [40.3 %] vs. 104/372 [28.0 %]; RR 1.43 [1.17–1.75]) and nonpolypoid (136/375 [36.3 %] vs. 102/372 [27.4 %]; RR 1.30 [1.05–1.61]) adenomas, and proximal (143/375 [38.1 %] vs. 111/372 [29.8 %]; RR 1.28 [1.05–1.57]) and distal (144/375 [38.4 %] vs. 98/372 [26.3 %]; RR 1.46 [1.18–1.80]) lesions were found with TXI. APC was higher with TXI (1.36 [SD 1.79] vs. 0.89 [SD 1.35]; incident rate ratio 1.53 [1.25–1.88]). Conclusions TXI increased ADR and APC among patients undergoing colonoscopy for various indications. TXI increased detection of polyps < 10 mm, both in the proximal and distal colon, and may help to improve colonoscopy quality indicators.

Background: Chemoprevention's ability to slow down or prevent the progression of BD-IPMNs is extremely appealing. Aspirin (ASA), Ace Inhibitors/Angiotensin Receptor Blockers (ACEIs/ARBs) and Statins (STATs) are frequently prescribed drugs with a possible beneficial effect on different cancer types. Their effect on IPMNs is largely unknown. Aim: To evaluate the association between the use of ASA, ACEIs/ARBs and STATs and the risk of progression of BD-IPMNs in follow-up. Materials and methods: multicenter, retrospective cohort study on patients with presumed BD-IPMNs without relative or absolute indication for surgery. Pharmacological exposures and risk factors were collected. We identified clinically relevant progression (occurrence of radiological absolute or relative indication for surgery) and any progression (occurrence of clinically relevant progression OR any dimension increase OR the occurrence of new cysts). Results: Overall 594 patients were included. ACEIs were associated with a lower occurrence of any progression (HR = 0.70; 95% CI 0.49-0.98, p = 0.04) and clinically relevant progression, HR = 0.42 (95% CI 0.20-0.88; p = 0.02). No significant effect was shown for factors associated with the occurrence of pancreas cancer such as smoking, alcohol consumption and 1st degree family history of pancreas cancer. Among pharmacological exposures, no convincing effect was shown for the chronic use of ASA, ARB and STAT. Conclusions: ACEIs might have an effect in slowing the progression of BD-IPMNs. ASA, STAT and ARBs show no convincing effect on the progression of BD-IPMNs. Further, prospective, and long-term multicenter studies are needed to verify such association and to define the potential underlying mechanisms. (c) 2022 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Aims Virtual chromoendoscopy techniques to enhance imaging during colonoscopy have shown controversial results in increasing Adenoma Detection Rate (ADR). A new imaging modality, Texture and Color Enhancing Imaging (TXI, Exera X1, Olympus, Japan) was recently proposed as a substitute to standard white light (WLI) colonoscopy. We performed an interim analysis of an ongoing multicenter, randomized trial to assess the efficacy of TXI in detection of colorectal neoplasia.

Background Gastroenteropancreatic neuroendocrine neoplasms [GEP-NENs] have rarely been reported in association with inflammatory bowel diseases [IBDs]. Methods An ECCO COllaborative Network For Exceptionally Rare case reports project [ECCO-CONFER] collects cases of GEP-NENs diagnosed in patients with IBD. Results GEP-NEN was diagnosed in 100 IBD patients; 61% female, 55% Crohn’s disease, median age 48 years (interquartile range [IQR] 38-59]). The most common location was the appendix [39%] followed by the colon [22%]. Comprehensive IBD-related data were available for 50 individuals with a median follow-up of 30 months [IQR 11-70] following NEN diagnosis. Median duration of IBD at NEN diagnosis was 84 months [IQR 10-151], and in 18% of cases NEN and IBD were diagnosed concomitantly. At diagnosis, 20/50 were stage-I [T1N0M0], and 28/50 were graded G1 [ki67 ≤2%]. Incidental diagnosis of NEN and concomitantly IBD diagnosis were associated with an earlier NEN stage [p = 0.01 and p = 0.02, respectively]. Exposure to immunomodulatory or biologic therapy was not associated with advanced NEN stage or grade. Primary GEP-NEN were more frequently found in the segment affected by IBD [62% vs 38%]. At the last follow-up data, 47/50 patients were alive, and only two deaths were related to NEN. Conclusions In the largest case series to date, prognosis of patients with GEP-NEN and IBD seems favourable. Incidental NEN diagnosis correlates with an earlier NEN stage, and IBD-related therapies are probably independent of NEN stage and grade. The association of GEP-NEN location and the segment affected by IBD may suggest a possible role of inflammation in NEN tumorigenesis

The peak of incidence of inflammatory bowel disease (IBD) overlaps with the peak of reproductive age. Moreover, women affected by IBD are often concerned with the possible negative effects of their disease and medications on pregnancy and birth outcomes. From a physician point of view, managing IBD in pregnancy is challenging. Disease activity is the major cause of poor pregnancy outcomes and, therefore, achieving and maintaining IBD remission for the whole duration of pregnancy is the main therapeutic goal. The challenges in selecting therapy lie in balancing the proven efficacy of each drug with the level of safety uncertainty. Except for methotrexate and thalidomide, for which it exits an absolute contraindication in pregnancy, the evidence actually available suggest that most medications can be safely used during pregnancy if appropriately prescribed. The risks associated with drug withdrawal may be higher than the known risks of the medications themselves on pregnancy outcomes. However, all the decisions should be shared with the patient, all available information should be discussed and any therapeutic strategy must be tailored according to patient's context, including disease pattern, activity, severity and acceptance of risk.

AbstractBackgroundThe long‐term course of ulcerative colitis after a severe attack is poorly understood. Second‐line rescue therapy with cyclosporine or infliximab is effective for reducing short‐term colectomy but the impact in the long‐term is controversial.ObjectiveThe purpose of this study was to evaluate the long‐term course of acute severe ulcerative colitis patients who avoid early colectomy either because of response to steroids or rescue therapy.MethodsThis was a multicentre retrospective cohort study of adult patients with acute severe ulcerative colitis admitted to Italian inflammatory bowel disease referral centres from 2005 to 2017. All patients received intravenous steroids, and those who did not respond received either rescue therapy or colectomy. For patients who avoided early colectomy (within 3 months from the index attack), we recorded the date of colectomy, last follow‐up visit or death. The primary end‐point was long‐term colectomy rate in patients avoiding early colectomy.ResultsFrom the included 372 patients with acute severe ulcerative colitis, 337 (90.6%) avoided early colectomy. From those, 60.5% were responsive to steroids and 39.5% to the rescue therapy. Median follow‐up was 44 months (interquartile range, 21–85). Colectomy‐free survival probability was 93.5%, 81.5% and 79.4% at 1, 3 and 5 years, respectively. Colectomy risk was higher among rescue therapy users than in steroid‐responders (log‐rank test, p = 0.02). At multivariate analysis response to steroids was independently associated with a lower risk of long‐term colectomy (adjusted odds ratio = 0.5; 95% confidence interval, 0.2–0.8), while previous exposure to antitumour necrosis factor‐α agents was associated with an increased risk (adjusted odds ratio = 3.0; 95% confidence interval, 1.5–5.7). Approximately 50% of patients required additional therapy or new hospitalisation within 5 years due to a recurrent flare. Death occurred in three patients (0.9%).ConclusionsPatients with acute severe ulcerative colitis avoiding early colectomy are at risk of long‐term colectomy, especially if previously exposed to antitumour necrosis factor‐α agents or if rescue therapy during the acute attack was required because of steroid refractoriness.

Background and objectives: Electrocardiograph abnormalities (i.e., QT interval prolongation) have been described in inflammatory bowel diseases (IBD). We aimed to measure the QT interval in a cohort of patients with IBD and to analyze its relationship with clinical and inflammatory activity. Materials and Methods: We performed a cross-sectional study that included 38 IBD outpatients and 38 "age- and sex-matched" healthy controls. Nine patients had active IBD, and 29 were in clinical remission. Among the latter, 10 patients had sustained (lasting >1 year) and 19 had short-term remission (≤1 year). Corrected QT (QTc) interval was measured on standard 12-lead electrocardiograph. A systematic review of the literature on studies investigating the QT interval in patients with IBD was also performed. Results: QTc interval values were similar between IBD patients and healthy controls (417.58 ± 22.05 ms vs. 409.13 ± 19.61 ms, respectively; p: 0.479). Patients with active IBD had significantly higher QTc values (435.11 ± 27.31 ms) than both controls (409.13 ± 19.61 ms) and patients in remission (412.14 ± 17.33 ms) (p: 0.031). Post hoc analysis showed that the difference in QTc values between active IBD and remission was attributable to the group of patients with sustained remission (p < 0.05). Lastly, a significant correlation between QTc interval and C-reactive protein (CRP) values was observed (Spearman test: r = 0.563; p: 0.0005). Conclusions: Our study demonstrates an association between QTc duration and both clinical and inflammatory activity in patients with IBD. The higher the CRP value, the longer is the QTc duration. For practical purposes, all patients with active IBD should undergo a standard ECG. Prescription of drugs able to modify the QT interval should be avoided in patients with active IBD. The systematic review of the literature indicated that this is the first published study demonstrating an association between the QTc duration and CRP values in patients with IBD.

Abstract Background Inflammatory bowel disease (IBD) patient’s knowledge is a key factor for shared treatment decision making. Some studies have already investigated IBD knowledge but never focused on patient’s awareness about the major disease outcomes nor clinical course nor therapeutic aspects. The aim of the present study is to assess disease knowledge in IBD patients using a novel 11 items questionnaire. Methods An 11 items questionnaire was developed. The questionnaire explored different aspects of IBD course and prognosis: pattern of symptoms, disease complications, need for surgery, risk and prevention of colon-rectal cancer (CRC), extra-intestinal manifestations (EIMs), predictors of poor prognosis, benefit/risk of immunosuppressive and biological therapy and IBD in pregnancy. The questionnaire was handed out to consecutive Crohn’s disease (CD) and ulcerative colitis (UC) patients in regular follow-up at a referral centre. Clinical and socio-demographic characteristics were collected in a dedicate database. Descriptive analysis of quantitative variables was presented as mean or median. Fisher test and Student’s t-test were used for categorical and continuous variables. A p < 0.05 was considered statistically significant. Results Three hundred and four patients were enrolled and 290 completed the questionnaire (95%). Of these 53% UC and 47% CD. The mean age was 51 years (range 18–83); 56% were male. Most of the patients were in clinical remission (85%). The mean number of appropriate answer was 4 upon 11. Overall only 26% answered successfully more than half of the items. Looking at the single items, two third of patients were aware of current strategies of CRC prevention, chance of EIMs and woman capability to become pregnant. The questions about immunosuppression and biologic therapy were more correctly answered by those patients who had experienced them (p = 0.000001), whereas those about the risk of surgery were not influenced by the patient’s previous clinical history (UC p = 1; CD p = 0.067). Only about one third of women were aware of the most relevant risk factor of worst pregnancy outcome. Age <40 years old (p = 0.00003), high level of education (high school and degree, p = 0.0015) and current or previous biologic therapy (p = 0.0007) were associated with a higher level of IBD knowledge. Conclusion These results suggest that the overall disease knowledge in IBD patients is low and should be improved. Young age, education and biologic exposure are associated with an adequate awareness of disease course. This questionnaire should be validated and correlated to other patient-related measures such as health engagement and health literacy in prospective studies.

Background: Hospitalization and death in patients with chronic pancreatitis (CP) are often due to extrapancreatic events. Recent guidelines recommend the use of the MUST score to assess CP patients' nutritional status, but its association with clinical outcomes has been poorly investigated. The aims of this study are to evaluate the incidence of extra-pancreatic events in patients with CP during follow-up and their association with the nutritional status. Methods: Retrospective analysis of single-centre cohort of CP patients prospectively enrolled and followed-up. Exocrine pancreatic insufficiency (EPI) was assessed by fecal elastase, MUST score calculated at diagnosis. The occurrence of hospitalizations or death were recorded. Differences between subgroups were analysed by Fisher's and T-test and hospitalization-free survival with Kaplan-Meier curves and Cox regression analysis. Results: Of 111 enrolled patients (64% male; mean age 57); 52% had alcoholic aetiology, 53% EPI, 10% severe CP and 26% a MUST score >= 2 at diagnosis. During a median follow-up of 37 months, 3.6% of patients died and 34.2% needed hospitalization, in 50% of cases for extrapancreatic events (2% cardiovascular events, 8% infections and 3% cancer). There was no significant association between EPI, BMI<20 kg/m(2), MUST score >= 2, alcoholic aetiology and extra pancreatic events or need of hospitalization. A baseline MUST score >= 2 had an accuracy of only 64.8% in predicting subsequent hospitalization. Conclusions: A sizeable portion of CP patients are at high risk of malnutrition and are hospitalized during the follow-up, often for extra-pancreatic events. The nutritional status evaluated with the MUST score lacks accuracy in predicting the risk of these events. (C) 2019 IAP and EPC. Published by Elsevier B.V. All rights reserved.

External pancreatic fistulae (EPF) developing in setting of disconnected pancreatic duct syndrome (DPDS) are associated with significant morbidity and surgery is the only effective treatment.To describe safety and efficacy of various endoscopic including endoscopic ultrasound (EUS) guided drainage techniques for resolving EPF in DPDS.Retrospective analysis of data base of 18 patients (15 males; mean age: 37.6 ± 7.1years) with EPF and DPDS who were treated with various endoscopic techniques including EUS guided transmural drainage.EPF developed post percutaneous drainage (PCD) (n = 15) or post-surgical necrosectomy (n = 3) of acute necrotic collections. All patients had refractory EPF with daily output of >50 ml/day with mean duration being 19.2 ± 6.1 weeks. One patient had failed surgical fistulo-jejunostomy. Various endoscopic techniques used were: transmural placement of pigtail stent through gastric opening of trans-gastric PCD (n = 5), EUS guided transmural puncture of fluid collection created by clamping PCD (n = 5) or by instillation of water though PCD (n = 3), direct EUS-guided puncture of fistula tract (n = 1) and EUS guided pancreaticogastrostomy (n = 4). EPF healed in 17/18 (94%) patients within 5–21 days and there has been no recurrence over follow up of 16.7 ± 12.8 weeks. Asymptomatic spontaneous external migration of stents was observed in 5/18 (29.4%) patients.Management of refractory EPFs in setting of DPDS is challenging. In our experience, combination of various endoscopic techniques including EUS guided transmural drainage appears to be safe and effective treatment modality for treating these complex EPF's. However, further studies to identify patient selection and best treatment approaches are needed.