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Background and Aims: Gastric outlet and biliary obstruction are common manifestations of GI malignancies and some benign diseases for which standard treatment would be surgical gastroenterostomy and hepaticojejunostomy (ie, "double bypass"). Therapeutic EUS has allowed for the creation of an EUS-guided double bypass. However, same-session double EUS-guided bypass has only been described in small proof-of-concept series and lacks a comparison with surgical double bypass., Methods: A retrospective multicenter analysis was performed of all consecutive same-session double EUS-guided bypass procedures performed in 5 academic centers. Surgical comparators were extracted from these centers' databases from the same time interval. Efficacy, safety, hospital stay, nutrition and chemotherapy resumption, long-term patency, and survival were compared., Results: Of 154 identified patients, 53 (34.4%) received treatment with EUS and 101 (65.6%) with surgery. At baseline, patients undergoing EUS exhibited higher American Society of Anesthesiologists scores and a higher median Charlson Comorbidity Index (9.0 [interquartile range {IQR}, 7.0-10.0] vs 7.0 [IQR, 5.0-9.0], P < .001). Technical success (96.2% vs 100%, P = .117) and clinical success rates (90.6% vs 82.2%, P = .234) were similar when comparing EUS and surgery. Overall (11.3% vs 34.7%, P = .002) and severe adverse events (3.8% vs 19.8%, P = .007) occurred more frequently in the surgical group. In the EUS group, median time to oral intake (0 days [IQR, 0-1] vs 6 days [IQR, 3-7], P < .001) and hospital stay (4.0 days [IQR, 3-9] vs 13 days [IQR, 9-22], P < .001) were significantly shorter., Conclusions: Despite being used in a patient population with more comorbidities, same-session double EUS-guided bypass achieved similar technical and clinical success and was associated with fewer overall and severe adverse events when compared with surgical gastroenterostomy and hepaticojejunostomy., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: For palliative drainage of inoperable perihilar cholangiocarcinoma (pCCA) uncovered metal stents are preferred over plastic stents. However, there is a lack of data on re-interventions at the long-term. The aim is to evaluate the potential difference in the number of re-interventions in patients surviving at least 6 months., Methods: Retrospective study including patients with pCCA who underwent plastic stent placement(s) or had metal stent(s) in situ for at least 6 months. The primary outcome was the number of re-interventions per patient-year. A propensity score matching (1:1) analysis was performed using age, Bismuth classification, reason for inoperability, pathological confirmation, systemic therapy and initial approach (endoscopic vs percutaneous)., Results: Patients in the metal stent group (n = 87) underwent fewer re-interventions compared with the plastic stent group (n = 40) (3.0 vs. 4.7 per patient-year; IRR, 0.64; 95% CI, 0.47 to 0.88). When only non-elective re-interventions were included, there was no significant difference (2.1 vs. 2.7; IRR, 0.76; 95% CI, 0.55 to 1.08). Results were similar in the propensity score-matched dataset., Conclusions: This study shows that, also in patients with inoperable pCCA who survive at least 6 months, placement of metal stent(s) leads to fewer re-interventions in comparison with plastic stents., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Pneumomediastinum is a potentially life-threatening condition. Patients can present with a variety of symptoms at the emergency department. Pneumomediastinum can be spontaneous or secondary due to perforation of the esophagus or tracheobronchial tree., Case Description: A 20-year old man was seen at the emergency department with the suspicion of esophageal perforation. He noticed subcutaneous 'crackles' arising after an episode of severe vomiting. In the emergency room a non-acute ill patient was seen with subcutaneous emphysema of the neck and chest. A CT-scan with oral contrast did not show esophageal contrast leakage or other pathology that could be the cause of his pneumomediastinum. Therefore, we diagnosed the patient with a spontaneous pneumomediastinum. He was discharged after an observation period of 24 hours., Conclusion: Spontaneous pneumomediastinum is a rare, self-limiting disease with an excellent prognosis. Differentiating spontaneous pneumomediastinum from more severe secondary causes will avoid unnecessary therapy and prolonged hospitalization.

Background: Intraductal papillary mucinous neoplasm (IPMN) with involvement of the main pancreatic duct usually requires surgical resection. Consensus is lacking whether to partially or completely resect the pancreatic portion with a dilated main pancreatic duct. Intraoperative pancreatoscopy may be useful to determine the extent of IPMN to tailor surgical resection and was recently studied in a large prospective international study. IPMN is increasingly utilized using a robotic approach. Studies describing the technical approach to intraoperative pancreatoscopy in robotic pancreatoduodenectomy and robotic distal pancreatectomy are lacking., Methods: During robotic pancreatoduodenectomy, pancreatoscopy is performed once the pancreas neck is transected. The scope is advanced via a laparoscopic port into the left and right-sided pancreatic duct, guided by robotic graspers. During robotic distal pancreatectomy, pancreatoscopy is performed before complete parenchymal transection. The scope is advanced through an anterior ductotomy to examine the duct and guide the pancreatic transection line. Tips and tricks how to perform the procedure efficiently without complications are detailed., Results: In total, 28 robot-assisted pancreatoscopies were performed during robotic pancreatoduodenectomy and robotic distal pancreatectomy. No intraoperative complications resulting from the intraoperative pancreatoscopy were noted. In the 2 described procedures, the added time required to perform the pancreatoscopy was 6 and 17 minutes, respectively. Both patients recovered without complication and were discharged on postoperative day 5 for the robotic pancreatoduodenectomy and day 6 for the robotic distal pancreatectomy., Conclusions: Intraoperative pancreatoscopy can be safely performed during both robotic pancreatoduodenectomy and robotic distal pancreatectomy for IPMN with the involvement of the main pancreatic duct. An international prospective study has recently been completed with this technique., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Necrotizing pancreatitis may result in a disrupted or disconnected pancreatic duct (DPD) with the potential for long-lasting negative impact on a patient's clinical outcome. There is a lack of detailed data on the full clinical spectrum of DPD, which is critical for the development of better diagnostic and treatment strategies., Methods: We performed a long-term post hoc analysis of a prospectively collected nationwide cohort of 896 patients with necrotizing pancreatitis (2005-2015). The median follow-up after hospital admission was 75 months (P25-P75: 41-151). Clinical outcomes of patients with and without DPD were compared using regression analyses, adjusted for potential confounders. Predictive features for DPD were explored., Results: DPD was confirmed in 243 (27%) of the 896 patients and resulted in worse clinical outcomes during both the patient's initial admission and follow-up. During hospital admission, DPD was associated with an increased rate of new-onset intensive care unit admission (adjusted odds ratio [aOR] 2.52; 95% confidence interval [CI] 1.62-3.93), new-onset organ failure (aOR 2.26; 95% CI 1.45-3.55), infected necrosis (aOR 4.63; 95% CI 2.87-7.64), and pancreatic interventions (aOR 7.55; 95% CI 4.23-13.96). During long-term follow-up, DPD increased the risk of pancreatic intervention (aOR 9.71; 95% CI 5.37-18.30), recurrent pancreatitis (aOR 2.08; 95% CI 1.32-3.29), chronic pancreatitis (aOR 2.73; 95% CI 1.47-5.15), and endocrine pancreatic insufficiency (aOR 1.63; 95% CI 1.05-2.53). Central or subtotal pancreatic necrosis on computed tomography (OR 9.49; 95% CI 6.31-14.29) and a high level of serum C-reactive protein in the first 48 hours after admission (per 10-point increase, OR 1.02; 95% CI 1.00-1.03) were identified as independent predictors for developing DPD., Discussion: At least 1 of every 4 patients with necrotizing pancreatitis experience DPD, which is associated with detrimental, short-term and long-term interventions, and complications. Central and subtotal pancreatic necrosis and high levels of serum C-reactive protein in the first 48 hours are independent predictors for DPD., (Copyright © 2023 by The American College of Gastroenterology.)

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 Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Competing Interests: Competing interests The authors declare that they have no conflict of interest.

Background and Aims: In the management of gastric outlet obstruction (GOO), EUS-guided gastroenterostomy (EUS-GE) seems to be safe and more effective than enteral stent placement. However, comparisons with laparoscopic GE (L-GE) are scarce. Our aim was to perform a propensity score-matched comparison between EUS-GE and L-GE., Methods: An international, multicenter, retrospective analysis was performed of consecutive EUS-GE and L-GE procedures in 3 academic centers (January 2015 to May 2020) using propensity score matching to minimize selection bias. A standard maximum propensity score difference of .1 was applied, also considering underlying disease and oncologic staging., Results: Overall, 77 patients were treated with EUS-GE and 48 patients with L-GE. By means of propensity score matching, 37 patients were allocated to both groups, resulting in 74 (1:1) matched patients. Technical success was achieved in 35 of 37 EUS-GE-treated patients (94.6%) versus 100% in the L-GE group (P = .493). Clinical success, defined as eating without vomiting or GOO Scoring System ≥2, was achieved in 97.1% and 89.2%, respectively (P = .358). Median time to oral intake (1 [interquartile range {IQR}, .3-1.0] vs 3 [IQR, 1.0-5.0] days, P < .001) and median hospital stay (4 [IQR, 2-8] vs 8 [IQR, 5.5-20] days, P < .001) were significantly shorter in the EUS-GE group. Overall (2.7% vs 27.0%, P = .007) and severe (.0% vs 16.2%, P = .025) adverse events were identified more frequently in the L-GE group., Conclusions: For patients with GOO, EUS-GE and L-GE showed almost identical technical and clinical success. However, reduced time to oral intake, shorter median hospital stay, and lower rate of adverse events suggest that the EUS-guided approach might be preferable., (Copyright © 2021 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Introduction: Adult-onset autoimmune enteropathy (AIE) is a rare cause of severe chronic diarrhea because of small intestinal villous atrophy. We report on patients with adult-onset AIE in an European referral center., Methods: Retrospective study including patients diagnosed with AIE in the Amsterdam UMC, location VUmc, between January 2003 and December 2019. Clinical, serological, and histological features and response to treatment were reported. The specificity of antienterocyte antibodies (AEA) was evaluated by examining the prevalence of AEA in (i) controls (n = 30) and in patients with (ii) AIE (n = 13), (iii) celiac disease (CD, n = 52), (iv) refractory celiac disease type 2 (n = 18), and (v) enteropathy-associated T-cell lymphoma (EATL, n = 10)., Results: Thirteen AIE patients were included, 8 women (62%), median age of 52 years (range 23-73), and 6 (46%) with an autoimmune disease. AEA were observed in 11 cases (85%), but were also found in CD (7.7%), refractory celiac disease type 2 (16.7%), and EATL (20%). Ten patients (77%) were human leukocyte antigen DQ2.5 heterozygous. Total parenteral nutrition was required in 8 cases (62%). Steroids induced clinical remission in 8 cases (62%). Step-up therapy with rituximab, cyclosporine, infliximab, and cladribine in steroid-refractory patients was only moderately effective. Four patients died (31%), but 4 (31%) others are in long-term drug-free remission after receiving immunosuppressive treatment, including 1 patient who underwent autologous stem cell transplantation., Discussion: Adult-onset AIE is a rare but severe enteropathy that occurs in patients susceptible for autoimmune disease. Four patients (31%) died secondary to therapy-refractory malabsorption, while immunosuppressive therapy leads to a long-lasting drug-free remission in one-third of patients., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Identification of molecular predictive markers of response to neoadjuvant chemoradiation could aid clinical decision-making in patients with localized oesophageal cancer. Therefore, we subjected pretreatment biopsies of 75 adenocarcinoma (OAC) and 16 squamous cell carcinoma (OSCC) patients to targeted next-generation DNA sequencing, as well as biopsies of 85 OAC and 20 OSCC patients to promoter methylation analysis of eight GI-specific genes, and subsequently searched for associations with histopathological response and disease-free (DFS) and overall survival (OS). Thereby, we found that in OAC, CSMD1 deletion (8%) and ETV4 amplification (5%) were associated with a favourable histopathological response, whereas SMURF1 amplification (5%) and SMARCA4 mutation (7%) were associated with an unfavourable histopathological response. KRAS (15%) and GATA4 (7%) amplification were associated with shorter OS. In OSCC, TP63 amplification (25%) and TFPI2 (10%) gene promoter methylation were associated with an unfavourable histopathological response and shorter DFS (TP63) and OS (TFPI2), whereas CDKN2A deletion (38%) was associated with prolonged OS. In conclusion, this study identified candidate genetic biomarkers associated with response to neoadjuvant chemoradiotherapy in patients with localized oesophageal cancer., (© 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Immune-mediated enteropathies are caused by excessive reactions of the intestinal immune system towards non-pathogenic molecules. Enteropathy leads to malabsorption-related symptoms and include (severe) chronic diarrhea, weight loss and vitamin deficiencies. Parenteral feeding and immunosuppressive therapy are needed in severe cases. Celiac disease has long been recognized as the most common immune-mediated enteropathy in adults, but the spectrum of immune-mediated enteropathies has been expanding. Histological and clinical features are sometimes shared among these enteropathies, and therefore it may be challenging to differentiate between them. Here, we provide an overview of immune-mediated enteropathies focused on clinical presentation, establishing diagnosis, immunopathogenesis, and treatment options., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

1:  ESGE recommends that each center implements a written policy regarding the management of iatrogenic perforations, including the definition of procedures that carry a higher risk of this complication. This policy should be shared with the radiologists and surgeons at each center. 2 : ESGE recommends that in the case of an endoscopically identified perforation, the endoscopist reports its size and location, with an image, and statement of the endoscopic treatment that has been applied. 3:  ESGE recommends that symptoms or signs suggestive of iatrogenic perforation after an endoscopic procedure should be rapidly and carefully evaluated and documented with a computed tomography (CT) scan. 4 : ESGE recommends that endoscopic closure should be considered depending on the type of the iatrogenic perforation, its size, and the endoscopist expertise available at the center. Switch to carbon dioxide (CO2) endoscopic insufflation, diversion of digestive luminal content, and decompression of tension pneumoperitoneum or pneumothorax should also be performed. 5 : ESGE recommends that after endoscopic closure of an iatrogenic perforation, further management should be based on the estimated success of the endoscopic closure and on the general clinical condition of the patient. In the case of no or failed endoscopic closure of an iatrogenic perforation, and in patients whose clinical condition is deteriorating, hospitalization and surgical consultation are recommended., Competing Interests: M. Barthet’s department has received a research grant from Boston Scientific. G. Paspatis has received consultancy fees from Boston Scientific (2019). A. Repici has received consultancy fees from Boston Scientific (2019 – 2020); his department has received a research grant from Boston Scientific (2018 – 2020). B. Saunders’ department has received a research grant and loan of equipment from Olympus (2019 to present). J.E. van Hooft has received lecture fees from Medtronics (2014 – 2015, 2019) and Cook Medical (2019), and consultancy fees from Boston Scientific (2014 – 2017); her department has received research grants from Cook Medical (2014 – 2018) and Abbott (2014 – 2017). M. Arvanitakis, A. Dhillon, J.M. Dumonceau, M. Fragaki, J.M. Gonzalez, S.Y. Turino, and R.L.J. van Wanrooij have no competing interests., (© Georg Thieme Verlag KG Stuttgart · New York.)

GWAS studies have identified variant rs 17810546 in a non-coding region on chromosome 3 as a risk factor for several auto-immune diseases, including Celiac Disease. In silico analysis reveals that this variant is located in a transcription regulatory site. By means of reporter constructs we show that this region can override the expression rate of a gene as determined by its native promoter and that this modulation is influenced by the genetic composition of the haplotype which rs17810546 forms with a nearby other variant, rs761008. Secondly, we present data that this genetically imprinted modulation could be involved in Celiac Disease through the IL12A gene which is located 40 Kb downstream of this regulatory region. Based on our findings it is most likely that the IL12A gene does so as part of the cytokine IL-35., (Copyright © 2019. Published by Elsevier B.V.)

Objectives: Aberrant intra-epithelial lymphocytes (IELs) are the hallmark of refractory coeliac disease type II RCDII and considered a premalignant cell population from which aggressive enteropathy-associated T cell lymphoma (EATL) can evolve. The aim of this study was to gain further insight in the origin and characteristics of aberrant IELs by analysing T-cell receptor (TCR) rearrangements, and by immunophenotypic analysis of aberrant IELs., Design: Duodenal biopsies from 18 RCDII patients and three RCDII cell lines were analysed for the presence of TCR delta, gamma, and beta rearrangements. In addition, IELs isolated from biopsies derived from RCDII patients were phenotypically analysed., Results: Aberrant IELs showed an upregulated expression of granzyme B and decreased expression of PCNA. TCR rearrangements in the aberrant IEL population in biopsies of RCDII patients were heterogenic, which is most likely due to a variation in maturity. Similarly, RCDII cell lines displayed a heterogenic TCR rearrangement pattern., Conclusion: Aberrant IELs originate from deranged immature T lymphocytes and display clear differentiation to a cytotoxic phenotype. Aberrant IELs displayed different stages of maturity between RCDII patients, of which only the patients harbouring the most mature aberrant IEL population developed an EATL., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Coeliac disease (CD) is the most common cause of villous atrophy and is increasingly recognized. The majority of CD patients responds to a gluten-free diet (GFD). However, some patients experience persistence or recurrence of symptoms despite a GFD. These patients require further diagnostic workup. We describe a 62-year-old female with recurring symptoms attributed to refractory coeliac disease (RCD) type I. A 66-year-old patient with a similar history had aberrant intraepithelial lymphocytes characteristic for RCD type II in her duodenum. Furthermore, in a third CD patient described here, microscopic colitis was responsible for diarrhoea that persisted despite strict dietary adherence. Microscopic colitis is strongly associated with CD and should be considered in patients with this disease. On the basis of these three illustrative case studies, we discuss the causes of non-responsive CD and their respective diagnostic workup.

Background: Diagnosing colorectal cancer (CRC) at an early stage improves survival. To what extent any delay affects outcome once patients are symptomatic is still unclear.Our objectives were to evaluate the association between diagnostic delay and survival in symptomatic patients with early stage CRC and late stage CRC., Methods: Prospective population-based observational study evaluating daily clinical practice in Northern Holland. Diagnostic delay was determined through questionnaire-interviews. Dukes' stage was classified into two groups: early stage (Dukes A or B) and late stage (Dukes C or D) cancer. Patients were followed up for 3.5 years after diagnosis., Results: In total, 272 patients were available for analysis. Early stage CRC was present in 136 patients while 136 patients had late stage CRC. The mean total diagnostic delay (SE) was 31 (1.5) weeks in all CRC patients. No significant difference was observed in the mean total diagnostic delay in early versus late stage CRC (p = 0.27).In early stage CRC, no difference in survival was observed between patients with total diagnostic delay shorter and longer than the median (Kaplan-Meier, log-rank p = 0.93).In late stage CRC, patients with a diagnostic delay shorter than the median had a shorter survival than patients with a diagnostic delay longer than the median (log-rank p = 0.01). In the multivariate Cox regression model with survival as dependent variable and median delay, age, open access endoscopy, number and type of symptoms as independent variables, the odd's ratio for survival in patients with long delay (>median) versus short delay (

Objective: To map the locations of advanced colorectal neoplasia in patients referred for colonoscopy or sigmoidoscopy and to compare the yield of advanced neoplasia and the distribution of advanced neoplasia per indication for endoscopy., Design: Observational., Method: In a multicentre survey in North Holland, the Netherlands (n = 18 hospitals), data on all colonoscopies and sigmoidoscopies performed during a three-month period in 2005 were analyzed. The locations and the histological features of all colonic neoplasia and the indications for endoscopy were recorded. Advanced neoplasm was defined as adenoma >or=10 mm in size, an adenoma with any villous features, or high-grade dysplasia or adenocarcinoma., Results: A total of 4623 patients underwent a total colonoscopy and 3004 patients underwent sigmoidoscopy. The prevalence of advanced neoplasia was 13% on colonoscopy and 6% on sigmoidoscopy. Of the advanced neoplasia found on colonoscopy, 67% were located in the distal colon and 33% in the proximal colon. Of the patients with advanced neoplasia in the proximal colon (n = 228), 51% had no abnormalities in the distal colon. The percentage of advanced neoplasia in the proximal colon varied from 23% in patients younger than 50 years to 41% in patients aged 80 years and older. Depending on the indication for endoscopy, the prevalence of advanced neoplasia in the proximal colon varied from 11-57%., Conclusion: Of the advanced colorectal neoplasms 33% were located in the proximal colon. With increasing age, a shift in tumour localization occurs from distal to proximal in the colon. Colonoscopy is the preferred method for the endoscopic diagnosing of colorectal neoplasia.