Effectiveness of endoscopic ultrasound (EUS)-guided choledochoduodenostomy vs. EUS-guided gallbladder drainage for jaundice in patients with malignant distal biliary obstruction after failed endoscopic retrograde cholangiopancreatography: Retrospective, multicenter study (GALLBLADEUS Study).

OBJECTIVES: The aim of this study was to compare endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) vs. EUS-gallbladder drainage (EUS-GBD) in cases of failed endoscopic retrograde cholangiopancreatography (ERCP) for jaundice resulting from malignant distal biliary obstruction (MDBO). METHODS: This multicenter retrospective study included patients with obstructive jaundice secondary to MDBO who underwent EUS-GBD or EUS-CDS with lumen-apposing metal stents after failed ERCP. The primary end-point was clinical success rate. Secondary end-points were technical success, periprocedural adverse events rate (<24 h), late adverse events rate (>24 h), overall survival, and time to recurrent biliary obstruction. RESULTS: A total of 78 patients were included: 41 underwent EUS-GBD and 37 underwent EUS-CDS. MDBO was mainly the result of pancreatic cancer (n = 63/78, 80.7%). Clinical success rate was similar for both procedures: 87.8% for EUS-GBD and 89.2% for EUS-CDS (P = 0.8). Technical success rate was 100% for EUS-GBD and 94.6% for EUS-CDS (P = 0.132). Periprocedural morbidity (<24 h) rates were similar between both groups: 4/41 (9.8%) for EUS-GBD and 5/37 (13.5%) for EUS-CDS (P = 0.368). There was a significantly higher rate of late morbidity (>24 h) among patients in the EUS-CDS group (8/37 [21.6%]) than in the EUS-GBD group (3/41 [7.3%]) (P = 0.042). The median follow-up duration was 4.7 months. Overall survival and time to recurrent biliary obstruction did not significantly differ between the groups. DISCUSSION: After failed ERCP for MDBO, EUS-GBD and EUS-CDS show comparable clinical success rates and technical success. EUS-GBD appears to be a promising alternative for MDBO, even as a second-line treatment after failed ERCP. Further studies are needed to validate these findings and compare the long-term outcomes of EUS-GBD and EUS-CDS.

Systematic Resection of the Visible Scar After Incomplete Endoscopic Resection of Rectal Neuroendocrine Tumors.

INTRODUCTION: When initial resection of rectal neuroendocrine tumors (r-NETs) is not R0, persistence of local residue could lead to disease recurrence. This study aimed to evaluate the interest of systematic resection of non-R0 r-NET scars. METHODS: Retrospective analysis of all the consecutive endoscopic revisions and resections of the scar after non-R0 resections of r-NETs. RESULTS: A total of 100 patients were included. Salvage endoscopic procedure using endoscopic submucosal dissection or endoscopic full-thickness resection showed an R0 rate of near 100%. Residual r-NET was found in 43% of cases. DISCUSSION: In case of non-R0 resected r-NET, systematic scar resection by endoscopic full-thickness resection or endoscopic submucosal dissection seems necessary.

PERcutaneous transhepatic CHOLangioscopy using a new single-operator short cholangioscope (PERCHOL): European feasibility study.

OBJECTIVES: A new short device for percutaneous endoscopic cholangioscopy was recently developed. However, feasibility and safety has not yet been evaluated. The aim of this study was to assess clinical success, technical success, and adverse events (AEs). METHODS: This observational multicenter retrospective study included all patients who underwent percutaneous cholangioscopy using a short cholangioscope between 2020 and 2022. The clinical success, defined as the complete duct clearance or obtaining at least one cholangioscopy-guided biopsy, was assessed. The histopathological accuracy, technical success, and the AE rate were also evaluated. RESULTS: Fifty-one patients (60 ± 15 years, 45.1% male) were included. The majority of patients had altered anatomy (n = 40, 78.4%), and biliary stones (n = 34, 66.7%) was the commonest indication. The technique was predominantly wire-guided (n = 44, 86.3%) through a percutaneous sheath (n = 36, 70.6%) following a median interval of 8.5 days from percutaneous drainage. Cholangioscopy-guided electrohydraulic lithotripsy was performed in 29 cases (56.9%), combined with a retrieval basket in eight cases (27.6%). The clinical success was 96.6%, requiring a median of one session (range 1-3). Seventeen patients (33.3%) underwent cholangioscopy-guided biopsies. There were four (7.8%) cholangioscopy-related AEs (cholangitis and peritonitis). Overall, the technical success and AE rates were 100% and 19.6%, respectively, in a median follow-up of 7 months. CONCLUSION: Percutaneous endoscopic cholangioscopy with a new short device is effective and safe, requiring a low number of sessions to achieve duct clearance or accurate histopathological diagnosis.

Acinar-to-Ductal Metaplasia (ADM): On the Road to Pancreatic Intraepithelial Neoplasia (PanIN) and Pancreatic Cancer.

Adult pancreatic acinar cells show high plasticity allowing them to change in their differentiation commitment. Pancreatic acinar-to-ductal metaplasia (ADM) is a cellular process in which the differentiated pancreatic acinar cells transform into duct-like cells. This process can occur as a result of cellular injury or inflammation in the pancreas. While ADM is a reversible process allowing pancreatic acinar regeneration, persistent inflammation or injury can lead to the development of pancreatic intraepithelial neoplasia (PanIN), which is a common precancerous lesion that precedes pancreatic ductal adenocarcinoma (PDAC). Several factors can contribute to the development of ADM and PanIN, including environmental factors such as obesity, chronic inflammation and genetic mutations. ADM is driven by extrinsic and intrinsic signaling. Here, we review the current knowledge on the cellular and molecular biology of ADM. Understanding the cellular and molecular mechanisms underlying ADM is critical for the development of new therapeutic strategies for pancreatitis and PDAC. Identifying the intermediate states and key molecules that regulate ADM initiation, maintenance and progression may help the development of novel preventive strategies for PDAC.

Single-use duodenoscopes are an efficient tool for emergency ERCP in real life.

Background Biliary tract emergencies are managed with endoscopic retrograde cholangiopancreatography (ERCP) using duodenoscopes, which are reusable devices that require high-level disinfection to minimize risk of cross-contamination. Recent reports about newly developed single-use duodenoscopes (SUDs) suggest equivalent performance with reusable duodenoscopes, but the effectiveness of SUDs in emergency ERCP has not yet been studied. Patients and methods We conducted a prospective case series of emergency ERCP procedures using SUDs (EXALT model D-Boston Scientific, United States) in a real-life, tertiary care setting without any possibility of using a back-up reusable duodenoscope. Results Twenty-one emergent ERCPs (acute cholangitis 48%, severe jaundice 38 %, others 14 %) were performed in 19 patients (mean age 49.5±15 years). Almost all procedures (20 of 21; 95 %) were technically and clinically successful, whereas selective cannulation failed in one case. Among the successful ERCPs, five (24 %) were achieved by a novice operator. The image was often considered skewed toward yellow tones (48 %), whereas stiffness and pushability for stent insertion were found suboptimal in 5 % of the procedures, without any impact on procedure success. Conclusions SUDs are effective and appropriate devices for emergent situations in real life even in non-expert hands and even if a regular duodenoscope is unavailable as a backup.

Single-operator cholangioscopy monitoring of a remaining bile duct after congenital choledochal cyst surgery: a case report with an innovative approach.

Video 1Single-operator cholangioscopy monitoring of a remaining bile duct after congenital choledochal cyst surgery: a case report with an innovative approach. After removing remaining pancreatic stones in the remnant bile duct, we inserted a Spyglass choledochoscope. Mucosa was regular and monochromatic. We performed biopsies with a Spybite miniforceps in the remnant cyst and its junction.

Pneumatic dilation for the treatment of persistent post-laparoscopic fundoplication dysphagia: long-term efficacy and safety.

BACKGROUND: Post-laparoscopic fundoplication (LF) dysphagia occurs in 5%-17% of patients and optimal management remains a topic of expert discussion. We assessed the efficacy and safety of pneumatic dilation (PD) in patients with persistent post-lLF dysphagia. METHODS: Medical files of patients treated with PD for persistent post-fundoplication-associated dysphagia were reviewed. The primary outcome was long-term clinical success. Secondary endpoints were initial clinical success, dysphagia recurrence rate, and PD-related complication incidence. RESULTS: Overall, 46 patients (74% women, 57.9±11.9 years) underwent 74 PD (mean: 1.6±0.8). A 30 mm, 35 mm, and 40 mm balloon was used in 45.9%, 43.2%, and 10.8%, respectively, of dilations. Among 45 patients with available follow-up, the overall long-term success rate of PD was 31/45 (68.9% [55.4-82.4]). Initial clinical success was 36/45 (80% [68.3-91.7]). Dysphagia recurred in 9 patients (25%; 95%CI 10.9-39.1) and 4 of these were effectively treated with a new dilation. Among 14 non-responders to PD, 11 underwent surgery. Four complications (2 perforations, 1 muscularis dilaceration, and 1 peri-procedural bleeding) occurred in 4 patients (incidence: 5.4% [95%CI; 0.3-10.6]) and were treated with partially covered self-expandable esophageal stents andhemostatic clips. CONCLUSIONS: Pneumatic balloon dilation for post-fundoplication-associated symptoms is associated with a satisfactory long-term success rate and acceptable safety profile.

Identification of endoscopic predictors of biliary malignancy during digital cholangioscopy.

OBJECTIVES: Biliary brushings and biopsies obtained during endoscopic retrograde cholangiopancreatography (ERCP) have a low sensitivity for the diagnosis of malignant biliary strictures. While cholangioscopic analysis is useful, visual criteria have not yet been defined. The aim of this study was to identify visual criteria for the diagnosis of indeterminate biliary strictures (IDBS). METHODS: A multicenter study was conducted based on the analysis of cholangioscopic recordings of IBDS. Diagnostic criteria were identified in a study group and verified in a validation group. RESULTS: Four criteria were identified to be associated with malignancy, one negatively ("endobiliary material," odds ratio [OR] 0.62, 95% confidence interval [CI] 0.41-0.92) and three positively ("vascularized villous projections," OR 1.52, 95% CI 1.03-2.24; "twisted or dilated vessels," OR 2.18, 95% CI 1.47-3.24; and "dark color of the mucosa," OR 1.82, 95% CI 1.23-2.70). Between two playbacks, the mean (95% CI) sensitivity of the observer's visual diagnosis increased from 66.1% (60-72) to 73.8% (69-78) (P = 0.004); in the second playback, the kappa value for interobserver agreement ranged between 0.36 (color) and 0.56 (endobiliary material), with a significant improvement (P = 0.0031-0.0001) between the first and second playbacks. Blind assessment by endoscopists not involved in this study had a diagnostic accuracy of 73% (71.4-74.5). CONCLUSION: The four identified cholangioscopic features are easy to implement in clinical practice and have the potential to increase the level of diagnostic confidence during the workup of IDBS.

Endoscopic internal drainage of complex bilomas and biliary leaks by transmural or transpapillary/transfistulary access.

BACKGROUND AND AIMS: Bilomas most frequently result from postoperative bile leaks. The endoscopic conventional treatment is sphincterotomy ± stent placement. In complex cases, such as altered anatomy or failure of conventional treatment, transpapillary/transfistulary (TP/TF) drainage or EUS-guided transmural drainage (EUS-TD) may obviate additional biliary surgery. This study reports our experience with treating biloma secondary to refractory biliary leak with TP/TF drainage or EUS-TD and evaluates the safety and outcomes associated with this approach. METHODS: This observational study focused on consecutive patients managed for biliary leakage (diagnosis based on imaging and/or bile outflow from a surgical drain) at a tertiary care hospital (2007-2017). TP/TF drainage was performed by double-pigtail stent(s) placement to drain the biloma through the leak during ERCP. For EUS-TD, plastic stent(s) were placed under EUS control. Primary outcomes were a composite of clinical success (patient free of sepsis after percutaneous drain removal and, in patients with benign disease, removal of all endoscopically placed stents, without need for reintervention) and biloma regression (<3 cm) at last follow-up. RESULTS: Thirty patients (men, 57%; median age, 55 years) were included. Most biliary leaks resulted from cholecystectomy (27%) and hepatectomy (50%). Initial EUS-TD and TP/TF drainage were performed in 14 (47%) and 16 (53%) patients, respectively. At last follow-up (median, 33.2 months), clinical success and primary outcome were achieved in 70.4% of patients (EUS-TD, 75%; TP/TF, 67%). Additional surgery was necessary in 1 patient. Rate of serious adverse events was 23% (7/30), of which 13% (4/30) were procedure related. There were 4 deaths during the course of treatment, 2 of which were related to endoscopic interventions (hemorrhage and fibrillation). CONCLUSIONS: TP/TF drainage or EUS-TD is technically feasible with high clinical success and may avoid the need for additional surgery in complex cases or in patients with altered anatomy.

Functionally deficient TRPV6 variants contribute to hereditary and familial chronic pancreatitis.

The recent discovery of TRPV6 as a pancreatitis susceptibility gene served to identify a novel mechanism of chronic pancreatitis (CP) due to Ca2+ dysregulation. Herein, we analyzed TRPV6 in 81 probands with hereditary CP (HCP), 204 probands with familial CP (FCP), and 462 patients with idiopathic CP (ICP) by targeted next-generation sequencing. We identified 25 rare nonsynonymous TRPV6 variants, 18 of which had not been previously reported. All 18 variants were characterized by a Ca2+ imaging assay, with 8 being identified as functionally deficient. Evaluation of functionally deficient variants in the three CP cohorts revealed two novel findings: (i) functionally deficient TRPV6 variants appear to occur more frequently in HCP/FCP patients than in ICP patients (3.2% vs. 1.5%) and (ii) functionally deficient TRPV6 variants found in HCP and FCP probands appear to be more frequently coinherited with known risk variants in SPINK1, CTRC, and/or CFTR than those found in ICP patients (66.7% vs 28.6%). Additionally, genetic analysis of available HCP and FCP family members revealed complex patterns of inheritance in some families. Our findings confirm that functionally deficient TRPV6 variants represent an important contributor to CP. Importantly, functionally deficient TRPV6 variants account for a significant proportion of cases of HCP/FCP.

Severe acute ischemic colitis: What is the place of endoscopy in the management strategy?

Background and study aims Ischemic colitis (IC) is potentially lethal. Clinical and biology information and results of computed tomography (CT) scan and/or colonoscopy are used to assess its severity. However, decision-making about therapy remains a challenge. Patients and methods This was a retrospective, single-center study between 2006 and 2015. Patients with severe IC who underwent endoscopic evaluation were included. The aims were to determine outcomes depending on endoscopic findings and assess the role of endoscopy in the management. Results A total of 71 patients were included (men = 48 (68%), mean age = 71 ±â€Š13 years). There was hemodynamic instability in 29 patients (41 %) and severity signs on CT scan in 18 (38 %). Twenty-nine patients (41 %) underwent surgery and 24 (34 %) died. The endoscopic grades were: 15 grade 1 (21 %), 32 grade 2 (45 %), and 24 grade 3 (34%). Regarding patients with grade 3 IC, 55 % had hemodynamic instability, 58 % had severity signs on CT scan, 68 % underwent surgery, and 55 % died. The decision to perform surgery was based on hemodynamic status in 62 % of cases, CT scan data in 14 %, endoscopic findings in 10 %, and other in 14 %. Colectomy was more frequent in patients with grade 3 IC ( P  < 0.05). A mismatch between mucosal aspect (necrosis) and serous (normal) was observed in 13 patients (46 %). Risk factors for colectomy in univariate analysis were aortic aneurysm surgery, hemodynamic instability, no colic enhancement on CT scan, and endoscopic grade 3. Risk factors for mortality in multivariate analysis were hemodynamic instability, colectomy, and Charlson score > 5 ( P  < 0.05). Conclusions This study suggests a low impact of endoscopy on surgical decision making. Hemodynamic instability was the first indication for colectomy. A discrepancy between endoscopic mucosal (necrosis) and surgical serous (normal) aspects was frequently noted.

Endoscopic Dilation of Post-Sleeve Gastrectomy Stenosis: Long-Term Efficacy and Safety Results.

INTRODUCTION: Post-sleeve gastrectomy (SG) stenoses occur in about 5% of cases. Hydrostatic dilation (HD) and pneumatic dilation (PD) have been proposed as treatments, but efficacy data remain scarce. Objective is to describe long-term efficacy and safety of HD and PD. METHODS: This retrospective study in a referral endoscopy center included patients with symptomatic post-SG stenosis treated with endoscopic balloon dilation (EBD). Stenosis was defined as "organic" if luminal narrowing was evident, "functional" for a deformation, or "combined." Endoscopic treatment consisted of ≥ 1 HD (15-20 mm) and/or ≥ 1 PD (30-35 mm). Initial success was defined as improvement of stenosis-related symptoms at 1 month and long-term success as persistence of improvement at last follow-up. RESULTS: Forty-four patients (73% women; mean age 45.5 ± 11 years; mean follow-up 26 ± 23 months) underwent EBD between 2013 and 2019. HD and PD were used in 15 (34%) and 29 (66%) patients, respectively, (mean dilation number: 1.8 ± 1.1). Post-SG stenoses were considered organic in 10 (23%), functional in 21 (48%), and combined in 13 (29%) patients. Initial success was achieved in 42 (96%) patients, while 35 (80%) patients had no symptom recurrence at last follow-up. Perforation occurred in one patient. HD was more frequently used in organic stenoses (8/10), while PD in functional and combined stenoses (18/21 and 9/13, respectively; p < 0.001). Rates of success did not differ by type of stenosis. CONCLUSION: Endoscopic dilation is an effective treatment for post-SG stenoses, providing long-term symptom relief. PD should be preferred in cases of functional stenoses, and HD used for organic stenoses.

What Should Guide the Performance of Venous Resection During Pancreaticoduodenectomy for Pancreatic Ductal Adenocarcinoma with Venous Contact?

Complete surgical resection, most often associated with perioperative chemotherapy, is the only way to offer a chance of cure for patients with pancreatic cancer. One of the most important factors in determining survival outcome that can be influenced by the surgeon is the R0 resection. However, the proximity of mesenteric vessels in cephalic pancreatic tumors, especially the mesenterico-portal venous axis, results in an increased risk of vein involvement and/or the presence of malignant cells in the venous bed margin. A concomitant venous resection can be performed to decrease the risk of a positive margin. Given the additional technical difficulty that this implies, many surgeons seek a path between the tumor and the vein, hoping for the absence of tumor infiltration into the perivascular tissue on pathologic analysis, particularly in cases with administration of neoadjuvant therapy. The definition of optimal surgical margin remains a subject of debate, but at least 1 mm is an independent predictor of survival after pancreatic cancer surgical resection. Although preoperative radiologic assessment is essential for accurate planning of a pancreatic resection, intraoperative decision-making with regard to resection of the mesenterico-portal vein in tumors with a venous contact remains unclear and variable. Although venous histologic involvement and perivascular infiltration are not accurately predictable preoperatively, clinicians must examine the existing criteria and normograms to guide their surgical management according to the integration of new imaging techniques, preoperative chemotherapy use, tumor biology and molecular histopathology, and surgical techniques.

Endoscopic management of anastomotic leak after esophageal or gastric resection for malignancy: a multicenter experience.

BACKGROUND: Most anastomotic leaks after surgical resection for esophageal or esophagogastric junction malignancies are treated endoscopically with esophageal stents. Internal drainage by double pigtail stents has been used for the endoscopic management of leaks following bariatric surgery, and recently introduced for anastomotic leaks after resections for malignancies. Our aim was to assess the overall efficacy of the endoscopic treatment for anastomotic leaks after esophageal or gastric resection for malignancies. METHODS: We conducted a multicenter retrospective study in four digestive endoscopy tertiary referral centers in France. We included consecutive patients managed endoscopically for anastomotic leak following esophagectomy or gastrectomy for malignancies between January 2016 and December 2018. The primary outcome was the efficacy of the endoscopic management on leak closure. RESULTS: Sixty-eight patients were included, among which 46 men and 22 women, with a mean ± SD age of 61 ± 11 years. Forty-four percent had an Ivor Lewis procedure, 16% a tri-incisional esophagectomy, and 40% a total gastrectomy. The median time between surgery and the diagnosis of leak was 9 (6-13) days. Endoscopic treatment was successful in 90% of the patients. The efficacy of internal drainage and esophageal stents was 95% and 77%, respectively (p = 0.06). The mortality rate was 3%. The only predictive factor of successful endoscopic treatment was the initial use of internal drainage (p = 0.002). CONCLUSION: Endoscopic management of early postoperative leak is successful in 90% of patients, preventing highly morbid surgical revisions. Internal endoscopic drainage should be considered as the first-line endoscopic treatment of anastomotic fistulas whenever technically feasible.

Safety of different electrocautery modes for endoscopic sphincterotomy: a Bayesian network meta-analysis.

BACKGROUND AND AIMS: Post-endoscopic retrograde cholangiopancreatography acute pancreatitis (PAP) and post-sphincterotomy hemorrhage are known adverse events of post-endoscopic retrograde cholangiopancreatography. Various electrosurgical currents can be used for endoscopic sphincterotomy. The extent to which this influences adverse events remains unclear. We assessed the comparative safety of different electrosurgical currents, through a Bayesian network meta-analysis of published studies merging direct and indirect comparison of trials. METHODS: We performed a Bayesian random-effects network meta-analysis of randomized controlled trials that compared the safety of different electrocautery modes for endoscopic sphincterotomy. RESULTS: Nine studies comparing four electrocautery modes (blended cut, pure cut, endocut, and pure cut followed by blended cut) with a combined enrollment of 1615 patients were included. The pooled results of the network meta-analysis did not show a significant difference in preventing post-sphincterotomy pancreatitis when comparing electrocautery modes. However, pure cut was associated with a statistically significant increased risk of bleeding compared with endocut [relative risk = 4.30; 95% confidence interval (1.53-12.87)]. On the other hand, the pooled results of the network meta-analysis showed no significant difference in prevention of bleeding when comparing blended cut versus endocut, pure cut followed by blended cut versus endocut, pure cut followed by blended cut versus blended cut, pure cut versus blended cut, and pure cut versus pure cut followed by blended cut. The results of rank probability found that endocut was most likely to be ranked the best. CONCLUSION: No electrocautery mode was superior to another with regard to preventing PAP. Endocut was superior with respect to preventing bleeding. Therefore, we suggest performing endoscopic sphincterotomy with endocut.