A Randomized Controlled Phase 2 Dose-Finding Trial to Evaluate the Efficacy and Safety of Camostat in the Treatment of Painful Chronic Pancreatitis: The TACTIC Study.

BACKGROUND & AIMS: Chronic pancreatitis (CP) causes an abdominal pain syndrome associated with poor quality of life. We conducted a clinical trial to further investigate the efficacy and safety of camostat, an oral serine protease inhibitor that has been used to alleviate pain in CP. METHODS: This was a double-blind randomized controlled trial that enrolled adults with CP with a baseline average daily worst pain score ≥4 on a numeric rating system. Participants were randomized (1:1:1:1) to receive camostat at 100, 200, or 300 mg 3 times daily or placebo. The primary end point was a 4-week change from baseline in the mean daily worst pain intensity score (0-10 on a numeric rating system) using a mixed model repeated measure analysis. Secondary end points included changes in alternate pain end points, quality of life, and safety. RESULTS: A total of 264 participants with CP were randomized. Changes in pain from baseline were similar between the camostat groups and placebo, with differences of least squares means of -0.11 (95% CI, -0.90 to 0.68), -0.04 (95% CI, -0.85 to 0.78), and -0.11 (95% CI, -0.94 to 0.73) for the 100 mg, 200 mg, and 300 mg groups, respectively. Multiple subgroup analyses were similar for the primary end point, and no differences were observed in any of the secondary end points. Treatment-emergent adverse events attributed to the study drug were identified in 42 participants (16.0%). CONCLUSION: We were not able to reject the null hypothesis of no difference in improvements in pain or quality of life outcomes in participants with painful CP who received camostat compared with placebo. Studies are needed to further define mechanisms of pain in CP to guide future clinical trials, including minimizing placebo responses and selecting targeted therapies. CLINICALTRIALS: gov, Number: NCT02693093.

The timing of recurrence after endoscopic papillectomy.

BACKGROUND: Endoscopic papillectomy (EP) offers a safe and effective method for resection of ampullary adenomas. Data regarding the long-term resolution of adenoma following EP are limited. The aim of this study therefore was to examine the timing of recurrence after EP of ampullary adenomas. METHODS: This was a single-center retrospective study including patients who received EP for ampullary adenomas from 8/2000 to 1/2018. Patients with confirmed complete eradication of adenoma were included in the recurrence analysis with recurrence defined as finding adenomatous histology after 1 negative surveillance endoscopy. Kaplan-Meier estimates were calculated to determine recurrence rates. RESULTS: Of the 165 patients who underwent EP, 136 patients (mean age 61.9, 51.5% female) had adenomatous histology with a mean lesion size of 21.2 mm. A total of 124 (91.2%) achieved complete eradication with a follow-up of 345.8 person-years. Recurrence occurred in 20 (16.1%) patients at a mean of 3.2 (± 3) years (range 0.5-9.75 years) for a recurrence rate of 5.8 (95% CI 3.6-8.8) per 100 person-years. Nine (45%) recurrences occurred after the 1st 2 years of surveillance. Recurrence rate did not differ by baseline pathology [low-grade dysplasia: 5.2 (95% CI 3.0-9.0), high-grade dysplasia: 6.9 (95% CI 2.3-15.5), adenocarcinoma: 7.7 (95% CI 0.9-25.1)]. CONCLUSION: Recurrence remains a significant concern after EP. Given the timing of recurrence, long surveillance periods may be necessary. Larger multicenter studies are needed, however, to determine appropriate surveillance intervals.

Endoscopic Ultrasound-guided Transluminal Gallbladder Drainage in Patients With Acute Cholecystitis: A Prospective Multicenter Trial.

OBJECTIVE: To evaluate the safety and efficacy of endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) using a lumen-apposing metal stent (LAMS). BACKGROUND: For patients with acute cholecystitis who are poor surgical candidates, EUS-GBD using a LAMS is an important treatment alternative to percutaneous gallbladder drainage. METHODS: We conducted a regulatory-compliant, prospective multicenter trial at 7 tertiary referral centers in the United States of America and Belgium. Thirty consecutive patients with mild or moderate acute cholecystitis who were not candidates for cholecystectomy were enrolled between September 2019 and August 2021. Eligible patients had a LAMS placed transmurally with 30 to 60-day indwell if removal was clinically indicated, and 30-day follow-up post-LAMS removal. Endpoints included days until acute cholecystitis resolution, reintervention rate, acute cholecystitis recurrence rate, and procedure-related adverse events (AEs). RESULTS: Technical success was 93.3% (28/30) for LAMS placement and 100% for LAMS removal in 19 patients for whom removal was attempted. Five (16.7%) patients required reintervention. Mean time to acute cholecystitis resolution was 1.6±1.5 days. Acute cholecystitis symptoms recurred in 10.0% (3/30) after LAMS removal. Five (16.7%) patients died from unrelated causes. Procedure-related AEs were reported to the FDA in 30.0% (9/30) of patients, including one fatal event 21 days after LAMS removal; however, no AEs were causally related to the LAMS. CONCLUSIONS: For selected patients with acute cholecystitis who are at elevated surgical risk, EUS-GBD with LAMS is an alternative to percutaneous gallbladder drainage. It has high technical and clinical success, with low recurrence and an acceptable AE rate. Clinicaltrials.gov, Number: NCT03767881.

Combined Drainage and Protocolized Necrosectomy Through a Coaxial Lumen-apposing Metal Stent for Pancreatic Walled-off Necrosis: A Prospective Multicenter Trial.

OBJECTIVE: We evaluated a protocolized endoscopic necrosectomy approach with a lumen-apposing metal stent (LAMS) in patients with large symptomatic walled-off pancreatic necrosis (WON) comprising significant necrotic content, with or without infection. SUMMARY BACKGROUND DATA: Randomized trials have shown similar efficacy of endoscopic treatment compared with surgery for infected WON. DESIGN: We conducted a regulatory, prospective, multicenter single-arm clinical trial examining the efficacy and safety of endoscopic ultrasound -guided LAMS with protocolized necrosectomy to treat symptomatic WON ≥6 cm in diameter with >30% solid necrosis. After LAMS placement, protocolized WON assessment was conducted and endoscopic necrosectomy was performed for insufficient WON size reduction and persistent symptoms. Patients with radiographic WON resolution to ≤ 3 cm and/or 60-day LAMS indwell had LAMS removal, then 6-month follow-up. Primary endpoints were probability of radiographic resolution by 60 days and procedure-related serious adverse events. RESULTS: Forty consecutive patients were enrolled September 2018 to March 2020, of whom 27 (67.5%) were inpatients and 19 (47.5%) had clinical evidence of infection at their index procedure. Mean WON size was 15.0 ± 5.6 cm with mean 53.2% ± 16.7% solid necrosis. Radiographic WON resolution was seen in 97.5% (95% CI, 86.8%, 99.9%) by 60 days, without recurrence in 34 patients with 6-month follow-up data. Mean time to radiographic WON resolution was 34.1 ± 16.8 days. Serious adverse events occurred in 3 patients (7.5%), including sepsis, vancomycin-resistant enterococcal bacteremia and shock, and upper gastrointestinal bleeding. There were no procedure-related deaths. CONCLUSIONS: Endoscopic ultrasound-guided drainage with protocolized endoscopic necrosectomy to treat large symptomatic or infected walled-off necrotic pancreatic collections was highly effective and safe. Clinicaltrials.-gov no: NCT03525808.

Soft self-expandable metal stent to treat painful pancreatic duct strictures secondary to chronic pancreatitis: a prospective multicenter trial.

BACKGROUND AND AIMS: Fully covered self-expandable metal stents (FCSEMSs) may offer a treatment option for pain associated with a dilated pancreatic duct (PD) in chronic pancreatitis (CP), but optimal patient selection and FCSEMS design, efficacy, and safety remain uncertain. We studied an investigational pancreatic FCSEMS for treatment of CP-associated pain. METHODS: Patients with painful CP, a dominant distal PD stricture, and PD dilation upstream were enrolled in a prospective, multicenter, single-arm trial studying 6-month indwell of a 4- to 6-cm-long soft pancreatic FCSEMS. Primary efficacy and safety endpoints were pain reduction 6 months after FCSEMS indwell (performance goal ≥53%) and PD stenting-related serious adverse events (SAEs), respectively (performance goal <32%). The primary efficacy endpoint was assessed in patients with sufficiently severe and frequent pain at FCSEMS placement as a first stent or in exchange of a plastic stent. RESULTS: Among 67 patients (mean age, 52.7 ± 12.5 years; mean time since CP diagnosis, 6.4 ± 6.4 years), 34 (50.7%) had plastic stent placement within 90 days of FCSEMS placement, and 46 patients were eligible for the primary efficacy endpoint analysis. Technical success was 97.0% (65/67). The observed primary efficacy (26.1%, 12/46) and safety endpoints (31.3%, 21/67) failed to meet the a priori study hypotheses. Study stent migration occurred in 47.7% of patients (31/65). CONCLUSIONS: Six-month treatment with an FCSEMS did not lead to an expected degree of pain reduction, and migrations and SAEs were common. Further study is needed to clarify optimal decompressive strategy, FCSEMS design, and patient selection. (Clinical trial registration number: NCT02802020.).

Per-oral pancreatoscopy-guided lithotripsy vs. extracorporeal shock wave lithotripsy for treating refractory main pancreatic duct stones in chronic pancreatitis: Protocol for an open-label multi-center randomized clinical trial.

BACKGROUNDS/OBJECTIVES: Patients with chronic pancreatitis may develop pancreatic duct stones that can obstruct outflow leading to ductal hypertension and pain. Both endoscopic retrograde pancreatography (ERP) with per-oral pancreatoscopy (POP) and intraductal lithotripsy and extracorporeal shock wave lithotripsy (ESWL) are feasible options to attempt ductal stone clearance. This study aims to compare POP-guided lithotripsy with ESWL in the management of refractory symptomatic main pancreatic duct stones. METHODS: This is an open-label, multi-center, parallel, randomized clinical trial. Patients with chronic pancreatitis and main pancreatic duct stones ≥5 mm who fail standard ERP methods for stone removal will be eligible for this study. In total, 150 subjects will be randomized 1:1 to either ESWL or POP. A maximum of 4 sessions of either ESWL or POP will be allowed in each arm, with crossover permitted thereafter. The primary outcome is complete stone clearance and secondary outcomes include quality of life, pain scores, number of interventions, and daily opiate requirements. CONCLUSIONS: This study aims to answer the question of which lithotripsy method is superior in removing refractory pancreatic duct stones while addressing the effects of lithotripsy on quality of life and pain in patients with chronic calcific pancreatitis (ClinicalTrials.gov NCT04115826).

Choledochoduodenostomy is associated with fewer post-transplant biliary complications compared to Roux-en-Y in primary sclerosing cholangitis patients.

BACKGROUND: For primary sclerosing cholangitis (PSC) patients undergoing liver transplantation (LT), a consensus regarding biliary reconstruction remains unresolved. Choledochoduodenostomy (CDD) represents an alternative to Roux-en-Y (RY) and duct-to-duct. We compared long-term post-transplant outcomes between CDD and RY. METHODS: This was a retrospective review of patients transplanted for PSC who received CDD or RY, with minimum 12-months follow-up. The primary outcome was need for biliary intervention, with either percutaneous transhepatic cholangiography (PTC) or endoscopic retrograde cholangiopancreatography (ERCP). Secondary outcomes included biliary stricture(s) and cholangitis admission(s). RESULTS: Ninety-three patients were transplanted between August 2004 and October 2019 (34 living donor [LDLT] and 59 deceased donor [DDLT]; 40 RY, 53 CDD). Need for either ERCP or PTC was similar (45.0% RY vs. 32.1% CDD, P = .203), though RY exhibited more anastomotic strictures (AS) (35.0% RY vs. 11.3% CDD, P = .006), which was also observed in LDLT subanalyses (50.0% LDLT/RY vs. 10.0% LDLT/CDD; P = .036). Cholangitis admissions were more frequent in RY versus CDD (37.5% vs. 15.1%, P = .013). CONCLUSIONS: CDD does not impart greater risk of biliary complications, and RY may have an incremental effect combined with LDLT status for predisposing to AS. CDD maintains standard endoscopic access without additional risk of biliary complications, thus should be considered when anatomically feasible.

Clinical Outcomes and Patency after Transjugular Intrahepatic Portosystemic Shunt Reduction for Overshunting Adverse Events.

PURPOSE: To assess clinical outcomes and patency after transjugular intrahepatic portosystemic shunt (TIPS) reduction for overshunting adverse events. MATERIALS AND METHODS: This multicenter, retrospective observational study included 33 patients (male-to-female ratio, 20:13; mean age, 59 years; mean Model for End-Stage Liver Disease [MELD] score, 15) who underwent TIPS reduction between 2007 and 2020. Procedure indications included medically refractory hepatic encephalopathy (HE) (85%), post-TIPS hepatic insufficiency (HI) (12%), and heart failure (3%). The measured outcomes included improvement in HE (classified using the West Haven system) and HI, patency of reduced TIPS, and transplant-free survival (TFS). RESULTS: TIPS reductions were successfully performed using parallel stent (94%) or other (6%) techniques at a median of 120 days after TIPS creation (HE, median, 164 days; HI, median, 5 days). The portosystemic pressure gradient increased from a mean of 10 to 17 mm Hg (P < .001). The overall HE rate after TIPS reduction was 54%; HE was persistent, improved, and resolved in 21%, 32%, and 46% cases, respectively. In patients with HI, the MELD score increased from a mean of 22 before TIPS to 34 after TIPS (P = .061), but without improvement (0%) in HI after TIPS reduction (mean MELD score, 30; P = .266). Recurrent ascites occurred in 14% of the patients. The median shunt patency was 961 days (95% confidence interval, 476-1,447). The 30-day, 6-month, 1-year, and 3-year shunt patency rates were 92%, 81%, 74%, and 37%, respectively. The median TFS was not reached. The 30-day, 6-month, 1-year, and 3-year survival rates were 97%, 90%, 81%, and 60%, respectively. CONCLUSIONS: Although TIPS reduction may be an effective and durable approach to treat post-TIPS medically refractory HE, shunt reduction may not achieve meaningful benefit for HI.

Digital Cholangioscopic Interpretation: When North Meets the South.

BACKGROUND: Digital single-operator cholangioscopy (DSOC) (SpyGlass DS™, Boston Scientific, MA, USA) allows for high-definition imaging of the biliary tree. The superior visualization has led to the development of two different sets of criteria to evaluate and classify indeterminate biliary strictures: the Monaco criteria and the criteria in Carlos Robles-Medranda's publication (CRM). Our objective was to assess the interrater agreement (IA) of DSOC interpretation for indeterminate biliary strictures using the two newly published criteria. METHODS: Forty de-identified DSOC video recordings were sent to 15 interventional endoscopists with experience in cholangioscopy. They were asked to score the videos based on the presence of Monaco Classification criteria: stricture, lesion, mucosal changes, papillary projections, ulceration, white linear bands or rings, and vessels. Next, they scored the videos using CRM criteria: villous pattern, polypoid pattern, inflammatory pattern, flat pattern, ulcerate pattern and honeycomb pattern. The endoscopists then diagnosed the recordings as neoplastic or non-neoplastic based on the criteria. Intraclass correlation (ICC) analysis was done to evaluate interrater agreement for both criteria set and final diagnosis. RESULTS: Recordings of 26 malignant lesions and 14 benign lesions were scored. The IA using both the Monaco criteria and CRM criteria ranged from poor to excellent (range 0.1-0.76) and (range 0.1-0.62), respectively. Within the Monaco criteria, IA was excellent for lesion (0.75) and fingerlike papillary projections (0.74); good for tortuous vessels (0.7), mucosal features (0.62), uniform papillary projections (0.53), and ulceration (0.58); and fair for white linear bands (0.4). Within the CRM criteria, the IA was good for villous pattern (0.62), flat pattern (0.62), and honeycomb pattern; fair for ulcerated pattern (0.56), polypoid pattern (0.52) and inflammatory pattern (0.54). The diagnostic IA using Monaco criteria was good (0.65), while the diagnostic IA using CRM was fair (0.58). The overall diagnostic accuracy using the Monaco classification was 61% and CRM criteria were 57%. CONCLUSION: The IOA and accuracy rate of DSOC using visual criteria from both Monaco Criteria and CRM are similar. However, some criteria from both sets suffer from poor IA, thus affecting the overall diagnostic accuracy. More formal training and refinements in visual criteria with additional validation are needed to improve diagnostic accuracy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02166099.

Direct Endoscopic Necrosectomy With and Without Hydrogen Peroxide for Walled-off Pancreatic Necrosis: A Multicenter Comparative Study.

INTRODUCTION: Endoscopic necrosectomy has emerged as the preferred treatment modality for walled-off pancreatic necrosis. This study was designed to evaluate the safety and efficacy of direct endoscopic necrosectomy with and without hydrogen peroxide (H2O2) lavage. METHODS: Retrospective chart reviews were performed for all patients undergoing endoscopic transmural management of walled-off pancreatic necrosis at 9 major medical centers from November 2011 to August 2018. Clinical success was defined as the resolution of the collection by imaging within 6 months, without requiring non-endoscopic procedures or surgery. RESULTS: Of 293 patients, 204 met the inclusion criteria. Technical and clinical success rates were 100% (204/204) and 81% (166/189), respectively. For patients, 122 (59.8%) patients had at least one H2O2 necrosectomy (H2O2 group) and 82 (40.2%) patients had standard endoscopic necrosectomy. Clinical success was higher in the H2O2 group: 106/113 (93.8%) vs 60/76 (78.9%), P = 0.002. On a multivariate analysis, the use of H2O2 was associated with higher clinical success rate (odds ratio 3.30, P = 0.033) and earlier resolution (odds ratio 2.27, P < 0.001). During a mean follow-up of 274 days, 27 complications occurred. Comparing procedures performed with and without H2O2 (n = 250 vs 183), there was no difference in post-procedure bleeding (7 vs 9, P = 0.25), perforation (2 vs 3, P = 0.66), infection (1 vs 2, P = 0.58), or overall complication rate (n = 13 [5.2%] vs 14 [7.7%], P = 0.30). DISCUSSION: H2O2-assisted endoscopic necrosectomy had a higher clinical success rate and a shorter time to resolution with equivalent complication rates relative to standard necrosectomy.See the visual abstract at http://links.lww.com/AJG/B714.(Equation is included in full-text article.).

Probe-based confocal laser endomicroscopy in the evaluation of dominant strictures in patients with primary sclerosing cholangitis: results of a U.S. multicenter prospective trial.

BACKGROUND AND AIMS: Patients with primary sclerosing cholangitis (PSC) and dominant biliary strictures carry increased risk for the development of cholangiocarcinoma. Although ERCP-based techniques including brush cytology and intraductal biopsy sampling represent first-line tissue sampling methods for dominant strictures, sensitivity is low. Probe-based confocal laser endomicroscopy (pCLE) offers microscopic-level imaging of subepithelial biliary mucosa. Because data regarding the use of pCLE in PSC are limited, we aimed to investigate its diagnostic performance in dominant strictures. METHODS: This was a multicenter prospective study involving PSC patients with dominant strictures. ERCP with pCLE was performed with use of the Miami classification (2+ criteria for malignant diagnosis) and Paris classification. Final malignant diagnoses required histopathologic confirmation, and benign diagnoses required a minimum of 1 year of follow-up without development of cancer. RESULTS: Fifty-nine patients (mean age, 49 years; 59% men) with 63 strictures were included in the study. Stricture locations included the common bile duct (31.7%), bifurcation (22.2%), and common hepatic duct (19%). Seven patients (11.9%) were found to have cholangiocarcinoma. The sensitivity and specificity of pCLE was 85.7% (95% confidence interval [CI], 42.1-99.6) and 73.1% (95% CI, 58.9-84.4), respectively. Within specific stricture locations, the highest sensitivity was seen at the bifurcation (100%; 95% CI, 2.5-100) and the right hepatic duct (100%; 95% CI, 29.2-100). The lowest sensitivities were seen at the common bile duct (25%; 95% CI, 5.5-57.2) and the left hepatic duct (28.6%; 95% CI, 3.7-70.9). CONCLUSIONS: In this prospective multicenter study, pCLE had a high sensitivity in detecting cholangiocarcinoma, but technical aspects of the probe may limit evaluation in the common bile duct and left hepatic duct. Further evaluation is needed to elucidate the role of pCLE in the algorithm of excluding neoplasia in biliary strictures associated with PSC. (Clinical trial registration number: NCT02736708.).

Combination of ERCP-Based Modalities Increases Diagnostic Yield for Biliary Strictures.

BACKGROUND: Biliary stricture evaluation with brush cytology and intraductal forceps biopsy carries a low sensitivity, but the combination of newer modalities may improve sensitivity. AIM: To determine whether the addition of advanced modalities increases diagnostic yield of ERCP-based sampling. METHODS: This single-center retrospective study evaluates patients with biliary strictures sampled using brush cytology. Operating characteristics were calculated for individual and combinations of modalities including cholangioscopy, fluoroscopy- and cholangioscopy-directed intraductal biopsy, fluorescence in situ hybridization (FISH), and confocal laser endomicroscopy. Analyses under Standard Criteria (SC) included malignant results as "positive" and Expanded Criteria (EC) included "suspicious" and "high-grade dysplasia" results as "positive." RESULTS: A total of 614 patients were included, and 354 (57.8%) received brush cytology alone, which had a sensitivity of 38.5% (SC) to 40.3% (EC) and a specificity of 97.8% (EC) to 99.3% (SC). Combining brush cytology with fluoroscopy-guided biopsy (n = 259, 42.2%) had a sensitivity of 62.5% (SC) to 67.9% (EC) and specificity of 90.2% (EC) to 96.7% (SC). Adding FISH to brush cytology had a sensitivity of 84.2% (SC) to 87.5% (EC) and specificity of 54.1% (SC and EC), while cholangioscopy visualization addition resulted in a sensitivity of 80.4% (SC) to 92.2% (EC) and specificity of 67.3% (EC) to 89.1% (SC). There were no significant differences in sensitivity and specificity using SC and EC. CONCLUSIONS: Brush cytology has a low sensitivity, but the addition of other modalities increases sensitivity. There was no difference in specificity between the SC and the EC, supporting the inclusion of "suspicious" impressions with malignant results at our center.

Time Given to Trainees to Attempt Cannulation During Endoscopic Retrograde Cholangiopancreatography Varies by Training Program and Is Not Associated With Competence.

Advanced endoscopy training programs (AETPs) were developed as a result of the lack of comprehensive endoscopic retrograde cholangiopancreatography (ERCP) training during gastroenterology fellowships. There is no standardized curriculum for AETPs and the influence of program- and trainer-associated factors on trainee competence in ERCP has not been investigated adequately. In prior work, we showed that advanced endoscopy trainees (AETs) achieve ERCP competence at varying rates.1,2 The aims of this study were to measure the variability in time given to AETs to attempt cannulation between AETPs and throughout the 1-year training period, and to determine the association between AET cannulation time and AET competence at the end of training.

Endoscopic radiofrequency ablation plus a novel oral 5-fluorouracil compound versus radiofrequency ablation alone for unresectable extrahepatic cholangiocarcinoma.

BACKGROUND AND AIMS: Endoscopic radiofrequency ablation (RFA) is a new ablative treatment for unresectable extrahepatic cholangiocarcinoma (EHCC). A novel 5-fluorouracil compound, S-1 (Taiho Pharmaceutical Co, Ltd, Tokushima Plant. Japan), has been widely used as a key drug with first-line or second-line chemotherapy for the treatment of advanced cholangiocarcinoma. The aim of this study was to evaluate the clinical efficacy and safety of endoscopic RFA combined with S-1 for the treatment of unresectable locally advanced EHCC. METHODS: Patients with unresectable EHCC were prospectively randomized to 1 of 2 groups: the RFA + S-1 group and the RFA group. Median overall survival (OS), stent patency time, Karnofsky performance status (KPS) score, and adverse events rate were analyzed. RESULTS: The median OS was longer in the RFA + S-1 group (n = 37) than that in the RFA group (n = 38) (16.0 months [95% confidence interval, 13.1-19.0] vs 11.0 months [95% confidence interval, 9.7-12.3]; P < .001). Stent patency time was significantly longer in the RFA + S-1 group than that in the RFA group (6.6 ± 1.5 vs 5.6 ± .1 months, P = .014). KPS scores at postoperative month 9 (51.6 ± 17.0 vs 40.4 ± 16.4, P = .012) and month 12 (35.2 ± 18.3 vs 23.9 ± 11.4, P = .014) were all higher in the RFA + S-1 group than those in the RFA group (P < .05). The incidence of ERCP-related adverse events was not significantly different between RFA+S-1 and RFA groups (8.1% vs 10.5%, P > .05). CONCLUSIONS: For the treatment of locally advanced EHCC, endoscopic RFA combined with S-1 is associated with longer survival and stent patency and improved functional status than RFA alone. (Clinical trial registration number: NCT02592538.).

Endoscopic Ultrasound Placement of Preloaded Fiducial Markers Shortens Procedure Time Compared to Back-Loaded Markers.

BACKGROUND & AIMS: Fiducial markers are inert radiopaque gold or carbon markers implanted in or near pancreatic tumor to demarcate areas for image-guided radiation therapy. Endoscopic ultrasound (EUS) pre-loaded fiducial needles (PLNs) have been developed to circumvent technical issues associated with traditional back-loaded fiducials (BLNs). We performed a randomized controlled trial to compare procedure times in patients with pancreatic adenocarcinoma undergoing EUS-guided placement of BLNs vs PLNs. METHODS: In a prospective study, 44 patients with pancreatic adenocarcinoma referred for fiducial marker placement at 2 tertiary care centers were assigned to groups that received PLNs (n = 22) or BLNs (n = 22); each group had the same proportion of patients with tumors of different locations (head or neck vs body or tail).The procedure was standardized among all endoscopists and placement of a minimum of 3 markers inside the tumor was defined as technical success. The times for procedure and fiducial placement were recorded, total number of fiducial markers used documented, and grade of procedure difficulty ranked by passing the needle or deploying the fiducials. Other recorded variables included tumor characteristics, fluoroscopy use, and the number of fiducials clearly seen by EUS and fluoroscopy. The primary aim was to compare the duration of EUS-guided fiducial insertion of BLNs vs PLNs. RESULTS: The median placement time was significantly shorter in the PLN group (9 min) than the BLN group (16 min) (P < .001). However, the 44% reduction in time did not reach pre-specified levels (≥60%). Similar results were found after stratifying by tumor location. Deployment of BLNs was easier than deployment of PLNs (P = .03). There was no significant difference between groups in technical success, number of fiducials placed, EUS or fluoroscopic visualization, or adverse events. During simulation computed tomography and image-guided radiation therapy, there was no difference between groups in visualization of fiducials, migration rate, or accuracy of placement. CONCLUSIONS: In a randomized controlled trial of 44 patients with pancreatic adenocarcinoma, we found EUS-guided placement of PLNs to require less time and produce similar results compared with BLNs. Further refinements in PLN delivery system are needed to increase the ease of deployment. Clinicaltrials.gov no: NCT02332863.

Pancreatoscopy-guided laser dissection and ablation for treatment of benign and neoplastic pancreatic disorders: an initial report (with videos).

BACKGROUND AND AIMS: Per-oral pancreatoscopy (POP) permits direct evaluation of the pancreatic duct for the visualization and sampling of neoplastic lesions and treatment of pancreatic duct stones by using intraductal lithotripsy techniques. Pancreatic laser endotherapy of mucosa has been described in animal models for tumor ablation, but human experience is lacking. We describe 3 unique and challenging clinical situations that benefited from pancreatic laser dissection and ablation. CASE DESCRIPTION: Case 1 was a 75-year-old woman with presumed divisum-associated chronic pancreatitis who had recurrent acute pancreatitis despite minor papilla sphincterotomy and therapeutic stent placement. POP showed a side-branch intraductal papillary mucinous neoplasm within the neck of the pancreas. POP-guided holmium laser ablation of neoplastic tissue was performed, followed by pancreatic stent placement every 6 months, with no further hospitalizations at 20 months of follow-up. Case 2 was a 69-year-old woman with divisum-associated chronic calcific pancreatitis and recalcitrant mid-body stenosis. Previous attempts at balloon dilation and stent placement failed to resolve the stenosis. POP-guided holmium laser dissection of the stenosis was pursued, with immediate radiographic resolution. Case 3 was a 65-year-old woman with chronic calcific pancreatitis and a large stone burden who underwent POP-guided electrohydraulic lithotripsy and partial stone extraction followed by stent placement. Unfortunately, the stent fractured during the subsequent removal attempt because the fragment was impacted in the pancreatic body. POP-guided laser dissection and lithotripsy were used to debulk dense fibrous tissue and stones surrounding the stent fragment, respectively, followed by removal. CONCLUSIONS: Pancreatoscopy-guided laser endotherapy is a novel and potentially useful technique to manage difficult benign and neoplastic pancreatic disorders.

Treating Biliary-Enteric Anastomotic Strictures with Enteroscopy-ERCP Requires Fewer Procedures than Percutaneous Transhepatic Biliary Drains.

BACKGROUND: Biliary-enteric anastomotic strictures (AS) in long-limb surgical biliary bypass (LLBB) require percutaneous transhepatic biliary drains (PTBD), enteroscopy-assisted ERCP (E-ERCP), or surgical revision. AIM: To compare E-ERCP and PTBD for AS treatment. METHODS: E-ERCP stricturoplasty included dilation, cautery, and stent; PTBD included balloon dilation and serial drain upsizing events. RESULTS: From May 2008 to October 2015, 71 patients (37 M, median age 52) had E-ERCP (n = 45) or PTBD (n = 26) for AS in Roux-en-Y hepaticojejunostomy: liver transplant (n = 28), cholecystectomy injury revision (n = 21), other (n = 13) or Whipple's resection (n = 9). Median follow-up is 11 months (range 1-56) in 67 (94%) patients. Technical success, clinical improvement, and adverse events between E-ERCP and PTBD were similar (76% vs. 77%, p = 0.89; 82% vs. 85%, p = 0.80, and 6% vs. 5%, p = 0.60, respectively). However, E-ERCP had fewer post-procedural hospitalization days (0.2 ± 0.65 vs. 4.5±10, p = 0.0001), mean procedures (4.4 ± 6.3 vs. 9.5 ± 8, p = 0.006), and median months of treatment to resolve AS (1, range 1-22 vs. 7, range 3-23; p = 0.003). Two patients in PTBD group required surgery. CONCLUSIONS: (1) Technical success and clinical improvement are seen in the majority of LLBB patients with biliary-enteric AS undergoing E-ERCP or PTBD. (2) E-ERCP is associated with fewer procedures, post-procedure hospitalization days, and months to resolve AS. When expertise is available, E-ERCP to identify and treat AS should be considered as an alternative to PTBD.

Increased Incidence of Pseudoaneurysm Bleeding With Lumen-Apposing Metal Stents Compared to Double-Pigtail Plastic Stents in Patients With Peripancreatic Fluid Collections.

BACKGROUND & AIMS: There have been few studies that compared the effects of lumen-apposing metal stents (LAMS) and double-pigtail plastic stents (DPS) in patients with peripancreatic fluid collections from pancreatitis. We aimed to compare technical and clinical success and adverse events in patients who received LAMS vs DPS for pancreatic pseudocysts and walled-off necrosis. METHODS: We performed a retrospective study of endoscopic ultrasound-mediated drainage in 149 patients (65% male; mean age, 47 y) with pancreatic pseudocysts or walled-off necrosis (97 received LAMS and 152 received DPS), from January 2011 through September 2016 at a single center. We collected data on patient characteristics, outcomes, hospitalizations, and imaging findings. Technical success was defined as LAMS insertion or a minimum of 2 DPS. Clinical success was defined as resolution of pancreatic pseudocysts or walled-off necrosis based on imaging results. The primary outcome was resolution of peripancreatic fluid collection with reduced abdominal pain or obstructive signs or symptoms. Secondary outcomes included the identification and management of adverse events, number of additional procedures required to resolve fluid collection, and the recurrence of fluid collection. RESULTS: Patients who received LAMS had larger peripancreatic fluid collections than patients who received DPS prior to intervention (P = .001), and underwent an average 1.7 interventions vs 1.9 interventions for patients who received DPS (P = .93). Technical success was achieved for 90 patients with LAMS (92.8%) vs 137 patients with DPS (90.1%) (odds ratio [OR] for success with DPS, 0.82; 95% CI, 0.33-2.0; P = .67). Despite larger fluid collections in the LAMS group, there was no significant difference in proportions of patients with clinical success following placement of LAMS (82 of 84 patients, 97.6%) vs DPS (118 of 122 patients, 96.7%) (OR for clinical success with DPS, 0.73; 95% CI, 0.13-4.0; P = .71). Adverse events developed in 24 patients who received LAMS (24.7%) vs 27 patients who received DPS (17.8%) (OR for an adverse event in a patient receiving a DPS, 0.82; 95% CI, 0.33-2.0; P = .67). However, patients with LAMS had a higher risk of pseudoaneurysm bleeding than patients with DPS (OR, 10.0; 95% CI, 1.19-84.6; P = .009). CONCLUSIONS: In a retrospective study of patients undergoing drainage of pancreatic pseudocysts or walled-off necrosis, we found LAMS and DPS to have comparable rates of technical and clinical success and adverse events. Drainage of walled-off necrosis or pancreatic pseudocysts using DPS was associated with fewer bleeding events overall, including pseudoaneurysm bleeding, but bleeding risk with LAMS should be weighed against the trend of higher actionable perforation and infection rates with DPS.

Efficacy and Safety of Digital Single-Operator Cholangioscopy for Difficult Biliary Stones.

BACKGROUND & AIMS: It is not clear whether digital single-operator cholangioscopy (D-SOC) with electrohydraulic and laser lithotripsy is effective in removal of difficult biliary stones. We investigated the safety and efficacy of D-SOC with electrohydraulic and laser lithotripsy in an international, multicenter study of patients with difficult biliary stones. METHODS: We performed a retrospective analysis of 407 patients (60.4% female; mean age, 64.2 years) who underwent D-SOC for difficult biliary stones at 22 tertiary centers in the United States, United Kingdom, or Korea from February 2015 through December 2016; 306 patients underwent electrohydraulic lithotripsy and 101 (24.8%) underwent laser lithotripsy. Univariate and multivariable analyses were performed to identify factors associated with technical failure and the need for more than 1 D-SOC electrohydraulic or laser lithotripsy session to clear the bile duct. RESULTS: The mean procedure time was longer in the electrohydraulic lithotripsy group (73.9 minutes) than in the laser lithotripsy group (49.9 minutes; P < .001). Ducts were completely cleared (technical success) in 97.3% of patients (96.7% of patients with electrohydraulic lithotripsy vs 99% patients with laser lithotripsy; P = .31). Ducts were cleared in a single session in 77.4% of patients (74.5% by electrohydraulic lithotripsy and 86.1% by laser lithotripsy; P = .20). Electrohydraulic or laser lithotripsy failed in 11 patients (2.7%); 8 patients were treated by surgery. Adverse events occurred in 3.7% patients and the stone was incompletely removed from 6.6% of patients. On multivariable analysis, difficult anatomy or cannulation (duodenal diverticula or altered anatomy) correlated with technical failure (odds ratio, 5.18; 95% confidence interval, 1.26-21.2; P = .02). Procedure time increased odds of more than 1 session of D-SOC electrohydraulic or laser lithotripsy (odds ratio, 1.02; 95% confidence interval, 1.01-1.03; P < .001). CONCLUSIONS: In a multicenter, international, retrospective analysis, we found D-SOC with electrohydraulic or laser lithotripsy to be effective and safe in more than 95% of patients with difficult biliary stones. Fewer than 5% of patients require additional treatment with surgery and/or extracorporeal shockwave lithotripsy to clear the duct.

Technical feasibility, diagnostic yield, and safety of microforceps biopsies during EUS evaluation of pancreatic cystic lesions (with video).

BACKGROUND AND AIMS: Through-the-needle microforceps are a recent addition to the EUS armamentarium for evaluation of pancreatic cystic lesions (PCLs). The main aim of this study was to assess the technical feasibility, diagnostic yield, and safety of EUS-guided microforceps biopsy for PCLs. METHODS: Our electronic endoscopy database was queried to identify patients who underwent EUS-guided FNA (EUS-FNA) of PCLs and microforceps biopsies during the same procedure. A biopsy was done on the wall of the cyst with the microforceps through the 19-gauge needle, and cyst fluid was collected for cytology and carcinoembryonic antigen (CEA) levels. Adverse events were recorded per published American Society for Gastrointestinal Endoscopy criteria. RESULTS: Twenty-seven patients underwent EUS-FNA and microforceps biopsy of PCLs from February 2016 to July 2017. Fourteen cysts were located in the pancreatic head and/or uncinate, and 13 were located in the body and/or tail region. Microforceps biopsies were technically successful in all cases and provided a pathology diagnosis in 24 of 27 cases (yield 88.9%). Microforceps biopsies diagnosed mucinous cyst in 9 patients (33.3%), serous cystadenoma in 4 (14.8%), neuroendocrine tumor in 1 (3.7%), and benign and/or inflammatory cyst in 10 (37.1%). In 7 patients (26%), microforceps biopsy results drastically changed the diagnosis, providing diagnoses otherwise not suggested by cytology or cyst fluid CEA levels. However, cytology provided a diagnosis of mucinous cyst in 4 cases (14.8%) not detected by microforceps biopsies. No adverse events were noted. CONCLUSION: Microforceps biopsies were associated with high technical success, and an excellent safety profile and may be a useful adjunctive tool, complementing existing EUS-FNA sampling protocols for PCLs.