Endoscopic ultrasound-guided gallbladder drainage with long-term lumen-apposing metal stent indwell: 1-year results from a prospective nationwide observational study.

BACKGROUND AND AIM: This study aimed to determine safety and risk factors for adverse events (AEs) of endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) with long-term indwell of lumen-apposing metal stents (LAMS). METHODS: This study is a multicenter prospective observational study on consecutive high surgical-risk patients requiring gallbladder drainage who underwent EUS-GBD with LAMS over 12 months. Centralized telephone follow-up interviews were conducted every 3 months for 1 year. Patients were censored at LAMS removal, cholecystectomy, or death. AE-free survival was determined using log-rank tests. Cumulative risks were estimated using life-table analysis. RESULTS: Eighty-two patients were included (53.7% male, median [interquartile range] age of 84.6 [76.5-89.8] years, and 85.4% with acute cholecystitis). Technical success was achieved in 79 (96.3%), and clinical success in 73 (89%). No patient was lost to follow-up; 45 patients (54.9%) completed 1-year follow-up with in situ LAMS. Median (interquartile range) LAMS indwell time was 364 (47-367) days. Overall, 12 (14.6%) patients presented 14 AEs, including 5 (6.1%) recurrent biliary events (3 acute cholangitis, 1 mild acute pancreatitis, and 1 acute cholecystitis). Patients with pancreatobiliary malignancy had an increased risk of recurrent biliary events (33% vs 1.5%, P = 0.001). The overall 1-year cumulative risk of recurrent biliary events was 9.7% (4.1-21.8%). The 1-year risk of AEs and of severe AEs was 18.8% (11-31.2%) and 7.9% (3.3-18.2%), respectively. Pancreatobiliary malignancy was the single risk factor for recurrent biliary events; LAMS misdeployment was the strongest risk factor for AEs. CONCLUSIONS: Long-term LAMS indwell does not increase the risk of delayed AEs following EUS-GBD.

Plastic pigtail vs lumen-apposing metal stents for drainage of walled-off necrosis (PROMETHEUS study): an open-label, multicenter randomized trial.

BACKGROUND: Lumen-apposing metal stents (LAMS) have displaced double-pigtail plastic stents (DPS) as the standard treatment for walled-off necrosis (WON),ß but evidence for exclusively using LAMS is limited. We aimed to assess whether the theoretical benefit of LAMS was superior to DPS. METHODS: This multicenter, open-label, randomized trial was carried out in 9 tertiary hospitals. Between June 2017, and Oct 2020, we screened 99 patients with symptomatic WON, of whom 64 were enrolled and randomly assigned to the DPS group (n = 31) or the LAMS group (n = 33). The primary outcome was short-term (4-weeks) clinical success determined by the reduction of collection. Secondary endpoints included long-term clinical success, hospitalization, procedure duration, recurrence, safety, and costs. Analyses were by intention-to-treat. CLINICALTRIALS: gov, NCT03100578. RESULTS: A similar clinical success rate in the short term (RR, 1.41; 95% CI 0.88-2.25; p = 0.218) and in the long term (RR, 1.2; 95% CI 0.92-1.58; p = 0.291) was observed between both groups. Procedure duration was significantly shorter in the LAMS group (35 vs. 45-min, p = 0.003). The hospital admission after the index procedure (median difference, - 10 [95% CI - 17.5, - 1]; p = 0.077) and global hospitalization (median difference - 4 [95% CI - 33, 25.51]; p = 0.82) were similar between both groups. Reported stent-related adverse events were similar for the two groups (36 vs.45% in LAMS vs. DPS), except for de novo fever, which was significantly 26% lower in LAMS (RR, 0.26 [0.08-0.83], p = 0.015). CONCLUSIONS: The clinical superiority of LAMS over DPS for WON therapy was not proved, with similar clinical success, hospital stay and similar safety profile between both groups, yet a significant reduction in procedure time was observed. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT03100578.

Is ERCP still the elective primary biliary drainage technique in patients with malignant distal biliary obstruction?

Endoscopic retrograde cholangiopancreatography (ERCP) has been established as the first line therapy for the resolution of biliary and pancreatic diseases. The main disadvantage of the procedure is the rate of adverse events, around 10%1. So, despite being a minimally invasive procedure, ERCP has a non-negligible rate of adverse effects (AEs) and secondary mortality.

Is ERCP still the elective primary biliary drainage technique in patients with malignant distal biliary obstruction? Response to Garcia-Cano et al.

We have read the letter from García-Cano et al. regarding our Editorial and are very grateful for the response as it contributes to deepening the debate we aim to generate on the topic. We are aware that changing a paradigm is always difficult, takes years, and requires publication of good quality studies. However, the way to progress in medicine and provide the best for patients involves questioning existing paradigms and considering the possibility of changing them. Currently, the outcomes of endoscopic ultrasonography guided transmural biliary drainage (EUS-TBD) have been progressively improving and the rate of adverse events (AE) has considerably decreased. The data currently available suggest that primary EUS-TBD in a specific setting is not inferior to ERCP drainage and may even entail a lower rate of AE.

Prospective multicenter assessment of the impact of EUS-guided gastroenterostomy on patient quality of life in unresectable malignant gastric outlet obstruction.

BACKGROUND AND AIMS: EUS-guided gastroenterostomy (EUS-GE) is increasingly used for malignant gastric outlet obstruction (GOO) in inoperable patients. However, the impact of EUS-GE on patient quality of life (QoL) has not been evaluated prospectively. METHODS: Consecutive patients with unresectable malignant GOO who underwent EUS-GE between August 2019 and May 2021 at 4 Spanish centers were prospectively assessed using the European Organization for Research and Treatment of Cancer QoL Questionnaire Core 30 at baseline and 1 month after the procedure. Centralized follow-up by telephone calls was undertaken. The Gastric Outlet Obstruction Scoring System (GOOSS) was used to assess oral intake, defining clinical success as a GOOSS ≥2. Differences between baseline and 30-day QoL scores were assessed using a linear mixed model. RESULTS: Sixty-four patients were enrolled, 33 (51.6%) men, with a median age of 77.3 years (interquartile range, 65.5-86.5). The most common diagnoses were pancreatic (35.9%) and gastric (31.3%) adenocarcinoma. Thirty-seven patients (57.9%) presented a 2/3 baseline Eastern Cooperative Oncology Group performance status score. Oral intake was restarted within 48 hours in 61 patients (95.3%), and the median postprocedure hospital stay was 3.5 days (interquartile range, 2-5). The 30-day clinical success rate was 83.3%. A clinically significant increase of 21.6 points (95% confidence interval, 11.5-31.7) in the global health status scale was documented, with significant improvements in nausea and vomiting, pain, constipation, and appetite loss. CONCLUSIONS: EUS-GE relieves GOO symptoms in patients with unresectable malignancy, allowing rapid oral intake and hospital discharge. It also provides a clinically relevant increase in QoL scores at 30 days from baseline. (Clinical trial registration number: NCT04660695.).

Endoscopic treatment of disconnected pancreatic duct syndrome secondary to acute necrotizing pancreatitis in a patient with pancreas divisum.

A 50-year old male with acute necrotizing pancreatitis had an unfavorable evolution in the third week of disease, with development of large volume ascites and walled-off necrosis affecting the head and body of pancreas, suspected to be infected, with viable parenchyma in the tail of pancreas. Endoscopic ultrasound guided drainage of the collection was performed through placement of a lumen apposing metal stent. Selective cannulation of main pancreatic duct was only possible though the minor papilla and after contrast media injection a type 1 pancreas divisum and partial disruption of dorsal pancreatic duct were diagnosed.

The volume of ERCP per endoscopist is associated with a higher technical success and a lower post-ERCP pancreatitis rate. A prospective analysis.

INTRODUCTION: conflicting results have been reported regarding the influence of the annual volume of endoscopic retrograde cholangiopancreatography (ERCP) on outcome. OBJECTIVE: to evaluate the influence of case volume on ERCP outcomes. PATIENTS AND METHODS: an analysis of a prospective database was performed, comparing the outcomes of ERCP in three consecutive periods defined by the number of endoscopists performing ERCP: five endoscopists in period I (P1), four in period II (P2) and three in period III (P3). Only patients with biliary ERCP in accessible and naïve papilla were included. Primary variables were cannulation rates and adverse effects (AE). The American Society of Gastrointestinal Endoscopy (ASGE) complexity grades III and IV were considered as highly complex procedures. RESULTS: a total of 2,561 patients were included: 727 (P1), 972 (P2) and 862 (P3). There were no differences in age and sex between groups (p > 0.05). The cannulation rate was significantly higher in P2 and P3: 92.4 % vs 93.3 % vs 93 % (p = 0.037). The AE rate was 13.8 %, 12.6 % and 10.3 % (p > 0.05), respectively. The rate of post-ERCP pancreatitis was significantly lower in P3: 8.5 %, 7.3 % and 5 % (p = 0.01). The rate of complex procedures was 12 %, 14.8 % and 27 % (p < 0.0001), respectively. Two endoscopists participated in all periods and only one had significantly improved outcomes. Cannulation and post-ERCP pancreatitis rates remained significantly better in P3 after adjusting for sex, complexity and endoscopist. CONCLUSION: a higher annual volume of ERCP per endoscopist was associated with a higher rate of cannulation and a lower rate of post-ERCP pancreatitis, despite the greater complexity of the procedures. These beneficial effects seem to differ between endoscopists.

Next-generation sequencing of bile cell-free DNA for the early detection of patients with malignant biliary strictures.

OBJECTIVE: Despite significant progresses in imaging and pathological evaluation, early differentiation between benign and malignant biliary strictures remains challenging. Endoscopic retrograde cholangiopancreatography (ERCP) is used to investigate biliary strictures, enabling the collection of bile. We tested the diagnostic potential of next-generation sequencing (NGS) mutational analysis of bile cell-free DNA (cfDNA). DESIGN: A prospective cohort of patients with suspicious biliary strictures (n=68) was studied. The performance of initial pathological diagnosis was compared with that of the mutational analysis of bile cfDNA collected at the time of first ERCP using an NGS panel open to clinical laboratory implementation, the Oncomine Pan-Cancer Cell-Free assay. RESULTS: An initial pathological diagnosis classified these strictures as of benign (n=26), indeterminate (n=9) or malignant (n=33) origin. Sensitivity and specificity of this diagnosis were 60% and 100%, respectively, as on follow-up 14 of the 26 and eight of the nine initially benign or indeterminate strictures resulted malignant. Sensitivity and specificity for malignancy of our NGS assay, herein named Bilemut, were 96.4% and 69.2%, respectively. Importantly, one of the four Bilemut false positives developed pancreatic cancer after extended follow-up. Remarkably, the sensitivity for malignancy of Bilemut was 100% in patients with an initial diagnosis of benign or indeterminate strictures. Analysis of 30 paired bile and tissue samples also demonstrated the superior performance of Bilemut. CONCLUSION: Implementation of Bilemut at the initial diagnostic stage for biliary strictures can significantly improve detection of malignancy, reduce delays in the clinical management of patients and assist in selecting patients for targeted therapies.

Endoscopic ultrasound-guided drainage using lumen-apposing metal stent of malignant afferent limb syndrome in patients with previous Whipple surgery: Multicenter study (with video).

OBJECTIVES: Endoscopic ultrasound-guided digestive anastomosis (EUS-A) is a new alternative under evaluation in patients presenting with afferent limb syndrome (ALS) after Whipple surgery. The aim of the present study is to analyze the safety and effectiveness of EUS-A in ALS. METHODS: This is an observational multicenter study. All patients ≥18 years old with previous Whipple surgery presenting with ALS who underwent an EUS-A using a lumen-apposing metal stent (LAMS) between 2015 and 2021 were included. The primary outcome was clinical success, defined as resolution of the ALS or ALS-related cholangitis. Furthermore, technical success, adverse event rate, and mortality were evaluated. RESULTS: Forty-five patients (mean age: 65.5 ± 10.2 years; 44.4% male) were included. The most common underlying disease was pancreatic cancer (68.9%). EUS-A was performed at a median of 6 weeks after local tumor recurrence. The most common approach used was the direct/freehand technique (66.7%). Technical success was achieved in 95.6%, with no differences between large (≥15 mm) and small LAMS (97.4% vs. 100%, P = 0.664). Clinical success was retained in 91.1% of patients. A complementary treatment by dilation of the stent followed by endoscopic retrograde cholangiopancreatography through the LAMS was performed in three cases (6.7%). There were six recurrent episodes of cholangitis (14.6%) and two procedure-related adverse events (4.4%) after a median follow-up of 4 months. Twenty-six patients (57.8%) died during the follow-up due to disease progression. CONCLUSION: EUS-A is a safe and effective technique in the treatment of malignant ALS, achieving high clinical success with an acceptable recurrence rate.

Diagnostic accuracy and interobserver agreement of digital single-operator cholangioscopy for indeterminate biliary strictures.

BACKGROUND AND AIMS: Digital single-operator cholangioscopy (d-SOC) with cholangioscopic biopsy sampling has shown promise in the evaluation of indeterminate biliary strictures. Some studies have suggested higher sensitivity for visual impression compared with biopsy sampling, although assessors were not blinded to previous investigations. We aimed to investigate the diagnostic accuracy and interobserver agreement (IOA) of d-SOC in the visual appraisal of biliary strictures when blinded to additional information. METHODS: A multicenter, international cohort study was performed. Cholangioscopic videos in patients with a known final diagnosis were systematically scored. Pseudonymized videos were reviewed by 19 experts in 2 steps: blinded for patient history and investigations and unblinded. RESULTS: Forty-four high-quality videos were reviewed of 19 benign and 25 malignant strictures. The sensitivity and specificity for the diagnosis of malignancy was 74.2% and 46.9% (blinded) and 72.7% and 62.5% (unblinded). Cholangioscopic certainty of a malignant diagnosis led to overdiagnosis (sensitivity, 90.6%; specificity, 33%), especially if no additional information was provided. The IOA for the presence of malignancy was fair for both assessments (Fleiss' κ = .245 [blinded] and κ = .321 [unblended]). For individual visual features, the IOA ranged from slight to moderate for both assessments (κ = .059-.400 vs κ = .031-.452). CONCLUSIONS: This study showed low sensitivity and specificity for blinded and unblinded d-SOC video appraisal of indeterminate biliary strictures, with considerable interobserver variation. Although reaching a consensus on the optical features of biliary strictures remains important, optimizing visually directed biopsy sampling may be the most important role of cholangioscopy in biliary stricture assessment.

The safety and efficacy of a new 20-mm lumen apposing metal stent (lams) for the endoscopic treatment of pancreatic and peripancreatic fluid collections: a large international, multicenter study.

BACKGROUND: Lumen apposing metal stent (LAMS) allows an easy access to peripancreatic fluid collections (PPFCs) and the possibility of performing direct endoscopic necrosectomy (DEN). The aim of our study was to evaluate the safety and efficacy of a new 20-mm LAMS in the management of PPFCs. This novel stent represents the largest diameter LAMS available on the market to date. METHODS: This is an international, multicenter retrospective study involving 20 centers. Consecutive patients who underwent EUS-guided PPFC drainage using a 20-mm LAMS were included. Primary outcomes were technical and clinical success. Secondary outcomes were rate and the severity of adverse events. RESULTS: A total 105 patients underwent PPFC drainage using the new 20-mm LAMS and 106 LAMS were placed. Technical success was 100% (106/106). 7/105 patients died due to causes not related to the stent. Clinical success was achieved in 92/98 patients (93.9%). Significant adverse events occurred in 8/98 patients (8.16%): 4 cases (4.08%) of bleeding, 3 cases (3.06%) of suprainfection, 1 case of gastric outlet obstruction. CONCLUSIONS: This multicenter study demonstrated acceptable rates of technical and clinical success using a new 20-mm LAMS for PPFC, including walled-off pancreatic necrosis (WOPN). The results of our study suggest that a new 20-mm LAMS is non-inferior in terms of safety, efficacy, and adverse events as compared to smaller diameter LAMS in the management of PPFCs, including pancreatic psuedocysts (PP) and WOPN. Randomized controlled studies will be needed to determine the ideal size of LAMS need to achieve the greatest clinical benefit with the minimized risk exposure for this high-risk patient population.

Endoscopic management of local complications of chronic pancreatitis.

Endoscopic treatment of local complications in patients with chronic pancreatitis has gained ground over the surgical alternative in the last few years. The lower aggressiveness of endoscopic treatment, as well as the possibility to use it repeatedly in high-risk patients, has favored this development. In addition, the incorporation of new, highly accurate endoscopic therapeutic options such as pancreatoscopy-guided lithotripsy and endoscopic ultrasound-guided treatments make endoscopic treatment the first choice in many cases, despite discordant data in the literature. This article reviews the endoscopic treatment of the most common local complications of chronic pancreatitis, such as pancreatolithiasis, pseudocysts, and pancreatic, biliary, and duodenal ductal stenosis.

Stent placement prior to initiation of chemotherapy in patients with obstructive, nonoperative left sided tumors is associated with fewer stomas.

BACKGROUND AND OBJETIVES: Due to the potential risks associated with stent placement, European Society Gastrointestinal Endoscopy does not recommend prophylactic insertion of stents in patients without symptoms. The aim was to compare complication rates, need of surgery, colostomy formation, and survival between stent placement prior to start of chemotherapy (SEMS group) and upfront ChT (ChT group) in patients with endoscopically non-transverable metastatic left-sided colorectal cancer. METHODS: Gender, age, CEA, tumor location, sites of metastatic disease, peritoneal involvement, liver involvement, and angiogenesis inhibitors administration, were recorded. Complication rates, need of surgery, stoma creation, and survival were compared between both groups by univariate and multivariate test. Complications of SEMS placement in both groups were compared. RESULTS: We studied 75 men and 40 women, with a mean age of 66.3 years. Overall complication and perforation rates were similar but patients in the ChT group had a significant higher need of surgery and subsequent stoma creation. Perforation after SEMS placement rates were higher in patients receiving ChT than in patients without ChT. Survival was related to peritoneal carcinomatosis and administration of biological agents. CONCLUSIONS: SEMS placement prior to ChT administration dismissed the need of subsequent surgery and decreased the rates of permanent stoma formation.

Surgical anterior cavoplasty for managing a case of early acute outflow obstruction after liver transplantation.

HVOO following liver transplantation is rarely treated surgically because it tends to debut subacutely. However, acute HVOO is a surgical emergency that compromises the viability of the graft. We report a case of HVOO diagnosed intra-operatively during surgical revision for a suspected arterial thrombosis in a 10-month-old male recipient of a second graft (segments II-III) for familial intrahepatic cholestasis. HVOO was related to a stenosis at the first transplant hepato-caval anastomosis, left in place to obtain longer venous cuffs for retransplantation. An anterior cavoplasty was necessary to resolve the issue. The new anastomosis was created under total vascular exclusion after gaining control of the supradiaphragmatic vena cava, because the inferior vena cava was unsuitable for further surgery. This approach (normally used as a means to avoid sternotomy in patients with hepatic or renal tumours associated with venous thrombosis) allows adequate vascular control and, in selected cases, offers a surgical alternative for treating HVOO.

Multicenter study on endoscopic ultrasound-guided expandable biliary metal stent placement: choice of access route, direction of stent insertion, and drainage route.

BACKGROUND AND AIM: Endoscopic ultrasonography-guided biliary drainage (EUS-BD) using expandable biliary metal stents has emerged as an acceptable alternative in patients with failed endoscopic retrograde cholangiopancreatography for malignant biliary obstruction. However, there is no consensus over the preferred access route (transhepatic or extrahepatic), direction of stent insertion (antegrade or retrograde) or drainage route (transluminal or transpapillary) in patients potentially suitable for multiple methods. The present study compares success and complication rates in patients undergoing EUS-BD via different methods. METHODS: This was a multicenter retrospective analysis. Records of patients who underwent EUS-BD for malignant obstructive jaundice at four centers were entered in a standard database. Success and complications were compared for different techniques. RESULTS: Sixty-eight patients were analyzed. EUS-BD was successful in 65 patients (95.6%). There was no significant difference in the success rates of different techniques. Complications were seen in 14 patients (20.6%) and mortality in three patients (4.4%). Complications were significantly higher for the transhepatic route compared to the transduodenal route (30.5% vs 9.3%, P=0.03). There was no significant difference in complication rates among transluminal and transpapillary stent placements, or direct and rendezvous stenting. Logistic regression analysis showed transhepatic access to be the only independent risk factor for complications (P=0.031, t=2.2). CONCLUSION: EUS-BD can be carried out with high success rates regardless of the choice of access route, stent direction or drainage route. However, complications are significantly higher with transhepatic access. The transduodenal route should be chosen for EUS-guided and rendezvous stent placements, when both routes are available.

Palliation of Gastric Outlet Obstruction in Case of Biliary Obstruction-A Retrospective, Multicenter Study: The B-GOOD Study.

BACKGROUND: EUS-guided gastroenterostomy (EUS-GE) is a novel and effective procedure for the management of malignant gastric outlet obstruction (GOO) with more durable results when compared to enteral stenting (ES). However, data comparing EUS-GE to ES in patients already treated with EUS-guided choledocoduodenostomy (EUS-CDS) for distal malignant biliary obstruction (DMBO) are lacking. We aimed to compare outcomes of EUS-GE and ES for the palliation of GOO in this specific population of patients. METHODS: A multicenter, retrospective analysis of patients with DMBO treated by EUS-CDS and subsequent GOO treated by EUS-GE or ES from 2016 to 2021 was conducted. Primary outcomes were overall AEs rate and dysfunction of the EUS-CDS after GOO treatment. Secondary outcomes included clinical success, technical success, procedure duration, length of hospital stay and relapse of GOO symptoms. RESULTS: A total of 77 consecutive patients were included in the study: 25 patients underwent EUS-GE and 52 underwent ES. AEs rate and patency outcomes of the EUS-CDS after GOO treatment were comparable between the two groups (12.5% vs. 17.3%; p = 0.74). No recurrence of GOO symptoms was registered in the EUS-GE group while 11.5% of ES patients had symptoms recurrence, even if not statistically significant (p = 0.16), after a mean follow-up period of 63.5 days. CONCLUSION: EUS-GE and ES are both effective and safe for the palliation of GOO in patients already treated by EUS-CDS for DMBO with no difference in the biliary stent dysfunction rate and overall AEs. EUS-GE is associated with less recurrence of GOO symptoms.

Endoscopic submucosal dissection in Spain: outcomes and development possibilities.

Endoscopic submucosal dissection (ESD) allows endoscopic, curative, en-bloc resection of superficial malignant or premalignant lesions. This procedure was conceived over 10 years ago in Japan, but has not experienced great expansion in Western countries for different reasons. This article reviews ESD indications and outcomes, and reflects on the reasons that prevent ESD from becoming common clinical practice in Western hospitals. Finally, recommendations on ESD training in our setting are made.