Prospective, Multi-Institutional, Real-Time Next-Generation Sequencing of Pancreatic Cyst Fluid Reveals Diverse Genomic Alterations That Improve the Clinical Management of Pancreatic Cysts.

BACKGROUND & AIMS: Next-generation sequencing (NGS) of pancreatic cyst fluid is a useful adjunct in the assessment of patients with pancreatic cyst. However, previous studies have been retrospective or single institutional experiences. The aim of this study was to prospectively evaluate NGS on a multi-institutional cohort of patients with pancreatic cyst in real time. METHODS: The performance of a 22-gene NGS panel (PancreaSeq) was first retrospectively confirmed and then within a 2-year timeframe, PancreaSeq testing was prospectively used to evaluate endoscopic ultrasound-guided fine-needle aspiration pancreatic cyst fluid from 31 institutions. PancreaSeq results were correlated with endoscopic ultrasound findings, ancillary studies, current pancreatic cyst guidelines, follow-up, and expanded testing (Oncomine) of postoperative specimens. RESULTS: Among 1933 PCs prospectively tested, 1887 (98%) specimens from 1832 patients were satisfactory for PancreaSeq testing. Follow-up was available for 1216 (66%) patients (median, 23 months). Based on 251 (21%) patients with surgical pathology, mitogen-activated protein kinase/GNAS mutations had 90% sensitivity and 100% specificity for a mucinous cyst (positive predictive value [PPV], 100%; negative predictive value [NPV], 77%). On exclusion of low-level variants, the combination of mitogen-activated protein kinase/GNAS and TP53/SMAD4/CTNNB1/mammalian target of rapamycin alterations had 88% sensitivity and 98% specificity for advanced neoplasia (PPV, 97%; NPV, 93%). Inclusion of cytopathologic evaluation to PancreaSeq testing improved the sensitivity to 93% and maintained a high specificity of 95% (PPV, 92%; NPV, 95%). In comparison, other modalities and current pancreatic cyst guidelines, such as the American Gastroenterology Association and International Association of Pancreatology/Fukuoka guidelines, show inferior diagnostic performance. The sensitivities and specificities of VHL and MEN1/loss of heterozygosity alterations were 71% and 100% for serous cystadenomas (PPV, 100%; NPV, 98%), and 68% and 98% for pancreatic neuroendocrine tumors (PPV, 85%; NPV, 95%), respectively. On follow-up, serous cystadenomas with TP53/TERT mutations exhibited interval growth, whereas pancreatic neuroendocrine tumors with loss of heterozygosity of ≥3 genes tended to have distant metastasis. None of the 965 patients who did not undergo surgery developed malignancy. Postoperative Oncomine testing identified mucinous cysts with BRAF fusions and ERBB2 amplification, and advanced neoplasia with CDKN2A alterations. CONCLUSIONS: PancreaSeq was not only sensitive and specific for various pancreatic cyst types and advanced neoplasia arising from mucinous cysts, but also reveals the diversity of genomic alterations seen in pancreatic cysts and their clinical significance.

Pancreatic Cancer Screening for At-Risk Individuals (Pancreas Scan Study): Yield, Harms, and Outcomes From a Prospective Multicenter Study.

INTRODUCTION: Guidelines endorse pancreatic cancer screening in genetically susceptible individuals. We conducted a prospective, multicenter study to determine yield, harms, and outcomes of pancreatic cancer screening. METHODS: All high-risk individuals undergoing pancreatic cancer screening at 5 centers from 2020 to 2022 were prospectively enrolled. Pancreas findings were designated as low-risk (fatty or chronic pancreatitis-like changes), intermediate-risk (neuroendocrine tumor [NET] <2 cm or branch-duct intraductal papillary mucinous neoplasm [IPMN]), or high-risk lesions (high-grade pancreatic intraepithelial neoplasia/dysplasia, main-duct IPMN, NET >2 cm, or pancreatic cancer). Harms from screening included adverse events during screening or undergoing low-yield pancreatic surgery. Annual screening was performed using endoscopic ultrasound and or magnetic resonance cholangiopancreatography. Annual screening for new-onset diabetes using fasting blood sugar was also performed ( ClinicalTrials.gov : NCT05006131). RESULTS: During the study period, 252 patients underwent pancreatic cancer screening. Mean age was 59.9 years, 69% were female, and 79.4% were White. Common indications were BRCA 1/2 (36.9%), familial pancreatic cancer syndrome kindred (31.7%), ataxia telangiectasia mutated (3.5%), Lynch syndrome (6.7%), Peutz-Jeghers (4.3%), and familial atypical multiple mole melanoma (3.5%). Low-risk lesions were noted in 23.4% and intermediate-risk lesions in 31.7%, almost all of which were branch-duct IPMN without worrisome features. High-risk lesions were noted in 2 patients (0.8%), who were diagnosed with pancreas cancer at stages T2N1M0 and T2N1M1. Prediabetes was noted in 18.2% and new-onset diabetes in 1.7%. Abnormal fasting blood sugar was not associated with pancreatic lesions. There were no adverse events from screening tests, and no patient underwent low-yield pancreatic surgery. DISCUSSION: Pancreatic cancer screening detected high-risk lesions with lower frequency than previously reported. No harms from screening were noted.

Safety and efficacy of a novel resection system for direct endoscopic necrosectomy of walled-off pancreas necrosis: a prospective, international, multicenter trial.

BACKGROUND AND AIMS: Direct endoscopic necrosectomy (DEN) of walled-off pancreatic necrosis (WOPN) lacks dedicated instruments and requires repetitive and cumbersome procedures. This study evaluated the safety and efficacy of a new powered endoscopic debridement (PED) system designed to simultaneously resect and remove solid debris within WOPN. METHODS: This was a single-arm, prospective, multicenter, international device trial conducted from November 2018 to August 2019 at 10 sites. Patients with WOPN ≥6 cm and ≤22 cm and with >30% solid debris were enrolled. The primary endpoint was safety through 21 days after the last DEN procedure. Efficacy outcomes included clearance of necrosis, procedural time, adequacy of debridement, number of procedures until resolution, hospital stay duration, and quality of life. RESULTS: Thirty patients (mean age, 55 years; 60% men) underwent DEN with no device-related adverse events. Of 30 patients, 15 (50%) achieved complete debridement in 1 session and 20 (67%) achieved complete debridement within 2 or fewer sessions. A median of 1.5 interventions (range, 1-7) were required. Median hospital stay was 10 days (interquartile range, 22). There was an overall reduction of 91% in percent necrosis within WOPN from baseline to follow-up and 85% in collection volume. Baseline WOPN volume was positively correlated with the total number of interventions (ρ = .363, P = .049). CONCLUSIONS: The new PED system seems to be a safe and effective treatment tool for WOPN, resulting in fewer interventions and lower hospital duration when compared with published data on using conventional instruments. Randomized controlled trials comparing the PED system with conventional DEN are needed. (Clinical trial registration number: NCT03694210.).

Endoscopic full-thickness resection of polyps involving the appendiceal orifice: a multicenter international experience.

BACKGROUND: Endoscopic resection of lesions involving the appendiceal orifice remains a challenge. We aimed to report outcomes with the full-thickness resection device (FTRD) for the resection of appendiceal lesions and identify factors associated with the occurrence of appendicitis. METHODS: This was a retrospective study at 18 tertiary-care centers (USA 12, Canada 1, Europe 5) between November 2016 and August 2020. Consecutive patients who underwent resection of an appendiceal orifice lesion using the FTRD were included. The primary outcome was the rate of R0 resection in neoplastic lesions, defined as negative lateral and deep margins on post-resection histologic evaluation. Secondary outcomes included the rates of: technical success (en bloc resection), clinical success (technical success without need for further surgical intervention), post-resection appendicitis, and polyp recurrence. RESULTS: 66 patients (32 women; mean age 64) underwent resection of colonic lesions involving the appendiceal orifice (mean [standard deviation] size, 14.5 (6.2) mm), with 40 (61 %) being deep, extending into the appendiceal lumen. Technical success was achieved in 59/66 patients (89 %), of which, 56 were found to be neoplastic lesions on post-resection pathology. Clinical success was achieved in 53/66 (80 %). R0 resection was achieved in 52/56 (93 %). Of the 58 patients in whom EFTR was completed who had no prior history of appendectomy, appendicitis was reported in 10 (17 %), with six (60 %) requiring surgical appendectomy. Follow-up colonoscopy was completed in 41 patients, with evidence of recurrence in five (12 %). CONCLUSIONS: The FTRD is a promising non-surgical alternative for resecting appendiceal lesions, but appendicitis occurs in 1/6 cases.

Comparison of Biliary Drainage Techniques for Malignant Biliary Obstruction: A Systematic Review and Network Meta-analysis.

BACKGROUND AND AIMS: Endoscopic retrograde cholangiopancreatography (ERCP), percutaneous transhepatic biliary drainage, and endoscopic ultrasound (EUS)-guided biliary drainage are all established techniques for drainage of malignant biliary obstruction. This network meta-analysis (NMA) was aimed at comparing all 3 modalities to each other. MATERIALS AND METHODS: Multiple databases were searched from inception to October 2019 to identify relevant studies. All the patients were eligible to receive any one of the 3 interventions. Data extraction and risk of bias assessment was performed using standardized tools. Outcomes of interest were technical success, clinical success, adverse events, and reintervention. Direct meta-analyses were performed using the random-effects model. NMA was conducted using a multivariate, consistency model with random-effects meta-regression. The GRADE approach was followed to rate the certainty of evidence. RESULTS: The final analysis included 17 studies with 1566 patients. Direct meta-analysis suggested that EUS-guided biliary drainage had a lower reintervention rate than ERCP. NMA did not show statistically significant differences to favor any one intervention with certainty across all the outcomes. The overall certainty of evidence was found to be low to very low for all the outcomes. CONCLUSIONS: The available evidence did not favor any intervention for drainage of malignant biliary obstruction across all the outcomes assessed. ERCP with or without EUS should be considered first to allow simultaneous tissue acquisition and biliary drainage.

Challenges of developing and executing a multi-site registry for a novel device with evolving indications for use.

BACKGROUND: The introduction of new technologies in endoscopy has been met with uncertainty, skepticism, and lack of standardization or training parameters, particularly when disruptive devices or techniques are involved. The widespread availability of a novel endoscopic suturing device (OverStitch™) for tissue apposition has enabled the development of applications of endoscopic suturing. METHODS: The American Gastroenterological Association partnered with Apollo Endosurgery to develop a registry to capture in a pragmatic non-randomized study the safety, effectiveness, and durability of endoscopic suturing in approximating tissue in the setting of bariatric revision and fixation of endoprosthetic devices. RESULTS: We highlight the challenges of the adoption of novel techniques by examining the process of developing and executing this multicenter registry to assess real-world use of this endoscopic suturing device. We also present our preliminary data on the safety and effectiveness of the novel device as it is applied in the treatment of obesity. CONCLUSIONS: The Prospective Registry for Trans-Orifice Endoscopic Suturing Applications (ES Registry) was an effective Phase 4, postmarketing registry aimed at capturing pragmatic, real-world use of a novel device. These findings serve to solidify the role of endoscopic suturing in clinical practice.

Liver Biopsy in Pregnancy: Two Case Reports and Review of the Literature.

The etiology of most cases of liver diseases in pregnancy can be diagnosed with a thorough history, physical examination, laboratory values, serology, and noninvasive imaging. However, atypical clinical and laboratory presentations of liver diseases/chemistries require a liver biopsy to render an accurate diagnosis in cases where the biopsy results affect the timing of delivery or impact choice of medical therapy. According to the American College of Gastroenterology, liver biopsy can be effectively and safely conducted in pregnant women. Conventional routes of performing a liver biopsy include the percutaneous, transjugular route, and surgical methods. Endoscopic ultrasound-guided liver biopsy is a recent technique that has not yet gained widespread adoption but can potentially serve as an alternative route for obtaining the liver sample. Adverse events associated with liver biopsy include abdominal pain and hemorrhage. Maternal and fetal outcomes are limited to increased risk of preterm birth and small for gestational age neonate. However, very few studies have formally evaluated the safety of liver biopsy in pregnant women. In this review, we present two successful cases of liver biopsy performed during pregnancy and summarize the most recent evidence regarding the safety and outcomes of the procedure in pregnancy to assist clinicians in their decision to perform a liver biopsy during pregnancy or postpone it until after delivery.

Prospective evaluation of an assessment tool for technical performance of duodenoscopes.

OBJECTIVE: While single-use and detachable-tip duodenoscopes have been recently developed to overcome risks of infection transmission, there are no reliable tools to objectively assess their technical performance. We evaluated the reliability and validity of a newly developed tool to assess the technical performance of reusable duodenoscopes. METHODS: An assessment tool was developed to measure duodenoscope performance based on three distinct criteria: maneuverability, mechanical/imaging characteristics and ability to perform requisite interventions. The assessment tool was tested prospectively on duodenoscopes used in endoscopic retrograde cholangiopancreatography (ERCP) procedures at nine academic medical centers over a 6-month period. The main outcome was reliability of the duodenoscope assessment tool, which was estimated using Cronbach's coefficient alpha (α). The secondary outcome was validity of the assessment tool. RESULTS: The assessment tool evaluated technical performance of reusable duodenoscopes in 1080 ERCP procedures. Indications were biliary in 92.8% and pancreatic in 7.2% procedures. The overall Cronbach's coefficient α for maneuverability was 0.81, assessment of mechanical/imaging characteristics was 0.92, and ability to perform requisite interventions was 0.87. On multiple linear regression analysis, prolonged procedure duration, older patient age and pancreatic interventions were significantly positively associated with higher (worse) scores. CONCLUSIONS: The newly developed assessment tool appears reliable and valid for evaluating the technical performance of duodenoscopes. Registration: ClinicalTrials.gov Identifier: NCT04004533.

An Endoscopic Transluminal Approach, Compared With Minimally Invasive Surgery, Reduces Complications and Costs for Patients With Necrotizing Pancreatitis.

BACKGROUND & AIMS: Infected necrotizing pancreatitis is a highly morbid disease with poor outcomes. Intervention strategies have progressed from open necrosectomy to minimally invasive approaches. We compared outcomes of minimally invasive surgery vs endoscopic approaches for patients with infected necrotizing pancreatitis. METHODS: We performed a single-center, randomized trial of 66 patients with confirmed or suspected infected necrotizing pancreatitis who required intervention from May 12, 2014, through March 24, 2017. Patients were randomly assigned to groups that received minimally invasive surgery (laparoscopic or video-assisted retroperitoneal debridement, depending on location of collection, n = 32) or an endoscopic step-up approach (transluminal drainage with or without necrosectomy, n = 34). The primary endpoint was a composite of major complications (new-onset multiple organ failure, new-onset systemic dysfunction, enteral or pancreatic-cutaneous fistula, bleeding and perforation of a visceral organ) or death during 6 months of follow-up. RESULTS: The primary endpoint occurred in 11.8% of patients who received the endoscopic procedure and 40.6% of patients who received the minimally invasive surgery (risk ratio 0.29; 95% confidence interval 0.11-0.80; P = .007). Although there was no significant difference in mortality (endoscopy 8.8% vs surgery 6.3%; P = .999), none of the patients assigned to the endoscopic approach developed enteral or pancreatic-cutaneous fistulae compared with 28.1% of the patients who underwent surgery (P = .001). The mean number of major complications per patient was significantly higher in the surgery group (0.69 ± 1.03) compared with the endoscopy group (0.15 ± 0.44) (P = .007). The physical health scores for quality of life at 3 months was better with the endoscopic approach (P = .039) and mean total cost was lower ($75,830) compared with $117,492 for surgery (P = .039). CONCLUSIONS: In a randomized trial of 66 patients, an endoscopic transluminal approach for infected necrotizing pancreatitis, compared with minimally invasive surgery, significantly reduced major complications, lowered costs, and increased quality of life. Clinicaltrials.gov no: NCT02084537.

Gastrointestinal Bleeding in Patients with Severe SARS-CoV-2.

Gastrointestinal symptoms are common and frequently reported in Coronavirus Disease-2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is unclear if SARS-CoV-2 is associated with increased risk of gastrointestinal bleeding (GIB). Nevertheless, GIB in COVID-19 patients poses unique challenges to patients due to high-risk of concomitant respiratory failure and to endoscopy personnel due to risk of airborne transmission during endoscopic procedures. Many management issues related to COVID-19 are still being studied. In this case series, we attempt to discuss the important clinical implications related to the management of GIB in COVID-19 patients.

Endoscopic Retrograde Cholangiopancreatography-Related Complications and Their Management Strategies: A "Scoping" Literature Review.

Endoscopic retrograde cholangiopancreatography (ERCP) is a well-known procedure with both diagnostic and therapeutic utilities in managing pancreaticobiliary conditions. With the advancements of endoscopic techniques, ERCP has become a relatively safe and effective procedure. However, as ERCP is increasingly being utilized for different advanced techniques, newer complications have been noticed. Post-ERCP complications are known, and mostly include pancreatitis, infection, hemorrhage, and perforation. The risks of these complications vary depending on several factors, such as patient selection, endoscopist's skills, and the difficulties involved during the procedure. This review discusses post-ERCP complications and management strategies with new and evolving concepts.

Current and future implications of COVID-19 on gastroenterology training and clinical practice.

The novel coronavirus disease 2019 (COVID-19) pandemic has affected almost every country on the globe, affecting 185 countries with more than 2.6 million cases and 182,000 deaths as of April 22, 2020. The United States (US) has seen an exponential surge in the COVID-19 patients and has become the epicentre with more than 845,000 confirmed cases and 46,000 deaths. The governments and healthcare providers all over the world are racing with time to reduce the rate of increase in active cases by social distancing to flatten the curve of this pandemic. Practicing gastroenterologists are facing multiple challenges in the safe practice of medicine because of patient's inability to visit physicians' offices, endoscopy centers and the threat of potential virus spread through gastrointestinal secretions by endoscopies in emergent cases. The gastroenterological associations from Europe and North America have made position statements to guide gastroenterologists to navigate through the clinical practice during the COVID-19 pandemic. Gastroenterology fellows are on the frontlines during the COVID-19 pandemic, experiencing personal, physical and economic stresses. They had to balance the programmatic changes to meet the demands of the patient care with the additional pressure to meet training requirements. Given the imperatives for social and physical distancing, training programmes have to implement innovative educational methods to substitute traditional teaching. Healthcare organisations must synchronise institutional workforce needs with trainee safety, education and well-being. In this perspective, we have discussed the challenges that can be anticipated and implementing strategies to support fellows during the times of the COVID-19 pandemic.

Optimal sequences of same-visit bidirectional endoscopy: Systematic review and meta-analysis.

BACKGROUND AND AIM: Same-visit colonoscopy and esophagogastroduodenoscopy (EGD) have become common. Recent studies showed conflicting results regarding the performance, safety, and efficacy of different sequences. We conducted this meta-analysis to determine the most favorable performance and discomfort between an EGD followed by colonoscopy (E-C) and colonoscopy followed by EGD (C-E). METHODS: The authors searched the databases of MEDLINE and EMBASE. Outcomes of interest were performance (including cecal intubation time, adenoma detection rate, and polyp detection rate), discomfort score (patients and endoscopists; Likert scale), and sedation uses. Pooled mean differences (MD) or odds ratios (OR) were calculated with 95% confidence intervals (CI). RESULTS: Six randomized controlled trials were included in the meta-analysis. The authors found that there was significantly lower sedative use including fentanyl (14.70; 95% Cl: 8.20-21.20) and propofol (15.58; 95% Cl: 3.27-27.89) in the E-C group compared with the C-E group. There was a significantly better discomfort score in patients and endoscopists after both procedures in the E-C group than in the C-E group with pooled MD of 0.64 points (95% Cl: 0.09-1.20) and 0.47 (95% Cl: 0.05-0.90), respectively. There were no differences in cecal intubation time, adenoma detection rate, or polyp detection rate between the two groups. CONCLUSION: The present study found that the discomfort score was better in the E-C group. However, there was no difference in polyp and adenoma detection. Therefore, the E-C group is the optimal sequence.

Digital pancreatoscopy in the evaluation of main duct intraductal papillary mucinous neoplasm: a multicenter study.

BACKGROUND: The aim of this study was to investigate the outcomes of digital pancreatoscopy in main duct intraductal papillary mucinous neoplasm (MD-IPMN). METHODS: This was a multicenter retrospective study. Outcomes analyzed were safety, incremental pathology yield compared with previous cross-sectional/endoscopic ultrasound (EUS) imaging, and whether the surgical procedure was dictated by the pancreatoscopy. RESULTS: A total of 31 patients were enrolled from six tertiary care centers. Overall, 42 % of cases had findings on pancreatoscopy that were not seen on cross-sectional imaging or EUS. Digital pancreatoscopy dictated the type of surgery performed in 13 patients (42 %) who underwent surgery. However, in patients with a diffusely dilated pancreatic duct (> 10 mm), the pancreatoscopy dictated the type of surgery in 77 % of cases vs. 17 % of cases in the focally dilated pancreatic duct group (10/13 vs. 3/18; P = 0.001). CONCLUSION: Digital pancreatoscopy should be considered in the diagnostic algorithm of MD-IPMN in patients with a diffusely dilated pancreatic duct and without any focal lesions seen on cross-sectional imaging or EUS.

Biliary drainage: role of EUS guidance.

BACKGROUND AND AIMS: EUS-guided biliary drainage is a technique being increasingly used when ERCP fails, and it has been the focus of multiple studies and investment in recent years. However, the proportion of cases for which it is really indicated has not been established. The aim of this study is to determine how often EUS-guided biliary drainage is needed in a tertiary-care level therapeutic endoscopy unit. METHODS: This is a prospective cohort study at a single tertiary-care center with a high volume of therapeutic endoscopy. A thousand consecutive ERCPs performed from November 1, 2013 to September 12, 2014 were screened, and those with previous biliary intervention were excluded (n = 476). EUS-guided biliary drainage was performed in suitable patients with failed ERCP and malignant biliary obstruction. The main outcome measures were the rates of ERCP failure and EUS-guided biliary drainage. RESULTS: A total of 524 native papilla ERCPs were performed (41.2% male; median age 60 years, range 6-97 years; 9.4% outside failed ERCP; 1.9% surgically altered anatomy). The ampulla was reached in 518 (98.9%) and not reached in 6 (1.1%) because of surgically altered anatomy (n = 2), malignant duodenal stenosis (n = 3), or both (n = 1). The overall ERCP failure rate was 1.7% (9/524). Cannulation was successful in 99.4% (515/518) and unsuccessful in 0.6% (3/518) of cases in which the ampulla was reached. EUS-guided biliary drainage was indicated in 0.6% (3/524) of all referred native papilla ERCPs, or 33% (3/9) of those patients with failed ERCP; EUS-biliary drainage was successful in all cases. CONCLUSIONS: In a tertiary-care center, use of advanced ERCP techniques results in a high technical success rate. EUS-guided biliary drainage was required in only 0.6% of native papilla ERCPs, and although a number of excellent indications exist, it should not replace good ERCP technique.