Endoscopic therapies for bariatric surgery complications.

PURPOSE OF REVIEW: The aim of this review is to present the current state of the field, highlight recent developments, and describe the clinical outcomes of endoscopic therapies for bariatric surgery complications. RECENT FINDINGS: The field of interventional endoscopy now presents a range of minimally invasive procedures for addressing postbariatric complications. Lumen-opposing metal stents have emerged as a reliable solution for managing gastrojejunal strictures following Roux-en-Y gastric bypass, whether with or without associated leaks. Additionally, they serve as a conduit for performing endoscopic retrograde cholangiopancreatography (ERCP) post-RYGB via EUS-directed ERCP (EDGE). Gastric peroral endoscopic myotomy, originally designed for gastroparesis, has demonstrated effectiveness in treating postgastric sleeve stenosis, particularly the challenging helical stenosis cases. Furthermore, innovative endoscopic antireflux techniques are showing encouraging outcomes in addressing gastroesophageal reflux disease (GERD) following sleeve gastrectomy. Additionally, several modifications have been proposed to enhance the efficacy of transoral outlet reduction (TORe), originally developed to treat weight regain due to gastrojejunal anastomotic issues post-RYGB. SUMMARY: Endoscopic management of bariatric surgery complications is continuously evolving. The development of new techniques and devices allows endoscopists to provide novel, minimally invasive alternatives that were not possible in the near past. Many techniques, however, are limited to expert centers because they are technically demanding, and specialized training in bariatric endoscopy is still required.

American Society for Gastrointestinal Endoscopy-European Society of Gastrointestinal Endoscopy guideline on primary endoscopic bariatric and metabolic therapies for adults with obesity.

This joint ASGE-ESGE guideline provides an evidence-based summary and recommendations regarding the role of endoscopic bariatric and metabolic therapies (EBMTs) in the management of obesity. The document was developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. It evaluates the efficacy and safety of EBMT devices and procedures that currently have CE mark or FDA-clearance/approval, or that had been approved within five years of document development. The guideline suggests the use of EBMTs plus lifestyle modification in patients with a BMI of ≥ 30 kg/m2, or with a BMI of 27.0-29.9 kg/m2 with at least 1 obesity-related comorbidity. Furthermore, it suggests the utilization of intragastric balloons and devices for endoscopic gastric remodeling (EGR) in conjunction with lifestyle modification for this patient population.

American Society for Gastrointestinal Endoscopy-European Society of Gastrointestinal Endoscopy guideline on primary endoscopic bariatric and metabolic therapies for adults with obesity.

This joint ASGE-ESGE guideline provides an evidence-based summary and recommendations regarding the role of endoscopic bariatric and metabolic therapies (EBMTs) in the management of obesity. The document was developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. It evaluates the efficacy and safety of EBMT devices and procedures that currently have CE mark or FDA-clearance/approval, or that had been approved within five years of document development. The guideline suggests the use of EBMTs plus lifestyle modification in patients with a BMI of ≥30 kg/m2, or with a BMI of 27.0-29.9 kg/m2 with at least 1 obesity-related comorbidity. Furthermore, it suggests the utilization of intragastric balloons and devices for endoscopic gastric remodeling (EGR) in conjunction with lifestyle modification for this patient population.

Validation of GPT-4 for clinical event classification: A comparative analysis with ICD codes and human reviewers.

BACKGROUND AND AIM: Effective clinical event classification is essential for clinical research and quality improvement. The validation of artificial intelligence (AI) models like Generative Pre-trained Transformer 4 (GPT-4) for this task and comparison with conventional methods remains unexplored. METHODS: We evaluated the performance of the GPT-4 model for classifying gastrointestinal (GI) bleeding episodes from 200 medical discharge summaries and compared the results with human review and an International Classification of Diseases (ICD) code-based system. The analysis included accuracy, sensitivity, and specificity evaluation, using ground truth determined by physician reviewers. RESULTS: GPT-4 exhibited an accuracy of 94.4% in identifying GI bleeding occurrences, outperforming ICD codes (accuracy 63.5%, P < 0.001). GPT-4's accuracy was either slightly lower or statistically similar to individual human reviewers (Reviewer 1: 98.5%, P < 0.001; Reviewer 2: 90.8%, P = 0.170). For location classification, GPT-4 achieved accuracies of 81.7% and 83.5% for confirmed and probable GI bleeding locations, respectively, with figures that were either slightly lower or comparable with those of human reviewers. GPT-4 was highly efficient, analyzing the dataset in 12.7 min at a cost of 21.2 USD, whereas human reviewers required 8-9 h each. CONCLUSION: Our study indicates GPT-4 offers a reliable, cost-efficient, and faster alternative to current clinical event classification methods, outperforming the conventional ICD coding system and performing comparably to individual expert human reviewers. Its implementation could facilitate more accurate and granular clinical research and quality audits. Future research should explore scalability, prompt and model tuning, and ethical implications of high-performance AI models in clinical data processing.

A Combined DNA/RNA-based Next-Generation Sequencing Platform to Improve the Classification of Pancreatic Cysts and Early Detection of Pancreatic Cancer Arising From Pancreatic Cysts.

OBJECTIVE: We report the development and validation of a combined DNA/RNA next-generation sequencing (NGS) platform to improve the evaluation of pancreatic cysts. BACKGROUND AND AIMS: Despite a multidisciplinary approach, pancreatic cyst classification, such as a cystic precursor neoplasm, and the detection of high-grade dysplasia and early adenocarcinoma (advanced neoplasia) can be challenging. NGS of preoperative pancreatic cyst fluid improves the clinical evaluation of pancreatic cysts, but the recent identification of novel genomic alterations necessitates the creation of a comprehensive panel and the development of a genomic classifier to integrate the complex molecular results. METHODS: An updated and unique 74-gene DNA/RNA-targeted NGS panel (PancreaSeq Genomic Classifier) was created to evaluate 5 classes of genomic alterations to include gene mutations (e.g., KRAS, GNAS, etc.), gene fusions and gene expression. Further, CEA mRNA ( CEACAM5 ) was integrated into the assay using RT-qPCR. Separate multi-institutional cohorts for training (n=108) and validation (n=77) were tested, and diagnostic performance was compared to clinical, imaging, cytopathologic, and guideline data. RESULTS: Upon creation of a genomic classifier system, PancreaSeq GC yielded a 95% sensitivity and 100% specificity for a cystic precursor neoplasm, and the sensitivity and specificity for advanced neoplasia were 82% and 100%, respectively. Associated symptoms, cyst size, duct dilatation, a mural nodule, increasing cyst size, and malignant cytopathology had lower sensitivities (41-59%) and lower specificities (56-96%) for advanced neoplasia. This test also increased the sensitivity of current pancreatic cyst guidelines (IAP/Fukuoka and AGA) by >10% and maintained their inherent specificity. CONCLUSIONS: PancreaSeq GC was not only accurate in predicting pancreatic cyst type and advanced neoplasia but also improved the sensitivity of current pancreatic cyst guidelines.

Endoscopic sleeve gastroplasty for treatment of class 1 and 2 obesity (MERIT): a prospective, multicentre, randomised trial.

BACKGROUND: Endoscopic sleeve gastroplasty (ESG) is an endolumenal, organ-sparing therapy for obesity, with wide global adoption. We aimed to explore the efficacy and safety of ESG with lifestyle modifications compared with lifestyle modifications alone. METHODS: We conducted a randomised clinical trial at nine US centres, enrolling individuals aged 21-65 years with class 1 or class 2 obesity and who agreed to comply with lifelong dietary restrictions. Participants were randomly assigned (1:1·5; with stratified permuted blocks) to ESG with lifestyle modifications (ESG group) or lifestyle modifications alone (control group), with potential retightening or crossover to ESG, respectively, at 52 weeks. Lifestyle modifications included a low-calorie diet and physical activity. Participants in the primary ESG group were followed up for 104 weeks. The primary endpoint at 52 weeks was the percentage of excess weight loss (EWL), with excess weight being that over the ideal weight for a BMI of 25 kg/m2. Secondary endpoints included change in metabolic comorbidities between the groups. We used multiple imputed intention-to-treat analyses with mixed-effects models. Our analyses were done on a per-protocol basis and a modified intention-to-treat basis. The safety population was defined as all participants who underwent ESG (both primary and crossover ESG) up to 52 weeks. FINDINGS: Between Dec 20, 2017, and June 14, 2019, 209 participants were randomly assigned to ESG (n=85) or to control (n=124). At 52 weeks, the primary endpoint of mean percentage of EWL was 49·2% (SD 32·0) for the ESG group and 3·2% (18·6) for the control group (p<0·0001). Mean percentage of total bodyweight loss was 13·6% (8·0) for the ESG group and 0·8% (5·0) for the control group (p<0·0001), and 59 (77%) of 77 participants in the ESG group reached 25% or more of EWL at 52 weeks compared with 13 (12%) of 110 in the control group (p<0·0001). At 52 weeks, 41 (80%) of 51 participants in the ESG group had an improvement in one or more metabolic comorbidities, whereas six (12%) worsened, compared with the control group in which 28 (45%) of 62 participants had similar improvement, whereas 31 (50%) worsened. At 104 weeks, 41 (68%) of 60 participants in the ESG group maintained 25% or more of EWL. ESG-related serious adverse events occurred in three (2%) of 131 participants, without mortality or need for intensive care or surgery. INTERPRETATION: ESG is a safe intervention that resulted in significant weight loss, maintained at 104 weeks, with important improvements in metabolic comorbidities. ESG should be considered as a synergistic weight loss intervention for patients with class 1 or class 2 obesity. This trial is registered with ClinicalTrials.gov, NCT03406975. FUNDING: Apollo Endosurgery, Mayo Clinic.

Endoluminal bariatric and metabolic therapies: state-of-the-art.

PURPOSE OF REVIEW: The aim of this review is to present the current state of the field, highlight recent developments, and describe the clinical outcomes of these endoluminal bariatric and metabolic procedures. RECENT FINDINGS: The landscape of endoluminal devices and techniques for treating obesity has expanded significantly, with FDA-approved therapies currently available to patients with a body mass index values as high as 50 kg/m 2 . Although notable advancements have been made in this area, there is a need for further emphasis to be placed on the metabolic improvements resulting from these therapies, in addition to the conventional focus on weight loss outcomes. Some of these procedures are now FDA approved for the treatment of metabolic disease as opposed to weight loss. To achieve the most favorable results, it is imperative that all endoluminal interventions are combined with a moderately intensive diet and lifestyle program lasting at least 12 months. SUMMARY: Endoluminal metabolic and bariatric therapy represents a bridge between lifestyle counseling, pharmaceutical interventions, and the most efficacious treatment for obesity, bariatric surgery. By virtue of its minimally invasive approach, this therapy may be an appealing option for patients who are ineligible for, or averse to, bariatric surgery and who have experienced suboptimal outcomes or unable to afford medical treatments. Furthermore, these interventions may be particularly beneficial in the early stages of obesity.

Incidence, severity, and mortality of post-ERCP pancreatitis: an updated systematic review and meta-analysis of 145 randomized controlled trials.

BACKGROUND AND AIMS: The incidence, severity, and mortality of post-ERCP pancreatitis (PEP) largely remain unknown with changing trends in ERCP use, indication, and techniques. We sought to determine the incidence, severity, and mortality of PEP in consecutive and high-risk patients based on a systemic review and meta-analysis of patients in placebo and no-stent arms of randomized control trials (RCTs). METHODS: The MEDLINE, Embase, and Cochrane databases were searched from the inception of each database to June 2022 to identify full-text RCTs evaluating PEP prophylaxes. The incidence, severity, and mortality of PEP from the placebo or no-stent arms of RCTs were recorded for consecutive and high-risk patients. A random-effects meta-analysis for a proportions model was used to calculate PEP incidence, severity, and mortality. RESULTS: One hundred forty-five RCTs were found with 19,038 patients in the placebo or no-stent arms. The overall cumulative incidence of PEP was 10.2% (95% confidence interval [CI], 9.3-11.3), predominantly among the academic centers conducting such RCTs. The cumulative incidences of severe PEP and mortality were .5% (95% CI, .3-.7) and .2% (95% CI, .08-.3), respectively, across 91 RCTs with 14,441 patients. The cumulative incidences of PEP and severe PEP were 14.1% (95% CI, 11.5-17.2) and .8% (95% CI, .4-1.6), respectively, with a mortality rate of .2% (95% CI, 0-.3) across 35 RCTs with 3733 patients at high risk of PEP. The overall trend for the incidence of PEP among patients randomized to placebo or no-stent arms of RCTs has remained unchanged from 1977 to 2022 (P = .48). CONCLUSIONS: The overall incidence of PEP is 10.2% but is 14.1% among high-risk patients based on this systematic review of placebo or no-stent arms of 145 RCTs; this rate has not changed between 1977 and 2022. Severe PEP and mortality from PEP are relatively uncommon.

Endoscopic Retrograde Cholangiopancreatography Performed by Trainees Is Not Associated with Increased Immediate Adverse Events or Technical Failure Rates.

BACKGROUND/AIM: Training endoscopists to perform endoscopic retrograde cholangiopancreatography (ERCP) is critical to address the increasing patient population with pancreatobiliary diseases. Concerns remain about ERCP safety and success involving trainees. We compared the technical success and immediate adverse events between ERCP with and without trainee involvement. METHODS: Retrospective analysis of 28,271 ERCP procedures in a national sample of the United States over 12 years. Demographics, procedure and fluoroscopy time, visualization and cannulation of main structures, adverse events, and technical success rates were compared between ERCP with and without trainees. Categorical variables were compared using Pearson's chi-square test and continuous variables using a standard t-test. Univariate and multivariate regressions were performed adjusting for age, gender, ethnicity, US region, ASA class and clinical setting. RESULTS: Approximately 49.5% of ERCPs had a trainee involved. The ampulla was visualized in 97.4% with trainee vs. 97.3% without trainee involvement (P = 0.858). The common bile duct was visualized and cannulated in 90.4% with trainees vs. 91.7% without trainees involved (P < 0.001). The ERCP was incomplete in 5.9% of cases with trainees vs. 6.4% without trainees involved (P = 0.207). Trainee participation added 8.7 min to average procedure time (aOR: 1.02, P < 0.001) and 2.0 min to fluoroscopy time (aOR: 1.00, P = 0.796). Adverse events (aOR: 0.89, P = 0.704) and technical success (aOR: 0.83, P = 0.571) were similar in both groups. CONCLUSIONS: Trainee involvement leads to increased procedure duration but is not associated with increased immediate adverse events, or technical failure. Our study supports ERCP safety and success with trainee participation.

Transoral Outlet Reduction (TORe) for the Treatment of Weight Regain and Dumping Syndrome after Roux-en-Y Gastric Bypass.

Obesity is a chronic relapsing disease of global pandemic proportions. In this context, an increasing number of patients are undergoing bariatric surgery, which is considered the most effective weight loss treatment for long-term improvement in obesity-related comorbidities. One of the most popular bariatric surgeries is the Roux-en-Y gastric bypass (RYGB). Despite its proven short- and long-term efficacy, progressive weight regain and dumping symptoms remain a challenge. Revisional bariatric surgery is indicated when dietary and lifestyle modification, pharmaceutical agents and/or psychological therapy fail to arrest weight regain or control dumping. However, these re-interventions present greater technical difficulty and are accompanied by an increased risk of peri- and postoperative complications with substantial morbidity and mortality. The endoscopic approach to gastrojejunal anastomotic revision, transoral outlet reduction (TORe), is used as a minimally invasive treatment that aims to reduce the diameter of the gastrojejunal anastomosis, delaying gastric emptying and increasing satiety. With substantial published data supporting its use, TORe is an effective and safe bariatric endoscopic technique for addressing weight regain and dumping syndrome after RYGB.

Simple risk score to predict the likelihood of a positive EUS in idiopathic acute pancreatitis.

BACKGROUND AND AIMS: We sought to derive a risk score, DORM65, of known variables to predict the likelihood of a positive EUS in patients with idiopathic acute pancreatitis (IAP). METHODS: A retrospective cohort study of 180 patients with IAP was performed across 3 tertiary care centers between January 2018 and December 2021. Multivariate logistic regression modeling was performed to predict a positive EUS. Accuracy of the models was assessed by the area under the receiver-operating characteristic curve (AUROCC). RESULTS: The diagnostic yield of EUS was 58.9% (95% confidence interval [CI], 51.7-66.1). The DORM65 scores of 5 predictors present before EUS with the best discrimination were a delayed EUS (defined as ≥82 days from the last episode of AP), obesity, not having had a repeated transabdominal US, male sex, and age ≥65 years at the time of EUS. For those at the lowest risk score group, the positive EUS rate was 13.0% compared with 100% in those at the highest risk group (relative risk, 7.67; P < .001). A score of 3 or more had a positive predictive value of 86.0% with a sensitivity of 34.9% and specificity of 91.9%. The model had a high predictive accuracy (AUROCC, .774; 95% CI, .707-.841). Adding 3 additional predictors (no cholecystectomy, no MRCP, and a single episode of AP) did not increase the accuracy significantly (AUROCC, .805; 95% CI, .742-.867). CONCLUSIONS: DORM65 is easily calculated and accurately predicts a positive EUS in patients with IAP. Further validation is needed.

Gastric per-oral endoscopic myotomy (G-POEM) for the treatment of gastric sleeve stenosis: a feasibility and safety study.

BACKGROUND: Traditional endoscopic treatments have limited success in gastric sleeve stenosis (GSS). Gastric peroral endoscopic myotomy (G-POEM) could conceivably obliterate the twist/angulation that causes GSS through a tunneled stricturotomy. We report early outcomes of G-POEM for GSS treatment. METHODS: We retrospectively reviewed all patients with GSS treated with G-POEM at our center. The primary end point was clinical success, defined as symptom improvement with resumption of adequate oral intake, without requiring further intervention. RESULTS: 13 patients (mean age 43 ±â€Š10.9 years; 12 female) underwent G-POEM for predominantly helical (11/13, 85 %) GSS. Three (23 %) had concurrent sleeve leak and 10 (77 %) had prior GSS treatment. Two intraoperative complications occurred, with no deviation to the procedure; no major complications occurred. At median follow-up of 175 (interquartile range [IQR] 119-260) days, clinical success was achieved in 10 patients (77 %). Median Gastroparesis Cardinal Symptom Index score in responders decreased from 2.06 (IQR 1.5-2.8) to 0.39 (IQR 0.2-0.5). Three patients (23 %) required surgical revision. CONCLUSIONS: G-POEM was feasible and safe, and may provide an alternative option for those averse to undergoing surgical revision for treatment of GSS.

Zenker's peroral endoscopic myotomy, or flexible or rigid septotomy for Zenker's diverticulum: a multicenter retrospective comparison.

BACKGROUND: Treatment of Zenker's diverticulum has evolved from open surgery to endoscopic techniques, including flexible and rigid endoscopic septotomy, and more recently, peroral endoscopic myotomy (Z-POEM). This study compared the effectiveness of flexible and rigid endoscopic septotomy with that of Z-POEM. METHODS: Consecutive patients who underwent endoscopic septotomy (flexible/rigid) or Z-POEM for Zenker's diverticulum between 1/2016 and 9/2019 were included. Primary outcomes were clinical success (decrease in Dakkak and Bennett dysphagia score to ≤ 1), clinical failure, and clinical recurrence. Secondary outcomes included technical success and rate/severity of adverse events. RESULTS: 245 patients (110 females, mean age 72.63 years, standard deviation [SD] 12.37 years) from 12 centers were included. Z-POEM was the most common management modality (n = 119), followed by flexible (n = 86) and rigid (n = 40) endoscopic septotomy. Clinical success was 92.7 % for Z-POEM, 89.2 % for rigid septotomy, and 86.7 % for flexible septotomy (P = 0.26). Symptoms recurred in 24 patients (15 Z-POEM during a mean follow-up of 282.04 [SD 300.48] days, 6 flexible, 3 rigid [P = 0.47]). Adverse events occurred in 30.0 % rigid septotomy patients, 16.8 % Z-POEM patients, and 2.3 % flexible septotomy patients (P < 0.05). CONCLUSIONS: There was no difference in outcomes between the three treatment approaches for symptomatic Zenker's diverticulum. Rigid endoscopic septotomy was associated with the highest rate of complications, while flexible endoscopic septotomy appeared to be the safest. Recurrence following Z-POEM was similar to flexible and rigid endoscopic septotomy. Prospective studies with long-term follow-up are required.

The Attitude of Practitioners Towards Endoscopic Sleeve Gastroplasty.

BACKGROUND AND AIM: Despite widespread adoption and encouraging results seen over the last 5 years, no consensus exists regarding the endoscopic sleeve gastroplasty (ESG) technique, training, or preprocedure and postprocedure management of the patient. The aim of our survey was to assess practice trends and preferences of bariatric endoscopists with respect to ESG. METHODS: Using a digital platform, we conducted a worldwide survey by emailing a link with an electronic questionnaire to 1200 bariatric endoscopists trained to perform endoscopic suturing using the Apollo Overstitch suturing device (Apollo Endosurgery). RESULTS: We received 221 responses that were included in the analysis. Fifty-one responders (36.4%) required 1 to 10 procedures, and 37 (26.4%) needed 11 to 20 procedures to become proficient at ESG. Ninety-six (68.6%) stated that lower body mass index thresholds should be adopted for Asian and Arab patients. There was no consensus on the ideal number of sutures, with 45 (32.1%), 42 (30%), 36 (25.7%), 13 (9.3%), and 4 (2.9%) recommending 4 to 6, 5 to 7, 6 to 8, 7 to 9, and 8 to 12 sutures, respectively. The primary barriers to establishing an endobariatric program were the inability to establish a cash pay model, 77 (95.1%); lack of institutional support, 61 (75.3%); and difficulty in establishing an ambulatory surgical center/hospital to perform ESG, 73 (90.1%). CONCLUSIONS: ESG practice trends remain heterogenous among practitioners in regard to indication, technique, and preprocedure and postprocedure management. Specific ESG guidelines are warranted, and this survey will assist in providing the framework for these guidelines to be written.

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.

AGA Clinical Practice Update on Evaluation and Management of Early Complications After Bariatric/Metabolic Surgery: Expert Review.

DESCRIPTION: Endoscopic techniques are paramount in the identification and management of complications after surgery, though collaboration with other specialties is obligatory. Unfortunately, the evaluation and treatment algorithms are not standardized and there is a paucity of high-quality prospective studies to provide clarity regarding the best approach. The purpose of this clinical practice update is to apprise the clinician with respect to the endoscopic evaluation and management of patients with early (<90 days) complications after undergoing bariatric/metabolic surgery. METHODS: The best practice advice outlined in this expert review are based on available published evidence, including observational studies and systematic reviews, and incorporates expert opinion where applicable. BEST PRACTICE ADVICE 1: Clinicians performing endoscopic approaches to treat early major postoperative complications should do so in a multidisciplinary manner with interventional radiology and bariatric/metabolic surgery co-managing the patient. Daily communication is advised. BEST PRACTICE ADVICE 2: Clinicians embarking on incorporating endoscopic management of bariatric/metabolic surgical complications into their clinical practice should have a comprehensive knowledge of the indications, contraindications, risks, benefits, and outcomes of each of the endoscopic treatment techniques. They should also have knowledge of the risks and benefits of alternative methods such as surgical and interventional radiological based approaches. BEST PRACTICE ADVICE 3: Clinicians incorporating endoscopic management of bariatric/metabolic surgical complications into their clinical practice should have expertise in interventional endoscopy techniques, including but not limited to: using concomitant fluoroscopy, stent deployment and retrieval, managing stenosis, and managing percutaneous drains. BEST PRACTICE ADVICE 4: Clinicians should screen all patients undergoing endoscopic management of bariatric/metabolic surgical complications and dietary intolerance for comorbid medical (nutrient deficiencies, infection, pulmonary embolism) and psychological (depression, anxiety) conditions. BEST PRACTICE ADVICE 5: Endoscopic approaches to managing complications of bariatric/metabolic surgery may be considered for patients in the immediate, early and late postoperative periods depending on hemodynamic stability. BEST PRACTICE ADVICE 6: Clinicians incorporating endoscopic management of bariatric/metabolic surgical complications into their clinical practice should have a detailed understanding of the pathophysiologic mechanisms initiating and perpetuating conditions such as staple-line leaks. This will allow for a prompt diagnosis and appropriate therapy to be targeted not only at the area of interest, but also any concomitant downstream stenosis. BEST PRACTICE ADVICE 7: Clinicians should recognize that the goal for endoscopic management of staple-line leaks are often not necessarily initial closure of the leak site, but rather techniques to promote drainage of material from the perigastric collection into the gastric lumen such that the leak site closes by secondary intention.

Efficacy of Endoscopic Submucosal Dissection for Superficial Gastric Neoplasia in a Large Cohort in North America.

BACKGROUND & AIMS: Endoscopic submucosal dissection (ESD) is a widely accepted treatment option for superficial gastric neoplasia in Asia, but there are few data on outcomes of gastric ESD from North America. We aimed to evaluate the safety and efficacy of gastric ESD in North America. METHODS: We analyzed data from 347 patients who underwent gastric ESD at 25 centers, from 2010 through 2019. We collected data on patient demographics, lesion characteristics, procedure details and related adverse events, treatment outcomes, local recurrence, and vital status at the last follow up. For the 277 patients with available follow-up data, the median interval between initial ESD and last clinical or endoscopic evaluation was 364 days. The primary endpoint was the rate of en bloc and R0 resection. Secondary outcomes included curative resection, rates of adverse events and recurrence, and gastric cancer-related death. RESULTS: Ninety patients (26%) had low-grade adenomas or dysplasia, 82 patients (24%) had high-grade dysplasia, 139 patients (40%) had early gastric cancer, and 36 patients (10%) had neuroendocrine tumors. Proportions of en bloc and R0 resection for all lesions were 92%/82%, for early gastric cancers were 94%/75%, for adenomas and low-grade dysplasia were 93%/ 92%, for high-grade dysplasia were 89%/ 87%, and for neuroendocrine tumors were 92%/75%. Intraprocedural perforation occurred in 6.6% of patients; 82% of these were treated successfully with endoscopic therapy. Delayed bleeding occurred in 2.6% of patients. No delayed perforation or procedure-related deaths were observed. There were local recurrences in 3.9% of cases; all occurred after non-curative ESD resection. Metachronous lesions were identified in 14 patients (6.9%). One of 277 patients with clinical follow up died of metachronous gastric cancer that occurred 2.5 years after the initial ESD. CONCLUSIONS: ESD is a highly effective treatment for superficial gastric neoplasia and should be considered as a viable option for patients in North America. The risk of local recurrence is low and occurs exclusively after non-curative resection. Careful endoscopic surveillance is necessary to identify and treat metachronous lesions.

Endoscopic-mediated, biliary hydrodynamic injection mediating clinically relevant levels of gene delivery in pig liver.

BACKGROUND AND AIMS: Gene therapy could provide curative therapies to many inherited monogenic liver diseases. Clinical trials have largely focused on adeno-associated viruses (AAVs) for liver gene delivery. These vectors, however, are limited by small packaging size, capsid immune responses, and inability to redose. As an alternative, nonviral, hydrodynamic injection through vascular routes can successfully deliver plasmid DNA (pDNA) into mouse liver but has achieved limited success in large animal models. METHODS: We explored hydrodynamic delivery of pDNA through the biliary system into the liver of pigs using ERCP and a power injector to supply hydrodynamic force. Human factor IX (hFIX), deficient in hemophilia B, was used as a model gene therapy. RESULTS: Biliary hydrodynamic injection was well tolerated without significant changes in vital signs, liver enzymes, hematology, or histology. No off-target pDNA delivery to other organs was detected by polymerase chain reaction. Immunohistochemistry revealed that 50.19% of the liver stained positive for hFIX after hydrodynamic injection at 5.5 mg pDNA, with every hepatic lobule in all liver lobes demonstrating hFIX expression. hFIX-positive hepatocytes were concentrated around the central vein, radiating outward across all 3 metabolic zones. Biliary hydrodynamic injection in pigs resulted in significantly higher transfection efficiency than mouse vascular hydrodynamic injection at matched pDNA per liver weight dose (32.7%-51.9% vs 18.9%, P < .0001). CONCLUSIONS: Biliary hydrodynamic injection using ERCP can achieve higher transfection efficiency into hepatocytes compared with AAVs at magnitudes of less cost in a clinically relevant human-sized large animal. This technology may serve as a platform for gene therapy of human liver diseases.

Endoscopic gastrointestinal anastomosis: a review of established techniques.

Technologic advancements in the field of therapeutic endoscopy have led to the development of minimally invasive techniques to create GI anastomosis without requiring surgery. Examples of the potential clinical applications include bypassing malignant and benign gastric outlet obstruction, providing access to the pancreatobiliary tree in those who have undergone Roux-en-Y gastric bypass, and relieving pancreatobiliary symptoms in afferent loop syndrome. Endoscopic GI anastomosis is less invasive and less expensive than surgical approaches, result in improved outcomes, and therefore are more appealing to patients and providers. The aim of this review is to present the evolution of luminal endoscopic gastroenteric and enteroenteric anastomosis dating back to the first compression devices and to describe the clinical techniques being used today, such as magnets, natural orifice transluminal endoscopic surgery, and EUS-guided techniques. Through continued innovation, endoscopic interventions will rise to the forefront of the therapeutic arsenal available for patients requiring GI anastomosis.

Assessment of the learning curve for EUS-guided gastroenterostomy for a single operator.

BACKGROUND AND AIMS: EUS-guided gastroenterostomy (EUS-GE) is increasingly used as an alternative to surgery and enteral stent placement to manage gastric outlet obstruction (GOO). However, no data are available on the learning curve (LC) for EUS-GE. Defining the LC is necessary to create adequate subspecialty training programs and quality assurance. METHODS: This study is a retrospective analysis of a prospectively maintained dataset of patients who underwent EUS-GE at 1 tertiary referral center. Primary outcome was the LC for EUS-GE defined by the number of cases needed to achieve proficiency and mastery using cumulative sum (CUSUM) analysis. Moving average graphs and sequential time-block analysis were also performed to assess procedural time. Secondary outcomes included efficacy and safety of EUS-GE. RESULTS: Eighty-seven consecutive patients underwent EUS-GE, mostly for malignant GOO. For consistency, 14 patients were excluded from analysis (noncautery-assisted EUS-GE, 11; surgical anatomy, 3). The same endoscopist performed all procedures using the same freehand technique. Technical success was achieved in 68 of 73 patients (93%). Immediate adverse events occurred in 4 patients (5.5%), whereas late adverse events occurred only in 1 patient (1%), all managed conservatively or endoscopically. All immediate adverse events occurred during the first 39 cases. Clinical success (defined as resuming at least an oral liquid diet within a week) was achieved in 97% of patients. The mean procedural time was 36 minutes (standard deviation, 24). Evaluation of the CUSUM curve revealed that 25 cases were needed to achieve proficiency and 40 cases to achieve mastery. These results were confirmed with the average moving curve and sequential time-block analysis. CONCLUSIONS: We report, for the first time, data on the LC for EUS-GE. About 25 procedures can be considered as the threshold to achieve proficiency and about 40 cases are needed to reach mastery of the technique.