AGA Rapid Clinical Practice Update on the Management of Patients Taking GLP-1 Receptor Agonists Prior to Endoscopy: Communication.

DESCRIPTION: The purpose of this American Gastroenterological Association (AGA) Institute Rapid Clinical Practice Update (CPU) Communication is to review the available evidence and provide expert advice regarding the evolving management of patients taking GLP-1 receptor agonists prior to endoscopy. METHODS: This CPU was commissioned and approved by the AGA Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the CPUC and external peer review through standard procedures of Clinical Gastroenterology and Hepatology. This communication incorporates important and recently published studies in this field, and it reflects the experiences of the authors who are experts in bariatric medicine and/or endoscopy.

Transoral Outlet Reduction: Expert Tips, Tricks, and Troubleshooting.

Transoral outlet reduction (TORe) is an incisionless, endoscopic procedure to address weight recurrence after Roux-en-Y gastric bypass. Given the chronic, progressive nature of obesity and the minimally invasive, anatomy preserving technique of TORe, the procedure is expected to be met with high patient acceptance and widening clinical adoption. Nevertheless, the approach to TORe has been heterogeneous. As endoscopic bariatric therapies are increasingly incorporated into the multidisciplinary management of obesity, it is crucial to have a standardized, evidence-based framework for their implementation. In this review, based on the available literature and the authors' combined experience of over 1,000 TORe procedures, we present our approach to patient selection, procedural technique, troubleshooting, and patient aftercare unique to TORe.

Development of a novel endoscopic suturing simulator: validation and impact on clinical learning curve (with video).

BACKGROUND AND AIMS: Endoscopic suturing is a complex skill with broad applications. The aim of this study was to develop and validate a novel endoscopic suturing simulator and scoring system for the purse-string suture pattern. METHODS: This was a prospective study of an endoscopic suturing simulator that consists of a circular opening representing a dilated gastrojejunal anastomosis of Roux-en-Y gastric bypass with 12 small target holes around its circumference. Purse-string suturing is performed in a counterclockwise fashion. Time allotted is 5 minutes, and each successful bite is awarded 10 points. Participants were divided into the novice, intermediate, and experienced groups. Validity evidence based on content, validity evidence based on other variables, and validity evidence based on consequences of testing were assessed. RESULTS: Seventeen subjects (3 novice, 7 intermediate, and 7 experienced) participated in the study. Validity evidence based on content: The content validity index for realism, relevance, and representativeness was 0.89, 1.00, and 1.00, respectively. Validity evidence based on other variables: The novice, intermediate, and experienced groups scored 30.0 ± 8.2, 57.1 ± 28.1, and 131.2 ± 51.7 (P = .001). Validity evidence based on consequences of testing: The simulator group required 5 ± 5 transoral outlet reduction cases before being able to independently complete an entire purse-string, whereas the non-simulator group required 38 ± 11 clinical cases (P < .0001). CONCLUSIONS: This novel endoscopic suturing simulator seems realistic, relevant, and representative of the clinical suturing experience. In addition, it seems effective at objectively assessing suturing skills and shortening the clinical learning curve.

Bariatric Endoscopic Antral Myotomy: A Pilot Study Assessing Technical Feasibility, Physiologic Changes, and Preliminary Efficacy.

BACKGROUND AND AIMS: Gastric balloons and endoscopic sleeve gastroplasty appear to work by delaying gastric emptying. We hypothesized that pylorus-sparing antral myotomy would inhibit the antral pump inducing gastric retention and similarly result in weight loss. METHODS: Single-center pilot study to assess bariatric endoscopic antral myotomy (BEAM) via submucosal tunneling. Primary outcomes included feasibility, safety, and efficacy at 6 and 12 months. Secondary outcomes included changes in gastric emptying rate and GCSI score. RESULTS: Six subjects underwent successful BEAM. One required needle decompression, and another developed pulmonary embolism, treated without sequela. At 6 and 12 months, patients achieved 9.1±8.9% and 12.2±7.1% TWL (P<0.0005). Gastric emptying rate was delayed by 36.6% in those with ≥10% TWL. GCSI increased significantly at 12 months, particularly early satiety. CONCLUSION: This pilot study suggests BEAM is feasible and appears to induce delayed gastric emptying that is associated with significant weight loss, without symptoms of gastroparesis.

Endoscopic ultrasound-guided liver palpation as a screening tool for advanced fibrosis and cirrhosis in patients with suspected metabolic dysfunction-associated steatotic liver disease: a pilot study.

BACKGROUND AND AIMS: Endoscopic liver "palpation" can be performed by indenting the liver surface under endoscopic ultrasound (EUS). Indentation depth is measured with the use of sonographic calipers. We hypothesized that fibrotic livers are more difficult to indent, and that indentation can accurately predict liver fibrosis staging. We compared EUS-guided liver palpation and conventional screening modalities in patients with suspected metabolic dysfunction-associated steatotic liver disease. METHODS: This was a cross-sectional pilot study. Consecutive patients at 3 hospitals from 2021 to 2023 underwent EUS-guided palpation with liver biopsy. Liver palpation was compared with fibrosis-4 index (FIB-4), aspartate transaminase to platelet ratio index (APRI), nonalcoholic fatty liver disease fibrosis score (NFS), and transient elastography in predicting fibrosis staging on histology. Area under the receiver operating characteristic curve analysis was performed. RESULTS: Seventy-three patients were included. Mean age was 49.1 years, and 71.2% were female. Mean body mass index was 41.1 kg/m.2 Indentation depth was negatively correlated with fibrosis stage (Kruskal-Willis test, P < .0001). EUS palpation demonstrated c-statistics of 0.79 and 0.95 in discriminating advanced fibrosis and cirrhosis, respectively. EUS liver palpation was superior to NFS in predicting advanced fibrosis (P = .0057) and superior to APRI and NFS in predicting cirrhosis (P = .0099 and P = .045, respectively). EUS palpation was not significantly different from FIB-4. EUS palpation was superior to transient elastography in predicting cirrhosis (P = .045). When optimal cutoffs were used, indentation measurement ≤3.5 mm yielded 100% predictive value for ruling in advanced fibrosis, and ≥4.0 mm yielded 100% predictive value for ruling out cirrhosis. CONCLUSIONS: EUS liver palpation is a novel, accurate, and easy-to-use screening tool for advanced fibrosis and cirrhosis in patients with metabolic dysfunction-associated steatotic liver disease.

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.

The effect of endoscopic gastric plication on portosystemic pressure gradient in patients with nonalcoholic fatty liver disease and compensated advanced chronic liver disease.

BACKGROUND: The goals of therapy for patients with nonalcoholic fatty liver disease and compensated advanced chronic liver disease include weight loss and reduction of the portosystemic pressure gradient (PPG) to decrease the risk of hepatic decompensation. Endoscopic gastric plication (EGP) is an effective endoscopic weight loss procedure. This study aimed to assess the effect of EGP on PPG. METHODS: In this prospective pilot study, patients with nonalcoholic fatty liver disease and compensated advanced chronic liver disease underwent endoscopic ultrasound-guided PPG measurement prior to and at 6 months following EGP. Primary outcomes were the change in PPG and proportion of patients experiencing ≥ 20 % reduction in PPG at 6 months. Secondary outcomes included percent total weight loss (TWL) and changes in noninvasive tests of fibrosis. RESULTS: 20 patients were included. Baseline median body mass index and liver stiffness measurement were 40.2 kg/m2 (range 30.1-56.7) and 14.7 kPa (range 8.2-36), respectively. At 6 months, median PPG decreased from 5.4 mmHg (range 0.7-19.6) to 1.8 mmHg (range 0.4-17.6) (P = 0.002), with 79 % (11/14) experiencing ≥ 20 % reduction. Patients experienced 12.5 % (6.5 %-26.1 %) TWL (P < 0.001) at 6 months, with 89 % (17/19) achieving ≥ 7 % and 68 % (13/19) achieving ≥ 10 % TWL. There were significant improvements in noninvasive tests of fibrosis. CONCLUSION: EGP appeared to be effective at reducing PPG in patients with nonalcoholic fatty liver disease and compensated advanced chronic liver disease.

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.

Efficacy and Safety of Gastric Per-Oral Endoscopic Myotomy (G-POEM): A Systematic Review and Meta-Analysis.

BACKGROUND: Gastric per-oral endoscopic myotomy (G-POEM) is an innovative treatment that has become increasingly utilized for patients with refractory gastroparesis. The aim of this systematic review and meta-analysis was to evaluate the safety and effectiveness of G-POEM for the treatment of gastroparesis. METHODS: Individualized search strategies were developed through February 2021 in accordance with the PRISMA and MOOSE guidelines. This meta-analysis was performed by calculating pooled proportions and mean difference preprocedure and postprocedure with rates estimated using random effects models. Measured outcomes included technical success, clinical success, improvement in gastroparesis cardinal symptom index (GCSI), change in gastric emptying rate, alterations in impedance planimetry (functional lumen imaging probe [FLIP]) assessment, and adverse events. RESULTS: A total of 20 studies (n=797 patients; 67.41% female) were included. The mean age was 48.92±11.61 y, with an average duration of 4.24±1.11 y since gastroparesis diagnosis. Technical success was 98.47% [(95% CI: 97.14, 99.19);I2=0.00] with a mean myotomy length of 3.78±1.16 cm. In terms of clinical success, mean preprocedure GCSI scores were 3.38±0.37 and improved significantly postprocedure [weighted mean difference -1.56 (95% CI: -1.89 to -1.24); I2=82.53; P<0.001]. Gastric retention after 4 hours demonstrated ~50% improvement (preprocedure 43.08±9.24% versus postprocedure 22.97±10.19%; P<0.001). FLIP assessment with 40 mL and 50 mL balloons demonstrated a significant increase in diameter, distensibility index, and cross-sectional area postprocedure (all P<0.05). Procedure-associated adverse events occurred among 10.92% [(95% CI 5.09 to 19.32); I2=82.85] of patients. CONCLUSION: G-POEM appears safe and highly effective for the treatment of patients with refractory gastroparesis regardless of symptom predominance or etiology.

Obesity Is Associated with Altered Rectal Sensitivity in Chronic Constipation.

BACKGROUND: Defecation dysfunction may contribute to chronic constipation (CC), but the impact of obesity on anorectal physiology in CC remains unclear. We aimed to evaluate the relationship between obesity and anorectal function on physiologic testing in patients presenting with CC. METHODS: This was a retrospective cohort study of consecutive adults who underwent high resolution anorectal manometry (HRAM) at a tertiary center for CC. Patient demographics, clinical history, surgical/obstetric history, medications, and HRAM results were reviewed. Patients were classified into obese (BMI > 30 kg/m2) vs non-obese (BMI < 30 kg/m2) groups at the time of HRAM. Fisher-exact/student t-test for univariate analyses and general linear regression for multivariable analysis were performed. RESULTS: 383 adults (mean 50.3 years; 85.8% female) with CC were included. On HRAM, patients with obesity had lower anal sphincter resting tone (37.3 vs 48.5 mmHg, p = 0.005) and maximum squeeze pressure (104.8 mmHg vs 120.0 mmHg, p = 0.043). No significant differences in dyssynergia (61% vs 53%, p = 0.294) and failed balloon expulsion (18% vs 25%, p = 0.381) were found between obese and non-obese groups. On balloon distention testing, the maximum tolerated (163.5 vs 147.6 mL, p = 0.042) and urge sensation (113.9 vs 103.7 mL, p = 0.048) volumes were significantly increased among patients with obesity. After adjusting for potential confounders, obesity remained independently associated with increased maximum tolerated volume (ß-coefficient 13.7, p = 0.049). CONCLUSION: Obesity was independently associated with altered rectal sensitivity among patients with CC. Altered rectal sensation may play an important role in CC among patients with obesity. Anorectal physiology testing should be considered to understand the pathophysiology and guide management.

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.

Regression of Hepatic Fibrosis After Endoscopic Gastric Plication in Nonalcoholic Fatty Liver Disease.

INTRODUCTION: Fibrosis stage is the strongest predictor of mortality in patients with nonalcoholic fatty liver disease (NAFLD). There is currently no approved therapy that specifically targets fibrosis. This study aims to assess the effect of endoscopic gastric plication on hepatic fibrosis in patients with underlying NAFLD. METHODS: This is a retrospective analysis of prospectively collected registry of patients with obesity and NAFLD with clinically significant hepatic fibrosis (≥F2) who underwent endoscopic gastric plication. Full-thickness plications were placed in the gastric body using a commercially available platform to reduce the gastric volume. The primary outcome included various noninvasive tests (NITs) of hepatic fibrosis based on clinical chemistry and/or imaging. The secondary outcomes included NITs of hepatic steatosis, other metabolic outcomes, including hemoglobin A1c, insulin resistance, and total weight loss (TWL), and adverse events. RESULTS: Forty-five patients (age 51 ± 13 years and body mass index 40.7 ± 6.9 kg/m 2 ) were included. All patients underwent endoscopic gastric plication successfully. At 6-12 months, there were significant reductions in biochemistries (alanine aminotransferase: 49.7 ± 36.8 U/L to 24.2 ± 12.0 U/L [ P < 0.0001], aspartate aminotransferase: 39.1 ± 24.1 U/L to 24.1 ± 10.0 U/L [ P < 0.0001]), composite fibrosis score (NAFLD fibrosis score: 0.48 ± 1.51 to -1.18 ± 1.56 [ P < 0.0001], fibrosis-4 index: 1.4 ± 1.2 to 1.2 ± 0.7 [ P = 0.03]), and imaging-based markers of fibrosis (vibration-controlled transient elastography: 13.9 ± 7.5 kPa to 8.9 ± 4.8 kPa ( P < 0.0001) and Agile 3+: 0.53 ± 0.28 to 0.37 ± 0.28 [ P = 0.001]). There were significant reductions in controlled attenuation parameter, Homeostatic Model Assessment for Insulin Resistance, and hemoglobin A1c ( P < 0.05 for all). At 12 months, patients experienced 15.5% ± 7.9% TWL, with 63% reaching at least 10% TWL. DISCUSSION: Endoscopic gastric plication seems effective at treating NAFLD, with significant reduction in NITs of hepatic fibrosis even in patients with cirrhosis.

Endoscopic therapy for gastroesophageal reflux disease: where are we, where are we going?

PURPOSE OF REVIEW: Gastroesophageal reflux disease (GERD) is the most common chronic condition with increasing prevalence in the Western world. Despite medical therapy, a considerable proportion of patients continue to experience symptoms, thus fueling the demand for minimally invasive GERD treatment options. This review will assess the currently available endoscopic approaches by analyzing their outcomes data, indication for use and limitations. RECENT FINDINGS: With increasing evidence of the safety and efficacy of endoscopic therapies, recent guidelines and consensus society documents have updated their recommendations for the endoscopic treatment of GERD. In this review, we have comprehensively assessed the current landscape of endoscopic approaches for the treatment of GERD and provided insight into future directions. SUMMARY: Endoscopic therapies for GERD show promise as new treatments emerge and existing therapies evolve into safer and more reproducible options. They are well positioned to cater to a large subset of the population suffering from chronic condition of GERD.

Combining transoral outlet reduction with pharmacotherapy yields similar 1-year efficacy with improved safety compared with surgical revision for weight regain after Roux-en-Y gastric bypass (with videos).

BACKGROUND AND AIMS: Transoral outlet reduction (TORe) and antiobesity medication (AOM) are effective treatments for weight regain after Roux-en-Y gastric bypass (RYGB). This study aims to assess the efficacy of combination therapy (TORe + AOM) for treating weight regain and to compare the safety and efficacy of combination therapy with AOM alone, TORe alone, and surgical revision of RYGB. METHODS: This was a retrospective study of RYGB patients with weight regain who underwent combination therapy, defined as initiation of at least 1 AOM within 6 months before or after TORe. Outcomes were weight loss after combination therapy and comparison of combination therapy with AOM alone, TORe alone, and surgical revision. RESULTS: One hundred forty-five RYGB patients underwent combination therapy. Most commonly prescribed AOMs were topiramate, phentermine/topiramate, phentermine, and liraglutide. At 12 months, patients experienced 15.2% ± 7.4% total weight loss (TWL). Ninety percent of patients achieved ≥5% TWL at 12 months. Combination therapy was associated with greater weight loss than AOM alone (15.2% ± 7.4% vs 6.8% ± 8.2% TWL, P < .0001) or TORe alone (15.2% ± 7.4% vs 8.7% ± 8.3% TWL, P < .0001), with similar serious adverse event rates (2.1% vs 4.7% vs .6% for combination therapy vs AOM alone vs TORe alone, P > .05). Combination therapy yielded similar weight loss to surgical revision (15.2% ± 7.4% vs 16.4% ± 13.1% TWL, P = .34), with a lower serious adverse event rate (2.1% vs 14.3%, P = .0004). CONCLUSIONS: Combination of TORe with AOM is superior to either therapy alone, providing similar efficacy to surgical revision with a better safety profile for the treatment of weight regain after RYGB.

Short-term outcomes after peroral endoscopic myotomy, Heller myotomy, and pneumatic dilation in patients with achalasia: a nationwide analysis.

BACKGROUND AND AIMS: Peroral endoscopic myotomy (POEM), laparoscopic Heller myotomy (LHM), and pneumatic dilation (PD) are the most common modalities for management of achalasia. Our study aimed to directly compare their short-term outcomes and safety profile in a hospitalized cohort in the United States. METHODS: The National Readmission Database (2016-2019) was queried using International Classification of Diseases, Tenth Revision, Clinical Modification codes to identify a cohort of inpatient admissions who underwent POEM, LHM, or PD. Baseline demographic variables, resource utilization, periprocedural outcomes, and 30-day readmissions were analyzed. A univariate and multivariate logistic regression model was used to compare odds of readmission with POEM as a reference. RESULTS: LHM was the most performed procedure (n = 9710) as compared with PD (n = 2453) and POEM (n = 1911). Patients undergoing PD were older with a higher Charlson Comorbidity Index. The 30-day readmission rate was 4.3%, 3.9%, and 12.6% for POEM, LHM, and PD, respectively. Compared with POEM, the adjusted odds of readmission for PD was 2.42 (95% confidence interval, 1.56-3.75). There was no statistically significant difference in odds of readmission for LHM (.91; 95% confidence interval, .62-1.33) compared with POEM. Within the 30-day readmitted population, 13.1% of PD and 3.4% of LHM patients required achalasia-related procedural intervention. The rate of bleeding (4.3%), blood transfusion (2.3%), and mortality were higher (1.1%) in PD as compared with POEM and LHM. CONCLUSIONS: In the United States, the risk of readmission and resource utilization are higher in patients with achalasia undergoing PD. The outcomes are comparable between POEM and LHM, but there is a significant difference between the utilization of these myotomy procedures.

Impact of second-generation transoral incisionless fundoplication on atypical GERD symptoms: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Transoral incisionless fundoplication (TIF) using the EsophyX device (EndoGastric Solutions, Inc, Redmond, Wash, USA) is a minimally invasive endoscopic fundoplication technique. Our study aimed to assess the efficacy of TIF for atypical GERD symptoms in patients with chronic or refractory GERD. METHODS: A systematic search of 4 major databases was performed. All original studies assessing atypical GERD using a validated symptom questionnaire (the reflux symptom index [RSI]) were included. The RSI score was assessed before and after TIF at a 6- and 12-month follow-up. Data on technical success rate, adverse events, proton pump inhibitor (PPI) use, and patient satisfaction were also collected. Only TIF procedures currently in practice using the EsophyX device (ie, TIF 2.0) and TIF with concomitant hiatal hernia repair were included in the review. RESULTS: Ten studies (564 patients) were included. At the 6- and 12- month follow-up, there was a mean reduction of 15.72 (95% confidence interval, 12.15-19.29) and 14.73 (95% confidence interval, 11.74-17.72) points, respectively, in the RSI score post-TIF, with a technical success rate of 99.5% and a pooled adverse event rate of 1%. At both time intervals, more than two-thirds of the patients were satisfied with their health condition and roughly three-fourths of the patients were off daily PPIs. CONCLUSIONS: Our study shows that TIF using the EsophyX device is safe and effective in reducing atypical GERD symptoms at 6 and 12 months of follow-up. It improves patient-centered outcomes and can be a minimally invasive therapeutic option for patients suffering from atypical GERD symptoms on chronic medical therapy.

Reconsideration of the Gastroparetic Syndrome.

PURPOSE OF REVIEW: Gastroparesis is a chronic disorder characterized by a constellation of foregut symptoms, including postprandial nausea, vomiting, distension, epigastric pain, and regurgitation in the absence of gastric outlet obstruction. Despite considerable research over the past decades, there remains to be only nominal understanding of disease classification, diagnostic criteria, pathogenesis, and preferred therapy. RECENT FINDINGS: We critically reassess current approaches for disease identification and stratification, theories of causation, and treatment for gastroparesis. Gastric scintigraphy, long considered a diagnostic standard, has been re-evaluated in light of evidence showing low sensitivity, whereas newer testing modalities are incompletely validated. Present concepts of pathogenesis do not provide a unified model linking biological impairments with clinical manifestations, whereas available pharmacological and anatomical treatments lack explicit selection criteria or evidence for sustained effectiveness. We propose a disease model that embodies the re-programming of distributed neuro-immune interactions in the gastric wall by inflammatory perturbants. These interactions, combined with effects on the foregut hormonal milieu and brain-gut axis, are postulated to generate the syndromic attributes characteristically linked with gastroparesis. Research linking models of immunopathogenesis with diagnostic and therapeutic paradigms will lead to reclassifications of gastroparesis that guide future trials and technological developments. KEY POINTS: • The term gastroparesis embodies a heterogenous array of symptoms and clinical findings based on a complex assimilation of afferent and efferent mechanisms, gastrointestinal locations, and pathologies. • There currently exists no single test or group of tests with sufficient capacity to be termed a definitional standard for gastroparesis. • Present research regarding pathogenesis suggests the importance of immune regulation of intrinsic oscillatory activity involving myenteric nerves, interstitial cells of Cajal, and smooth muscle cells. • Prokinetic pharmaceuticals remain the mainstay of management, although novel treatments are being studied that are directed to alternative muscle/nerve receptors, electromodulation of the brain-gut axis, and anatomical (endoscopic, surgical) interventions.

Adjustable intragastric balloon for treatment of obesity: a multicentre, open-label, randomised clinical trial.

BACKGROUND: Intragastric balloons are anatomy-preserving, minimally invasive obesity therapies. Enhanced tolerance and durability could help broaden clinical adoption. We investigated the safety and efficacy of an adjustable intragastric balloon (aIGB) in adults with obesity. METHODS: In this prospective, multicentre, open-label, randomised clinical trial done at seven US sites, adults aged 22-65 years with obesity were randomly assigned (2:1) to aIGB with lifestyle intervention or lifestyle intervention alone (control) for 32 weeks. Balloon volume could be increased to facilitate weight loss or decreased for tolerability. Coprimary endpoints included mean percentage total bodyweight loss and responder rate (≥5% total bodyweight loss) at 32 weeks. We used a multiple imputed intention-to-treat population analysis. This study was registered with ClinicalTrials.gov, NCT02812160. FINDINGS: Between Aug 9, 2016, and Dec 7, 2018, we randomly assigned 288 patients to aIGB (n=187 [65%]) or control (n=101 [35%]) groups. Mean total bodyweight loss at 32 weeks was 15·0% (95% CI 13·9-16·1) in the aIGB group versus 3·3% (2·0-4·6) in the control group (p<0·0001). Clinical response was observed in 171 (92%) patients in the aIGB group. Adjustments to the aIGB occurred in 145 (80%) patients for weight loss plateau or intolerance. Upward volume adjustment facilitated an additional mean 5·2% (4·5-5·8) total bodyweight loss. Downward volume adjustment allowed 21 (75%) patients in the aIGB group to complete the full duration of therapy. Intolerance caused early removal of the device in 31 (17%) patients. No micronutrient deficiencies were observed in the aIGB cohort. Device-related serious adverse events were observed in seven (4%) patients, without any deaths. INTERPRETATION: When aIGB was combined with lifestyle modification, significant weight loss was achieved and maintained for 6 months following removal. Balloon volume adjustability permitted individualised therapy, maximising weight loss and tolerance. FUNDING: Spatz Medical.

Effect of Endoscopic Bariatric and Metabolic Therapies on Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Weight loss via lifestyle intervention remains the mainstay of treatment for nonalcoholic fatty liver disease (NAFLD). Endoscopic bariatric and metabolic therapies (EBMTs) have recently been developed as an alternative treatment option for obesity. This study aimed to assess the effect of FDA-approved EBMTs on NAFLD. METHODS: We searched MEDLINE, EMBASE, Web of Science and Cochrane Central through December 2020 for studies that assessed changes in liver outcomes following EBMT. Primary Outcomes: Liver fibrosis. SECONDARY OUTCOMES: Liver biochemistry, steatosis, NAFLD histological changes and insulin sensitivity. The Grading of Recommendations, Assessment, Development, and Evidence (GRADE) approach was conducted to assess quality of evidence. RESULTS: Of 4994 potential studies, 18 studies with 863 patients were included. Average weight loss was 14.5% of initial weight at a 6-month follow-up. Primary outcomes: Following EBMT, liver fibrosis significantly reduced by standardized mean difference (SMD) of 0.7 (95% CI, 0.1, 1.3; P = .02). SECONDARY OUTCOMES: There were significant improvements in other NAFLD surrogates including alanine aminotransferase (-9.0 U/L; 95% CI, -11.6, -6.4; P < .0001), hepatic steatosis (SMD: -1.0; 95% CI, -1.2, -0.8; P < .0001) and histologic NAFLD activity score (-2.50; 95% CI, -3.5, -1.5; P < .0001). Other metabolic parameters including insulin resistance and waist circumference also significantly improved. The overall quality of the evidence for primary outcomes was low to very low. CONCLUSIONS: EBMTs appear effective at treating NAFLD with significant improvement in liver fibrosis. Given the worsening NAFLD pandemic and limitations of currently available therapies, EBMTs should be further investigated as a potential treatment option for this patient population.

Comparison of distal primary obesity surgery endolumenal techniques for the treatment of obesity (with videos).

BACKGROUND AND AIMS: Distal primary obesity surgery endolumenal (POSE) procedures involve plication of the gastric body, sparing the fundus. We aim to assess the efficacy of distal POSE procedures and to compare plication techniques (single-helix vs double-helix approaches). METHODS: This is a prospective registry study of patients who underwent distal POSE procedures using 2 techniques: the single-helix plication technique, in which a single plication with serosa-to-serosa approximation is obtained with each device activation, and the double-helix plication technique, where 2 serosa-to-serosa plications with an internal mucosa-to-mucosa approximation are obtained with each device activation. RESULTS: One hundred ten patients (90 women; mean age, 43 ± 13 years) underwent distal POSE procedures. Baseline body mass index was 38.2 ± 6.1 kg/m2. Technical success was 100%. An average of 21 ± 5 plications were placed per case. The gastric body was shortened by 74%. At 12 months, patients experienced 15.8% ± 8.9% total weight loss (TWL) (P < .0001), with 93% and 61% achieving at least 5% and 10% TWL, respectively. Blood pressure, insulin resistance, and liver enzymes improved. The serious adverse event rate was .9%, including a case of gastric perforation. Of 110 patients, 42 and 68 underwent distal POSE procedures using a single- or double-helix technique, respectively. The double-helix technique resulted in greater reduction in gastric volume (length reduction by 78% vs 65%, P < .0001), weight loss (20.3% ± 8.3% vs 13.4% ± 8.3% TWL, P = .005), and proportion of patients achieving 10% TWL (94.7% vs 58.3%, P = .03) than the single-helix technique. CONCLUSIONS: Distal POSE techniques appear to be effective at treating obesity and its related comorbidities. The double-helix technique is associated with greater gastric volume reduction, weight loss, and response rate.