Safe Continuation of Glucagon-like Peptide 1 Receptor Agonists at Endoscopy: A Case Series of 57 Adults Undergoing Endoscopic Sleeve Gastroplasty.

PURPOSE: Glucagon-like receptor agonists (GLP1-RAs) have raised peri-procedural concerns due to their potential to delay gastric emptying. The American Association of Anesthesiologists has advised pausing a single dose before elective endoscopy. However, a subsequent directive from multiple gastroenterology societies underscored the need for further assessment to substantiate this practice. We aimed to evaluate the frequency of serious adverse events and retained gastric products during endoscopic sleeve gastroplasty (ESG) with uninterrupted GLP1-RA use. MATERIALS AND METHODS: We conducted a retrospective evaluation of all patients undergoing ESG while on GLP1-RAs at three centers from August 2022 to February 2024. Per standard protocol, all patients had refrained from solid foods for at least 24 h and maintained nil per os for 12 h preceding their ESG. Records were reviewed for patient characteristics and medication type and doses. Primary outcomes included serious adverse events and retained gastric products based on patient records, procedure reports, and procedural videos. RESULTS: Fifty-seven consecutive adults (89.5% women, mean age of 44 ± 9 years, mean BMI of 40.1 ± 8.1 kg/m2, 35.1% with T2DM, and 26.3% with pre-T2DM) underwent ESG without stopping GLP1-RAs, which included semaglutide (45.6%), liraglutide (19.3%), dulaglutide (22.8%), and tirzepatide (12.3%). During intubation, endoscopy, and recovery, there were no instances of retained gastric solids, pulmonary aspiration, gastroesophageal regurgitation, or hypoxia. CONCLUSION: A ≥ 24-h pre-endoscopy liquid-only diet with ≥ 12-h pre-endoscopy fast may negate the need for GLP1-RA interruption for routine upper endoscopy in adults with native gastric anatomy.

Early Successful Experiences of Surgical Conversion of Endoscopic Gastric Plication to Roux-en-Y Gastric Bypass.

BACKGROUND: The primary obesity surgery endoluminal (POSE) procedure is an innovative incision-less endoscopic bariatric procedure that is increasingly used. However, variable weight loss response and recurrence post-endoscopic bariatric procedures have at times necessitated laparoscopic bariatric conversion. The safety and approach of conversion to laparoscopic sleeve gastrectomy (LSG) or Roux-en-Y gastric bypass (RYGB), however, have been an active point of discussion within revisional bariatric surgery. METHODS: This retrospective review of four consecutive patients is the largest description of medium-term postoperative outcomes and technical highlights of a laparoscopic conversion of POSE to RYGB. Chart review was completed to evaluate patients' post-POSE clinical course and perioperative outcomes after surgical conversion. RESULTS: Early data suggests varied weight loss trajectory with POSE and marked improvement in weight response after surgical conversion. Qualitative review reveals successful single-staged conversions contrary to previous smaller case series describing staged conversions involving endoscopic removal of plications followed by RYGB. Review additionally reveals key perioperative considerations for successful conversions to include intraoperative endoscopy, upper gastrointestinal fluoroscopic studies, and at times computed tomography. The latter study and laparoscopic view of the post-POSE stomach challenge the prior notion that distal POSE allows for easy revision to LSG. CONCLUSIONS: Our case series underscores the complex multifactorial nature of metabolic disease and the increasing importance of a conscientious approach to conversion bariatric surgery as the adoption of POSE and the bariatric patient population continues to grow.

Novel through-the-scope suture closure of colonic EMR defects (with video).

BACKGROUND AND AIMS: Large colon polyps removed by EMR can be complicated by delayed bleeding. Prophylactic defect clip closure can reduce post-EMR bleeding. Larger defects can be challenging to close using through-the-scope clips (TTSCs), and proximal defects are difficult to reach using over-the-scope techniques. A novel, through-the-scope suturing (TTSS) device allows direct closure of mucosal defects without scope withdrawal. The goal of this study was to evaluate the rate of delayed bleeding after the closure of large colon polyp EMR sites with TTSS. METHODS: A multicenter retrospective cohort study was performed involving 13 centers. All defect closure by TTSS after EMR of colon polyps ≥2 cm from January 2021 to February 2022 were included. The primary outcome was rate of delayed bleeding. RESULTS: A total of 94 patients (52% female; mean age, 65 years) underwent EMR of predominantly right-sided (n = 62 [66%]) colon polyps (median size, 35 mm; interquartile range, 30-40 mm) followed by defect closure with TTSS during the study period. All defects were successfully closed with TTSS alone (n = 62 [66%]) or with TTSS and TTSCs (n = 32 [34%]), using a median of 1 (interquartile range, 1-1) TTSS system. Delayed bleeding occurred in 3 patients (3.2%), with 2 requiring repeated endoscopic evaluation/treatment (moderate). CONCLUSION: TTSS alone or with TTSCs was effective in achieving complete closure of all post-EMR defects, despite a large lesion size. After TTSS closure with or without adjunctive devices, delayed bleeding was seen in 3.2% of cases. Further prospective studies are needed to validate these findings before wider adoption of TTSS for large polypectomy closure.

Retained Food During Esophagogastroduodenoscopy Is a Risk Factor for Gastric-to-Pulmonary Aspiration.

BACKGROUND: Residual food (RF) during esophagogastroduodenoscopy (EGD) is thought, but not proven, to be a risk factor for gastric-to-pulmonary aspiration. AIMS: The aims of this study were to determine the prevalence of RF during EGD, to investigate whether RF was associated with an increased risk of aspiration, especially when monitored anesthesia care (MAC) or general anesthesia (GA) were administered, and to determine whether aspiration associated with RF led to a more severe clinical outcome. METHODS: Patients undergoing EGD between October 2012 and September 2018 were identified. Patient age, sex, aspiration events, RF, sedation type, structural foregut abnormalities, and diagnoses associated with impaired esophageal or gastric motility were noted. The clinical course after an aspiration event was evaluated. RESULTS: RF was identified during 4% of 81,367 EGDs. Aspiration events occurred during 41 (5/10,000) procedures. Aspiration was more likely to occur in patients with RF (odds ratio [OR] 15.1) or those receiving MAC or GA (OR 9.6 and 16.8 relative to conscious sedation, respectively). RF and MAC/GA were synergistically associated with increased odds of aspiration. In a multivariate nominal logistic regression model, older age (OR 2.6), MAC (OR 3.8), GA (OR 4.4), vagotomy (OR 5.2), achalasia (OR 3.8), and RF (OR 10.0) were risk factors for aspiration. Aspiration events in the presence or absence of RF led to similar clinical outcomes. CONCLUSIONS: While aspiration events are rare in patients undergoing EGD, RF and the use of MAC or GA were associated with substantially increased odds of aspiration.

Endoscopic removal of a retained esophageal stent using the stent-in-stent technique.

Video 1Stent-in-stent technique for removal of retained esophageal self-expanding metal stent.

Food Residue During Esophagogastroduodenoscopy Is Commonly Encountered and Is Not Pathognomonic of Delayed Gastric Emptying.

BACKGROUND AND AIMS: Retained gastric food (RGF) identified during esophagogastroduodenoscopy (EGD) is often attributed to gastroparesis. This retrospective study evaluated the prevalence of RGF, risk factors for RGF, and the association between RGF and delayed gastric emptying (GE). METHODS: The prevalence and odds ratios for RGF in patients with structural foregut abnormalities or medical risk factors for delayed GE were determined from 85,116 EGDs performed between 2012 and 2018. The associations between RGF, delayed GE, and medical comorbidities were evaluated in 2991 patients without structural abnormalities who had undergone EGD and gastric emptying scintigraphy. The relationship between medication use and RGF was evaluated in 249 patients without structural or medical risk factors for RGF. RESULTS: RGF was identified during 3% of EGDs. The odds of RGF were increased in patients with type 1 diabetes (12%, OR 1.7, P ≤ 0.001), type 2 diabetes (6%, OR 1.4, P ≤ 0.001), gastroparesis (14%, OR 4.8, P ≤ 0.001), amyloidosis (5%, OR 1.7, P ≤ 0.001), and structural foregut abnormalities (6%, OR 2.6, P ≤ 0.001). Overall, the PPV of RGF for delayed GE was 55%. However, the PPV varied from 32% in patients without risk factors to 79% in patients with type 1 diabetes. Opioids, cardiovascular medications, and acid suppressants were associated with RGF. CONCLUSIONS: RGF is common during EGD. The PPV of RGF for delayed GE varies depending on underlying risk factors (type 1 diabetes, type 2 diabetes, gastroparesis, and amyloidosis). Acid suppressants or antacids, cardiovascular medications, and opioids are associated with RGF independent of delayed GE.

Erosive Esophagitis Portends a Benign Clinical Course in the Majority of Patients.

INTRODUCTION: Indefinite proton pump inhibitor (PPI) therapy and endoscopic evaluation for Barrett's esophagus is recommended for erosive esophagitis (EE). However, the clinical course of EE remains undefined. METHODS: Adults with EE on esophagogastroduodenoscopy (EGD) were identified at Mayo Clinic Rochester between January 2003 and September 2005. Patients with repeat EGD performed after index endoscopy were included. Patients with a history of upper gastrointestinal surgery, esophageal cancer, achalasia, or Barrett's on initial EGD were excluded. RESULTS: Of 219 patients identified, 98 had LA grade A, 72 LA grade B, and 49 LA grade C esophagitis. Persistent EE was found in 27% on repeat endoscopy. No patients progressed to more severe grades of esophagitis. While discontinuation of PPI was associated with persistent esophagitis, long-term healing of esophagitis occurred in the majority of patients despite discontinuation of PPI. Grade A or B esophagitis and the absence of hiatal hernia were also independent predictors of esophagitis healing on multivariate analysis. The rate of Barrett's esophagus was similar among patients with LA grade A/B and C esophagitis on initial EGD (5% vs. 14%, p = 0.6). CONCLUSION: The majority of patients with EE demonstrated healing at follow-up endoscopy regardless of continued PPI use. A small proportion developed Barrett's esophagus, including those with LA grade A and B esophagitis, highlighting a potential role for repeat endoscopy in all grades of EE. A more conservative long-term PPI strategy may be reasonable in patients with LA grade A or B esophagitis in the absence of hiatal hernia.

A Novel Oncolytic Herpes Capable of Cell-Specific Transcriptional Targeting of CD133± Cancer Cells Induces Significant Tumor Regression.

The topic of cancer stem cells (CSCs) is of significant importance due to its implications in our understanding of the tumor biology as well as the development of novel cancer therapeutics. However, the question of whether targeting CSCs can hamper the growth of tumors remains mainly unanswered due to the lack of specific agents for this purpose. To address this issue, we have developed the first mutated version of herpes simplex virus-1 that is transcriptionally targeted against CD133+ cells. CD133 has been portrayed as one of the most important markers in CSCs involved in the biology of a number of human cancers, including liver, brain, colon, skin, and pancreas. The virus developed in this work, Signal-Smart 2, showed specificity against CD133+ cells in three different models (hepatocellular carcinoma, colorectal cancer, and melanoma) resulting in a loss of viability and invasiveness of cancer cells. Additionally, the virus showed robust inhibitory activity against in vivo tumor growth in both preventive and therapeutic mouse models as well as orthotopic model highly relevant to potential clinical application of this virus. Therefore, we conclude that targeting CD133+ CSCs has the potential to be pursued as a novel strategy against cancer. Stem Cells 2018;36:1154-1169.

Ral signaling pathway in health and cancer.

The Ral (Ras-Like) signaling pathway plays an important role in the biology of cells. A plethora of effects is regulated by this signaling pathway and its prooncogenic effectors. Our team has demonstrated the overactivation of the RalA signaling pathway in a number of human malignancies including cancers of the liver, ovary, lung, brain, and malignant peripheral nerve sheath tumors. Additionally, we have shown that the activation of RalA in cancer stem cells is higher in comparison with differentiated cancer cells. In this article, we review the role of Ral signaling in health and disease with a focus on the role of this multifunctional protein in the generation of therapies for cancer. An improved understanding of this pathway can lead to development of a novel class of anticancer therapies that functions on the basis of intervention with RalA or its downstream effectors.

Automated synthesis of a library of triazolated 1,2,5-thiadiazepane 1,1-dioxides via a double aza-Michael strategy.

The construction of a 96-member library of triazolated 1,2,5-thiadiazepane 1,1-dioxides was performed on a Chemspeed Accelerator (SLT-100) automated parallel synthesis platform, culminating in the successful preparation of 94 out of 96 possible products. The key step, a one-pot, sequential elimination, double-aza-Michael reaction, and [3 + 2] Huisgen cycloaddition pathway has been automated and utilized in the production of two sets of triazolated sultam products.

Multicapillary Flow Reactor: Synthesis of 1,2,5-Thiadiazepane 1,1-Dioxide Library Utilizing One-Pot Elimination and Inter-/Intramolecular Double aza-Michael Addition Via Microwave-Assisted, Continuous-Flow Organic Synthesis (MACOS).

A microwave-assisted, continuous-flow organic synthesis (MACOS) protocol for the synthesis of functionalized 1,2,5-thiadiazepane 1,1-dioxide library, utilizing a one-pot elimination and inter-/intramolecular double aza-Michael addition strategy is reported. The optimized protocol in MACOS was utilized for scale-out and further extended for library production using a multicapillary flow reactor. A 50-member library of 1,2,5-thiadiazepane 1,1-dioxides was prepared on a 100- to 300-mg scale with overall yields between 50 and 80% and over 90 % purity determined by proton nuclear magnetic resonance (1H-NMR) spectroscopy.

Synthesis of a Library of 1,5,2-Dithiazepine 1,1-Dioxides. Part 1: A One-Pot Sulfonylation/Thia-Michael Protocol.

A novel one-pot sulfonylation/intramolecular thia-Michael protocol is reported for the synthesis of 1,5,2-dithiazepine 1,1-dioxides. Sulfonylation between cysteine ethyl ester/cysteamine and 2-chloroethanesulfonyl chloride, followed by in situ intramolecular thia-Michael addition, was achieved and afforded the titled 1,5,2-dithiazepine-1,1-dioxide scaffolds. Diversification was demonstrated for future library synthesis.

Synthesis of a Library of 1,5,2-Dithiazepine 1,1-Dioxides. Part 2: Routes to Bicyclic Sultams.

The synthesis of a library of bicyclic sultams incorporating the 1,5,2-dithiazepine 1,1-dioxide moiety is reported. Following scaffold synthesis via a one-pot sulfonylation/intramolecular thia-Michael protocol, several additional cyclization strategies have been realized enabling access to new bicyclic sultams.

Application of a Double Aza-Michael Reaction in a 'Click, Click, Cy-Click' Strategy: From Bench to Flow.

The development of a 'click, click, cy-click' process utilizing a double aza-Michael reaction to generate functionalized 1,2,5-thiadiazepane 1,1-dioxides is reported. Optimization in flow, followed by scale out of the inter-/intramolecular double aza-Michael addition has also been realized using a microwave-assisted, continuous flow organic synthesis platform (MACOS). In addition, a facile one-pot, sequential strategy employing in situ Huisgen cycloaddition post-double aza-Michael has been accomplished, and is applicable to library synthesis.