Through-the-scope suture closure of nonampullary duodenal endoscopic mucosal resection defects: a retrospective multicenter cohort study.

BACKGROUND: Delayed bleeding is among the most common adverse events associated with endoscopic mucosal resection (EMR) of nonampullary duodenal polyps. We evaluated the rate of delayed bleeding and complete defect closure using a novel through-the-scope (TTS) suturing system for the closure of duodenal EMR defects. METHODS: We reviewed the electronic medical records of patients who underwent EMR for nonampullary duodenal polyps of ≥ 10 mm and prophylactic defect closure with TTS suturing between March 2021 and May 2022 at centers in the USA. We evaluated the rates of delayed bleeding and complete defect closure. RESULTS: 36 nonconsecutive patients (61 % women; mean [SD] age, 65 [12] years) underwent EMR of ≥ 10-mm duodenal polyps followed by attempted defect closure with TTS suturing. The mean (SD) lesion size was 29 (19) mm, defect size was 37 (25) mm; eight polyps (22 %) involved > 50 % of the lumen circumference. Complete closure was achieved in all cases (78 % with TTS suturing alone), using a median of one TTS suturing kit. There were no cases of delayed bleeding and no adverse events attributed to application of the TTS suturing device. CONCLUSION: Prophylactic closure of nonampullary duodenal EMR defects using TTS suturing resulted in a high rate of complete closure and no delayed bleeding events.

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.

Iatrogenic perforation during lumen-apposing metal stent deployment closed using an over-the-scope stent fixation clip device.

Video 1Endoscopic closure of an iatrogenic perforation caused during EUS-guided gastrojejunostomy for malignant gastric outlet obstruction treated with an over-the-scope stent fixation clip device.

Zenker's peroral endoscopic myotomy for management of large Zenker's diverticulum.

BACKGROUND: Zenker's diverticulum peroral endoscopic myotomy (zPOEM) is a minimally invasive treatment strategy for Zenker's diverticulum, with excellent results for management of small-to-moderate Zenker's diverticulum. We evaluated its use in the management of large Zenker's diverticulum. METHODS: This was a retrospective multicenter cohort study across 11 international centers including adult patients with large Zenker's diverticulum ≥ 40 mm treated by zPOEM between March 2017 and March 2022. The primary outcome was clinical success (dysphagia score ≤ 1 without need for further intervention). Secondary outcomes included technical success (complete myotomy as intended), adverse events (AEs), and rate of recurrence. RESULTS: 83 patients (male 62.7 %, mean age 72.6 [SD 11.5] years) underwent zPOEM for treatment of large Zenker's diverticulum (median size 50 mm, interquartile range [IQR] 41-55 mm, range 40-80 mm). The zPOEM procedure was technically successful in 82 patients (98.8 %), with a mean procedure time of 48.7 (SD 23.2) minutes. Clinical success was achieved in 71 patients (85.5 %). Median (IQR) symptom scores improved significantly from baseline for dysphagia (2 2 3 vs. 0 [0-2]; P < 0.001), regurgitation (3 2 3 4 vs. 0 [0-0]; P < 0.001), and respiratory symptoms (2 [0-3] vs. 0 [0-0]; P < 0.001). Among patients achieving clinical success, only one recurrence (1.4 %) was recorded during a median follow-up of 12.2 months (IQR 3-28). Post-procedure AEs, all mild to moderate, occurred in four patients (4.8 %). CONCLUSION: This study demonstrated safe and effective use of zPOEM in the management of large Zenker's diverticulum.

A novel through-the-scope helix tack-and-suture device for mucosal defect closure following colorectal endoscopic submucosal dissection: a multicenter study.

BACKGROUND: Complete closure of large mucosal defects following colorectal endoscopic submucosal dissection (ESD) with through-the-scope (TTS) clips is oftentimes not possible. We aimed to report our early experience of using a novel TTS suturing system for the closure of large mucosal defects after colorectal ESD. METHODS: We performed a retrospective multicenter cohort study of consecutive patients who underwent attempted prophylactic defect closure using the TTS suturing system after colorectal ESD. The primary outcome was technical success in achieving complete defect closure, defined as a < 5 mm residual mucosal defect in the closure line using TTS suturing, with or without adjuvant TTS clips. RESULTS: 82 patients with a median defect size of 30 (interquartile range 25-40) mm were included. Technical success was achieved in 92.7 % (n = 76): TTS suturing only in 44 patients (53.7 %) and a combination of TTS suturing to approximate the widest segment followed by complete closure with TTS clips in 32 (39.0 %). Incomplete/partial closure, failure of appropriate TTS suture deployment, and the need for over-the-scope salvage closure methods were observed in 7.3 % (n = 6). One intraprocedural bleed, one delayed bleed, and three intraprocedural perforations were observed. There were no adverse events related to placement of the TTS suture. CONCLUSION: The TTS suture system is an effective and safe tool for the closure of large mucosal defects after colorectal ESD and is an alternative when complete closure with TTS clips alone is not possible.

Technical details and outcomes of peroral endoscopic myotomy with fundoplication: the first U.S. experience (with video).

BACKGROUND AND AIMS: Peroral endoscopic myotomy (POEM) is an established endoscopic treatment for achalasia; however, post-POEM rates of GERD remain a significant cause of concern. Single-session POEM with fundoplication (POEM-F) to treat achalasia was recently described to reduce post-POEM GERD. This study aims to report the technical feasibility, safety, and early outcomes of the first U.S. cohort of POEM-F. METHODS: We retrospectively reviewed all patients with achalasia treated with POEM-F at our center. The primary endpoint was technical success, defined as the successful completion of all steps of the POEM-F procedure. RESULTS: Six patients (mean age, 50 ± 4.8 years; 1 woman) underwent POEM-F for achalasia. Technical success was achieved in all patients (6/6), and no major immediate or delayed (up to 30 days postprocedure) adverse events were seen. At the 1-month follow-up visit, the mean Eckardt score decreased from 8.8 ± 1.1 to .3 ± .5. The GERD health-related quality of life and reflux symptom index scores obtained at the 1-month follow-up, with patients on proton pump inhibitors, were 2.3 ± 3.7 and 2.2 ± 2.5, respectively. CONCLUSIONS: This first case series on POEM-F in the United States suggests that POEM-F is feasible and safe with excellent short-term outcomes.

Endoscopic full-thickness resection with through-the-scope suture closure for gastrointestinal stromal tumor.

Video 1Endoscopic full-thickness resection with through-the-scope suture closure for gastrointestinal stromal tumor.

Biliary Endoscopy in Altered Anatomy.

Endoscopic retrograde cholangiopancreatography (ERCP) is the standard treatment of biliary disease with high success rates of greater than 90% in patients with standard anatomy. However, alterations in upper gastrointestinal anatomy can significantly complicate endoscopic biliary intervention. The past decade has seen significant advances in the endoscopic management of patients with altered anatomy. This review article will provide tips and tricks for successful biliary access in the most common surgical alterations with a focus on the management of biliary diseases following Roux-en-Y (RY) reconstructions.

Endoscopic through-the-scope suturing.

BACKGROUND AND AIMS: There is growing interest in closure of larger mucosal defects, given the increasing use of endoscopic resection for early GI neoplasia and the advent of submucosal endoscopy, including peroral endoscopic myotomy. Existing closure methods include through-the-scope clips, over-the-scope clips, and over-the-scope suturing. Although over-the-scope clips and over-the-scope suturing allow closure of large defects, both require endoscope removal for device application and may have difficulty in treating lesions in the proximal colon or the small intestine. Hence, a significant gap exists for a through-the-scope device capable of closing larger defects. The novel X-Tack system (Apollo Endosurgery, Austin, Tex, USA) offers through-the-scope suturing (TTSS), which eliminates the need to withdraw the endoscope from the patient before applying therapy. METHODS: We demonstrate the possible indications for endoscopic mucosal adhesion with TTSS through a video case series. We present 5 cases to illustrate the use of TTSS in the closure of a duodenal EMR defect, a cecal EMR defect, mucostomy after esophageal and gastric peroral endoscopic myotomy, and, finally, for primary closure of a gastrogastric fistula. RESULTS: All defects were successfully closed with 1 to 2 TTSS systems. There were no postprocedure adverse events, including bleeding or perforation, at a median of 30 (range 14-30) days of follow-up. CONCLUSIONS: TTSS is a valuable addition to mucosal closure devices, which allows closure through a gastroscope or a colonoscope, without requiring endoscope removal for device application. Likely applications include larger or more distant defects and those located within tight spaces. Pending further clinical evaluation, important areas for research include assessment of the learning curve, comparative trials with other closure devices, and cost-effectiveness analysis.

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.

Novel 15-mm-long lumen-apposing metal stent for endoscopic ultrasound-guided drainage of pancreatic fluid collections located ≥10 mm from the luminal wall.

BACKGROUND: Endoscopic ultrasound (EUS)-guided drainage of pancreatic fluid collections (PFCs) by cautery-enhanced lumen-apposing metal stents (LAMS) has largely been limited to collections located < 10 mm from the luminal wall. We present outcomes of the use of a novel 15-mm-long cautery-enhanced LAMS for drainage of PFCs located ≥ 10 mm away. METHODS: This international, multicenter study analyzed all adults with PFCs located ≥ 10 mm from the luminal wall who were treated by EUS-guided drainage using the 15-mm-long cautery-enhanced LAMS. The primary outcome was technical success. Secondary outcomes included clinical success (decrease in PFC size by ≥ 50 % at 30 days and resolution of clinical symptoms without surgical intervention), complications, and recurrence. RESULTS: 35 patients (median age 57 years; interquartile range [IQR] 47-64 years; 49 % male) underwent novel LAMS placement for drainage of PFCs (26 walled-off necrosis, 9 pseudocysts), measuring 85 mm (IQR 64-117) maximal diameter and located 11.8 mm (IQR 10-12.3; range 10-14) from the gastric/duodenal wall. Technical and clinical success were high (both 97 %), with recurrence in one patient (3 %) at a median follow-up of 123 days (58-236). Three complications occurred (9 %; one mild, two moderate). CONCLUSIONS: The 15-mm-long cautery-enhanced LAMS was feasible and safe for drainage of PFCs located 10-14 mm from the luminal wall.

Zenker's diverticulum: advancing beyond the tunnel.

BACKGROUND AND AIMS: Zenker's diverticulum (ZD) is attributed to a poorly compliant cricopharyngeus muscle, and the mainstay of treatment is a cricopharyngeal myotomy. We present a video series summarizing endoscopic treatment options for ZD and related conditions. METHODS: We review the rationale and key technique for various endoscopic treatment modalities for ZD, cricopharyngeal bar, and other esophageal diverticula. RESULTS: Standard flexible endoscopic cricopharyngeal myotomy involves the division of the common wall or septum of the ZD, aiming for complete transection of the cricopharyngeus. However, recurrence rates are high, likely owing to incomplete myotomy. Zenker's peroral endoscopic myotomy (Z-POEM) uses a proximal submucosal tunnel to provide direct visualization of the cricopharyngeus and septum, allowing confirmation of complete myotomy. We demonstrate an over-the-septum modification to simplify the technique. Submucosal fibrosis, commonly seen in patients with prior treatment, limits submucosal dissection. We present a hybrid technique to overcome this, whereby a traditional septotomy is performed until submucosal tissue is visualized. The intact mucosal flap after Z-POEM in a large ZD may contribute to residual dysphagia. We propose Z-POEM with mucosotomy for large ZD. Finally, we demonstrate modifications for treatment of other esophageal diseases, including cricopharyngeal bar and non-Zenker's esophageal diverticula. CONCLUSION: Endoscopic treatment options for ZD and related conditions are rapidly expanding. With careful tailoring to individual patient characteristics, our expanding arsenal of options allows effective and safe treatment of a broad spectrum of patients.

Therapeutic Endoscopy and the Esophagus: State of the Art and Future Directions.

Therapeutic gastrointestinal endoscopy is rapidly evolving, and this evolution is quite apparent for esophageal diseases. Minimally invasive endoluminal therapy now allows outpatient treatment of many esophageal diseases that were traditionally managed surgically. In this review article, we explore the most exciting new developments. We discuss the use of peroral endoscopic myotomy for treatment of achalasia and other related diseases, as well as the modifications that have allowed its use in treatment of Zenker diverticulum. We cover endoscopic treatment of gastroesophageal reflux disease and Barrett's esophagus. Further, we explore advanced endoscopic resection techniques.

Rethinking the need for overnight admission after peroral endoscopic myotomy (POEM): a pandemic-driven approach to the future.

Background and study aims COVID-19 has significantly impacted endoscopic assessment and management of multiple conditions. Our group recommenced treatment of highly symptomatic achalasia patients (Eckardt score ≥ 6) adopting a same-day discharge (SDD) algorithm and present early outcomes of its utilization. Patients and methods We enrolled all outpatients undergoing POEM at a single tertiary referral center. Patients qualified for SDD if all of the following a priori criteria were met: 1) ASA grade I-III; 2) No intraprocedural adverse events (AEs); 3) Secure mucosal closure; 4) Post-procedure pain/nausea responsive to oral medications; and 5) Patients tolerating clear fluids. Results In 17 potential SDD candidates (female 82.4 %, median age 51 years [IQR 48-64]) undergoing POEM, SDD was achieved in 14 (82.4 %). The remaining were admitted due to post-procedure pain/nausea (n = 2) and intraprocedural concerns (capnoperitoneum requiring needle decompression, n = 1). There were no post-procedure AEs or unexpected readmissions. Conclusions This study demonstrates the safety and feasibility of a SDD algorithm for POEM patients and challenges the necessity of routine post-POEM hospital admission. Critically important during the COVID-19 pandemic, this may in fact constitute a changing standard for POEM post-procedure care.

Percutaneous transcystic cholangioscopy-assisted rendezvous ERCP in a hostile abdomen.

Video 1Percutaneous transcystic cholangioscopy-assisted rendezvous ERCP in a hostile abdomen.

Gastric Per-Oral Endoscopic Myotomy for Treatment of Chronic Proximal Staple Line Leak Precipitated by Downstream Stenosis.

Laparoscopic sleeve gastrectomy is now the most commonly performed bariatric surgery. Although considered a safe procedure, adverse events such as staple line leak in the context of sleeve stenosis can result in significant patient morbidity and health economic burden. Correction of the downstream stenosis is mandatory for closure of the staple line leak. Conventional endoscopic therapies offer high initial success rates, though ultimately a significant proportion proceed to revision surgery. Gastric per-oral endoscopic myotomy (G-POEM) is a novel, minimally invasive procedure which allows for a full-thickness myotomy of the stenosed segment, potentially conferring similar anatomical correction to surgical seromyotomy. We present a case of recalcitrant chronic proximal staple line leak in the context of a downstream gastric stenosis managed by G-POEM.

Integrated Modeling Program, Applied Chemical Theory (IMPACT).

We provide an overview of the IMPACT molecular mechanics program with an emphasis on recent developments and a description of its current functionality. With respect to core molecular mechanics technologies we include a status report for the fixed charge and polarizable force fields that can be used with the program and illustrate how the force fields, when used together with new atom typing and parameter assignment modules, have greatly expanded the coverage of organic compounds and medicinally relevant ligands. As we discuss in this review, explicit solvent simulations have been used to guide our design of implicit solvent models based on the generalized Born framework and a novel nonpolar estimator that have recently been incorporated into the program. With IMPACT it is possible to use several different advanced conformational sampling algorithms based on combining features of molecular dynamics and Monte Carlo simulations. The program includes two specialized molecular mechanics modules: Glide, a high-throughput docking program, and QSite, a mixed quantum mechanics/molecular mechanics module. These modules employ the IMPACT infrastructure as a starting point for the construction of the protein model and assignment of molecular mechanics parameters, but have then been developed to meet specialized objectives with respect to sampling and the energy function.

A Polarizable Force Field and Continuum Solvation Methodology for Modeling of Protein-Ligand Interactions.

A polarizable force field, and associated continuum solvation model, have been developed for the explicit purpose of computing and studying the energetics and structural features of protein binding to the wide range of ligands with potential for medicinal applications. Parameters for the polarizable force field (PFF) are derived from gas-phase ab initio calculations and then utilized for applications in which the protein binding to ligands occurs in aqueous solvents, wherein the charge distributions of proteins and ligands can be dramatically altered. The continuum solvation model is based on a self-consistent reaction field description of solvation, incorporating an analytical gradient, that allows energy minimizations (and, potentially, molecular dynamics simulations) of protein/ligand systems in continuum solvent. This technology includes a nonpolar model describing the cost of cavity formation, and van der Waals interactions, between the continuum solvent and protein/ligand solutes. Tests of the structural accuracy and computational stability of the methodology, and timings for energy minimizations of proteins and protein/ligand systems in the condensed phase, are reported. In addition, the derivation of polarizability, electrostatic, exchange repulsion, and torsion parameters from ab initio data is described, along with the use of experimental solvation energies for determining parameters for the solvation model.