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

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

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

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

Safety and efficacy of EUS-guided coil and glue injection for the primary prophylaxis of gastric variceal hemorrhage.

BACKGROUND AND AIMS: Gastric variceal bleeding (GVB) is associated with high morbidity and mortality. EUS-guided coil and cyanoacrylate (CYA) injection (EUS-CCI) has been shown to be an effective therapy in acute bleeding and secondary prophylaxis; however, there is a paucity of data on primary prophylaxis. METHODS: In this single-center observational study, adult patients with high-risk gastric varices (GV; size >10 mm or cherry red spot) without prior bleeding underwent EUS-CCI for the primary prophylaxis of GVB between June 2009 and December 2019. The primary outcome was post-treatment GVB. RESULTS: Eighty patients with a mean variceal size of 22.5 ± 9.4 mm and a mean length of follow-up of 3.0 ± 2.4 years were included. The etiology of portal hypertension was cirrhosis in 71 patients (88.7%) and noncirrhotic in 9 (11.3). The mean model for end-stage liver disease score was 12.3 ± 3.7 in patients with cirrhosis. The mean coil number was 1.5 (range, 1-3) and mean glue volume injected 2 mL (range, .5-5). Technical success was achieved in 100%, 96.7% had EUS confirmation of GV obliteration, and 67.7% were obliterated with 1 treatment session. Post-treatment GVB occurred in 2 patients (2.5%) and adverse events in 4 (4.9%). No deaths related to GVB occurred, and emergent transjugular intrahepatic shunts were not needed during the follow-up period. CONCLUSIONS: In patients with high-risk GV, EUS-CCI for primary prophylaxis is highly effective at preventing GVB with a low rate of adverse events. Primary prophylaxis of high-risk GV with coil and CYA glue injection should be considered in centers with the appropriate expertise.

Endoscopic ultrasound-guided gastroenterostomy using an oroenteric catheter-assisted technique: a retrospective analysis.

BACKGROUND : This study evaluated an oroenteric catheter (OEC)-assisted technique to distend the enteric loop for endoscopic ultrasound-guided gastroenterostomy (EUS-GE) in patients with gastric outlet obstruction (GOO). METHODS : Patient outcomes were reviewed. Proximal enteric loops were filled with water via an OEC (7 Fr or 8 Fr), providing a target for EUS-GE using a lumen-apposing metal stent (15-mm caliber). Clinical success was defined as toleration of a non-liquid diet by Day 3. RESULTS : 42 patients (mean age 73.1 [SEM 2.8] years; 23 male) underwent EUS-GE for malignant (n = 37) and benign (n = 5) duodenal strictures. EUS-GE creation was successful in 41/42 (98 %), with mean procedure time of 36 (SEM 3) minutes and no serious complications. Clinical success was achieved in 39/42 (93 %) at 5.7 (SEM 2.6) months' follow-up. Of 14 patients who died, 13 (93 %) maintained oral intake until death. EUS-GE provided good symptom relief in all 28 surviving patients until follow-up. CONCLUSIONS : OEC-assisted EUS-GE provided satisfactory relief of GOO symptoms, with high technical success (98 %) and no serious complications.

Endoscopic ultrasound-guided gastroenterostomy versus open surgical gastrojejunostomy: clinical outcomes and cost effectiveness analysis.

BACKGROUND: Early data suggests that endoscopic ultrasound-guided gastroenterostomy (EUS-GE) is a safe and efficacious option for gastric outlet obstruction (GOO). However, there is a scarcity of data comparing outcomes with open gastrojejunostomy (OGJ). METHODS: Single-center retrospective cohort study of adult patients hospitalized with GOO who underwent EUS-GE or OGJ between January 1, 2014 and February 28, 2020. Primary outcomes were technical and clinical success. RESULTS: Sixty-six patients were included of which 40 (60.0%) underwent EUS-GE and 26 (40.0%) underwent OGJ. Baseline characteristics were similar with respect to age (70.5 vs 69.7, p = 0.81), sex (42.5% vs 42.3% female, p = 0.99), median length of follow-up (98.0 vs 166.5 days, p = 0.8), prior failed intervention for GOO (22.5% vs 26.9%, p = 0.68), and the presence of altered anatomy (12.5% vs 30.8%, p = 0.07) between EUS-GE and OGJ, respectively. Technical success was achieved in 37 (92.5%) of EUS-GE and 26 (100%) of OGJ patients (p = 0.15). EUS-GE was associated with faster resumption of oral intake (1.3 vs 4.7 days, p < 0.001) and shorter length of stay (5 vs 14.5 days, p < 0.001). There were no significant differences in symptom recurrence (17.5% vs 19.2%, HR 1.85, CI 0.52-6.65, p = 0.34), reintervention (20% vs 11.5%, HR 0.82, CI 0.22-3.15, p = 0.78), death within 30 days (12.5% vs 3.8%, HR 0.80, CI 0.09-6.85, p = 0.84), or 30-day readmission (17.5% vs 24.1%, HR 1.69, CI 0.53-5.41, p = 0.37) between EUS-GE and OGJ, respectively. EUS-GE patients initiated chemotherapy sooner (17.7 vs 31.3 days, p = 0.033) and had lower overall costs as compared to OGJ ($49,387 vs $124,192, p < 0.001). CONCLUSION: There were no significant differences in technical or clinical success, symptom recurrence, reintervention, 30-day readmission, or 30-day mortality between EUS-GE and OGJ. EUS-GE patients experienced shorter delays to resumption of oral intake and chemotherapy, had shorter lengths of stay, and reduced hospital costs. Further prospective comparative studies are warranted to verify our results.

Effectiveness of combination endoscopic therapy for colonic anastomotic leaks.

BACKGROUND: Colonic anastomotic leaks are associated with significant morbidity and mortality. Whereas small case series suggest that fully covered self-expandable metal stents (FCSEMS) are effective, no larger studies have examined the impact of combination endoscopic therapy on colonic anastomotic leaks. METHODS: Our retrospective cohort study reviewed 51 patients undergoing endoscopic therapy for colonic anastomotic leaks between 2011 and 2018. Patients receiving combination therapy involving FCSEMS plus local closure (n = 24) were compared with patients receiving FCSEMS alone (n = 18) or endoscopic suturing alone (n = 9). The primary outcomes were technical and clinical success (resolution of leak, removal of percutaneous drains, avoidance of surgical reoperation, and reversal of temporary diversion). RESULTS: Clinical success was achieved in 55 % of patients. Clinical success was achieved in 18/24 patients (75 %) with combination therapy compared with 6/18 patients receiving FCSEMS alone (33 %, adjusted risk ratio [RR] 2.16, 95 % confidence interval [CI] 1.10 - 4.24; P = 0.02) and 4 /9 patients undergoing endoscopic suturing alone (44 %, RR 1.91, 95 %CI 0.84 - 4.31; P = 0.10). Stent migration occurred in 40 % of patients. CONCLUSIONS: This large series demonstrates that combination therapy was associated with a higher rate of clinical success, and future prospective studies are warranted.

Competence in Endoscopic Ultrasound and Endoscopic Retrograde Cholangiopancreatography, From Training Through Independent Practice.

BACKGROUND & AIMS: It is unclear whether participation in competency-based fellowship programs for endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) results in high-quality care in independent practice. We measured quality indicator (QI) adherence during the first year of independent practice among physicians who completed endoscopic training with a systematic assessment of competence. METHODS: We performed a prospective multicenter cohort study of invited participants from 62 training programs. In phase 1, 24 advanced endoscopy trainees (AETs), from 20 programs, were assessed using a validated competence assessment tool. We used a comprehensive data collection and reporting system to create learning curves using cumulative sum analysis that were shared with AETs and trainers quarterly. In phase 2, participating AETs entered data into a database pertaining to every EUS and ERCP examination during their first year of independent practice, anchored by key QIs. RESULTS: By the end of training, most AETs had achieved overall technical competence (EUS 91.7%, ERCP 73.9%) and cognitive competence (EUS 91.7%, ERCP 94.1%). In phase 2 of the study, 22 AETs (91.6%) participated and completed a median of 136 EUS examinations per AET and 116 ERCP examinations per AET. Most AETs met the performance thresholds for QIs in EUS (including 94.4% diagnostic rate of adequate samples and 83.8% diagnostic yield of malignancy in pancreatic masses) and ERCP (94.9% overall cannulation rate). CONCLUSIONS: In this prospective multicenter study, we found that although competence cannot be confirmed for all AETs at the end of training, most meet QI thresholds for EUS and ERCP at the end of their first year of independent practice. This finding affirms the effectiveness of training programs. Clinicaltrials.gov ID NCT02509416.

Setting minimum standards for training in EUS and ERCP: results from a prospective multicenter study evaluating learning curves and competence among advanced endoscopy trainees.

BACKGROUND AND AIMS: Minimum EUS and ERCP volumes that should be offered per trainee in "high quality" advanced endoscopy training programs (AETPs) are not established. We aimed to define the number of procedures required by an "average" advanced endoscopy trainee (AET) to achieve competence in technical and cognitive EUS and ERCP tasks to help structure AETPs. METHODS: American Society for Gastrointestinal Endoscopy (ASGE)-recognized AETPs were invited to participate; AETs were graded on every fifth EUS and ERCP examination using a validated tool. Grading for each skill was done using a 4-point scoring system, and learning curves using cumulative sum analysis for overall, technical, and cognitive components of EUS and ERCP were shared with AETs and trainers quarterly. Generalized linear mixed-effects models with a random intercept for each AET were used to generate aggregate learning curves, allowing us to use data from all AETs to estimate the average learning experience for trainees. RESULTS: Among 62 invited AETPs, 37 AETs from 32 AETPs participated. Most AETs reported hands-on EUS (52%, median 20 cases) and ERCP (68%, median 50 cases) experience before starting an AETP. The median number of EUS and ERCPs performed per AET was 400 (range, 200-750) and 361 (range, 250-650), respectively. Overall, 2616 examinations were graded (EUS, 1277; ERCP-biliary, 1143; pancreatic, 196). Most graded EUS examinations were performed for pancreatobiliary indications (69.9%) and ERCP examinations for ASGE biliary grade of difficulty 1 (72.1%). The average AET achieved competence in core EUS and ERCP skills at approximately 225 and 250 cases, respectively. However, overall technical competence was achieved for grade 2 ERCP at about 300 cases. CONCLUSION: The thresholds provided for an average AET to achieve competence in EUS and ERCP may be used by the ASGE and AETPs in establishing the minimal standards for case volume exposure for AETs during their training. (Clinical trial registration number: NCT02509416.).

Utilization of an overtube for placement of a lumen-apposing metal stent for removal of a capsule endoscope retained proximal to an ileal stricture.

Video 1Narration of case and demonstration of overture-mediated lumen-apposing metal stent placement for removal of retained capsule endoscopy.

Epiphrenic diverticula: An added source of complexity in achalasia management.

Epiphrenic (pulsion) esophageal diverticula can occur in the setting of underlying esophageal motility disorders such as achalasia and present a unique management challenge to the gastroenterologist. Asymptomatic diverticula do not require treatment, but symptomatic diverticula require therapy targeted to the underlying esophageal motility disorder, or else the diverticula will recur. Generally, laparoscopic or combined laparoscopic/thoracoscopic myotomy, diverticulectomy, and anterior fundoplication are required. However, therapeutic options for epiphrenic diverticula are evolving as peroral endoscopic myotomy (POEM) becomes more commonplace. We review two cases of achalasia complicated by epiphrenic diverticula at our institution. In the first case, type II achalasia was identified and the patient underwent laparoscopic myotomy. In the second case, type III achalasia was present and the patient underwent successful POEM. We discuss the presentation, pathophysiology, and management of epiphrenic diverticula as well as the expanding role for POEM in diverticula.

Underwater Endoscopic Mucosal Resection.

Although an established standard, conventional endoscopic mucosal resection (EMR) has disseminated despite an absence of studies demonstrating the value of submucosal injection. Several consequences of poorly executed submucosal injection may increase the difficulty and risk of EMR. Underwater EMR (UEMR), an alternative resection method for colonic neoplasms, avoids the need for submucosal injections. In comparison with reported outcomes of EMR, UEMR achieves similar rates of complete resection with comparable safety, with lower rates of recurrence and fewer repeat procedures. UEMR also compares favorably with endoscopic submucosal dissection in terms of procedure time and rates of complete resection, recurrence, and complications.

Endoscopic Management of Portal Hypertension-related Bleeding.

Gastrointestinal bleeding as a sequela of portal hypertension can be catastrophic and fatal. Endoscopic and endosonographic therapy play a critical role in management of such bleeding- both for hemostasis of active bleeding and bleeding prophylaxis. Variceal band ligation is established as the standard intervention for esophageal varices. For other sources of portal hypertension-related bleeding, or for salvage therapy for esophageal varices, a variety of endoscopic techniques are available. Endoscopic ultrasound may be used to enhance endoscopic management, particularly for gastric and ectopic varices.

The Evolution of Endoscopic Cystgastrostomy.

The lumen-apposing metal stent is the first stent specifically designed for endoscopic ultrasound-guided transluminal drainage of extraintestinal fluid collections. With the "hot" electrocautery-enhanced delivery system, this platform marks the most recent evolutionary stage of endoscopic therapy of pancreatic fluid collections. The lumen-apposing metal stent platform has made endoscopic drainage of pancreatic fluid collections easier and safer, while serving as a port for safe entry into the cyst cavity to extend the reach of endoscopic diagnosis and therapy. Tools conceived for endoscopic ultrasound-guided transluminal intervention have emerged and are opening the door to new frontiers of endoscopic transluminal therapy.

Quality bowel preparation for surveillance colonoscopy in patients with inflammatory bowel disease is a must.

Colonoscopy is routinely performed in patients with inflammatory bowel disease (IBD) for surveillance of dysplasia. Thorough bowel preparation is necessary to facilitate lesion detection. Patients with IBD do not have poorer bowel preparation outcomes but may have decreased preparation tolerance affecting adherence to surveillance protocols. A low-fiber prepreparation diet may improve preparation tolerance without affecting preparation quality. The standard preparation regimen should consist of split-dose administration of a polyethylene glycol-based purgative. Low-volume, hyperosmolar purgatives may be considered in patients with previous preparation intolerance, heightened anxiety, stenotic disease, or dysmotility. Appropriate patient education is critical to enhance preparation quality.

Comparison of dot chromosome sequences from D. melanogaster and D. virilis reveals an enrichment of DNA transposon sequences in heterochromatic domains.

BACKGROUND: Chromosome four of Drosophila melanogaster, known as the dot chromosome, is largely heterochromatic, as shown by immunofluorescent staining with antibodies to heterochromatin protein 1 (HP1) and histone H3K9me. In contrast, the absence of HP1 and H3K9me from the dot chromosome in D. virilis suggests that this region is euchromatic. D. virilis diverged from D. melanogaster 40 to 60 million years ago. RESULTS: Here we describe finished sequencing and analysis of 11 fosmids hybridizing to the dot chromosome of D. virilis (372,650 base-pairs) and seven fosmids from major euchromatic chromosome arms (273,110 base-pairs). Most genes from the dot chromosome of D. melanogaster remain on the dot chromosome in D. virilis, but many inversions have occurred. The dot chromosomes of both species are similar to the major chromosome arms in gene density and coding density, but the dot chromosome genes of both species have larger introns. The D. virilis dot chromosome fosmids have a high repeat density (22.8%), similar to homologous regions of D. melanogaster (26.5%). There are, however, major differences in the representation of repetitive elements. Remnants of DNA transposons make up only 6.3% of the D. virilis dot chromosome fosmids, but 18.4% of the homologous regions from D. melanogaster; DINE-1 and 1360 elements are particularly enriched in D. melanogaster. Euchromatic domains on the major chromosomes in both species have very few DNA transposons (less than 0.4 %). CONCLUSION: Combining these results with recent findings about RNAi, we suggest that specific repetitive elements, as well as density, play a role in determining higher-order chromatin packaging.