Combined Drainage and Protocolized Necrosectomy Through a Coaxial Lumen-apposing Metal Stent for Pancreatic Walled-off Necrosis: A Prospective Multicenter Trial.

OBJECTIVE: We evaluated a protocolized endoscopic necrosectomy approach with a lumen-apposing metal stent (LAMS) in patients with large symptomatic walled-off pancreatic necrosis (WON) comprising significant necrotic content, with or without infection. SUMMARY BACKGROUND DATA: Randomized trials have shown similar efficacy of endoscopic treatment compared with surgery for infected WON. DESIGN: We conducted a regulatory, prospective, multicenter single-arm clinical trial examining the efficacy and safety of endoscopic ultrasound -guided LAMS with protocolized necrosectomy to treat symptomatic WON ≥6 cm in diameter with >30% solid necrosis. After LAMS placement, protocolized WON assessment was conducted and endoscopic necrosectomy was performed for insufficient WON size reduction and persistent symptoms. Patients with radiographic WON resolution to ≤ 3 cm and/or 60-day LAMS indwell had LAMS removal, then 6-month follow-up. Primary endpoints were probability of radiographic resolution by 60 days and procedure-related serious adverse events. RESULTS: Forty consecutive patients were enrolled September 2018 to March 2020, of whom 27 (67.5%) were inpatients and 19 (47.5%) had clinical evidence of infection at their index procedure. Mean WON size was 15.0 ± 5.6 cm with mean 53.2% ± 16.7% solid necrosis. Radiographic WON resolution was seen in 97.5% (95% CI, 86.8%, 99.9%) by 60 days, without recurrence in 34 patients with 6-month follow-up data. Mean time to radiographic WON resolution was 34.1 ± 16.8 days. Serious adverse events occurred in 3 patients (7.5%), including sepsis, vancomycin-resistant enterococcal bacteremia and shock, and upper gastrointestinal bleeding. There were no procedure-related deaths. CONCLUSIONS: Endoscopic ultrasound-guided drainage with protocolized endoscopic necrosectomy to treat large symptomatic or infected walled-off necrotic pancreatic collections was highly effective and safe. Clinicaltrials.-gov no: NCT03525808.

Feasibility of a new bariatric fully endoscopic duodenal-jejunal bypass: a pilot study in adult obese pigs.

This study assessed a new natural orifice transluminal endoscopic surgery (NOTES) bariatric endoscopic procedure in obese adult pigs. This 14-week prospective study compared 6 adult male Yucatan test pigs with baseline mean age 1.5 years to 2 control pigs. The test pigs received a fully endoscopic NOTES-based duodenal-jejunal bypass including measurement of the bypassed limb and creation of a gastrojejunal anastomosis (GJA) using a gastrojejunal lumen-apposing metal stent (GJ-LAMS) at Week 0, placement of a duodenal exclusion device (DED) at Week 2, and endoscopic examinations at Weeks 6 and 10. At Week 14, the pigs were sacrificed for necropsy. All endoscopic procedures were technically successful. By Week 14, the controls had gained a mean 1.1 ± 2.1 kg (+ 1.6%) while the intervention animals lost a mean 6.8 ± 3.9 kg (- 10.5%) since baseline. GJ-LAMS migrations occurred in 3 pigs, two of which also had DED migration and/or partial dislocation. Two other pigs died, one with aberrant splenic vein positioning near the GJA and the other from an unknown cause. An endoscopic bariatric bypass procedure with controlled bypass length was technically successful in all the cases and led to weight loss in test animals. Safety concerns must be further addressed.

Efficacy and safety of endoscopic duodenal stent versus endoscopic or surgical gastrojejunostomy to treat malignant gastric outlet obstruction: systematic review and meta-analysis.

Background and study aims Malignant disease accounts for up to 80 % of gastric outlet obstruction (GOO) cases, which may be treated with duodenal self-expanding metal stents (SEMS), surgical gastrojejunostomy (GJ), and more recently endoscopic-ultrasound-guided gastroenterostomy (EUS-GE). These three treatments have not been compared head-to-head in a randomized trial. Methods We searched the Embase and MEDLINE databases for studies published January 2015-February 2021 assessing treatment of malignant GOO using duodenal SEMS, endoscopic (EUS-GE) or surgical (laparoscopic or open) GJ. Efficacy outcomes assessed included technical and clinical success rates, GOO recurrence and reintervention. Safety outcomes included procedure-related bleeding or perforation, and stent-related events for the duodenal SEMS and EUS-GE arms. Results EUS-GE had a lower rate of technical success (95.3%) than duodenal SEMS (99.4 %) or surgical GJ (99.9%) ( P  = 0.0048). For duodenal SEMS vs. EUS-GE vs. surgical GJ, rates of clinical success (88.9 % vs. 89.0 % vs. 92.3 % respectively, P  = 0.49) were similar. EUS-GE had a lower rate of GOO recurrence based on limited data ( P  = 0.0036), while duodenal SEMS had a higher rate of reintervention ( P  = 0.041). Overall procedural complications were similar (duodenal SEMS 18.7 % vs. EUS-GE 21.9 % vs. surgical GJ 23.8 %, P  = 0.32), but estimated bleeding rate was lowest ( P  = 0.0048) and stent occlusion rate was highest ( P  = 0.0002) for duodenal SEMS. Conclusions Duodenal SEMS, EUS-GE, and surgical GJ showed similar clinical efficacy for the treatment of malignant GOO. Duodenal SEMS had a lower procedure-related bleeding rate but higher rate of reintervention.

Feasibility of Conversion of a New Bariatric Fully Endoscopic Bypass Procedure to Bariatric Surgery: a Porcine Pilot Study.

PURPOSE: Bariatric endoscopic procedures are emerging as alternatives to bariatric surgical procedures. This study aimed to assess if a natural orifice transluminal endoscopic surgery (NOTES) bariatric procedure could be converted to a surgical duodenal-jejunal bypass (DJB) or sleeve gastrectomy (SG). MATERIALS AND METHODS: This 12-week prospective study compared 4 test pigs to 3 control (no procedures) pigs aged 3 months at baseline. The test pigs received a fully endoscopic NOTES-based bypass including measurement of the bypassed limb and creation of a gastrojejunal anastomosis (GJA) using gastrojejunal lumen-apposing metal stents (GJ-LAMS) at Week 0, placement of a duodenal exclusion device (DED) at Week 2, and randomization to DJB or SG surgery at Week 8 with subsequent 4-week follow-up. At Week 12, the pigs were sacrificed and necropsy was performed. RESULTS: Endoscopic procedures were technically successful. One pig did not receive a DED due to early GJ-LAMS migration leading to premature closure of the GJA. At Week 8, all 4 pigs were doing well, and the remaining 3 GJ-LAMS and 3 DEDs were uneventfully endoscopically removed. Two one-anastomosis DJB were performed, and 2 SG were performed, closing in one case the site of the previous GJA. The surgical procedures were technically feasible and uneventful during follow-up. Necropsy assessments showed no local or peritoneal inflammation or abscess and no leakage or fistula. CONCLUSION: An endoscopic bariatric bypass can be transitioned to a one-anastomosis duodenal-jejunal bypass or sleeve gastrectomy, without complications.

First fully endoscopic metabolic procedure with NOTES gastrojejunostomy, controlled bypass length and duodenal exclusion: a 9-month porcine study.

We conducted a pilot study of a potential endoscopic alternative to bariatric surgery. We developed a Natural Orifice Transluminal Endoscopic Surgery (NOTES) gastric bypass with controlled bypass limb length using four new devices including a dedicated lumen-apposing metal stent (GJ-LAMS) and pyloric duodenal exclusion device (DED). We evaluated procedural technical success, weight change from baseline, and adverse events in growing Landrace/Large-White pigs through 38 weeks after GJ-LAMS placement. Six pigs (age 2.5 months, mean baseline weight 26.1 ± 2.7 kg) had initial GJ-LAMS placement with controlled bypass limb length, followed by DED placement at 2 weeks. Technical success was 100%. GJ-LAMS migrated in 3 of 6, and DED migrated in 3 of 5 surviving pigs after mucosal abrasion. One pig died by Day 94. At 38 weeks, necropsy showed 100-240 cm limb length except for one at 760 cm. Weight gain was significantly lower in the pigs that underwent endoscopic bypass procedures compared to expected weight for age. This first survival study of a fully endoscopic controlled bypass length gastrojejunostomy with duodenal exclusion in a growing porcine model showed high technical success but significant adverse events. Future studies will include procedural and device optimizations and comparison to a control group.

Safety and efficacy of lumen-apposing metal stents versus plastic stents to treat walled-off pancreatic necrosis: systematic review and meta-analysis.

Background and study aims Lumen-apposing metal stents (LAMS) are increasingly used for drainage of walled-off pancreatic necrosis (WON). Recent studies suggested greater adverse event (AE) rates with LAMS for WON. We conducted a systematic review and meta-analysis to compare the safety and efficacy of LAMS with double-pigtail plastic stents (DPPS) for endoscopic drainage of WON. The primary aim was to evaluate stent-related AEs. Methods In October 2019, we searched the Ovid (Embase, MEDLINE, Cochrane) and Scopus databases for studies assessing a specific LAMS or DPPS for WON drainage conducted under EUS guidance. Safety outcomes were AE rates of bleeding, stent migration, perforation, and stent occlusion. Efficacy outcomes were WON resolution and number of procedures needed to achieve resolution. A subanalysis including non-EUS-guided cases was performed. Results Thirty studies including one randomized controlled trial (total 1,524 patients) were analyzed. LAMS were associated with similar bleeding (2.5 % vs. 4.6 %, P =  0.39) and perforation risk (0.5 % vs. 1.1 %, P =  0.35) compared to DPPS. WON resolution (87.4 % vs. 87.5 %, P =  0.99), number of procedures to achieve resolution (2.09 vs. 1.88, P =  0.72), stent migration (5.9 % vs. 6.8 %, P =  0.79), and stent occlusion (3.8 % vs. 5.2 %, P =  0.78) were similar for both groups. Inclusion of non-EUS-guided cases led to significantly higher DPPS bleeding and perforation rates. Conclusions LAMS and DPPS were associated with similar rates of AEs and WON resolution when limiting analysis to EUS-guided cases. Higher bleeding rates were seen in historical studies of DPPS without EUS guidance. Additional high-quality studies of WON treatment using consistent outcome definitions are needed.

Age-associated NF-κB signaling in myofibers alters the satellite cell niche and re-strains muscle stem cell function.

Skeletal muscle is a highly regenerative tissue, but muscle repair potential is increasingly compromised with advancing age. In this study, we demonstrate that increased NF-κB activity in aged muscle fibers contributes to diminished myogenic potential of their associated satellite cells. We further examine the impact of genetic modulation of NF-κB signaling in muscle satellite cells or myofibers on recovery after damage. These studies reveal that NF-κB activity in differentiated myofibers is sufficient to drive dysfunction of muscle regenerative cells via cell-non-autonomous mechanisms. Inhibition of NF-κB, or its downstream target Phospholipase A2, in myofibers rescued muscle regenerative potential in aged muscle. Moreover, systemic administration of sodium salicylate, an FDA-approved NF-κB inhibitor, decreased inflammatory gene expression and improved repair in aged muscle. Together, these studies identify a unique NF-κB regulated, non-cell autonomous mechanism by which stem cell function is linked to lipid signaling and homeostasis, and provide important new targets to stimulate muscle repair in aged individuals.