Leonardo Rodriguez

Open label, prospective, randomized controlled trial of an endoscopic duodenal-jejunal bypass sleeve versus low calorie diet for pre-operative weight loss in bariatric surgery

BackgroundThe duodenal-jejunal bypass sleeve (DJBS) has been shown to achieve a completely endoscopic duodenal exclusion without the need for stapling. This report is the first randomized controlled trial for weight loss.MethodsIn a 12-week, prospective, randomized study, subjects received either a low fat diet and the DJBS or a low fat diet control (no device). Twenty-five patients were implanted with the device and 14 received the control. The groups were demographically similar. Both groups received counseling at baseline only, which consisted of a low calorie diet, and exercise/behavior modification advice. No additional counseling occurred in either group. Measurements included starting and monthly body weight and serum blood tests. The device group also had a plain abdominal film post implant, a monthly KUB and a 4-week post explant EGD.ResultsTwenty device (80%) subjects maintained the DJBS without a significant adverse event for the 12-week duration. At 12 weeks, the mean excess weight loss was 22% and 5% for the device and control groups, respectively (p < 0.001). Five subjects (20%) were endoscopically explanted early secondary to upper GI (UGI) bleeding (n = 3), anchor migration (n = 1) and sleeve obstruction (n = 1). The UGI bleeding occurred at a mean of 13.8 days post implant. EGD was performed in each of these cases with no distinct bleeding source identified. No blood transfusion was required. The migration occurred on day 47 and manifested as abdominal pain. The subject with the sleeve obstruction presented with abdominal pain and vomiting on day 30. Eight subjects (40%) underwent the 4 week post explant EGD at which time mild degrees of residual duodenal inflammation was noted.ConclusionThe DJBS achieves noninvasive duodenal exclusion and short term weight loss efficacy. Longer term randomized controlled sham trials for weight loss and treatment of T2DM are underway.

Endoscopic Duodenal Mucosal Resurfacing for the Treatment of Type 2 Diabetes: 6-Month Interim Analysis From the First-in-Human Proof-of-Concept Study

OBJECTIVE To assess procedural safety and glycemic indices at 6 months in a first-in-human study of duodenal mucosal resurfacing (DMR), a novel, minimally invasive, upper endoscopic procedure involving hydrothermal ablation of the duodenal mucosa, in patients with type 2 diabetes and HbA1c ≥7.5% (58 mmol/mol) on one or more oral antidiabetic agents. RESEARCH DESIGN AND METHODS Using novel balloon catheters, DMR was conducted on varying lengths of duodenum in anesthetized patients at a single medical center. RESULTS A total of 39 patients with type 2 diabetes (screening HbA1c 9.5% [80 mmol/mol]; BMI 31 kg/m2) were treated and included in the interim efficacy analysis: 28 had a long duodenal segment ablated (LS; ∼9.3 cm treated) and 11 had a short segment ablated (SS; ∼3.4 cm treated). Overall, DMR was well tolerated with minimal gastrointestinal symptoms postprocedure. Three patients experienced duodenal stenosis treated successfully by balloon dilation. HbA1c was reduced by 1.2% at 6 months in the full cohort (P < 0.001). More potent glycemic effects were observed among the LS cohort, who experienced a 2.5% reduction in mean HbA1c at 3 months postprocedure vs. 1.2% in the SS group (P < 0.05) and a 1.4% reduction at 6 months vs. 0.7% in the SS group (P = 0.3). This occurred despite net medication reductions in the LS cohort between 0 and 6 months. Among LS patients with a screening HbA1c of 7.5–10% (58–86 mmol/mol) and on stable antidiabetic medications postprocedure, HbA1c was reduced by 1.8% at 6 months (P < 0.01). CONCLUSIONS Single-procedure DMR elicits a clinically significant improvement in hyperglycemia in patients with type 2 diabetes in the short-term, with acceptable safety and tolerability. Long-term safety, efficacy, and durability and possible mechanisms of action require further investigation.

Effect of electrical stimulation of the lower esophageal sphincter in gastroesophageal reflux disease patients refractory to proton pump inhibitors.

AIM To evaluate the efficacy of lower esophageal sphincter (LES)-electrical stimulation therapy (EST) in a subgroup of patients that reported only partial response to proton pump inhibitors (PPIs) therapy, compared to a group of patient with complete response. METHODS Bipolar stitch electrodes were laparoscopically placed in the LES and connected to an implantable pulse generator (EndoStim BV, the Hague, the Netherlands), placed subcutaneously in the anterior abdominal wall. Stimulation at 20 Hz, 215 μsec, 3-8 mAmp in 30 min sessions was delivered starting on day 1 post-implant. Patients were evaluated using gastroesophageal reflux disease (GERD)-HRQL, symptom diaries; esophageal pH and esophageal manometry before and up to 24 mo after therapy and results were compared between partial and complete responders. RESULTS Twenty-three patients with GERD on LES-EST were enrolled and received continuous per-protocol stimulation through 12 mo and 21 patients completed 24 mo of therapy. Of the 23 patients, 16 (8 male, mean age 52.1 ± 12 years) had incomplete response to PPIs prior to LES-EST, while 7 patients (5 male, mean age 52.7 ± 4.7) had complete response to PPIs. In the sub-group with incomplete response to PPIs, median (IQR) composite GERD-HRQL score improved significantly from 9.5 (9.0-10.0) at baseline on-PPI and 24.0 (20.8-26.3) at baseline off-PPI to 2.5 (0.0-4.0) at 12-mo and 0.0 (0.0-2.5) at 24-mo follow-up (P < 0.05 compared to on-and off-PPI at baseline). Median (IQR) % 24-h esophageal pH < 4.0 at baseline in this sub-group improved significantly from 9.8% (7.8-11.5) at baseline to 3.0% (1.9-6.3) at 12 mo (P < 0.001) and 4.6% (2.0-5.8) at 24 mo follow-up (P < 0.01). At their 24-mo follow-up, 9/11 patients in this sub-group were completely free of PPI use. These results were comparable to the sub-group that reported complete response to PPI therapy at baseline. No unanticipated implantation or stimulation-related adverse events, or any untoward sensation due to stimulation were reported in either group and LES-EST was safely tolerated by both groups. CONCLUSION LES-EST is safe and effective in controlling symptoms and esophageal acid exposure in GERD patients with incomplete response to PPIs. These results were comparable to those observed PPI responders.

Electrical stimulation of the lower esophageal sphincter to address gastroesophageal reflux disease after sleeve gastrectomy

BACKGROUND Laparoscopic sleeve gastrectomy (LSG) can result in de novo and worsen preexisting gastroesophageal reflux disease (GERD). Post-LSG patients with GERD refractory to proton pump inhibitors (PPI) usually undergo more invasive, anatomy-altering Roux-en-Y gastric bypass surgery. Lower esophageal sphincter (LES) electrical stimulation (ES) preserves the anatomy and has been shown to improve outcomes in GERD patients. OBJECTIVE To evaluate the safety and efficacy of LES-ES in post-LSG patients with GERD not controlled with maximal PPI therapy. SETTING Prospective, international, multicenter registry. METHODS Patients with LSG-associated GERD partially responsive to PPI underwent LES-ES. GERD outcomes pre- and poststimulation were evaluated based on quality of life, esophageal acid exposure (after 6-12 mo), and PPI use. RESULTS Seventeen patients (11 female, 65%), treated at 6 centers between May 2014 and October, 2016 with a median follow-up of 12 months (range 6-24), received LES-ES. Median age was 48.6 years (interquartile range, 40.5-56), median body mass index 31.7 kg/m2 (27.9-39.3). All patients were on at least daily PPI preoperatively; at last follow-up, 7 (41%) were completely off PPI, 5 (29%) took PPI on an intermittent basis, and 5 (29%) were on single-dose PPI. Median GERD-health-related quality of life scores improved from 34 (on-PPI, 25-41) at baseline to 9 (6-13) at last follow-up (off-PPI, P<.001). Percentage of time with esophageal pH<4 improved from 13.2% (3.7-30.7) to 5.8% (1.1-54.4), P = .01. CONCLUSION LES-ES in post-LSG patients suffering from symptomatic, PPI-refractory GERD resulted in significant improvement of GERD-symptoms, esophageal acid exposure, and need for PPI. Preserving the post-LSG anatomy, it offers a valid option for patients unable or unwilling to undergo Roux-en-Y gastric bypass surgery.

Hydrothermal duodenal mucosal resurfacing: a novel procedural therapy for metabolic disease

This video demonstrates Revita duodenal mucosal resurfacing (DMR; Fractyl Laboratories, Inc, Waltham, Mass), an investigational, catheter-based, upper endoscopic procedure for the treatment of metabolic diseases, including type 2 diabetes (T2D) and nonalcoholic steatohepatitis (Video 1, available online at www.VideoGIE. org). The procedure uses hydrothermal ablation of approximately 10 cm of duodenal mucosa to elicit beneficial metabolic effects, including improvements in hyperglycemia in patients with T2D who are suboptimally controlled on oral antidiabetic medications. This video provides an overview of the procedure and describes the 6-month clinical results of a 43-year-old man (duration of T2D, 6 years) treated with DMR. At screening, the patient had a body mass index of 31, weight of 91.6 kg, hemoglobin A1c of 9.5%, and fasting plasma glucose (FPG) of 162 mg/dL. Six months after a single hydrothermal DMR procedure, the patient’s hemoglobin A1c had fallen to 7.2% and FPG had fallen to 132 mg/dL. The patient experienced a modest weight reduction (–2.3 kg), and his use of oral antidiabetic medications (n Z 2) did not change. Liver enzymes, followed as a safety signal, remained normal. Follow-up endoscopy at 90 days indicated full mucosal healing. Figure 1 depicts the duodenal mucosa (A) after