Corrigendum to: "Endoscopic duodenal mucosal resurfacing improves glycaemic and hepatic indices in type 2 diabetes: 6-month multicentre results" [JHEP Reports 5 (2019) 101041].

[This corrects the article DOI: 10.1016/j.jhepr.2019.10.006.].

Durable metabolic improvements 2 years after duodenal mucosal resurfacing (DMR) in patients with type 2 diabetes (REVITA-1 Study).

AIMS: Duodenal mucosal resurfacing (DMR) is an endoscopic procedure developed to improve metabolic parameters and restore insulin sensitivity in patients with diabetes. Here we report long-term DMR safety and efficacy from the REVITA-1 study. MATERIALS AND METHODS: REVITA-1 was a prospective, single-arm, open-label, multicenter study of DMR feasibility, safety, and efficacy in patients with type 2 diabetes (hemoglobin A1c [HbA1c] of 7.5-10.0% (58-86 mmol/mol)) on oral medication. Safety and glycemic (HbA1c), hepatic (alanine aminotransferase [ALT]), and cardiovascular (HDL, triglyceride [TG]/HDL ratio) efficacy parameters were assessed (P values presented for LS mean change). RESULTS: Mean ± SD HbA1c levels reduced from 8.5 ± 0.7% (69.1 ± 7.1 mmol/mol) at baseline (N = 34) to 7.5 ± 0.8% (58.9 ± 8.8 mmol/mol) at 6 months (P < 0.001); and this reduction was sustained through 24 months post-DMR (7.5 ± 1.1% [59.0 ± 12.3 mmol/mol], P < 0.001) while in greater than 50% of patients, glucose-lowering therapy was reduced or unchanged. ALT decreased from 38.1 ± 21.1 U/L at baseline to 32.5 ± 22.1 U/L at 24 months (P = 0.048). HDL and TG/HDL improved during 24-months of follow-up. No device- or procedure-related serious adverse events, unanticipated device effects, or hypoglycemic events were noted between 12 and 24 months post-DMR. CONCLUSIONS: DMR is associated with durable improvements in insulin sensitivity and multiple downstream metabolic parameters through 24 months post-treatment in type 2 diabetes. Clinical trial reg. no. NCT02413567, clinicaltrials.gov.

Duodenal mucosal resurfacing: proof-of-concept, procedural development, and initial implementation in the clinical setting.

BACKGROUND AND AIMS: We aimed to develop duodenal mucosal resurfacing (DMR), a minimally invasive upper endoscopic hydrothermal ablation procedure, to treat insulin-resistant metabolic diseases. METHODS: We completed a sham-controlled, rodent proof-of-concept study and longitudinal safety study in pigs to demonstrate feasibility to test DMR in humans. Subsequently, the DMR procedure was implemented in an open-label first-in-human (FIH) study of safety and efficacy in patients with type 2 diabetes (T2D). RESULTS: In rats, duodenal abrasion reduced hyperglycemia by 59 mg/dL on average, compared with no change from baseline in the sham treatment arm (P < .05). In pigs, the balloon catheter successfully and safely delivered hydrothermal ablation to the duodenal mucosa and superficial submucosa. Complete mucosal healing was demonstrated by week 6. In the FIH study, hydrothermal ablation was successfully administered with no evidence of perforation, pancreatitis, or hemorrhage. Duodenal biopsy specimens obtained 3 months postprocedure demonstrated full mucosal regrowth. No inflammation was observed, and there was minimal-to-mild collagen banding deposition observed in a proportion of ablation site biopsy specimens with no evidence of fibrotic scarring. Glycemic and hepatic measures improved through 6 months of follow-up. CONCLUSIONS: DMR shows potential as an endoscopic intervention that improves glycemic and hepatic parameters in patients with T2D. Further mechanistic and clinical studies are underway to further explore DMR as a treatment for metabolic disease.

Endoscopic duodenal mucosal resurfacing improves glycaemic and hepatic indices in type 2 diabetes: 6-month multicentre results.

Insulin resistance is a core pathophysiological defect underscoring type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). Both conditions improve with duodenal exclusion surgery. Duodenal mucosal resurfacing (DMR) is an endoscopic intervention developed to treat metabolic disease which has been shown to improve glycaemia in patients with poorly controlled T2DM. Herein, we aimed to further analyse the effects of DMR on hepatic and metabolic parameters in this patient cohort. METHODS: Eighty-five patients with T2DM who received endoscopic DMR treatment were enrolled from 5 centres and followed up for 6 months. We assessed safety in all patients. Efficacy was evaluated in patients who received at least 9 cm of duodenal ablation (n = 67). Endpoints included HbA1c, fasting plasma glucose, weight and aminotransferase levels. Metabolomic analysis was conducted in a subgroup (n = 14). Data were analysed using paired t test or ANOVA for repeated measures with Bonferroni correction and correction for initial weight loss if applicable. RESULTS: The DMR procedure was completed with no intraprocedural complications in the entire cohort. HbA1c was lower 6 months after DMR than at baseline (7.9 ± 0.2% vs. 9.0 ± 0.2% [mean ± SE], p ≪0.001). Fasting plasma glucose was also significantly lower 6 months after DMR compared to baseline (161 ± 7 mg/dl vs. 189 ± 6 mg/dl, p = 0.005). Body weight decreased slightly. At 6 months, alanine aminotransferase had decreased from 41 ± 3 IU/L to 29 ± 2 IU/L (p ≪0.001) and aspartate aminotransferase had decreased from 30 ± 2 IU/L to 23 ± 1 IU/L (p ≪0.001). Metabolomic analysis demonstrated that DMR had key lipid-lowering, insulin-sensitizing and anti-inflammatory effects, as well as increasing antioxidant capacity. Mean FIB-4 was also markedly decreased. CONCLUSION: Hydrothermal ablation of the duodenum by DMR elicits a beneficial metabolic response in patients with T2DM. DMR also improves hepatic indices, potentially through an insulin-sensitizing mechanism. These encouraging data deserve further evaluation in randomized controlled trials. LAY SUMMARY: Hydrothermal duodenal mucosal resurfacing (DMR) is an endoscopic technique designed to treat metabolic disease through ablation of the duodenal mucosa. DMR is a safe procedure which improves glycaemia and hepatic indices in patients with type 2 diabetes mellitus. DMR is an insulin-sensitizing intervention which can be complementary to lifestyle intervention approaches and pharmacological treatments aimed at preserving the pancreas and liver from failure. DMR is a potential therapeutic solution for patients with type 2 diabetes and fatty liver disease.

Endoscopic sutured gastroplasty: procedure evolution from first-in-man cases through current technique.

BACKGROUND: Endoscopic sutured gastroplasty (ESG) has evolved over time. With the advent of full-thickness endoscopic suturing, an efficient technique for ESG was developed and refined. METHODS: This prospective first-in-man trial started in April 2012 and represents the first use of full-thickness endoscopic suturing for primary obesity therapy. The trial focused on procedure development, reproducibility, safety, and short-term efficacy. The trial was performed at centers in five countries, in three phases. Phase I was evaluation of safety and technical feasibility of various procedure techniques; stitch patterns and sequences were assessed for efficiency, safety, and feasibility. Phase II entailed continued procedure refinement to establish a standardized technique. Phase III entailed evaluation of technical feasibility and weight loss outcomes in 77 patients; the procedure was performed using the standardized technique, and there was no procedure development. Data were prospectively collected into a registry. RESULTS: In Phase I, the procedure was created and modified to improve time efficiency. Safety and technical feasibility were established, and short-term weight loss was demonstrated. In Phase II, a number of stitch patterns were attempted, and the stitch pattern was modified and finalized. 22 patients were included, and 1-year total weight loss was 17.3 ± 2.6%. In Phase III, conformity with the final technique was high. 77 patients were included, with a mean BMI of 36.1 ± 0.6 kg/m2. Mean weight loss was 16.0 ± 0.8% at 6 months and 17.4 ± 1.2% at 12 months (n = 44). Postprocedural nausea, vomiting, and epigastric pain were frequently reported; there were no reported significant adverse events post-procedure or during the follow-up period. CONCLUSIONS: Following a methodical procedure development phase, ESG demonstrated safety and short-term efficacy in this trial. The procedure also achieved meaningful weight loss during the follow-up period.

Efficacy of Intragastric Balloon Treatment for Adolescent Obesity.

BACKGROUND: Several studies conducted in adults suggest that intragastric balloon (IGB) is an effective and safe method for weight loss. Although the prevalence of obesity in adolescents has increased in recent years, the outcomes of IGB treatment in this age group are not known. The aim of this study was to evaluate the safety and efficacy of IGB treatment for weight loss in adolescents followed up for 6 months. METHODS: This is a retrospective longitudinal study including 27 adolescents (14-19 years; 23 female). All participants were referred to IGB treatment by their attending physician, presented body mass index (BMI) ≥ 29 kg/m2 (>p97 BMI/age index) and failed to lose weight in clinical treatments. A liquid-filled nonadjustable IGB with a volume of 600 to 700 ml was used for 6 months. All patients were included in a multidisciplinary program, and adherence to this program was evaluated as the number of attended appointments. RESULTS: There were no serious complications or deaths. The BMI decreased from 37.04 to 31.18 kg/m2 (p < 0.0001), body weight decreased from 102.21 to 86.23 kg (p < 0.0001), and excess weight diminished from 35.18 to 19.12 kg (p < 0.0001). The % excess weight loss (%EWL) was 56.19 and % total weight loss (%TWL) 16.35. Adherence to the multidisciplinary program correlated directly with %EWL (r = 0.55; p = 0.0033) and %TWL (r = 0.53; p = 0.0052). CONCLUSION: Endoscopic treatment of obesity with an IGB is safe, effective, and may be an emerging therapeutic option for adolescents.

The Influence of the Orbera Intragastric Balloon Filling Volumes on Weight Loss, Tolerability, and Adverse Events: a Systematic Review and Meta-Analysis.

BACKGROUND: The Orbera intragastric balloon (IGB) has been approved by the US Food and Drug Administration for use in patients with a body mass index (BMI) between 30 and 40 kg/m2 and is in wide use worldwide as a primary and bridge obesity management tool. The balloon filling volume (BFV) ranges between 400 and 700 mL of saline. Our objective was to determine whether there is an association between BFV and clinically relevant endpoints, namely weight loss outcomes, balloon tolerability, and adverse events. METHODS: A systematic review of studies investigating the use of the Orbera IGB system for obesity treatment was performed. Data was examined using random effects modelling and meta-regression analyses. RESULTS: Forty-four studies (n = 5549 patients) reported BFV and % total body weight loss (TBWL) at 6 months. Pooled %TBWL at 6 months was 13.2% [95% CI 12.3-14.0]. A funnel plot demonstrated a low risk of publication bias. Meta-regression showed no statistically significant association between filling volume and %TBWL at 6 months (p = 0.268). Higher BFV was associated with lower rates of esophagitis (slope = -0.008, p < 0.001) and prosthesis migration (slope = -0.015, p < 0.001). There was no association between BFV and early removal (p = 0.1), gastroesophageal reflux symptom (p = 0.64), or ulcer rates (p = 0.09). CONCLUSIONS: No association was observed between Orbera IGB filling volume and weight loss outcomes. Higher volumes appear to be associated with lower migration and esophagitis rates; thus, a balloon filling volume of 600-650 mL is recommended.

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.

Metabolic improvements in obese type 2 diabetes subjects implanted for 1 year with an endoscopically deployed duodenal-jejunal bypass liner.

BACKGROUND: The purpose of this study was to evaluate the effect of the duodenal-jejunal bypass liner (DJBL), a 60-cm, impermeable fluoropolymer liner anchored in the duodenum to create a duodenal-jejunal bypass, on metabolic parameters in obese subjects with type 2 diabetes. METHODS: Twenty-two subjects (mean age, 46.2±10.5 years) with type 2 diabetes and a body mass index between 40 and 60 kg/m(2) (mean body mass index, 44.8±7.4 kg/m(2)) were enrolled in this 52-week, prospective, open-label clinical trial. Endoscopic device implantation was performed with the patient under general anesthesia, and the subjects were examined periodically during the next 52 weeks. Primary end points included changes in fasting blood glucose and insulin levels and changes in hemoglobin A1c (HbA1c). The DJBL was removed endoscopically at the end of the study. RESULTS: Thirteen subjects completed the 52-week study, and the mean duration of the implant period for all subjects was 41.9±3.2 weeks. Reasons for early removal of the device included device migration (n=3), gastrointestinal bleeding (n=1), abdominal pain (n=2), principal investigator request (n=2), and discovery of an unrelated malignancy (n=1). Using last observation carried forward, statistically significant reductions in fasting blood glucose (-30.3±10.2 mg/dL), fasting insulin (-7.3±2.6 µU/mL), and HbA1c (-2.1±0.3%) were observed. At the end of the study, 16 of the 22 subjects had an HbA1c<7% compared with only one of 22 at baseline. Upper abdominal pain (n=11), back pain (n=5), nausea (n=7), and vomiting (n=7) were the most common device-related adverse events. CONCLUSIONS: The DJBL improves glycemic status in obese subjects with diabetes and therefore represents a nonsurgical, reversible alternative to bariatric surgery.

Extreme bariatric endoscopy: stenting to reconnect the pouch to the gastrojejunostomy after a Roux-en-Y gastric bypass.

BACKGROUND: Among the possible complications of bariatric surgery, fistula and partial dehiscence of the gastric suture are well known. Reoperation often is required but results in significant morbidity. Endoscopic treatment of some bariatric complications is feasible and efficient. METHODS: A modified metallic stent was placed between the gastroaesophageal junction and the alimentary jejunal limb, allowing the passage of a nasoenteric feeding tube into the jejunal limb. RESULTS: Endoscopy showed disruption of nearly the entire staple line at the gastric pouch. The modified stent was placed and allowed wound healing. After 31 days, the stent had migrated and was removed endoscopically. Total closure of the fistula was reported 30 days afterward. CONCLUSIONS: Endoscopic treatment of some bariatric surgery complications is feasible and has been reported previously. This report presents a case of a serious leakage treated by placement of a self-expandable metal stent to bridge the fistula.

Small erosion of adjustable gastric band: endoscopic removal through incision in gastric wall.

The erosion of a laparoscopic adjustable gastric band (LAGB) can cause pain that is not controlled by analgesics. In such cases, early endoscopic removal may be indicated, but only when gastric penetration is greater than 50%. We report the case of a patient with severe shoulder pain due to a small area of LAGB erosion, which was treated with early endoscopic removal through an incision in the gastric wall. The pain worsened after eating and gastroscopy revealed slight gastric erosion of the band under the cardia. The gastric wall covering the LAGB was incised using an endoscopic needle knife. In a second upper endoscopy performed 7 days later at the endoscopy suite, endoscopic scissors were used to cut the thread and part of the band lock. The open band was then removed orally. This novel endoscopic incision in the gastric wall hastened band erosion and avoided abdominal reoperation.

Treatment of ring slippage after gastric bypass: long-term results after endoscopic dilation with an achalasia balloon (with videos).

BACKGROUND: Silastic rings are used in gastric bypass procedures for the treatment of obesity, but ring slippage may lead to gastric pouch outlet stenosis (GPOS). Conventional management has been ring removal through abdominal surgery. OBJECTIVE: To describe a novel, safe, minimally invasive, endoscopic technique for the treatment of GPOS caused by ring slippage after gastric bypass. DESIGN: Case series. SETTING: Federal University of Pernambuco and São Paulo University. PATIENTS: This study involved 39 consecutive patients who were screened for inclusion. INTERVENTION: Endoscopic dilation with an achalasia balloon. MAIN OUTCOME MEASUREMENTS: Technical success and safety of the procedure. RESULTS: Among the 39 patients, 35 underwent endoscopic dilation at the ring slippage site for the relief of GPOS. The 4 patients who did not undergo endoscopic dilation underwent surgical removal of the ring, based on the exclusion criteria. The endoscopic approach was successful in 1 to 4 sessions in 100% of cases with radioscopic control (n = 12). The duration of the procedures ranged from 5 to 30 minutes, and the average internment was 14.4 hours. Dilation promoted either rupture (65.7%) or stretching (34.3%) of the thread within the ring, thereby increasing the luminal diameter of the GPOS. Complications included self-limited upper digestive tract hemorrhage (n = 1) and asymptomatic ring erosion (n = 4). There were no recurrences of obstructive symptoms during the follow-up period (mean of 33.3 months). LIMITATIONS: This was not a randomized, comparison study, and the number of patients was relatively small. CONCLUSION: The technique described promotes the relief of GPOS with low overall morbidity and avoids abdominal reoperation for ring removal.

Cholecystectomy by single trocar access (SITRACC): the first multicenter study.

BACKGROUND: The advent of endoscopic surgery has radically changed surgery worldwide.The concept of minimally invasive procedures has spread quickly, allowing less pain and more rapid recovery for patients. The authors have developed a device for a new surgical approach, the so-called single trocar access (SITRACC). This study report the first multicenter study of cholecystectomies performed with SITRACC. METHODS: Between December 2008 and June 2009, 81 single trocar cholecystectomies were performed in 9 Brazilian surgery centers. RESULTS: The average operative time was 68 minutes. In all, 10 surgeries required 1 additional trocar because of technical problems, and 3 cholecystectomies were converted to standard video laparoscopies. CONCLUSION: A cholecystectomy using the SITRACC method is feasible and safe.

International multicenter study of safety and effectiveness of Swedish Adjustable Gastric Band in 1-, 3-, and 5-year follow-up cohorts.

BACKGROUND: No long-term, international, multicenter studies of the effectiveness and safety of the SAGB in morbid obesity have been previously published. The objective of this study was to assess the effectiveness and safety of the Swedish Adjustable Gastric Band (SAGB) at 6 bariatric centers in Australia, Europe, and Brazil, with < or =5 years of follow-up; the effect on patient covariates; and changes in co-morbidity. METHODS: A 2-phase study design was used, involving both retrospective and prospective data. SAGB was implanted by way of the pars flaccida 1, 3, and 5 years previously. The retrospective phase entailed a review of the records. The prospective phase included a subset of eligible patients who agreed to undergo additional clinical assessments. The percentage of excess weight loss (%EWL), patient level predictors, change in co-morbidities, and complications were analyzed. RESULTS: A total of 481 patients in 3 mutually exclusive follow-up cohorts (1 yr, n = 200; 3 yr, n = 184; 5 yr, n = 97) participated in the present study. Of these 481 patients, 339 (1 yr, n = 139; 3 yr, n = 131; 5 yr, n = 69) underwent prospective evaluations. The mean %EWL was 43.5% + or - 21.8%, 57.7% + or - 25.9%, and 49.8% + or - 27.6% and the mean change in body mass index was -7.64, -10.75, and -9.52 in the 1-, 3-, and 5-year cohorts, respectively (P <.001). Gender and age did not predict the %EWL; however, a greater preoperative body mass index was inversely related to the %EWL. Longer postimplantation times were associated with greater improvement in co-morbidities and with greater frequencies of reoperation. Fewer than 15% of the patients in the 5-year cohort had undergone band removal and 10% required band revisions. No fatal or life-threatening complications occurred. CONCLUSION: SAGB is safe and effective in inducing weight loss and improvement of co-morbidities in morbidly obese patients at international bariatric centers at 1, 3, and 5 years postoperatively.

Laparoscopic duodenal-jejunal exclusion in the treatment of type 2 diabetes mellitus in patients with BMI<30 kg/m2 (LBMI).

BACKGROUND: The association between medical and dietetic-behavioral treatments of type 2 diabetes mellitus (T2DM) has demonstrated to have variable results. The surgical treatment of T2DM is justifiable after the observation of a successful glycemic control in patients submitted to Roux-en-Y gastric bypass and biliopancreatic diversion. Experiments have shown an important role of the proximal intestine in glycemia decrease and diabetes control. METHODS: Twenty diabetic patients underwent laparoscopic duodenal-jejunal exclusion. The variables studied were body mass index (BMI), fasting glycemia, glycosylated hemoglobin (HbA1c), and C-peptide, in the preoperative period and after 3 and 6 months. RESULTS: There was a BMI decrease up to the third month and a weight stabilization between the third and sixth months. There was a significant reduction in fasting glycemia (43.8%) and HbA1c (22.8%) up to the sixth month (p<0.001). C-peptide did not show any significant alteration until the third month, although there was a considerable increase (25%) between the third and the sixth months (p<0.001). Only two patients were on oral medication after the sixth month. CONCLUSIONS: Preliminary results have shown an important effect of the laparoscopic duodenal-jejunal exclusion in the treatment of T2DM. Studies with longer follow-up and a larger number of patients are necessary to better define the role of this new and promising procedure.

Staplerless laparoscopic gastric bypass: a new option in bariatric surgery.

The staplerless Roux-en-Y gastric bypass (RYGBP) is a new option in bariatric surgery. The first to describe it was Himpens (2004) utilizing the LigaSure Atlas (LSA) in a series of 10 patients. The laparoscopic RYGBP is performed utilizing the LSA for the gastric and jejunal partition; after that, an imbricating running suture is performed to ensure stomach and bowel hermetic closure. All anastomoses are hand-sewn. Technical disadvantages are: learning curve; complications related to suture failure; possible thermal/electricity related injuries; longer operating time. Advantages are: stapler-associated bleeding, leaks, staple-line disruption, and fistulas are avoided; cost reduction. The staplerless RYGBP is complex; the surgeon involved requires expertise and ability. This technique will evolve and will be used by more surgeons. It is a new option for the surgeon preoccupied with costs, which is particularly important in developing countries.