Prospective evaluation of transoral outlet reduction (TORe) after Roux-en-Y gastric bypass (RYGB) failure.

BACKGROUND AND AIMS: Weight regain after RYGB is multifactorial including dilatation of the gastro-jejunal anastomosis. Transoral outlet reduction (TORe) procedure is a minimally invasive alternative to surgical anastomotic revision. METHODS: We conducted a prospective, multicenter, simple blind, randomized study in patients with weight regain following RYGB, comparing the efficacy of conventional nutritional and behavioral management associated with a TORe procedure (TORe group) with conventional management alone and a Sham procedure (Sham group). The main objective of this study was to evaluate the percentage of excess weight loss (%EWL) at 12 months after endoscopy. RESULTS: From January 2015 to January 2019, 73 subjects were randomized in four French Bariatric centers. The final analysis involved 50 subjects, 25 in each group, 44 women, 6 men, with an average BMI of 40.6 kg/m2. At 12 months, the average %EWL was significantly higher in the TORe group than in the Sham group (13.5 ± 14.1 vs. - 0.77 ± 17.1; p = 0.002). Cohen's d was 0.91, indicating a large effect size of the procedure on the %EWL. There was no significant difference between groups concerning the improvement of obesity-related comorbidities (diabetes and dyslipidemia) and quality of life at 12 months. We report frequent adverse events in the TORe group (20% had adverse events related to the procedure). Three adverse events were serious, including two perforations of the gastro-jejunal anastomosis after TORe group that led to the premature termination of the study. CONCLUSIONS: After RYGBP failure linked to the dilatation of the gastro-jejunal anastomosis, TORe procedure with nutritional management results in significantly higher %EWL at 12 months compared to patients with nutritional management alone. As surgery, this minimally invasive endoscopic procedure can be associated with severe adverse events.

Endoscopic trans-oral outlet reduction after bariatric surgery is safe and effective for dumping syndrome.

BACKGROUND: Dumping syndrome (DS) is a common complication of bariatric surgery. Treatments include dietary and behavioral changes, as well as pharmacotherapy and revision surgery. All can be costly or hard to adhere to. In recent years, evidence accumulates in favor of endoscopic trans-oral outlet reduction (TORe) as an effective treatment for DS, targeting the pathophysiology of rapid gastric clearance. The objective of this study is to assess the safety and efficacy of TORe for DS in a single referral center. METHODS: Patients after bariatric surgery suffering DS were followed, and data were retrospectively analyzed. Diagnosis and post-procedural assessment of DS were made clinically using Sigstad score. During the procedure, the anastomotic rim was cauterized. Afterwards, 2 non-interrupted "8-figure" sutures were placed, resulting in imbrication of additional gastric tissue on top of the anastomosis and narrowing to <1 cm at the end of the procedure. Patients were instructed to keep a liquid diet for 14 days and follow-up continued for 6 months. RESULTS: Between 8/2018 and 9/2019 TORe was carried out in 13 patients (M:F = 3:10) with mean age of 45.1 (range 25-56) and BMI of 33.5 (range 28.1-40.3). Average time since recent surgery was 5.5 years (range 1-9). Mean pre-procedure anastomosis diameter was 25.2 mm (range 15-30) and was reduced to a mean of 5.6 mm (range 5-10). Three patients (23%) were admitted overnight due to inability to drink which resolved spontaneously. No major complications were reported. At 6 months, the Sigstad score was significantly reduced (19.4 ± 3.6 vs 5.2 ± 5.5, P < 0.001), and 11/13 (85%) of patients had a complete resolution of their dumping symptoms. In addition, BMI decreased by a mean of 2.3 kg/m2 (-1 to 7.5, p = 0.002). CONCLUSION: TORe is a safe and effective treatment for patients suffering dumping syndrome and should be considered early in the treatment of DS.

Factors Associated with Weight Loss After Endoscopic Transoral Outlet Reduction (TORe).

INTRODUCTION: Endoscopic transoral outlet reduction (TORe) has emerged as a safe and effective treatment option for weight regain after Roux-en-Y Gastric Bypass (RYGB). Factors that predict successful weight loss after TORe are incompletely understood. The aims of this study were to evaluate procedural factors and patient factors that may affect percent total body weight loss (%TBWL) after TORe. METHODS: A retrospective cohort study was performed on patients after TORe. The primary outcomes were %TBWL at 6 and 12 months based on four procedural factors: purse-string (PS) vs. non-purse-string (NPS) suture pattern, gastric pouch sutures (N), change in the diameter of the gastrojejunal anastomosis, and change in the length of the gastric pouch. Secondary outcomes included patient factors that affected weight loss. RESULTS: Fifty-one patients underwent TORe. Weight loss for completers was 11.3 ± 7.6% and 12.2 ± 9.2% at 6 and 12 months. There was a correlation between %TBWL and change in pouch length at 6 and 12 months and number of sutures in the pouch at 6 months. The difference in %TBWL between PS and NPS groups at 6 months (PS, n=21, 12.3 ± 8.5% and NPS, n=8, 8.7 ± 3.7%) and 12 months (PS, n=21, 13.5 ± 9.2% and NPS, n=5, 7.0 ± 7.9%) did not reach statistical significance. For secondary outcomes, depression was associated with %TBWL. CONCLUSION: Change in pouch length and number of sutures in the pouch correlated positively while depression correlated negatively with weight loss after TORe. Further studies are needed to understand these effects.

Effect of Transoral Outlet Reduction on Hepatic Fibrosis in Roux-en-Y Gastric Bypass Patients with Weight Regain and Non-alcoholic Fatty Liver Disease.

PURPOSE: Weight regain after Roux-en-Y gastric bypass (RYGB) is associated with worsening of liver outcomes. However, the effect of transoral outlet reduction (TORe) on liver fibrosis in RYGB patients with weight regain and possible advanced fibrosis remains unknown. MATERIALS AND METHODS: This was a retrospective analysis of prospectively collected data of RYGB patients who underwent TORe for weight regain. Only patients with possible advanced fibrosis were included. TORe was performed using either an endoscopic suturing device (S-TORe) or plication device (P-TORe) to reduce the gastrojejunal anastomosis (GJA) and pouch sizes. Primary outcomes included changes in non-invasive tests (NITs) for fibrosis at 6-12 months. Secondary outcomes included weight loss and changes in insulin resistance and lipid profile at 6-12 months. RESULTS: Fifty RYGB patients were included. Baseline age and BMI were 55 ± 11 years and 40.1 ± 7.3 kg/m2. Baseline GJA and pouch sizes were 20 ± 7 mm and 5 ± 2 cm, respectively. Thirty patients (60%) underwent S-TORe and 20 patients (40%) underwent P-TORe. At 12 months following TORe, there were statistically significant improvements in NITs for fibrosis, including ALT, AST and FIB-4. There was a trend towards significant improvement in liver stiffness measurement on transient elastography. Patients experienced 8.8 ± 11.2% total weight loss (TWL) (p < 0.0001), with 60% experiencing at least 10% TWL. Additionally, there was a significant improvement in HbA1c and a trend toward significant improvement in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), suggestive of improved insulin sensitivity. CONCLUSION: TORe is associated with an improvement in hepatic fibrosis in patients with NAFLD and possible advanced fibrosis.

Endoscopic Transoral Outlet Reduction for the Treatment of Biliary Reflux Symptoms in Patients After One-Anastomosis Gastric Bypass-a Case Series.

PURPOSE: OAGB is the third most common bariatric surgery. Biliary reflux (BR) is an inherent complication of this unique anatomy, although there is still controversy regarding its significance and long-term risks including carcinogenesis. To date, there is no effective treatment for BR with conversion to RYGB reserved for refractory patients. TORe is an effective treatment for weight-regain and dumping syndrome after RYGB. We hypothesized that narrowing the anastomosis would decrease the amount of bile refluxate entering the stomach and esophagus in patients with BR symptoms after OAGB and alleviate symptoms. The purpose of this study is to evaluate the efficacy of TORe for the treatment of BR symptoms after OAGB. MATERIALS AND METHODS: BR was diagnosed clinically in patients after OAGB using the gastroesophageal reflux disease health-related quality of life (GERD-HRQL) instrument after treatment with high-dose proton pump inhibitor (PPI) excluded possible acid reflux. TORe was carried out using a suture pattern that narrowed and elongated the anastomosis. All patients were prospectively followed. RESULTS: Twelve patients, post-OAGB, underwent TORe for BR. Symptoms resolved in 9 (75%) patients. GERD-HRQL score at 6 months declined from an average of 33.7 (SD 1.9) before the procedure to 16.1 (SD 10, p < 0.001). In one case, a small perforation was identified during the procedure and was immediately sutured with no further sequela. DISCUSSION: TORe appears a safe and effective treatment for BR symptoms after OAGB, at least in the short term. Accurate tools for BR diagnosis, a larger cohort, and longer follow-up periods are needed to better show the effectiveness and durability of this treatment option.

Effects of Heterozygous Variants in the Leptin-Melanocortin Pathway on Transoral Outlet Reduction After Roux-en-Y Gastric Bypass: A Case-Control Study and Review of Literature.

BACKGROUND: Transoral outlet reduction (TORe) is a safe and effective technique for management of weight regain (WR) after Roux-en-Y Gastric Bypass (RYGB). Carriers of a heterozygous variant in the leptin melanocortin pathway (LMP) have been shown to be at high risk for WR in the mid- and long-term after RYGB. Our case series includes four patients with heterozygous LMP variants and presents novel data on their weight loss after TORe. METHODS: We performed a retrospective study of the Mayo Clinic Biobank and identified adult participants who had been genotyped and found to have or do not have a heterozygous variant in the LMP ("carriers" vs "non-carriers", respectively) and had undergone a TORe procedure. TBWL% at 1, 3, 6, 9, and 12 months ± 15 days were calculated based on baseline weight at TORe procedure. RESULTS: A total of 14 patients were included in the analysis: four patients (mean age 51.0 [5.2] years, 100% females, body mass index [BMI] 40.5 [8.7] kg/m2) with LMP variant and 10 non-carriers (age 55.4 [15.3] years, 90% females, BMI 37.3 [7.7] kg/m2). There were no baseline differences between carriers and non-carriers at time of TORe procedure. After TORE, carriers lost less weight when compared to non-carriers at 3, 6, 9, and 12 months. The difference at 12 months was statistically significant (1.6 vs 12.3%; p = 0.03). CONCLUSIONS: Patients with a LMP variant and that underwent RYGB showed decreased weight loss after undergoing TORe. Further and larger studies are needed to comprehend the effect of TORe on patients with LMP variants.

Transoral Outlet Reduction to Tackle Weight Regain After Roux-en-Y Gastric Bypass: a Single Center Initial Experience.

BACKGROUND: Long-term failure after Roux-en-Y gastric bypass (RYGB) is well known and occurs in 10-15% of patients according to the literature. Causes are multifactorial and dilatation of the gastro-jejunal anastomosis (GJA) is only one of these. A transoral outlet reduction (TORe) with endoscopic sutures to reinstall more restriction could be a valid and safe alternative to reduce regained weight after failed gastric bypass surgery. The objective of this article is to describe our single-center experience and discuss the adverse events of the technique. OBJECTIVES: To describe our single-center case series and adverse events after TORe for weight regain after RYGB. METHODS: We report a case series of 20 patients referred due to weight regain after RYGB with a dilated GJA. TORe was performed using an endoscopic full-thickness suture device (Apollo OverStitch®) to reduce the diameter of the GJA and the volume of the gastric reservoir. Prospectively collected data on technical feasibility, safety and efficacy are described with a median follow-up of 22 (6-38) months. RESULTS: Mean BMI was 44.5 kg/m2 at the time of RYGB. Postoperative nadir BMI was 27,7 kg/m2. The average time to TORe was 12.1 years after initial RYGB. Patients regained a mean 45.9% of excess body weight loss (EWL) before TORe and had a mean preprocedural BMI of 35.3 kg/m2. The aim was to reduce the aperture of the GJA to 5 mm which was done with a mean of 1.7 sutures and 3.5 stitches. The mean absolute weight loss was 13 kg and BMI reduction was 3.9 kg/m2 after 6 months. After a median follow-up of 22 months, a BMI of 31.4 kg/m2 was observed. Dumping symptoms resolved in four of our patients 6 weeks after TORe. Procedural adverse events were nausea and vomiting, sore throat, mild transient abdominal pain, diarrhea and constipation. All of them were treated conservatively. Due to a lack of weight loss, a suture failure was assumed in two of our patients. We describe one case of postprocedural mediastinitis, presumably due to a distal esophageal perforation, treated with a laparoscopic drainage without clinical evidence for perforation. CONCLUSIONS: Endoscopic TORe by narrowing the dilated GJA appears to be an efficient and safe minimal invasive option to tackle weight regain after RYGB and should be more used in clinical practice.

A novel approach for weight regain after Roux-en-Y gastric bypass: Staged transoral outlet reduction (TORe) followed by surgical type 1 distalization.

Video 1Transoral outlet reduction.Video 2. Laparoscopic type 1 distalization of the Roux limb.

Endoscopic bariatrics: current therapies and future directions.

Endoscopic bariatric therapies (EBTs) are endoscopic procedures indicated for weight loss in the obese population. They are shown to be safe and effective for patients who do not quality for bariatric surgery. There are currently no randomized controlled studies comparing bariatric surgery with EBTs. However, EBTs are more cost effective and have fewer complications. This review will examine currently available EBTs with published data.

Arabidopsis Target of Rapamycin Coordinates With Transcriptional and Epigenetic Machinery to Regulate Thermotolerance.

Global warming exhibits profound effects on plant fitness and productivity. To withstand stress, plants sacrifice their growth and activate protective stress responses for ensuring survival. However, the switch between growth and stress is largely elusive. In the past decade, the role of the target of rapamycin (TOR) linking energy and stress signalling is emerging. Here, we have identified an important role of Glucose (Glc)-TOR signalling in plant adaptation to heat stress (HS). Glc via TOR governs the transcriptome reprogramming of a large number of genes involved in heat stress protection. Downstream to Glc-TOR, the E2Fa signalling module regulates the transcription of heat shock factors through direct recruitment of E2Fa onto their promoter regions. Also, Glc epigenetically regulates the transcription of core HS signalling genes in a TOR-dependent manner. TOR acts in concert with p300/CREB HISTONE ACETYLTRANSFERASE1 (HAC1) and dictates the epigenetic landscape of HS loci to regulate thermotolerance. Arabidopsis plants defective in TOR and HAC1 exhibited reduced thermotolerance with a decrease in the expression of core HS signalling genes. Together, our findings reveal a mechanistic framework in which Glc-TOR signalling through different modules integrates stress and energy signalling to regulate thermotolerance.

Modified-ESD Plus APC and Suturing for Treatment of Weight Regain After Gastric Bypass.

BACKGROUND: Mechanisms for weight regain after gastric bypass are not fully understood and the process is likely multifactorial. The initial step in the management of weight regain is a comprehensive evaluation of contributing factors. While lifestyle modification is fundamental, it has limited efficacy which can be enhanced by medications and/or endoscopic revision. Anatomic changes such as larger pouch size and dilation of the gastrojejunal anastomosis (GJA) may contribute to increased postoperative weight gain. Endoluminal revisions offer an effective and less invasive management strategy for this population. METHODS: A 55-year-old female with history of RYGB in 2006 presented with weight regain. She was referred to our unit for endoscopic evaluation. RESULTS: During endoscopy, a large GJA (25 mm in diameter) was diagnosed. A novel trans-oral outlet reduction (TORe) was then performed. A modified ESD was first performed on the GJA, followed by argon plasma coagulation of the margins of the ESD. Then a purse-string TORe with suturing was performed, using a 10 mm balloon to size the GJA. On 6-month follow-up, patient lost 20 lb. and 12.26 %TBWL and EGD showed a 10 mm diameter GJA. On 1-year follow-up, patient weight loss was 14 lb. and 8.58 %TBWL. The follow-up endoscopy showed a 12 mm diameter GJA. CONCLUSION: Endoluminal therapies are safe, reproducible, and effective in the treatment of weight regain and should be utilized as a first-line approach to manage this condition. This novel-combined approach is feasible and may be more effective in the treatment of weight regain.

From hemoglobin to urchin spicules.

A retrospective of an academic career. The article poses the question about the values involved in a life in the academy, starting with the role of hemoglobin in the chick embryo and ending with the role of calcium in the sea urchin spine.

A Real-World, Insurance-Based Algorithm Using the Two-Fold Running Suture Technique for Transoral Outlet Reduction for Weight Regain and Dumping Syndrome After Roux-En-Y Gastric Bypass.

BACKGROUND AND AIMS: Transoral outlet reduction (TORe) by devitalization and/or endoscopic suturing (ES) has been implemented in the management of weight regain post-RYGB. This study aims to assess the efficacy and safety of TORe following an insurance-based algorithm. METHODS: A prospectively maintained database of patients who underwent TORe between September 2015 and January 2018 at a single academic center was reviewed. An algorithm was followed whereby management was based on insurance coverage. As part of the algorithm, all patients presented for a repeat endoscopy at 8 weeks. Patients did not receive any diet, lifestyle intervention, or pharmacotherapy. RESULTS: In total, 55 patients were included (median age 48 years), out of which 50 were females (90.9%). Patients presented for evaluation at a mean of 8.7 years post-RYGB. The main presenting symptom was combined dumping syndrome (DS) and weight regain (49.1%), followed by weight regain alone (45.5%). Twenty-nine patients required treatment at their second procedure, and 11 required treatment at their third procedure. Average percent total body weight loss (%TBWL) after TORe observed at 3-, 6-, 9-, and 12-month follow-up was 8.2, 9.3, 8.4, and 5.5%, respectively. The mean DS Severity Score was significantly reduced from 23.3 ± 12.4 before TORe to 16.3 ± 6.51 after TORe (p < 0.01). The adverse event rate from TORe was 14.5%. CONCLUSION: TORe is effective in halting ongoing weight regain and achieving moderate short-term weight loss as well as improving DS in post-RYGB patients. Durability at 1 year remains questionable due to weight recidivism.

Weight Regain After Bariatric Surgery: Prevalence, Etiology, and Treatment.

PURPOSE OF REVIEW: Obesity is a life-limiting disease that is associated with a number of co-morbidities. Bariatric surgery remains the most efficacious and durable weight loss method available to patients. However, a significant percentage of patients can regain weight resulting in frustration, depression, and return of obesity-related co-morbidities. The present review provides an overview of the most common therapeutic modalities available to combat weigh regain after weight loss surgery. RECENT FINDINGS: Given the high percentage of patients with weight regain after surgery, significant effort has been placed on developing treatment options in the last few years. Tremendous work has taken place in the realm of cognitive behavior therapy, appetite suppressants, and endoscopic procedures with the hope of reducing the need for revision surgery which can be associated with significant complications. Weight regain is unfortunately a common phenomenon associated with all weight loss modalities including bariatric surgery. We now have a number of treatment options that can reverse the weight loss trend.

Establishment of pseudovirus infection mouse models for in vivo pharmacodynamics evaluation of filovirus entry inhibitors.

Filoviruses cause severe and fatal viral hemorrhagic fever in humans. Filovirus research has been extensive since the 2014 Ebola outbreak. Due to their high pathogenicity and mortality, live filoviruses require Biosafety Level-4 (BSL-4) facilities, which have restricted the development of anti-filovirus vaccines and drugs. An HIV-based pseudovirus cell infection assay is widely used for viral entry studies in BSL-2 conditions. Here, we successfully constructed nine in vitro pseudo-filovirus models covering all filovirus genera and three in vivo pseudo-filovirus-infection mouse models using Ebola virus, Marburg virus, and Lloviu virus as representative viruses. The pseudo-filovirus-infected mice showed visualizing bioluminescence in a dose-dependent manner. A bioluminescence peak in mice was reached on day 5 post-infection for Ebola virus and Marburg virus and on day 4 post-infection for Lloviu virus. Two known filovirus entry inhibitors, clomiphene and toremiphene, were used to validate the model. Collectively, our study shows that all genera of filoviruses can be well-pseudotyped and are infectious in vitro. The pseudo-filovirus-infection mouse models can be used for in vivo activity evaluation of anti-filovirus drugs. This sequential in vitro and in vivo evaluation system of filovirus entry inhibitors provides a secure and efficient platform for screening and assessing anti-filovirus agents in BSL-2 facilities.