Brad Snyder

The REDUCE pivotal trial: a prospective, randomized controlled pivotal trial of a dual intragastric balloon for the treatment of obesity

BACKGROUND Saline-filled intragastric balloon devices are reversible endoscopic devices designed to occupy stomach volume and reduce food intake. OBJECTIVE To evaluate the safety and effectiveness of a dual balloon system plus diet and exercise in the treatment of obesity compared to diet and exercise alone. SETTING Academic and community practice, United States. METHODS Participants (n = 326) with body mass index (BMI) 30-40 kg/m(2) were randomized to endoscopic DBS treatment plus diet and exercise (DUO, n = 187) or sham endoscopy plus diet and exercise alone (DIET, n = 139). Co-primary endpoints were a between-group comparison of percent excess weight loss (%EWL) and DUO subject responder rate, both at 24 weeks. Thereafter DUO patients had the DBS retrieved followed by 24 additional weeks of counseling; DIET patients were offered DBS treatment. RESULTS Mean BMI was 35.4. Both primary endpoints were met. DUO weight loss was over twice that of DIET. DUO patients had significantly greater %EWL at 24 weeks (25.1% intent-to-treat (ITT), 27.9% completed cases (CC, n = 167) compared with DIET patients (11.3% ITT, P = .004, 12.3% CC, n = 126). DUO patients significantly exceeded a 35% response rate (49.1% ITT, P<.001, 54.5% CC) for weight loss dichotomized at 25%EWL. Accommodative symptoms abated rapidly with support and medication. Balloon deflation occurred in 6% without migrations. Early retrieval for nonulcer intolerance occurred in 9%. Gastric ulcers were observed; a minor device change led to significantly reduced ulcer size and frequency (10%). CONCLUSION The DBS was significantly more effective than diet and exercise in causing weight loss with a low adverse event profile.

Efficacy of Transoral Fundoplication vs Omeprazole for Treatment of Regurgitation in a Randomized Controlled Trial

BACKGROUND & AIMS Transoral esophagogastric fundoplication (TF) can decrease or eliminate features of gastroesophageal reflux disease (GERD) in some patients whose symptoms persist despite proton pump inhibitor (PPI) therapy. We performed a prospective, sham-controlled trial to determine if TF reduced troublesome regurgitation to a greater extent than PPIs in patients with GERD. METHODS We screened 696 patients with troublesome regurgitation despite daily PPI use with 3 validated GERD-specific symptom scales, on and off PPIs. Those with at least troublesome regurgitation (based on the Montreal definition) on PPIs underwent barium swallow, esophagogastroduodenoscopy, 48-hour esophageal pH monitoring (off PPIs), and high-resolution esophageal manometry analyses. Patients with GERD and hiatal hernias ≤2 cm were randomly assigned to groups that underwent TF and then received 6 months of placebo (n = 87), or sham surgery and 6 months of once- or twice-daily omeprazole (controls, n = 42). Patients were blinded to therapy during follow-up period and reassessed at 2, 12, and 26 weeks. At 6 months, patients underwent 48-hour esophageal pH monitoring and esophagogastroduodenoscopy. RESULTS By intention-to-treat analysis, TF eliminated troublesome regurgitation in a larger proportion of patients (67%) than PPIs (45%) (P = .023). A larger proportion of controls had no response at 3 months (36%) than subjects that received TF (11%; P = .004). Control of esophageal pH improved after TF (mean 9.3% before and 6.3% after; P < .001), but not after sham surgery (mean 8.6% before and 8.9% after). Subjects from both groups who completed the protocol had similar reductions in GERD symptom scores. Severe complications were rare (3 subjects receiving TF and 1 receiving the sham surgery). CONCLUSIONS TF was an effective treatment for patients with GERD symptoms, particularly in those with persistent regurgitation despite PPI therapy, based on evaluation 6 months after the procedure. Clinicaltrials.gov no: NCT01136980.

Progressive regression of left ventricular hypertrophy two years after bariatric surgery.

BACKGROUND Obesity is a systemic disorder associated with an increase in left ventricular mass and premature death and disability from cardiovascular disease. Although bariatric surgery reverses many of the hormonal and hemodynamic derangements, the long-term collective effects on body composition and left ventricular mass have not been considered before. We hypothesized that the decrease in fat mass and lean mass after weight loss surgery is associated with a decrease in left ventricular mass. METHODS Fifteen severely obese women (mean body mass index [BMI]: 46.7+/-1.7 kg/m(2)) with medically controlled hypertension underwent bariatric surgery. Left ventricular mass and plasma markers of systemic metabolism, together with body mass index (BMI), waist and hip circumferences, body composition (fat mass and lean mass), and resting energy expenditure were measured at 0, 3, 9, 12, and 24 months. RESULTS Left ventricular mass continued to decrease linearly over the entire period of observation, while rates of weight loss, loss of lean mass, loss of fat mass, and resting energy expenditure all plateaued at 9 [corrected] months (P <.001 for all). Parameters of systemic metabolism normalized by 9 months, and showed no further change at 24 months after surgery. CONCLUSIONS Even though parameters of obesity, including BMI and body composition, plateau, the benefits of bariatric surgery on systemic metabolism and left ventricular mass are sustained. We propose that the progressive decrease of left ventricular mass after weight loss surgery is regulated by neurohumoral factors, and may contribute to improved long-term survival.

Robotic-assisted Roux-en-Y gastric bypass: update from 2 high-volume centers

BACKGROUND Laparoscopic Roux-en-Y gastric bypass (RYGB) is a challenging operation in the most experienced hands. Robotic surgery allows the capabilities of the minimally invasive surgeon to be extended. An increasing number of robotic gastric bypasses are being performed each year with the assumption that the complication rates are decreased. The objectives of the present study were to review the results of robotic-assisted RYGB (RARYGB) from 2 high-volume centers, including 1 university and 1 private practice. METHODS We report the most recently compiled, largest series of RARYGB in the world to show the effectiveness, morbidity, and mortality of this method. Databases were searched for patients undergoing RARYGB from 2002 to 2010, and the endpoints were recorded. RESULTS A total of 1100 RARYGBs matched our search. The patients had a mean preoperative age of 46.9 years, mean weight of 131.9 kg, and mean body mass index of 47.9 kg/m(2). The mean operative time was 155 minutes. There were no conversions. The mean body mass index was 39.8 kg/m(2) at 3 months postoperatively (79% follow-up). Complications were few, and included 2 cases of pulmonary embolism (.19%), 3 cases of deep venous thrombosis (.27%), 1 case of gastrojejunal anastomotic leak (.09%), and 9 cases of staple line bleeding (.82%). No patients died. CONCLUSION RARYGB is safe and effective. Although the operative time might be increased, the complication rates, most notably of anastomotic leak, are extremely low.

Comparison of those who succeed in losing significant excessive weight after bariatric surgery and those who fail

BackgroundGastric bypass and adjustable gastric banding currently are the most commonly performed weight loss surgeries. The results are encouraging for most patients, but some patients have a better experience than others. This report aims to define differences between those who succeeded and those that failed to lose significant excessive weight after bariatric surgery.MethodsThe authors retrospectively reviewed their database over the past 4 years. They studied 484 bariatric patients who had 1 year of follow-up evaluation. Success was defined as more than 50% excess weight loss (EWL) and failure as less than 30% EWL. Student’s t-tests were performed between the groups of bypass patients, band patients, men, women, whites, and minorities.Results An overall success rate of 58% and a failure rate of 15% were observed. The successful group was significantly younger. The starting body mass index (BMI) was significantly lower for the successful band patients. The starting excess weight was significantly less in both the successful band and bypass groups, as was the starting weight. The successful whites were significantly younger, and the starting BMI was significantly lower in the successful minority group. The unsuccessful bypass patients and whites were significantly taller than the successful group. Gender was not a significant variable in success or failure regardless of procedure.ConclusionWithout consideration for the procedure performed, the patients who successfully lost weight were younger. The unsuccessful band patients had a higher starting BMI, whereas the successful band and bypass patients had lower average starting and excess weights. The successful bypass patients were significantly shorter. Among whites, the successful patients were significantly younger and shorter. The successful minorities had a lower starting BMI. These variables give further insight into the complexity of successful excess weight loss.

Past, present, and future: Critical analysis of use of gastric bands in obese patients

Adjustable gastric banding (AGB) is quickly becoming the most popular bariatric operation performed in the United States and Canada. Patients are particularly fond of the simplicity of the tool, the relatively low morbidity of the surgery, the quick recovery, and overall results. The gastric band has evolved over its 35-year history into a very successful adjustable tool used to restrict food consumption and limit caloric intake. The percent of excessive weight loss after banding can range from 30%–60% and depends on the time out from surgery. Along with weight loss, there is good resolution of the co-morbid conditions that are associated with excess weight and improvements in quality of life demonstrated after banding. Nutrition and follow up are extremely important after banding to ensure good compliance and adequate weight loss. Failure to follow the postoperative diet, exercise regiment, or mechanical failure of the band can lead to failure to lose adequate weight. While there are particular early and late complications associated with this surgery, the safety profile of the AGB is very appealing when compared to other bariatric operations. As we continue to reduce the morbidity of the procedure, the simple adjustable band concept has a lot of potential to remain a primary technique of maintaining long term weight loss. In conclusion, AGB has and continues to play an important role in the treatment of morbid obesity. It offers reasonably good weight loss results with very little morbidity, and the future of the adjustable band is bright.

A Randomized Trial Comparing Reflux Symptoms in Sleeve Gastrectomy Patients with or without Hiatal Hernia Repair

BACKGROUND The effect of laparoscopic sleeve gastrectomy (SG) on reflux symptoms is unclear. Many surgeons offer SG only to patients with minor or no reflux symptoms, fearing that patients with severe reflux symptoms will experience worsening of their condition after SG. Many also advocate crural repair at the time of SG to prevent de novo or worsening reflux symptoms. These decisions are made without suitable data to form such conclusions. OBJECTIVE To determine the effect of SG with or without hiatal hernia repair on reflux symptoms. SETTING University of Texas Health Sciences Center in Houston. METHODS The Gastrointestinal Symptom Rating Scale (GSRS) was administered to 100 consecutive, preoperative SG patients who were then randomly assigned into a crural repair group or nonrepair group in a parallel design. The patients were subsequently followed-up every 3 months for 1 year. We compared reflux symptoms of the 2 groups on the basis of demographic characteristics, body mass index, weight loss, presence and size of hiatal hernia, and GSRS for 12 months. RESULTS At 1 year, with 78% follow-up, the data demonstrated a significant decrease in the GSRS for both groups (P<.001); however, there was no difference between the groups (P = .35). Age, starting body mass index, percent excessive weight loss, and hiatal hernia size did not correlate with change in the GSRS score. The only variable that affected outcome was the preoperative GSRS. At 12 months, 38% of patients with a preoperative GSRS score less than the median score of the study population experienced worsening of their symptoms compared with only 2% of patients who had a preoperative GSRS score greater than the median. Overall, 19% experienced worsening reflux (5% de novo), 14% had no change, and 66% reported an improvement in symptoms. CONCLUSION These data suggest that a crural repair at the time of SG does not significantly reduce reflux symptoms compared with SG alone. Preoperative patients with significant reflux symptoms experienced a more significant improvement in symptoms after surgery compared with those who did not report significant reflux symptoms before surgery. The high incidence of reflux after SG observed in the current literature may be a result of a specific patient subpopulation who undergoes SG because of surgeon bias rather than an inherent property of SG itself or the presence of a hiatal hernia.

Failure of adjustable gastric banding: starting BMI of 46 kg/m2 is a fulcrum of success and failure

BACKGROUND To determine the body mass index (BMI) located at the fulcrum of success and failure in a prospective study conducted at the University of Texas Health Science Center at Houston. On average, our patients whose percentage of excess weight loss (%EWL) was >50% at 1 year had a significantly lower BMI than those with <30% EWL. METHODS We prospectively collected the weight loss data for 430 patients who had had an adjustable gastric band placed. We stratified the %EWL within 1 year for patients with a BMI of 30-59 kg/m2. A line was generated for the %EWL over time for BMI groups of 30-39, 40-49, and 50-59 kg/m(2) and compared with the average %EWL over time. The y-intercepts of the resulting four lines were graphed against the average BMI for each group. RESULTS The generated y-intercept line had an R2 of .9237. Using the equation of this line and the known y-intercept for the average, we solved for x, resulting in a BMI of 46 kg/m2. Patients with a BMI <46 kg/m2 had a 50% EWL at 1 year, and those with a BMI >46 kg/m2 had only a 33% EWL at 1 year. The %EWL between the groups was significantly different at all measured intervals (P <.0001). CONCLUSION A BMI of 46 kg/m2 identifies those at high risk of failure to lose a significant percentage of excess weight after adjustable gastric banding and who require closer follow-up. Furthermore, patients who have a BMI >46 kg/m2 should be advised that their weight loss might be suboptimal at 1 year.

Non-glycanated Decorin Is a Drug Target on Human Adipose Stromal Cells

Adipose stromal cells (ASCs) have been identified as a mesenchymal cell population recruited from white adipose tissue (WAT) by tumors and supporting cancer progression. We have previously reported the existence of a non-glycanated decorin isoform (ngDCN) marking mouse ASCs. We identified a peptide CSWKYWFGEC that binds to ngDCN and hence can serve as a vehicle for ASC-directed therapy delivery. We used hunter-killer peptides composed of CSWKYWFGEC and a pro-apoptotic moiety to deplete ASCs and suppress growth of mouse tumors. Here, we report the discovery of the human non-glycanated decorin isoform. We show that CSWKYWFGEC can be used as a probe to identify ASCs in human WAT and tumors. We demonstrate that human ngDCN is expressed on ASC surface. Finally, we validate ngDCN as a molecular target for pharmacological depletion of human ASCs with hunter-killer peptides. We propose that ngDCN-targeting agents could be developed for obesity and cancer treatment.

PDGFRα/PDGFRβ signaling balance modulates progenitor cell differentiation into white and beige adipocytes

The relative abundance of thermogenic beige adipocytes and lipid-storing white adipocytes in adipose tissue underlie its metabolic activity. The roles of adipocyte progenitor cells, which express PDGFRα or PDGFRβ, in adipose tissue function have remained unclear. Here, by defining the developmental timing of PDGFRα and PDGFRβ expression in mouse subcutaneous and visceral adipose depots, we uncover depot specificity of pre-adipocyte delineation. We demonstrate that PDGFRα expression precedes PDGFRβ expression in all subcutaneous but in only a fraction of visceral adipose stromal cells. We show that high-fat diet feeding or thermoneutrality in early postnatal development can induce PDGFRβ+ lineage recruitment to generate white adipocytes. In contrast, the contribution of PDGFRβ+ lineage to beige adipocytes is minimal. We provide evidence that human adipose tissue also contains distinct progenitor populations differentiating into beige or white adipocytes, depending on PDGFRβ expression. Based on PDGFRα or PDGFRβ deletion and ectopic expression experiments, we conclude that the PDGFRα/PDGFRβ signaling balance determines progenitor commitment to beige (PDGFRα) or white (PDGFRβ) adipogenesis. Our study suggests that adipocyte lineage specification and metabolism can be modulated through PDGFR signaling. Summary: White and beige adipocytes arise from distinct progenitor cell lineages. In both mice and humans, beige and white adipogenesis is induced by PDGFRα and PDGFRβ signaling, respectively.