Luis Ibáñez

Objective vs. Self-Reported Physical Activity and Sedentary Time: Effects of Measurement Method on Relationships with Risk Biomarkers

Purpose Imprecise measurement of physical activity variables might attenuate estimates of the beneficial effects of activity on health-related outcomes. We aimed to compare the cardiometabolic risk factor dose-response relationships for physical activity and sedentary behaviour between accelerometer- and questionnaire-based activity measures. Methods Physical activity and sedentary behaviour were assessed in 317 adults by 7-day accelerometry and International Physical Activity Questionnaire (IPAQ). Fasting blood was taken to determine insulin, glucose, triglyceride and total, LDL and HDL cholesterol concentrations and homeostasis model-estimated insulin resistance (HOMAIR). Waist circumference, BMI, body fat percentage and blood pressure were also measured. Results For both accelerometer-derived sedentary time (<100 counts.min−1) and IPAQ-reported sitting time significant positive (negative for HDL cholesterol) relationships were observed with all measured risk factors – i.e. increased sedentary behaviour was associated with increased risk (all p≤0.01). However, for HOMAIR and insulin the regression coefficients were >50% lower for the IPAQ-reported compared to the accelerometer-derived measure (p<0.0001 for both interactions). The relationships for moderate-to-vigorous physical activity (MVPA) and risk factors were less strong than those observed for sedentary behaviours, but significant negative relationships were observed for both accelerometer and IPAQ MVPA measures with glucose, and insulin and HOMAIR values (all p<0.05). For accelerometer-derived MVPA only, additional negative relationships were seen with triglyceride, total cholesterol and LDL cholesterol concentrations, BMI, waist circumference and percentage body fat, and a positive relationship was evident with HDL cholesterol (p = 0.0002). Regression coefficients for HOMAIR, insulin and triglyceride were 43–50% lower for the IPAQ-reported compared to the accelerometer-derived MVPA measure (all p≤0.01). Conclusion Using the IPAQ to determine sitting time and MVPA reveals some, but not all, relationships between these activity measures and metabolic and vascular disease risk factors. Using this self-report method to quantify activity can therefore underestimate the strength of some relationships with risk factors.

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.

Predictors of nonalcoholic steatohepatitis (NASH) in obese patients undergoing gastric bypass.

Background: Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are conditions gaining increasing recognition in hepatology as a potential cause of cirrhosis and end-stage liver disease. Obesity is one of the main risk factors. The aims of this study were to determine the frequency of NAFLD in obese patients and to identify variables that predict NASH. Methods: A prospective study was conducted of obese patients undergoing gastric bypass over a 20-month period. Assessment included liver function tests and evaluation of insulin resistance with the homeostatic model assessment (HOMA-IR). Liver biopsy was performed in all patients at the time of surgery. Clinical and biochemical variables were analyzed using a multivariate analysis to identify independent predictors of NASH. Results: 127 consecutive patients were included (62% female, 38% male, mean age 40±11 years, mean body mass index 42±6 kg/m2). Arterial hypertension was present in 52 patients (41%) and type 2 diabetes in 18 (14%). NAFLD was confirmed in 80 patients (63%), 47 (37%) had simple steatosis, and 33 (26%) had NASH. Cirrhosis was found in 2 patients corresponding to 1.6% of the total population. On multivariate analysis, AST >31 (IU/L) (OR 3.38, CI 1.17-9.8) and HOMA-IR >5.8 (OR 4.18, CI 1.39-12.49) independently predicted NASH. Conclusions: NAFLD is highly prevalent in morbidly obese patients. A high proportion of these patients exhibit NASH on histological examination. Insulin resistance represents the main predictor of NASH.

Weight Loss and Metabolic Improvement in Morbidly Obese Subjects Implanted for 1 Year With an Endoscopic Duodenal-Jejunal Bypass Liner

Objective:To evaluate safety, weight loss, and cardiometabolic changes in obese subjects implanted with the duodenal-jejunal bypass liner (DJBL) for 1 year. Background:The DJBL is an endoscopic implant that mimics the duodenal-jejunal bypass component of the Roux-en-Y gastric bypass. Previous reports have shown significant weight loss and improvement in type 2 diabetes for up to 6 months. Methods:Morbidly obese subjects were enrolled in a single arm, open label, prospective trial and implanted with the DJBL. Primary endpoints included safety and weight change from baseline to week 52. Secondary endpoints included changes in waist circumference, blood pressure, lipids, glycemic control, and metabolic syndrome. Results:The DJBL was implanted endoscopically in 39 of 42 subjects (age: 36 ± 10 years; 80% female; weight: 109 ± 18 kg; BMI: 43.7 ± 5.9 kg/m2); 24 completed 52 weeks of follow-up. Three subjects could not be implanted due to short duodenal bulb. Implantation time was 24 ± 2 minutes. There were no procedure-related complications and there were 15 early endoscopic removals. In the 52-week completer population, total body weight change from baseline was −22.1 ± 2.1 kg (P < 0.0001) corresponding to 19.9 ± 1.8% of total body weight and 47.0 ± 4.4% excess of weight loss. There were also significant improvements in waist circumference, blood pressure, total and low-density lipoprotein cholesterol, triglycerides, and fasting glucose. Conclusions:The DJBL is safe when implanted for 1 year, and results in significant weight loss and improvements in cardiometabolic risk factors. These results suggest that this device may be suitable for the treatment of morbid obesity and its related comorbidities. This study was registered at www.clinicaltrials.gov (NCT00985491).

Gastric Cancer after Roux-en-Y Gastric Bypass

Roux-en-Y gastric bypass (RYGBP) is one of the most commonly performed surgical procedures for morbid obesity. Several complications that may develop in the short- and long-term have been reported. We present a patient who presented with cancer in the bypassed stomach 8 years after RYGBP. Although the development of this lesion is rare and only a few cases have been reported, there are aspects worthy of discussion. Several monitoring, diagnostic and therapeutic alternatives are analyzed.

Wernicke's Encephalopathy after Roux-en-Y Gastric Bypass

Complications of bariatric operations include the development of nutritional deficiencies. If protracted vomiting is added, severe vitamin depletion could arise such as thiamine deficiency, resulting in the development of Wernickes encephalopathy (WE). This article describes the rapid onset of WE in a 6-week postoperative morbidly obese woman. Because the occurrence of micronutrient deficiencies is infrequent, although reports are increasing, symptoms may be misdiagnosed leading to possible irreversible effects on the central nervous system. The importance of a prompt diagnosis of this serious complication and of adequate therapy is emphasized.

Initial human experience with restrictive duodenal-jejunal bypass liner for treatment of morbid obesity

BACKGROUND The duodenal-jejunal bypass liner is an endoscopically placed and removable intestinal liner that creates a duodenal-jejunal bypass, leading to diabetes improvement and weight loss. The aim of the present study was to evaluate the clinical effects and safety of the duodenal-jejunal bypass liner combined with a restrictor orifice (flow restrictor). METHODS The device was endoscopically implanted in 10 patients (body mass index 40.8 +/- 4.0 kg/m(2)) and removed after 12 weeks. Dilation of the restrictor orifice was performed as clinically indicated with a 6-, 8-, or 10-mm diameter through-the-scope balloon. The measured outcomes included the percentage of excess weight loss, total weight loss, adverse events, and gastric emptying (GE) at baseline, weeks 4 and 12 of implantation, and 3-5 months after device removal. GE was measured by scintigraphy at 1, 2, and 4 hours after implantation. RESULTS The percentage of excess weight loss and total weight loss at explantation was 40% +/- 3% (range 21-64%) and 16.7 +/- 1.4 kg (range 12.0-26.0), respectively. The 4-hour GE was 98% +/- 1% at baseline, 72% +/- 6% at 4 weeks (P = 0.001 versus baseline), and 84% +/- 5% at 12 weeks (P <.05 versus baseline). After explantation, the rate of GE returned to normal in 7 of 8 subjects, but remained slightly delayed in 1 subject (84% at 4 hours). Episodes of nausea, vomiting, and abdominal pain required endoscopic dilation of the restrictor orifice with a 6-mm through-the-scope balloon in 7 patients and a 10-mm balloon in 1, with no clinically significant adverse events. CONCLUSION Endoscopic implantation of a combination flow restrictor and duodenal-jejunal bypass liner induced substantial weight loss. The implanted patients exhibited delayed GE that was reversed after device removal.

Laparoscopic Roux-en-Y gastric bypass versus laparoscopic adjustable gastric banding: five years of follow-up

BACKGROUND Bariatric surgery is an effective treatment for morbid obesity. Laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic adjustable gastric banding (LAGB) are commonly performed procedures. The aim of the present study was to evaluate and compare the long-term outcomes after LRYGB and LAGB. METHODS We studied the data from a prospective database of all patients undergoing LRYGB or LAGB with 5 years of follow-up. RESULTS From July 2001 to September 2003, 91 and 62 patients underwent LRYGB and LAGB, respectively. Of these patients, 73.6% of the LRYGB and 91.9% of the LAGB patients had 5 years of follow-up. Of the 91 and 62 patients, 89% and 82% were women, respectively. The mean age and body mass index was 34.5 ± 11.0 years and 39.6 ± 4.9 kg/m(2) for the LRYGB group and 38.4 ± 13.1 years and 35.8 ± 4.0 kg/m(2) for the LAGB group, respectively. The mean operative time was 150 ± 58 minutes for LYRGB and 73 ± 23 minutes for LAGB (P <.05). The conversion and reoperation rate was 8% and 4.3%, respectively, for the LRYGB group versus 0% for the LAGB group. Early postoperative complications were observed in 12 and 1 patient (P = .014) after LRYGB and LAGB, respectively. Late complications developed in 33 and 17 patients after LYRGB and LAGB, respectively (P = NS). The percentage of excess weight loss at 5 years postoperatively was 92.9% ± 25.6% and 59.1% ± 46.8% (P <.001) for LRYGB and LAGB, respectively. Surgical failure (percentage of excess weight loss <50%) at 5 years was 6% for LRYGB and 45.6% for LAGB. A late reoperation was needed in 24.1% of the LAGB patients. CONCLUSION A greater percentage of excess weight loss at 1 and 5 years was observed after LRYGB than LAGB. The LAGB group had a >40% rate of surgical failure and a 24.1% reoperation rate at 5 years of follow-up.

Prospective randomized study of T-tube versus biliary stent for common bile duct decompression after open choledocotomy.

The T-tube has been the alternative of choice for decompression following common bile duct (CBD) exploration. The development of laparoscopic surgery has suggested using a biliary stent as an alternative to the T-tube following choledochotomy. The purpose of this prospective randomized study was to compare clinical results obtained from patients who underwent open CBD exploration using a biliary stent versus those from patients with a T-tube for decompression. Between September 2000 and June 2002 a total of 81 patients were randomly assigned to a biliary stent or a T-tube as the decompression method following choledochotomy. An open CBD exploration was performed when CBD stones were suspected, in both elective and emergency settings. The length of the postoperative hospital stay was 6.8 ± 4.7 days for patients with the T-tube and of 5.2 ± 3.3 days for, patients with the biliary stent (p = 0.19). Postoperative complications were observed in 13 patients (30 %) with the T-tube and in 4 patients (11% ) with the biliary stent (p = 0.03). One patient with a biliary stent was reoperated because of an intraabdominal abscess, and another patient was reoperated because of biliary peritonitis following T-tube removal. Three patients (7%) with a biliary stent and one patient (3%) with a T-tube were rehospitalized. There were no deaths. The T-tube and biliary stent were removed 27.1 ± 10.8 days and 34.9 ± 12.9 days after surgery, respectively (p = 0.24). The biliary stent is a safe alternative to the T-tube as a biliary decompression method following an open CBD exploration.

Serial Analysis of Gene Expression Identifies Connective Tissue Growth Factor Expression as a Prognostic Biomarker in Gallbladder Cancer

Background: Gallbladder cancer (GBC) is an uncommon neoplasm in the United States, but one with high mortality rates. This malignancy remains largely understudied at the molecular level such that few targeted therapies or predictive biomarkers exist. Experimental Design: We built the first series of serial analysis of gene expression (SAGE) libraries from GBC and nonneoplastic gallbladder mucosa, composed of 21-bp long-SAGE tags. SAGE libraries were generated from three stage-matched GBC patients (representing Hispanic/Latino, Native American, and Caucasian ethnicities, respectively) and one histologically alithiasic gallbladder. Real-time quantitative PCR was done on microdissected epithelium from five matched GBC and corresponding nonneoplastic gallbladder mucosa. Immunohistochemical analysis was done on a panel of 182 archival GBC in high-throughput tissue microarray format. Results: SAGE tags corresponding to connective tissue growth factor (CTGF) transcripts were identified as differentially overexpressed in all pairwise comparisons of GBC (P < 0.001). Real-time quantitative PCR confirmed significant overexpression of CTGF transcripts in microdissected primary GBC (P < 0.05), but not in metastatic GBC, compared with nonneoplastic gallbladder epithelium. By immunohistochemistry, 66 of 182 (36%) GBC had high CTGF antigen labeling, which was significantly associated with better survival on univariate analysis (P = 0.0069, log-rank test). Conclusions: An unbiased analysis of the GBC transcriptome by SAGE has identified CTGF expression as a predictive biomarker of favorable prognosis in this malignancy. The SAGE libraries from GBC and nonneoplastic gallbladder mucosa are publicly available at the Cancer Genome Anatomy Project web site and should facilitate much needed research into this lethal neoplasm.