Multicenter, Phase 1, Open Prospective Trial of Gastric Electrical Stimulation for the Treatment of Obesity: First-in-Human Results with a Novel Implantable System.

BACKGROUND AND AIMS: To assess safety of the Exilis™ gastric electrical stimulation (GES) system and to investigate whether the settings can be adjusted for comfortable chronic use in subjects with morbid obesity. Gastric emptying and motility and meal intake were evaluated. METHOD: In a multicenter, phase 1, open prospective cohort study, 20 morbidly obese subjects (17 female, mean BMI of 40.8 ± 0.7 kg/m2) were implanted with the Exilis™ system. Amplitude of the Exilis™ system was individually set during titration visits. Subjects underwent two blinded baseline test days (GES ON vs. OFF), after which long-term, monthly follow-up continued for up to 52 weeks. RESULTS: The procedure was safe, and electrical stimulation was well tolerated and comfortable in all subjects. No significant differences in gastric emptying halftime (203 ± 16 vs. 212 ± 14 min, p > 0.05), food intake (713 ± 68 vs. 799 ± 69 kcal, p > 0.05), insulin AUC (2448 ± 347 vs. 2186 ± 204, p > 0.05), and glucose AUC (41 ± 2 vs.41 ± 2, p > 0.05) were found between GES ON and OFF. At week 4, 13, and 26, a significant (p < 0.01) reduction in weight loss was observed but not at week 52. At this time point, the mean excess weight loss (EWL) was 14.2 ± 4.5%. CONCLUSION: Gastric electrical stimulation with the Exilis™ system can be considered as safe. No significant effect on food intake, gastric emptying, or gastric motility was observed. The reduction in weight loss with Exilis™ GES was significant but short lasting. Further electrophysiological research is needed to gain more insight in optimal stimulation parameters and lead localization.

Differential effects of leptin on adiponectin expression with weight gain versus obesity.

BACKGROUND/OBJECTIVE: Adiponectin exerts beneficial effects by reducing inflammation and improving lipid metabolism and insulin sensitivity. Although the adiponectin level is lower in obese individuals, whether weight gain reduces adiponectin expression in humans is controversial. We sought to investigate the role of weight gain, and consequent changes in leptin, on altering adiponectin expression in humans. METHODS/RESULTS: Forty-four normal-weight healthy subjects were recruited (mean age 29 years; 14 women) and randomized to either gain 5% of body weight by 8 weeks of overfeeding (n=34) or maintain weight (n=10). Modest weight gain of 3.8±1.2 kg resulted in increased adiponectin level (P=0.03), whereas weight maintenance resulted in no changes in adiponectin. Further, changes in adiponectin correlated positively with changes in leptin (P=0.0085). In-vitro experiments using differentiated human white preadipocytes showed that leptin increased adiponectin mRNA and protein expression, whereas a leptin antagonist had opposite effects. To understand the role of leptin in established obesity, we compared adipose tissue samples obtained from normal-weight versus obese subjects. We noted, first, that leptin activated cellular signaling pathways and increased adiponectin mRNA in the adipose tissue from normal-weight participants, but did not do so in the adipose tissue from obese participants. Second, we noted that obese subjects had increased caveolin-1 expression, which attenuates leptin-dependent increases in adiponectin. CONCLUSIONS: Modest weight gain in healthy individuals is associated with increases in adiponectin levels, which correlate positively with changes in leptin. In vitro, leptin induces adiponectin expression, which is attenuated by increased caveolin-1 expression. In addition, the adipose tissue from obese subjects shows increased caveolin-1 expression and impaired leptin signaling. This leptin signal impairment may prevent concordant increases in adiponectin levels in obese subjects despite their high levels of leptin. Therefore, impaired leptin signaling may contribute to low adiponectin expression in obesity and may provide a target for increasing adiponectin expression, hence improving insulin sensitivity and cardio-metabolic profile in obesity.

Interactions of allelic variance of PNPLA3 with nongenetic factors in predicting nonalcoholic steatohepatitis and nonhepatic complications of severe obesity.

OBJECTIVE: Allelic variation (rs738409C→G) in adiponutrin (patatin-like phospholipase domain-containing protein 3, PNPLA3) has been associated with hepatic steatosis and liver fibrosis. The physiologic impact of the PNPLA3 G allele may be exacerbated in patients with severe obesity. In this study, we investigated the interactions of PNPLA3 rs738409 with a broad panel of metabolic and histologic characteristics of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NASH) in patients with medically complicated obesity. DESIGN AND METHODS: Consecutive patients undergoing bariatric surgery were selected for a prospective study. They underwent extensive laboratory and histologic (liver biopsy) assessment, as well as evaluation of rs738409 polymorphism by TaqMan assay. RESULTS: Only 12 (8.3%) of the 144 patients had normal liver histology, with 72 (50%) NASH, of whom 15 (10.4% of total patients) had fibrosis stage 2-3. PNPLA3 GG genotype correlated positively (P < 0.05) with serum levels of alanine aminotransferase (ALT), asparate aminotransferase (AST), glucose, fibrinogen, and insulin-dependent diabetes mellitus, homeostasis model assessment-insulin resistance, and presence of NASH. Multivariate analysis indicated that PNPLA3 rs738409 G versus C allele remained an (independent) risk factor for NASH, in addition to CK-18 >145 IU/l, glucose >100 mg/dl, and C-reactive protein (CRP) >0.8 mg/dl. The probability of NASH increased from 9% (no risk factor) to 82% if all four risk factors were present. CONCLUSIONS: In this cohort of patients with medically complicated obesity, PNPLA3 rs738409 G allelic expression is associated with hepatic (NASH) and nonhepatic complications of obesity, such as insulin resistance. These novel findings may be related to a greater impact of PNPLA3 variant in magnitude and scope in patients with severe obesity than in less obese populations. Further studies are needed to characterize the nature of these associations.

Combined liver transplantation and gastric sleeve resection for patients with medically complicated obesity and end-stage liver disease.

Obesity is increasingly common before and after liver transplantation (LT), yet optimal management remains unclear. Our aim was to analyze the effectiveness of a multidisciplinary protocol for obese patients requiring LT, including a noninvasive pretransplant weight loss program, and a combined LT plus sleeve gastrectomy (SG) for obese patients who failed to lose weight prior to LT. Since 2006, all patients referred LT with a BMI > 35 were enrolled. There were 37 patients who achieved weight loss and underwent LT alone, and 7 who underwent LT combined with SG. In those who received LT alone, weight gain to BMI > 35 was seen in 21/34, post-LT diabetes (DM) in 12/34, steatosis in 7/34, with 3 deaths plus 3 grafts losses. In patients undergoing the combined procedure, there were no deaths or graft losses. One patient developed a leak from the gastric staple line, and one had excess weight loss. No patients developed post-LT DM or steatosis, and all had substantial weight loss (mean BMI = 29). Noninvasive pretransplant weight loss was achieved by a majority, though weight gain post-LT was common. Combined LT plus SG resulted in effective weight loss and was associated with fewer post-LT metabolic complications. Long-term follow-up is needed.

Impaction and fracture of a video capsule in the small bowel requiring laparotomy for removal of the capsule fragments.

Capsule endoscopy has become an important diagnostic tool because of its high sensitivity and specificity for evaluation of the small-bowel mucosa. It is usually a safe procedure. The main complication has been retention of the video capsule in patients with unsuspected obstructive small-bowel disease. We describe a case of a 76-year-old man who underwent capsule endoscopy for the investigation of chronic abdominal pain. The patient returned several months after the procedure with recurrence of his symptoms. Investigations at that time showed that the capsule had been retained in a section of the distal ileum which showed stricture formation and that it had broken up into fragments. This is the first reported case of a fractured video capsule.

Laparoscopic gastric bypass after failed open horizontal stapled gastroplasty.

The number of people in the population who have undergone an operative procedure for morbid obesity is likely to rise steadily as the awareness and popularity of bariatric surgery continues to develop. As this number increases, the number of patients with long-term failures and complications from these procedures will also rise. Although previous operations, particularly open procedures, normally deter surgeons from choosing a laparoscopic approach, the evolving technical skill of laparoscopic surgeons should allow for the reconsideration of these inhibitions. In this case, we present of laparoscopic Roux-en-Y gastric bypass on a 48-year-old woman who had undergone horizontal gastric stapling 20 years prior to presentation.

Multifocal eosinophilic enteritis associated with a small intestinal obstruction in a standardbred horse.

A seven-year-old standardbred gelding developed marked signs of colic associated with an acute small intestinal obstruction. Surgical exploration revealed three intramural, circumferential constricting lesions in the small intestine, the two most severe of which were in the jejunum and were resected. The horse was euthanased owing to postoperative complications. Histopathological examination confirmed the diagnosis of idiopathic multifocal eosinophilic enteritis.

Laparoscopic antireflux surgery for supraesophageal complications of gastroesophageal reflux disease.

Gastroesophageal reflux disease can result in such supraesophageal complications as hoarseness, sore throat, cough, bronchitis, asthma, recurrent pneumonia, intermittent choking, chest pain, and ear pain. Appropriate patient care involves careful evaluation to decide on medical or surgical therapy. Preoperative testing must include endoscopy, 24-hour esophageal pH monitoring, and esophageal manometry. Additional evaluations, such as barium swallow, chest x-ray, bronchoscopy, and sinus radiographs, may be required. Medical treatment improves gastroesophageal reflux and supraesophageal symptoms. However, surgical therapy seems to provide better long-term results. A profile that predicts the best response to medical therapy has not been identified, although the best results with surgery are achieved in patients with nocturnal asthma, onset of reflux before pulmonary symptoms, laryngeal inflammation, and a good response to medical treatment.

Congenital diaphragmatic hernia in adults.

Congenital diaphragmatic hernia is rarely seen in adults. A review of the literature is presented, and 2 additional cases of Morgagni and Bochdalek hernias are presented. They were both repaired with the laparoscopic approach.

Manometric components of the lower esophageal double hump.

BACKGROUND/AIMS: The lower esophageal sphincter manometry of patients with hiatal hernia often displays a double hump configuration. It seems that this is due to gastric herniation above the high-pressure zone of the crura. This study examines this manometric phenomenon in patients with hiatal hernia and relates it to the lower esophageal antireflux barrier. METHODS: Manometric and 24-hour pH studies of 68 consecutive patients with suspected gastroesophageal reflux disease were analyzed to obtain information regarding the double hump and acid reflux. RESULTS: The findings of a manometric double hump correlated well with the presence of a hiatal hernia of >5 cm. The overall length of the sphincter complex was greater in patients with a double hump, but the length below the respiratory inversion point was constant. Resting pressures at the respiratory inversion point were significantly lower than those measured at either high-pressure zone. The location of the respiratory inversion point was seen most commonly at the superior margin of the distal high-pressure zone. Double hump patients with a negative acid reflux score were found to have higher pressures in the distal high-pressure zone than those patients with acid reflux. CONCLUSIONS: The two high-pressure zones comprising the manometric double hump represent the crural and muscular components of the lower esophageal sphincter. Descriptive information regarding the double hump phenomenon is given, and the importance of the crural component of the lower esophageal sphincter in preventing acid reflux is stressed.

Corticotropin-independent macronodular adrenal hyperplasia: a clinicopathologic correlation.

OBJECTIVES: To investigate the clinical presentation, laboratory findings, and pathologic characteristics of patients with corticotropin (ACTH)-independent macronodular adrenal hyperplasia. DESIGN: Retrospective review. SETTING: Academic medical center. PATIENTS: All patients with bilateral adrenocortical nodules associated with ACTH-independent hypercortisolism without clinicopathologic features of primary pigmented nodular adrenocortical disease with atrophic internodular adrenal cortex. MAIN OUTCOME MEASURES: Compare and contrast our findings with those previously reported; assess response to adrenalectomy. RESULTS: Nine patients met the criteria for corticotropin-independent macronodular adrenal hyperplasia. All patients had biochemical evidence of Cushing syndrome, although repetitive testing was frequently required. As a result, the diagnosis was delayed from 1 to 20 years. In all patients, both the low- and high-dose dexamethasone suppression tests failed to suppress cortisol secretion. No patient had elevated ACTH levels, and following curative bilateral adrenalectomy, no patient subsequently developed Nelson syndrome, with follow-up ranging from 1 to 8.5 years. Unique histologic features were identified in all cases. CONCLUSION: Amalgamating this series with other clinical reports plus basic research information, corticotropin-independent macronodular adrenal hyperplasia must be considered a separate and legitimate cause of Cushing syndrome.