ABSTRACT
AIMS: Ghrelin is a gastric-derived hormone that stimulates growth hormone (GH) secretion and has a multi-faceted role in the regulation of energy homeostasis, including glucose metabolism. Circulating ghrelin concentrations are modulated in response to nutritional status, but responses to ghrelin in altered metabolic states are poorly understood. We investigated the metabolic effects of ghrelin in obesity and early after Roux-en-Y gastric bypass (RYGB). MATERIALS AND METHODS: We assessed central and peripheral metabolic responses to acyl ghrelin infusion (1 pmol kg-1 min-1 ) in healthy, lean subjects (n = 9) and non-diabetic, obese subjects (n = 9) before and 2 weeks after RYGB. Central responses were assessed by GH and pancreatic polypeptide (surrogate for vagal activity) secretion. Peripheral responses were assessed by hepatic and skeletal muscle insulin sensitivity during a hyperinsulinaemic-euglycaemic clamp. RESULTS: Ghrelin-stimulated GH secretion was attenuated in obese subjects, but was restored by RYGB to a response similar to that of lean subjects. The heightened pancreatic polypeptide response to ghrelin infusion in the obese was attenuated after RYGB. Hepatic glucose production and hepatic insulin sensitivity were not altered by ghrelin infusion in RYGB subjects. Skeletal muscle insulin sensitivity was impaired to a similar degree in lean, obese and post-RYGB individuals in response to ghrelin infusion. CONCLUSIONS: These data suggest that obesity is characterized by abnormal central, but not peripheral, responsiveness to ghrelin that can be restored early after RYGB before significant weight loss. Further work is necessary to fully elucidate the role of ghrelin in the metabolic changes that occur in obesity and following RYGB.
Subject(s)
Anti-Obesity Agents/therapeutic use , Gastric Bypass , Ghrelin/therapeutic use , Human Growth Hormone/agonists , Insulin Resistance , Obesity, Morbid/drug therapy , Obesity, Morbid/surgery , Acylation , Anti-Obesity Agents/administration & dosage , Anti-Obesity Agents/adverse effects , Anti-Obesity Agents/chemistry , Cohort Studies , Combined Modality Therapy/adverse effects , Cross-Over Studies , Energy Metabolism/drug effects , Ghrelin/administration & dosage , Ghrelin/adverse effects , Ghrelin/chemistry , Gluconeogenesis/drug effects , Glucose Clamp Technique , Human Growth Hormone/blood , Human Growth Hormone/metabolism , Humans , Infusions, Intravenous , Liver/drug effects , Liver/metabolism , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , Obesity, Morbid/blood , Obesity, Morbid/metabolism , Pancreatic Polypeptide/agonists , Pancreatic Polypeptide/blood , Pancreatic Polypeptide/metabolism , Pancreatic Polypeptide-Secreting Cells/drug effects , Pancreatic Polypeptide-Secreting Cells/metabolism , Pituitary Gland, Anterior/drug effects , Pituitary Gland, Anterior/metabolism , Postoperative Care , Preoperative Care , Protein Precursors/agonists , Protein Precursors/blood , Protein Precursors/metabolism , Single-Blind MethodABSTRACT
OBJECTIVE: Questions remain regarding best surgical techniques to use for a laparoscopic sleeve gastrectomy (LSG) including the use of staple line reinforcement (SLR), bougie size (BS), and distance from the pylorus (DP) where the staple line is initiated. Our objectives were to assess the impact of these techniques on 30-day outcomes and to evaluate the impact of these techniques on weight loss and comorbidities at 1 year. METHODS: Using the MBSAQIP data registry, univariate analyses and hierarchical logistical regression models were developed to analyze outcomes for techniques of LSG at patient and surgeon-level. RESULTS: A total of 189,477 LSG operations were performed by 1634 surgeons at 720 centers from 2012 to 2014. Eighty percent of surgeons used SLR, 20% did not. SLR cases were associated with higher leak rates (0.96% vs 0.65%, odds ratio [OR] 1.20 95% confidence interval [CI] 1.00-1.43) and lower bleed rates (0.75% vs 1.00%, OR 0.74 95% CI 0.63-0.86) compared to no SLR at patient level. At the surgeon level, leak rates remained significant, but bleeding events became nonsignificant. BS ≥38 was associated with significantly lower leak rates compared to BS <38 at patient and surgeon level (patient level: 0.80% vs 0.96%, OR 0.72, 95% CI 0.62-0.94; surgeon level: 0.84% vs 0.95%, OR 0.90, 95% CI 0.80-0.99). BS ≥40 was associated with increased weight loss. DP had no impact on leaks or bleeds but showed an increase in weight loss with increasing DP. CONCLUSION: LSG is a safe procedure with a low morbidity rate. SLR is associated with increased leak rates. A surgeon should consider risks, benefits, and costs of these surgical techniques when performing a LSG and selectively utilize those that, in their hands, minimize morbidity while maximizing clinical effectiveness.
Subject(s)
Gastrectomy/methods , Laparoscopy/methods , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Pylorus/anatomy & histology , Treatment Outcome , Young AdultABSTRACT
The spectrum of nonalcoholic fatty liver disease (NAFLD) includes steatosis, nonalcoholic steatohepatitis (NASH), and cirrhosis. Recognition and timely diagnosis of these different stages, particularly NASH, is important for both potential reversibility and limitation of complications. Liver biopsy remains the clinical standard for definitive diagnosis. Diagnostic tools minimizing the need for invasive procedures or that add information to histologic data are important in novel management strategies for the growing epidemic of NAFLD. We describe an "omics" approach to detecting a reproducible signature of lipid metabolites, aqueous intracellular metabolites, SNPs, and mRNA transcripts in a double-blinded study of patients with different stages of NAFLD that involves profiling liver biopsies, plasma, and urine samples. Using linear discriminant analysis, a panel of 20 plasma metabolites that includes glycerophospholipids, sphingolipids, sterols, and various aqueous small molecular weight components involved in cellular metabolic pathways, can be used to differentiate between NASH and steatosis. This identification of differential biomolecular signatures has the potential to improve clinical diagnosis and facilitate therapeutic intervention of NAFLD.
Subject(s)
Lipids/blood , Lipids/urine , Non-alcoholic Fatty Liver Disease , Polymorphism, Single Nucleotide , Adult , Biomarkers/metabolism , Biomarkers/urine , Double-Blind Method , Female , Humans , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/blood , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/genetics , Non-alcoholic Fatty Liver Disease/urineABSTRACT
BACKGROUND: Bariatric surgery remains the most effective treatment for morbid obesity, and laparoscopic Roux-en-Y gastric bypass (LRYGB) continues to be the preferred operation. However, data for long-term outcomes are lacking. Our goal was to determine the long-term clinical outcomes after LRYGB. METHODS: Retrospective review of a prospectively maintained database was conducted on all patients who underwent LRYGB from 2001-2006. Only patients who had postoperative clinic visits both at ≤2 and ≥5 years were included. Data collected included patient demographics and postoperative clinical outcomes, including percent excess weight loss (%EWL), complications, and improvement or resolution of preoperative comorbidities (type 2 diabetes mellitus, hypertension, obstructive sleep apnea, and hyperlipidemia). Data were analyzed by using SAS (version 9.2) and SPSS (version 16) statistical software. RESULTS: There were 770 patients who underwent LRYGB at UAB from 2001-2006. Of these, 172 patients met inclusion criteria (148 women and 24 men) with a median age of 41 years and median body mass index of 46 kg/m(2). Median short- and long-term follow-up was 12 and 75 months, respectively. Mean %EWL was 69% for short-term and 65% for long-term follow-up (P = 0.0032). Of 172 patients, 66 experienced 81 complications at a median of 26 months after operation. The improvement or resolution of comorbidities was maintained in the long-term, and there was no statistically significant difference compared with improvement or resolution in the short-term. CONCLUSIONS: Although there was a statistically significant difference in %EWL between short- and long-term follow-up, both arms showed a clinically relevant %EWL (69 and 65%) and both were statistically significant compared with preoperative values. The improvement or resolution of comorbidities achieved with LRYGB was maintained in long-term follow-up. Thus, LRYGB resulted in significant improvement in clinical outcomes that were durable in the long term.
Subject(s)
Gastric Bypass/methods , Laparoscopy , Adult , Female , Humans , Male , Middle Aged , Retrospective Studies , Time Factors , Treatment Outcome , Young AdultABSTRACT
Human intestinal macrophages contribute to tissue homeostasis in noninflamed mucosa through profound down-regulation of pro-inflammatory cytokine release. Here, we show that this down-regulation extends to Toll-like receptor (TLR)-induced cytokine release, as intestinal macrophages expressed TLR3-TLR9 but did not release cytokines in response to TLR-specific ligands. Likely contributing to this unique functional profile, intestinal macrophages expressed markedly down-regulated adapter proteins MyD88 and Toll interleukin receptor 1 domain-containing adapter-inducing interferon beta, which together mediate all TLR MyD88-dependent and -independent NF-kappaB signaling, did not phosphorylate NF-kappaB p65 or Smad-induced IkappaBalpha, and did not translocate NF-kappaB into the nucleus. Importantly, transforming growth factor-beta released from intestinal extracellular matrix (stroma) induced identical down-regulation in the NF-kappaB signaling and function of blood monocytes, the exclusive source of intestinal macrophages. Our findings implicate stromal transforming growth factor-beta-induced dysregulation of NF-kappaB proteins and Smad signaling in the differentiation of pro-inflammatory blood monocytes into noninflammatory intestinal macrophages.
Subject(s)
Gene Expression Regulation, Enzymologic , I-kappa B Proteins/metabolism , Inflammation , Intestinal Mucosa/metabolism , Macrophages/metabolism , NF-kappa B/metabolism , Smad Proteins/metabolism , Cytokines/metabolism , Enzyme Inhibitors/chemistry , Humans , Monocytes/metabolism , NF-KappaB Inhibitor alpha , Oligonucleotide Array Sequence Analysis , Phosphorylation , Signal Transduction , Transforming Growth Factor beta/metabolismABSTRACT
BACKGROUND: Weight regain that begins 12-18 months after laparoscopic gastric bypass has been attributed to changes in resting metabolic rate (RMR), which is largely determined by lean body mass (LBM). An oral supplement containing beta-hydroxy-beta-methylbutyrate, glutamine, and arginine (HMB/Glu/Arg) has helped to restore LBM in cachexia due to cancer and in critically ill trauma patients. The objective of this study was to evaluate the effect of oral HMB/Glu/Arg on LBM and RMR following laparoscopic gastric bypass (LGB). METHODS: Patients who underwent LGB were randomized to receive 24 g of HMB/Glu/Arg dissolved in water twice daily for 8 weeks or to receive no supplement. Weight loss, LBM, and RMR were assessed preoperatively, 2 and 8 weeks postoperatively. LBM was determined by dual emission x-ray absorptiometry (DXA) and RMR was measured by indirect calorimetry. RESULTS: Thirty patients were enrolled: 80% white; 20% African American; 96.7% women; mean age 46.9±8.4 years; mean weight 113.4±11.6 kg; and mean body mass index (BMI) 43.3±4.1 kg/m2. The experimental and control groups included 14 and 16 patients, respectively, and there was no difference in baseline demographics and characteristics between the two groups. At 8 weeks, weight, BMI, LBM, and RMR significantly decreased by 15.7±2.5 kg, 6.0±1.0 kg/m2, 7.8±4.0 kg, and 290.6±234.9 kcal/day, respectively (P<0.0001 for each variable). However, when comparing these changes between the two groups, no statistical significance was observed. CONCLUSIONS: There is a significant decrease in weight, BMI, LBM, and RMR in all subjects after LGB, and these changes were not affected by the use of HMB/Glu/Arg. Potential preservation of LBM as a result of HMB/Glu/Arg requires further investigation. However, its consumption (78 calories per serving) did not adversely affect weight loss in the experimental group.
Subject(s)
Arginine/administration & dosage , Bariatric Surgery , Basal Metabolism , Dietary Supplements , Gastric Bypass , Glutamine/administration & dosage , Laparoscopy , Valerates/administration & dosage , Absorptiometry, Photon , Body Composition , Body Mass Index , Female , Humans , Male , Middle Aged , Nutritive Value , Postoperative Care , Weight LossABSTRACT
BACKGROUND: Virtual reality (VR) simulators and Web-based instructional videos are valuable supplemental training resources in surgical programs, but it is unclear how to optimally integrate them into minimally invasive surgical training. METHODS: Medical students were randomized to proficiency-based training on VR laparoscopy and endoscopy simulators by two different methods: proctored training (automated simulator feedback plus human expert feedback) or independent training (simulator feedback alone). After achieving simulator proficiency, trainees performed a series of laparoscopic and endoscopic tasks in a live porcine model. Prior to their entry into the animal lab, all trainees watched an instructional video of the procedure and were randomly assigned to either observe or not observe the actual procedure before performing it themselves. The joint effects of VR training method and procedure observation on time to successful task completion were evaluated with Cox regression models. RESULTS: Thirty-two students (16 proctored, 16 independent) completed VR training. Cox regression modeling with adjustment for relevant covariates demonstrated no significant difference in the likelihood of successful task completion for independent versus proctored training [Hazard Ratio (HR) 1.28; 95% Confidence Interval (CI) 0.96-1.72; p=0.09]. Trainees who observed the actual procedure were more likely to be successful than those who watched the instructional video alone (HR 1.47; 95% CI 1.09-1.98; p=0.01). CONCLUSIONS: Proctored VR training is no more effective than independent training with respect to surgical performance. Therefore, time-consuming human expert feedback during VR training may be unnecessary. Instructional videos, while useful, may not be adequate substitutes for actual observation when trainees are learning minimally invasive surgical procedures.
Subject(s)
Clinical Competence , Computer Simulation , Computer-Assisted Instruction , Education, Medical/methods , General Surgery/education , Laparoscopy/education , Adult , Animals , Endoscopy/education , Female , Humans , Male , Models, Animal , Swine , Young AdultABSTRACT
Mucosal surfaces play a major role in human immunodeficiency virus type 1 (HIV-1) transmission and pathogenesis, and yet the role of lamina propria macrophages in mucosal HIV-1 infection has received little investigative attention. We report here that vaginal and intestinal macrophages display distinct phenotype and HIV-1 permissiveness profiles. Vaginal macrophages expressed the innate response receptors CD14, CD89, CD16, CD32, and CD64 and the HIV-1 receptor/coreceptors CD4, CCR5, and CXCR4, similar to monocytes. Consistent with this phenotype, green fluorescent protein-tagged R5 HIV-1 entered macrophages in explanted vaginal mucosa as early as 30 min after inoculation of virus onto the epithelium, and purified vaginal macrophages supported substantial levels of HIV-1 replication by a panel of highly macrophage-tropic R5 viruses. In sharp contrast, intestinal macrophages expressed no detectable, or very low levels of, innate response receptors and HIV-1 receptor/coreceptors and did not support HIV-1 replication, although virus occasionally entered macrophages in intestinal tissue explants. Thus, vaginal, but not intestinal, macrophages are monocyte-like and permissive to R5 HIV-1 after the virus has translocated across the epithelium. These findings suggest that genital and gut macrophages have different roles in mucosal HIV-1 pathogenesis and that vaginal macrophages play a previously underappreciated but potentially important role in mucosal HIV-1 infection in the female genital tract.
Subject(s)
HIV-1/growth & development , Intestinal Mucosa/virology , Macrophages/virology , Vagina/virology , Antigens, CD/analysis , Female , Humans , Macrophages/chemistry , Organ Culture Techniques , Receptors, HIV/analysisABSTRACT
Bariatric surgery is efficacious for the treatment of severe obesity; however, little empirical research exists describing the demographic, psychosocial, and cognitive characteristics of patients presenting for the surgery. One hundred and sixty-nine morbidly obese patients seeking bariatric surgery underwent a presurgical psychological assessment, including cognitive testing. Morbidly obese individuals seeking bariatric surgery were similar in education, income status, and IQ compared with normative data. IQ was average, did not correlate with body mass index, and reflected a normal distribution. As a group, bariatric surgery patients endorsed minimal levels of depression and low levels of psychopathology. Obese individuals did demonstrate specific cognitive deficits on tests of executive function (e.g., problem solving and planning) when compared with normative data. This data suggests that bariatric surgery patients differ very little from other surgical populations on most demographic and psychosocial variables. The data does provide evidence for specific cognitive deficits in the area of executive functions at baseline in morbidly obese adults seeking bariatric surgery.
Subject(s)
Bariatric Surgery , Cognition Disorders/epidemiology , Executive Function , Obesity, Morbid/psychology , Adult , Case-Control Studies , Female , Humans , Male , Obesity, Morbid/epidemiology , Obesity, Morbid/surgery , Problem Solving , Southeastern United States/epidemiologyABSTRACT
BACKGROUND: Laparoscopy-assisted ERCP (LAERCP) allows the diagnosis and treatment of biliopancreatic conditions in patients with Roux-en-Y anatomy (RY). However, experience with this technique is limited. OBJECTIVES: To report on the experience with LAERCP in consecutive patients from a high-volume bariatric surgery center and to evaluate success rates of ERCP with the laparoscopy-assisted approach. DESIGN: Retrospective case series. SETTING: High-volume bariatric surgery center. PATIENTS: Consecutive patients undergoing LAERCP between 2003 and 2009. INTERVENTION: LAERCP. OUTCOMES: Immediate/delayed complications, biliary/pancreatic duct cannulation, endoscopic/laparoscopic interventions, postprocedure hospital stay, procedure duration. RESULTS: Ten patients underwent LAERCP: 9 after Roux-en-Y gastric bypass (RYGB) and 1 after antrectomy with RY (9 female, 1 male; 9 white, 1 black). Indications for the procedure were choledocholithiasis (n=4), biliary stricture (n=3), and sphincter of Oddi dysfunction (n=3). Endoscopic access was obtained to the gastric remnant (n=9) or biliopancreatic limb (n=1). Biliary cannulation was successfully achieved in 9 of 10 patients, biliary sphincterotomy was performed in all, pancreatography in 3 of 3, and sphincter of Oddi manometry in 2. In 1 patient, a 3F pancreatic duct stent was placed prophylactically. Mild post-ERCP pancreatitis developed in 2 patients, and 1 patient had a pneumothorax intraoperatively that was treated successfully. The mean duration of the procedure was 89 minutes (range 41-245), and the median postprocedure hospital stay was 2 days (mean 2.59, standard deviation 2.46). LIMITATIONS: Single-center, retrospective design. CONCLUSION: LAERCP is safe and successful for the diagnosis and therapy of biliopancreatic conditions in patients with RY. It additionally allows the diagnosis and treatment of internal hernias, a known complication of RYGB.
Subject(s)
Bariatric Surgery , Biliary Tract Diseases/diagnosis , Cholangiopancreatography, Endoscopic Retrograde/methods , Laparoscopy , Pancreatic Diseases/diagnosis , Adult , Biliary Tract Diseases/therapy , Female , Gastric Bypass , Humans , Male , Middle Aged , Pancreatic Diseases/therapy , Postoperative Complications/diagnosis , Postoperative Complications/therapy , Retrospective Studies , Sphincterotomy, Endoscopic , Treatment Outcome , Video RecordingABSTRACT
BACKGROUND: Ventriculoperitoneal shunt (VPS) is the mainstay of therapy for hydrocephalus. The aim of this study is to compare outcomes of laparoscopic (LVPS) versus open (OVPS) techniques for placement of distal VPS catheters. METHODS: All patients undergoing new VPS placement at a tertiary care center between January 2004 and August 2007 were included. Univariate analysis was performed. Wilcoxon rank-sum, chi-square, and Fisher's exact tests were used to make comparisons between LVPS and OVPS groups. Stepwise backward logistic regression was performed to predict complications requiring operative intervention. A Kaplan-Meier estimate of the survival function was calculated for shunt survival. All data is presented as median and range unless otherwise specified. RESULTS: Five hundred thirty-five consecutive patients underwent 579 VPS (258 LVPS, 321 OVPS). Median age (52.0 years) and American Society of Anesthesiologists (ASA) score (3) were similar in LVPS and OVPS groups. Body mass index (BMI) [27.8 (17.0-64.9) kg/m(2) versus 25.9 (12.3-44.4) kg/m(2), p = 0.007], previous operations [0.8 +/- 0.9 versus 0.6 +/- 0.7, p = 0.004 (mean +/- standard deviation)], estimated blood loss (EBL) [20 (0-175) ml versus 25 (0-500) ml, p < 0.001], operating room (OR) time [37.5 (17.0-152.0) min versus 52.0 (20.0-197.0) min, p < 0.001], and length of stay (LOS) [11 (1-77) days versus 14 (1-225) days, p = 0.016] were statistically different between the LVPS and OVPS groups, respectively. LVPS abdominal complication rate of 5.8% and OVPS rate of 6.9% were similar (p = 0.611). Previous abdominal operation [odds ratio (OR) 1.673, 95% confidence interval (CI) 1.100-2.543, p = 0.016] and previous VPS (OR 1.929, 95% CI 1.147-3.243, p = 0.016) were significant predictors of complications requiring operative intervention. Kaplan-Meier analysis demonstrated no difference in survival between LVPS and OVPS groups (p = 0.538), with overall shunt survival of 86.4% at 6 months and 83.0% at 1 year. CONCLUSIONS: LVPS is associated with decreased OR time, less blood loss, and shorter LOS with no difference in complication rate when compared OVPS. The laparoscopic approach for VPS is a safe, effective, and readily reproducible alternative to the traditional open approach.
Subject(s)
Laparoscopy/methods , Laparotomy/methods , Prosthesis Implantation/methods , Ventriculoperitoneal Shunt/methods , Adolescent , Adult , Aged , Aged, 80 and over , Catheters, Indwelling , Cohort Studies , Female , Follow-Up Studies , Humans , Intracranial Hypertension/etiology , Intracranial Hypertension/surgery , Kaplan-Meier Estimate , Male , Middle Aged , Postoperative Complications/epidemiology , Retrospective Studies , Ventriculoperitoneal Shunt/instrumentation , Young AdultABSTRACT
Intestinal macrophages, which are thought to orchestrate mucosal inflammatory responses, have received little investigative attention compared with macrophages from other tissues. Here we show that human intestinal macrophages do not express innate response receptors, including the receptors for LPS (CD14), Fcalpha (CD89), Fcgamma (CD64, CD32, CD16), CR3 (CD11b/CD18), and CR4 (CD11c/CD18); the growth factor receptors IL-2 (CD25) and IL-3 (CD123); and the integrin LFA-1 (CD11a/CD18). Moreover, resident intestinal macrophages also do not produce proinflammatory cytokines, including IL-1, IL-6, IL-10, IL-12, RANTES, TGF-beta, and TNF-alpha, in response to an array of inflammatory stimuli but retain avid phagocytic and bacteriocidal activity. Thus, intestinal macrophages are markedly distinct in phenotype and function from blood monocytes, although intestinal macrophages are derived from blood monocytes. To explain this paradox, we show that intestinal stromal cell-derived products downregulate both monocyte receptor expression and, via TGF-beta, cytokine production but not phagocytic or bacteriocidal activity, eliciting the phenotype and functional profile of intestinal macrophages. These findings indicate a mechanism in which blood monocytes recruited to the intestinal mucosa retain avid scavenger and host defense functions but acquire profound "inflammatory anergy," thereby promoting the absence of inflammation characteristic of normal intestinal mucosa despite the close proximity of immunostimulatory bacteria.
Subject(s)
Escherichia coli/immunology , Intestinal Mucosa/microbiology , Intestinal Mucosa/pathology , Macrophages/microbiology , Macrophages/pathology , Phagocytosis , Salmonella typhimurium/immunology , Antigens, Surface/metabolism , Culture Media, Conditioned/pharmacology , Cytokines/metabolism , Down-Regulation/drug effects , Escherichia coli/physiology , Humans , Inflammation/pathology , Intestinal Mucosa/immunology , Intestinal Mucosa/metabolism , Jejunum/metabolism , Jejunum/microbiology , Jejunum/pathology , Lipopolysaccharides/pharmacology , Macrophages/immunology , Macrophages/metabolism , Phenotype , Salmonella typhimurium/physiology , Stromal Cells/chemistry , Stromal Cells/metabolism , Transforming Growth Factor beta/genetics , Transforming Growth Factor beta/metabolismABSTRACT
BACKGROUND/AIMS: Obesity is a common and rapidly growing health problem today. Obesity is characterized by the increase of body fat and an excess of total body fat and, in particular, visceral fat accumulation, is considered to be a risk factor for type 2 diabetes mellitus. To determine whether the malfunction of the mesenteric adipose tissue plays an important role in the diabetic related metabolic syndrome, in this study, lipolysis and gene expression in the subcutaneous, omental and mesenteric adipose tissue of the diabetic subjects were evaluated. METHODS: Lipolysis and real time PCR were utilized to determine adipocyte function. RESULTS: Basal adipose tissue glycerol release is higher in diabetics than that of the non diabetics in all three fat depots. Isoproterenol (ISO) significantly increases glycerol release in subcutaneous, omental and mesenteric adipose tissues of non diabetic subjects but it stimulated glycerol release was significantly impaired in all three fat depots of the diabetic subjects. Gene expression studies indicate that leptin, Peroxisome proliferator-activated receptor-gamma (PPAR-gamma), Fatty acid translocase (FAT/CD36) and 11beta-hydroysteroid dehydrogenase (HSD) gene expression were significantly up regulated in the mesenteric adipose tissue of the diabetic patients. CONCLUSION: Human mesenteric adipose tissue in obese diabetic subjects has high basal glycerol release and impaired isoproterenol stimulated glycerol release. The obesity-related gene expressions in the mesenteric adipose tissue are up regulated, suggesting that the alterations of these genes in mesentery adipose depot may play a critical role in insulin resistance of type 2 diabetes and metabolic syndrome.
Subject(s)
Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/metabolism , Mesentery/metabolism , Obesity/complications , Obesity/metabolism , Omentum/metabolism , Subcutaneous Fat/metabolism , Adiponectin/genetics , Adiponectin/metabolism , CD36 Antigens/genetics , CD36 Antigens/metabolism , Diabetes Mellitus, Type 2/genetics , Fatty Acids/metabolism , Gene Expression Regulation/drug effects , Glycerol/metabolism , Humans , Isoproterenol/pharmacology , Leptin/genetics , Leptin/metabolism , Middle Aged , Obesity/genetics , PPAR gamma/genetics , PPAR gamma/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Subcutaneous Fat/drug effectsABSTRACT
BACKGROUND: To date, the noninvasive diagnostic tests for hepatic fibrosis in subjects with nonalcoholic fatty liver disease (NAFLD) have proven to be suboptimal. We evaluated the validity of a recently proposed "NAFLD fibrosis score" to identify liver fibrosis in morbidly obese individuals with elevated and normal alanine aminotransferase (ALT) levels. METHODS: Medical records of 401 patients that underwent a gastric bypass operation and intraoperative liver biopsy were analyzed. Three hundred thirty one patients with biopsy-proven NAFLD were included in the study (group A). These patients were divided into two ALT groups based on their levels according to the new proposed normal range: group B elevated level (ALT > 19 U/L in females and >30 U/L in males, n = 221) and group C normal ALT (n = 110). Diagnostic accuracy of the system was assessed for the presence/absence of any fibrosis, significant fibrosis (stage 2-4), and advanced fibrosis (stages 3 and 4) in all of the groups. RESULTS: The prevalence of advanced fibrosis in our cohort was about 14%. The low NAFLD fibrosis score demonstrated high accuracy for ruling out advanced fibrosis, with negative predictive value (NPV) of 98 and 99% in groups A and B, respectively. The NPV for significant fibrosis in groups A, B, and C was 87, 88, and 88%, respectively. The respective positive predictive value for the high NAFLD fibrosis score for the presence of any fibrosis was 88, 95, and 77% in groups A, B, and C. CONCLUSIONS: The NAFLD fibrosis score may be a useful noninvasive approach for excluding significant and advanced fibrosis and in morbidly obese patients.
Subject(s)
Fatty Liver/diagnosis , Gastric Bypass , Liver Cirrhosis/diagnosis , Obesity, Morbid/complications , Adult , Alanine Transaminase/blood , Biopsy, Needle , Fatty Liver/complications , Female , Humans , Liver/pathology , Liver Cirrhosis/complications , Male , Obesity, Morbid/surgery , Predictive Value of TestsABSTRACT
Hyperparathyroidism (HPT) can occur after gastric bypass because of the alteration in vitamin D and calcium absorption. Adequate serum vitamin D concentrations have not been clearly defined in this patient population. Vitamin D (Vit D) and parathyroid hormone (PTH) were assessed 1 year after laparoscopic gastric bypass (LGB). The prevalence of HPT and Vit D deficiency were determined and their association was evaluated using Fisher's exact test. Ninety-three patients (aged 44 +/- 1.1 years, 49.6 +/- 0.67 Kg/m2 body mass index, 79.6% female, 69.6% white) were evaluated. The prevalence of Vit D deficiency (less than 20 ng/mL) and HPT (greater than 65 pg/mL) was 23.6 per cent (n = 22) and 25.7 per cent (n = 28), respectively. Among patients with HPT, only eight of 28 (28.6%) had Vit D deficiency, and of those with Vit D deficiency, only eight of 22 (36.4%) had HPT. There was a weak inverse correlation (r = -0.37) between PTH and Vit D. Blacks are at higher risk for Vit D deficiency. There was no significant association between Vit D deficiency and HPT, Vit D deficiency and Roux limb length, or HPT and Roux limb length. After LGB, Vit D deficiency and hyperparathyroidism occur commonly. Body mass index and Roux limb length are not associated with these two conditions, but racial differences do exist. There is a weak inverse correlation between Vit D and PTH. Further research is needed to elucidate the causes, treatments, and significance of HPT after LGB.
Subject(s)
Gastric Bypass/methods , Hyperparathyroidism, Secondary/etiology , Laparoscopy , Obesity, Morbid/surgery , Vitamin D Deficiency/etiology , Adult , Chi-Square Distribution , Female , Humans , Hyperparathyroidism, Secondary/epidemiology , Male , Parathyroid Hormone/blood , Postoperative Complications/epidemiology , Prevalence , Prospective Studies , Vitamin D/blood , Vitamin D Deficiency/epidemiologyABSTRACT
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has been increasingly recognized as a common chronic liver condition. Previous studies have been variable regarding the histological outcomes after rapid weight loss. The aim of this study was to characterize the histopathologic changes in NASH following laparoscopic Roux-en-Y Gastric Bypass surgery (LRYGBP). METHODS: We retrospectively analyzed paired needle liver biopsies taken during and following LRYGBP in 39 patients according to the recent NIH-based NAFLD criteria. RESULTS: The cohort included 33 females and 6 males (range 24-57 years). 23 patients (58.9%) had steatohepatitis, 12 with fatty liver (30.7%), and 4 were normal (10.2%). Follow-up needle liver biopsies were performed at a mean interval of 18 months (range 6-41 months). No significant differences in length or number of portal tracts between the paired biopsies were noted. The mean decrease in weight and BMI was 50.2 kg and 18.2 kg/m2, respectively. The initial prevalence of hepatic pathology: steatosis (89.7%), hepatocellular ballooning (58.9%), and centrilobular/perisinusoidal fibrosis (50%) improved significantly after LRYGBP: steatosis (2.9%), ballooning (0%), and centrilobular fibrosis (25%). Mitigation in the lobular inflammation score (2.23+/-0.63 vs 1.95+/-0.56, P=0.01) and stage of fibrosis (1.14+/-1.05 to 0.72+/-0.97, P=0.002) were also noted. However, no improvements were detected in portal tract inflammation and fibrosis. CONCLUSIONS: Over a mean period of 18 months, histological improvements and resolution of NASH occurs after LRYGBP. Long-term studies are warranted to assess for potential changes in the portal regions or relapse of NASH that could result with weight regain or malnutrition.
Subject(s)
Fatty Liver/pathology , Gastric Bypass , Hepatitis/pathology , Obesity, Morbid/complications , Obesity, Morbid/surgery , Weight Loss , Adult , Body Mass Index , Fatty Liver/complications , Female , Follow-Up Studies , Hepatitis/complications , Humans , Laparoscopy , Male , Middle Aged , Obesity, Morbid/pathology , Remission Induction , Retrospective Studies , Treatment OutcomeABSTRACT
OBJECTIVE: To examine changes in the prevalence and severity of urinary incontinence (UI) and fecal incontinence in morbidly obese women undergoing laparoscopic weight loss surgery. METHODS: In a prospective cohort study, 101 women (aged 20-55 years) with body mass index (BMI) of 40 or more underwent laparoscopic Roux-en-Y gastric bypass and were followed to 6 and 12 months. Presence, severity, and effect of UI were assessed using the Medical, Epidemiological, and Social Aspects of Aging Questionnaire, Urogenital Distress Inventory, and Incontinence Impact Questionnaire. Fecal incontinence was assessed by self-report of anal leakage. RESULTS: Mean BMI decreased from 48.9+/-7.2 presurgery to 35.3+/-6.5 at 6 months and 30.2+/-5.7 at 12 months postsurgery. Prevalence of UI decreased from 66.7% presurgery to 41.0% at 6 months and 37.0% at 12 months (P<.001; 95% confidence interval [CI] for change 18.6-40.0%). Reduction in prevalence of UI was significantly associated with decreases in BMI (P=.01). Among incontinent women who lost 18 or more BMI points, 71% regained urinary continence at 12 months. Medical, Epidemiological, and Social Aspects of Aging Questionnaire urge and stress scores decreased (both P<.001; 95% CI 0.5-1.85 and 2.71-5.34, respectively), as did scores on the Urogenital Distress Inventory (P<.001; 95% CI 8.31-16.21) and Incontinence Impact Questionnaire (P<.001; 95% CI 4.71-14.60), indicating reduction in severity. Prevalence of fecal incontinence (solid or liquid stool) decreased from 19.4% to 9.1% at 6 months and 8.6% at 12 months (P=.018; 95% CI 2.1-19.4%). CONCLUSION: Prevalence of UI and fecal incontinence decreased after bariatric surgery. Magnitude of weight loss was associated with reduction in UI prevalence, strengthening the inference that improvements are attributable to weight loss. LEVEL OF EVIDENCE: II.
Subject(s)
Fecal Incontinence/therapy , Gastric Bypass/rehabilitation , Obesity, Morbid/surgery , Urinary Incontinence/therapy , Weight Loss , Adult , Body Mass Index , Female , Humans , Middle Aged , Prospective StudiesABSTRACT
BACKGROUND: Minimally invasive surgery (MIS) fellowship is one of the most sought-after positions after residency. The increased use of bariatric operations has provided an abundance of advanced cases. The aim of this article is to determine if the addition of an MIS fellowship program has any impact on morbidity and mortality in a university-based bariatric program. STUDY DESIGN: Data from all laparoscopic gastric bypasses (LGBs) performed by one surgeon (RHC) from September 2001 until June 2006 were prospectively entered into a database, which was reviewed for morbidity and mortality before (group 1) and after (group 2) development of the MIS program. Mean operative time, length of hospital stay, anastomotic leaks and strictures, gastrointestinal bleeds, internal hernia, and mortality were compared between the two groups of patients using t-tests with significance of p = 0.05. RESULTS: A total of 761 (group 1, n = 397; group 2, n = 364) LGBs were performed. For the total population, operating room time was 104 +/- 24 minutes and length of hospital stay was 2 +/- 0.3 days. Incidences of morbidities are as follows: leaks, 0.53%; marginal ulcer, 5.0%; anastomotic stricture, 6.7%; incarcerated internal hernia, 2.2%; gastric outlet obstruction, 0.53%; gastrointestinal bleed, 0.09%; and mortality, 0.13%. Comparing groups 1 and 2, mean operating room time was longer in group 2, but there was no marked difference between any of the other variables. CONCLUSIONS: Addition of an MIS fellowship does not change the morbidity and mortality of LGB when developed in the context of a university-based bariatric practice that uses a systematic approach to preoperative evaluation, operative technique, and postoperative management.
Subject(s)
Bariatric Surgery/education , Fellowships and Scholarships , Laparoscopy , Adult , Bariatric Surgery/mortality , Female , Hospitals, University , Humans , Length of Stay/statistics & numerical data , Male , Postoperative Complications/mortality , Prospective Studies , Treatment OutcomeABSTRACT
Four morbidly obese women who met the NIH criteria for bariatric surgery had laparoscopic Roux-en-Y gastric bypass. At operation, each was found to have intestinal malrotation. Two cases were completed laparoscopically, and two were converted to open operation because of difficulty defining the anatomy. All four operations were successful with no immediate complications and patients tolerated the procedures well. We present the four cases and offer recommendations should this unusual congenital defect be discovered at the time of laparoscopic gastric bypass.
Subject(s)
Gastric Bypass/methods , Intestines/abnormalities , Laparoscopy , Obesity, Morbid/surgery , Adult , Female , Humans , Incidental Findings , Intraoperative Period , Middle AgedABSTRACT
OBJECTIVE: The purpose of this study was to evaluate the sensitivity and specificity of seven CT signs in the diagnosis of internal hernia after laparoscopic Roux-en-Y gastric bypass. MATERIALS AND METHODS: With institutional review board approval, the CT scans of 18 patients (17 women, one man) with surgically proven internal hernia after laparoscopic Roux-en-Y gastric bypass were retrieved, as were CT studies of a control group of 18 women who had undergone gastric bypass but did not have internal hernia at reoperation. The scans were reviewed by three radiologists for the presence of seven CT signs of internal hernia: swirled appearance of mesenteric fat or vessels, mushroom shape of hernia, tubular distal mesenteric fat surrounded by bowel loops, small-bowel obstruction, clustered loops of small bowel, small bowel other than duodenum posterior to the superior mesenteric artery, and right-sided location of the distal jejunal anastomosis. Sensitivity and specificity were calculated for each sign. Stepwise logistic regression was performed to ascertain an independent set of variables predictive of the presence of internal hernia. RESULTS: Mesenteric swirl was the best single predictor of hernia; sensitivity was 61%, 78%, and 83%, and specificity was 94%, 89%, and 67% for the three reviewers. The combination of swirled mesentery and mushroom shape of the mesentery was better than swirled mesentery alone, sensitivity being 78%, 83%, and 83%, and specificity being 83%, 89%, and 67%, but the difference was not statistically significant. CONCLUSION: Mesenteric swirl is the best indicator of internal hernia after laparoscopic Roux-en-Y gastric bypass, and even minor degrees of swirl should be considered suspicious.