Evan P. Nadler

An update on 73 US obese pediatric patients treated with laparoscopic adjustable gastric banding: comorbidity resolution and compliance data

BACKGROUND Adolescent obesity continues to present one of the most difficult and important challenges for both the pediatric and adult medical communities. Evidence is mounting that bariatric surgery is the only reliable method for substantial and sustainable weight loss; however, the debate continues with regard to the optimal surgical procedure for both adolescents and adults. Although most US adult bariatric surgeons prefer the gastric bypass, our institution has demonstrated equivalent weight loss with significantly less morbidity using laparoscopic adjustable gastric banding (LAGB) in both adults and adolescents. This analysis is an update of our results in our first 73 patients, including resolution of comorbid conditions and compliance data. METHODS All adolescents aged 13 to 17 years who have undergone LAGB at our institution have been entered into our prospectively collected database since September 2001 and were reviewed. Data collected preoperatively included age, sex, race, body mass index (BMI), and presence of comorbid conditions. Postoperatively recorded data included length of stay, operative morbidity, need for reoperation, percentage of excess weight loss (%EWL), and BMI at 3-month intervals; status of any comorbid conditions, and number of postoperative visits and band adjustments. RESULTS Seventy-three adolescents aged 13 to 17 years (mean, 15.8 +/- 1.2 years) have undergone LAGB at our institution since September, 2001. Of these, 54 were female and 19 were male. The mean preoperative weight was 298 lb, with a BMI of 48 kg/m(2). The %EWL at 6 months, 1 year, and 2 years postoperatively was 35% +/- 16%, 57% +/- 23%, and 61% +/- 27%, respectively. One patient experienced a gastric perforation after a reoperation for band replacement because of a slip. One additional patient requested band removal because of restriction intolerance after a slip. A total of 6 patients developed band slippage, and 3 patients developed symptomatic hiatal hernias. Nutritional complications included asymptomatic iron deficiency in 13 patients, asymptomatic vitamin D deficiency in 4 patients, and mild subjective hair loss in 14 patients. In 21 patients who entered our Food and Drug Administration-approved study and had reached 1-year follow-up, there were 51 identified comorbid conditions. Of these, 35 (68.5%) were completely resolved, 9 (17.5%) were improved, 5 (10%) were unchanged, and 2 (4%) were aggravated after 1 year. Of 50 initial patients who underwent surgery more than 1 year ago, 2 patients lived a large distance from our institution, where band maintenance is being performed locally, and thus, the patients were excluded from the analysis. Two patients were lost to follow-up in the first year, and 3 patients were lost to follow-up in the second year, for an overall compliance rate of at least 89.5%. The mean number of office visits was 10 +/- 3 in the first year, and the mean number of adjustments was 6 +/- 2. CONCLUSIONS Laparoscopic adjustable gastric banding continues to represent an attractive treatment strategy for morbidly obese pediatric patients with a %EWL of more than 55% at both 1- and 2-year follow-up, with minimal morbidity compared with the gastric bypass. Furthermore, the weight loss associated with LAGB provides excellent resolution or improvement of comorbid conditions. Although there is a necessary commitment by the patient that involves frequent office visits and band adjustments, adolescents are entirely capable of this commitment, and noncompliance should not be a reason to dissuade adolescents from having LAGB. It remains, in our opinion, the optimal surgical option for pediatric patients with morbid obesity.

Laparoscopic adjustable gastric banding for morbidly obese adolescents affects android fat loss, resolution of comorbidities, and improved metabolic status.

BACKGROUND The distribution of weight loss and its impact on metabolic health has not been documented for laparoscopic adjustable gastric banding (LAGB) in the adolescent population. We hypothesized that LAGB in obese adolescents would result in loss of android fat mass, resolution of comorbidities, and improvement in metabolic status. STUDY DESIGN Adolescents ages 14 to 17 who met criteria for bariatric surgery were enrolled in our FDA-approved LAGB trial. Demographic data, body mass index, body composition and bone density, laboratory evaluations, and comorbid conditions were assessed pre- and postoperatively. RESULTS Forty-five patients had complete 1-year followup and 41 patients had complete 2-year followup. Mean preoperative weight was 299 + or - 57 lb and body mass index was 48 + or - 6.4 kg/m(2). The percent excess weight losses at 6 months, 1 year, and 2 years were 31 + or - 16, 46 + or - 21, and 47 + or - 22, respectively. At 1-year followup, patients after LAGB had a significant decrease in their total and android fat mass. In addition, 47 of 85 identified comorbidities (55%) were completely resolved and 25 (29%) were improved in comparison with baseline. Improvements in alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, hemoglobin A1c, fasting insulin, triglycerides, and high density lipoprotein, were also seen. CONCLUSIONS The percent excess weight loss after LAGB in morbidly obese adolescents is approximately 45% at 1- and 2-year followup, with the majority of weight loss consisting of android fat mass. Resolution or improvement of comorbidities is seen, and improved metabolic status, as demonstrated by liver function tests, lipid levels, and measures of glucose homeostasis, may be expected. These data support LAGB as an appropriate surgical option for morbidly obese adolescents.

Contrast extravasation predicts the need for operative intervention in children with blunt splenic trauma.

BACKGROUND Although the presence of a contrast blush (CB) on computed tomographic (CT) scan is associated with an increased failure rate of nonoperative management in adults with blunt splenic injury, little information is available for the pediatric population, where nonoperative management is the standard of care. Our aim was to determine whether the finding of CB on CT scan could predict failure of nonoperative therapy in children with blunt splenic injury. METHODS A retrospective analysis of 343 patients admitted with blunt splenic injury to our Level I pediatric trauma center over a 7-year period was performed. All CT scans were reviewed by a radiologist who was blinded to the patient outcome. We excluded 127 patients who either underwent immediate laparotomy without a CT scan or whose CT scans were unavailable at the time of this review. We divided the patients into two groups on the basis of the presence or absence of CB on the updated reading of the CT scan. Demographic variables analyzed included age, sex, mechanism of injury, Injury Severity Score, Glasgow Coma Scale score, initial hemoglobin and hematocrit, and emergency department pulse rate and systolic blood pressure. Outcome measures compared include length of stay, length of intensive care unit stay, the need for splenic intervention, and mortality. Continuous variables were compared using Students t test for normally distributed data and the Mann-Whitney test for skewed data. Categorical data were compared using chi2 analysis or Fishers exact test. Statistical significance was assigned to values of p < 0.05. RESULTS Among the study population (N = 216), 27 patients (12.5%) had CB on CT scan. Patients with CB had significantly lower hematocrit (p = 0.0004) and required operative intervention more frequently than those without CB (22% vs. 4%;p = 0.0008). Among patients with CB, mean pulse rate at presentation was higher in those that required splenic intervention (SI) (129 +/- 20.1) compared with those who underwent successful nonoperative therapy (100.4 +/- 23.1; p = 0.01). Only grade V injuries correlated with the need for laparotomy. CONCLUSION Children with blunt splenic injury who have CB on CT scan are more likely to require SI than those without CB. However, because the majority of patients with CB did not require SI, in the absence of hemodynamic instability, this finding may be insufficient to determine the need for SI. CB is a specific marker of active bleeding that may predict the need for early splenic intervention in a specific subset of patients at presentation.

NOX, a novel nitric oxide scavenger, reduces bacterial translocation in rats after endotoxin challenge

Endotoxemia promotes gut barrier failure and bacterial translocation (BT) by upregulating inducible nitric oxide synthase (iNOS) in the gut. We hypothesized that administration of a dithiocarbamate derivative, NOX, which scavenges nitric oxide (NO), may reduce intestinal injury and BT after lipopolysaccharide (LPS) challenge. Sprague-Dawley rats were randomized to receive NOX or normal saline via subcutaneously placed osmotic pumps before or after LPS challenge. Mesenteric lymph nodes, liver, spleen, and blood were cultured 24 h later. Transmucosal passage of Escherichia coli C-25 or fluorescent beads were measured in an Ussing chamber. Intestinal membranes were examined morphologically for apoptosis, iNOS expression, and nitrotyrosine immunoreactivity. NOX significantly reduced the incidence of bacteremia, BT, and transmucosal passage of bacteria and beads when administered before or up to 12 h after LPS challenge. LPS induced enterocyte apoptosis at the villus tips where bacterial entry was demonstrated by confocal microscopy. NOX significantly decreased the number of apoptotic nuclei and nitrotyrosine residues. NOX prevents LPS-induced gut barrier failure by scavenging NO and its toxic derivative, peroxynitrite.Endotoxemia promotes gut barrier failure and bacterial translocation (BT) by upregulating inducible nitric oxide synthase (iNOS) in the gut. We hypothesized that administration of a dithiocarbamate derivative, NOX, which scavenges nitric oxide (NO), may reduce intestinal injury and BT after lipopolysaccharide (LPS) challenge. Sprague-Dawley rats were randomized to receive NOX or normal saline via subcutaneously placed osmotic pumps before or after LPS challenge. Mesenteric lymph nodes, liver, spleen, and blood were cultured 24 h later. Transmucosal passage of Escherichia coli C-25or fluorescent beads were measured in an Ussing chamber. Intestinal membranes were examined morphologically for apoptosis, iNOS expression, and nitrotyrosine immunoreactivity. NOX significantly reduced the incidence of bacteremia, BT, and transmucosal passage of bacteria and beads when administered before or up to 12 h after LPS challenge. LPS induced enterocyte apoptosis at the villus tips where bacterial entry was demonstrated by confocal microscopy. NOX significantly decreased the number of apoptotic nuclei and nitrotyrosine residues. NOX prevents LPS-induced gut barrier failure by scavenging NO and its toxic derivative, peroxynitrite.

Management of Blunt Pancreatic Injury in Children

BACKGROUND AND METHODS Controversy persists regarding the management of pancreatic transection. Over the past 10 years, 51 patients admitted to the Childrens Hospital of Pittsburgh sustained blunt pancreatic injuries. We reviewed their medical records to clarify the optimal management strategy and to define distinguishing characteristics, if any, of patients with pancreatic transection. RESULTS Patients who sustained pancreatic transection had a significantly higher Injury Severity Score, length of stay, serum amylase, and serum lipase, than those patients who sustained pancreatic contusion. Patients who underwent laparotomy within 48 hours of injury for pancreatic transection had a significantly shorter length of stay than those who underwent laparotomy more than 48 hours after injury. CONCLUSION Serum amylase greater than 200 and serum lipase greater than 1,800 may be useful clinical markers for major pancreatic ductal injury when combined with physical examination. Early operative intervention for pancreatic transection results in shorter length of stay and fewer complications.

Adipocyte-derived exosomal miRNAs: a novel mechanism for obesity-related disease

Background:Obesity is frequently complicated by comorbid conditions, yet how excess adipose contributes is poorly understood. Although adipocytes in obese individuals induce systemic inflammation via secreted cytokines, another potential mediator has recently been identified (i.e., adipocyte-derived exosomes). We hypothesized that adipocyte-derived exosomes contain mediators capable of activating end-organ inflammatory and fibrotic signaling pathways.Methods:We developed techniques to quantify and characterize exosomes shed by adipocytes from seven obese (age: 12–17.5 y, BMI: 33–50 kg/m2) and five lean (age: 11–19 y, BMI: 22–25 kg/m2) subjects.Results:Abundant exosomal miRNAs, but no mRNAs, were detected. Comparison of obese vs. lean visceral adipose donors detected 55 differentially expressed miRNAs (P < 0.05; fold change ≥|1.2|). qRT-PCR confirmed downregulation of miR-148b (ratio = 0.2 (95% confidence interval = 0.1, 0.6)) and miR-4269 (0.3 (0.1, 0.8)), and upregulation of miR-23b (6.2 (2.2, 17.8)) and miR-4429 (3.8 (1.1−13.4)). Pathways analysis identified TGF-β signaling and Wnt/β-catenin signaling among the top canonical pathways expected to be altered with visceral adiposity based on projected mRNA targets for the 55 differentially expressed miRNAs. A select mRNA target was validated in vitro.Conclusion:These data show that visceral adipocytes shed exosomal-mediators predicted to regulate key end-organ inflammatory and fibrotic signaling pathways.

Regulation of bacterial translocation by nitric oxide

Abstract Nitric oxide (NO) appears to play a paradoxical role in intestinal physiology. Although NO has potent bactericidal effects, a growing body of evidence suggests that it mediates intestinal injury and breakdown of gut barrier function. Data from our lab and others show an increased incidence of bacterial translocation following endotoxin challenge, and upregulation of inducible NO synthase (iNOS) mRNA and protein in the intestine. These phenomena co-localize with enterocyte apoptosis at the tips of the intestinal villi and immunoreactivity to nitrotyrosine. Electron microscopy reveals swollen mitochondria, implicating these organelles as putative targets for NO or its reactive nitrogen intermediates. We review some of the literature and discuss our current work in trying to define this mechanism.

Monotherapy versus Multi-Drug Therapy for the Treatment of Perforated Appendicitis in Children

BACKGROUND Children with perforated appendicitis often have a prolonged hospital course complicated by surgical site or intra-abdominal infections. Treatment with multiple intravenous (IV) antibiotics after appendectomy has been the standard of care for these patients. We have recently adopted a protocol using piperacillin-tazobactam (PT) as a single agent in lieu of the standard multi-drug regimen (MD). We hypothesized that PT would be as effective as MD in reducing postoperative complications and would result in decreased resource utilization. METHODS We reviewed the medical records of all children admitted to our hospital between January 1, 1998 and December 31, 2001 with the diagnosis of perforated appendicitis. Patients who underwent operation within the first 24 h of admission were divided into two groups based on their antibiotic regimen: PT versus MD. Demographic data, duration of presenting symptoms, initial WBC, length of stay, and infectious complications were abstracted. Categorical data were compared using Chi square analysis; continuous variables were compared using Students t-test when the data were normally distributed and the Mann-Whitney U test when the data were skewed. RESULTS There was no difference between the PT (n = 51) and MD (n = 43) groups with respect to age, duration of presenting symptoms, initial WBC, or length of hospital stay. However, patients in the MD group had a significantly higher overall complication rate than those in the PT group (14/43 vs. 4/51, p = 0.002). Antibiotic-related complications including surgical site infections, venous catheter-related infections, intra-abdominal abscesses, and drug reactions were also higher in the MD group (10/43 vs. 4/51, p = 0.04). The outpatient charges for each patient based on an average of seven days of home antibiotics were

Morbidity in obese adolescents who meet the adult National Institutes of Health criteria for bariatric surgery

2,460 for the PT group and

Integrin αvβ6 and Mediators of Extracellular Matrix Deposition Are Up-Regulated in Experimental Biliary Atresia

4,349 for the MD group. CONCLUSIONS Children with perforated appendicitis can be managed effectively with a single broad-spectrum antibiotic after appendectomy. Monotherapy is not only more efficacious than multi-drug therapy, but may be more cost effective. The use of monotherapy for children with perforated appendicitis after adequate source control should be considered the treatment of choice.