Strengthening Surgery Strengthens Health Systems: A New Paradigm and Potential Pathway for Horizontal Development in Low- and Middle-Income Countries.

Global health is transitioning toward a focus on building strong and sustainable health systems in developing countries; however, resources, funding, and agendas continue to concentrate on "vertical" (disease-based) improvements in care. Surgical care in low- and middle-income countries (LMICs) requires the development of health systems infrastructure and can be considered an indicator of overall system readiness. Improving surgical care provides a scalable gateway to strengthen health systems in multiple domains. In this position paper by the Society of University Surgeons' Committee on Global Academic Surgery, we propose that health systems development appropriately falls within the purview of the academic surgeon. Partnerships between academic surgical institutions and societies from high-income and resource-constrained settings are needed to strengthen advocacy and funding efforts and support development of training and research in LMICs.

Correction to: Strengthening Surgery Strengthens Health Systems: A New Paradigm and Potential Pathway for Horizontal Development in Low- and Middle-Income Countries.

In the original article, Ziad C. Sifri's first and last names were interchanged. It is correct as reflected here.

Nonalcoholic fatty liver disease in severely obese adolescent and adult patients.

OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is increasingly an indication for liver transplantation in adults. While severe obesity (SO, BMI ≥40 kg m(-2) ) in adults is long standing, it is recent in duration in adolescents. With adolescent obesity on the rise, NAFLD is becoming the most frequent liver disease in adolescents. The hypothesis that SO adolescents and adults have different severity of NAFLD because of longer duration of obesity in SO adults was tested. DESIGN AND METHODS: Preoperative clinical data, NAFLD activity and NASH (Nonalcoholic steatohepatitis) scores from intraoperative liver biopsies were extracted from a prospective database of consecutively operated SO adolescents and adults (n = 24 each). Fasting preoperative serum inflammatory mediators were evaluated by ELISA. RESULTS: Other than age, baseline BMI, ethnicity and gender distribution, the incidence and extent of dyslipidemia, hypertension, and metabolic syndrome were comparable between groups. Histologic scores for steatosis and inflammation were similar. Adolescents have significantly higher NASH incidence, hepatocyte injury scores and fibrosis. This was associated with higher serum C-reactive protein and sCD14 levels. CONCLUSION: For comparable BMI and metabolic profile, SO adolescents have more advanced liver damage, more severe systemic inflammation, suggesting differences in NAFLD etiologies and more aggressive disease progression in the young obese population.

Patterns of surgical weight loss and resolution of metabolic abnormalities in superobese bariatric adolescents.

PURPOSE: The aim of the study was to compare the baseline and the 18-month follow-up for weight and metabolic characteristics of superobese (SO) (body mass index [BMI] ≥50 kg/m(2)) and morbidly obese (MO) (BMI <50 kg/m(2)) adolescents who participated in a prospective longitudinal study of gastric banding delivered in an adolescent multidisciplinary treatment program. METHODS: Clinical information was extracted from an institutional review board-approved database of bariatric adolescents. Fasting cytokine and acute phase protein serum levels were analyzed by enzyme-linked immunosorbent assay. Liver histopathologies were assessed using the Kleiner's classification score. RESULTS: Other than BMI, MO (n = 11) and SO (n = 7) patients have similar degree of insulin resistance, dyslipidemia, and nonalcoholic fatty liver disease. Serum C-reactive protein (10.2 ± 5.6 SO vs 4 ± 3.9 µg/mL MO [P < .02]) and leptin (71 ± 31 SO vs 45 ± 28 MO ng/mL [P = .04]) were more elevated in SO patients. Although weight loss is similar (30 ± 19 kg MO vs 28 ± 12 kg SO, P = .8 at 18 months; mean percent change in BMI, 22.8% ± 11.6% vs 20.5% ± 10.3% SO, P = .2), SO patients has less resolution of insulin resistance and dyslipidemia but experienced significantly improved health-related quality of life. CONCLUSIONS: The SO adolescents demonstrate equivalent short-term weight loss and improved quality of life but delayed metabolic response to a gastric banding-based weight loss treatment program compared with MO patients, illustrating the importance of early referral for timely intervention of MO patients.

Elevated systemic hepcidin and iron depletion in obese premenopausal females.

Hepcidin, the body's main regulator of systemic iron homeostasis, is upregulated in response to inflammation and is thought to play a role in the manifestation of iron deficiency (ID) observed in obese populations. We determined systemic hepcidin levels and its association with body mass, inflammation, erythropoiesis, and iron status in premenopausal obese and nonobese women (n = 20/group) matched for hemoglobin (Hb). The obese participants also had liver and abdominal visceral and subcutaneous adipose tissue assessed for tissue iron accumulation and hepcidin mRNA expression. Despite similar Hb levels, the obese women had significantly higher serum hepcidin (88.02 vs. 9.70 ng/ml; P < 0.0001) and serum transferrin receptor (sTfR) (P = 0.001) compared to nonobese. In the obese women hepcidin was not correlated with serum iron (r = -0.02), transferrin saturation (Tsat) (r = 0.17) or sTfR (r = -0.12); in the nonobese it was significantly positively correlated with Tsat (r = 0.70) and serum iron (r = 0.58), and inversely with sTfR (r = -0.63). Detectable iron accumulation in the liver and abdominal adipose tissue of the obese women was minimal. Liver hepcidin mRNA expression was ~700 times greater than adipose tissue production and highly correlated with circulating hepcidin levels (r = 0.61). Serum hepcidin is elevated in obese women despite iron depletion, suggesting that it is responding to inflammation rather than iron status. The source of excess hepcidin appears to be the liver and not adipose tissue. The ID of obesity is predominantly a condition of a true body iron deficit rather than maldistribution of iron due to inflammation. However, these findings suggest inflammation may perpetuate this condition by hepcidin-mediated inhibition of dietary iron absorption.

Decreased serum hepcidin and improved functional iron status 6 months after restrictive bariatric surgery.

Excess adiposity is associated with low-grade inflammation and decreased iron status. Iron depletion in obesity is thought to be mediated by an inflammation-induced increase in the body's main regulator of iron homeostasis, hepcidin. Elevated hepcidin can result in iron depletion as it prevents the release of dietary iron absorbed into the enterocytes, limiting replenishment of body iron losses. Weight reduction is associated with decreased inflammation; however, the impact of reduced inflammation on iron status and systemic hepcidin in obese individuals remains unknown. We determined prospectively the impact of weight loss on iron status parameters, serum hepcidin, inflammation, and dietary iron in 20 obese premenopausal females 6 months after restrictive bariatric surgery. At baseline, the presence of iron depletion was high with 45% of the women having serum transferrin receptor (sTfR) >28.1 nmol/l. Differences between baseline and 6 months after surgery for BMI (47.56 vs. 39.55 kg/m(2); P < 0.0001), C-reactive protein (CRP) (10.83 vs. 5.71 mg/l; P < 0.0001), sTfR (29.97 vs. 23.08 nmol/l; P = 0.001), and serum hepcidin (111.25 vs. 31.35 ng/ml; P < 0.0001) were significantly lower, whereas hemoglobin (Hb) (12.10 vs. 13.30 g/dl; P < 0.0001) and hematocrit (Hct) (36.58 vs. 38.78%; P = 0.001) were significantly higher. Ferritin and transferrin saturation (Tsat) showed minimal improvement at follow-up. At baseline, hepcidin was not correlated with sTfR (r = 0.02); however, at follow-up, significant correlations were found (r = -0.58). Change in interleukin-6 (IL-6) from baseline was marginally associated with decreased log serum hepcidin (Δ IL-6: ß = -0.22; P = 0.15), whereas change in BMI or weight was not. No significant difference in dietary iron was noted after surgery. Weight loss in obese premenopausal women is associated with reduced serum hepcidin and inflammation. Reduction in inflammation and hepcidin likely allow for enhanced dietary iron absorption resulting in an improved functional iron profile.

Laparoscopic adjustable gastric banding for the treatment of adolescent morbid obesity in the United States: a safe alternative to gastric bypass.

BACKGROUND: Morbid obesity (MO) has reached epidemic proportions and is a major health problem in developed nations. In the adolescent with MO, early intervention can minimize obesity-related comorbidities, avoid premature mortality, improve quality of life, and prevent obesity-related diseases as these patients mature into adulthood. The primary surgical treatment of adolescent patients meeting National Institutes of Health criteria for bariatric surgery has been the gastric bypass (GB). Although GB has led to weight loss and improvement of comorbid conditions, concerns remain over the high incidence of postoperative complications and life-style-altering long-term sequelae of gastrointestinal tract reconstruction. Based on the excellent results from international adult series as well as the authors' own experience of more than 300 adult patients, laparoscopic adjustable gastric banding (LAGB) as an alternative to GB to eligible adolescents was offered. METHODS: After medical, psychologic, and nutritional screening, 4 patients (ages 17-19 years) with a body mass index of 40 or more (range, 40-61) who failed medical attempts at weight loss were selected for LAGB. RESULTS: The operative time was 40 to 90 minutes. All patients were discharged on the day of surgery. There were no early complications. One patient had cholecystitis 6 months after surgery requiring laparoscopic cholecystectomy. For the 4 patients, the amount of excess weight loss was 57% at 30 months, 34% at 12 months, 87% at 7 months, and 15% at 4 months, respectively. CONCLUSIONS: In this preliminary series of the US experience in the use of LAGB for the management of adolescents with MO, the lack of operative morbidity, short operative time/hospital stay, and encouraging initial weight loss mirror the adult experience and illustrate that the LAGB is a safe and effective alternative to GB. These encouraging results support further evaluation of LAGB as a surgical option in a comprehensive adolescent weight loss program.

Diminished hepatic expression of the HNF-6 transcription factor during bile duct obstruction.

Hepatocyte nuclear factor 6 (HNF-6) is a member of the one cut family of transcription factors and potentially regulates expression of numerous target genes important for hepatocyte function. In the liver, HNF-6 is expressed not only in hepatocytes, but also in biliary epithelial cells (BEC). To evaluate the in vivo function of HNF-6, we examined the hepatic expression pattern of HNF-6 messenger RNA (mRNA) and protein after bile duct ligation (BDL)-mediated liver injury. We found that HNF-6 protein levels in BEC and hepatocytes were diminished within 15 hours of BDL injury and remained suppressed through the fifth day of injury. The onset of BEC proliferation in response to bile duct obstruction was associated with diminished HNF-6 protein levels. To maintain hepatic HNF-6 protein levels during BDL liver injury, we used mouse tail vein injections with recombinant adenovirus expressing HNF-6 complementary DNA (cDNA) (AdH6). We found that maintaining hepatic HNF-6 levels with AdH6 infection resulted in significant decreases in BEC proliferation at 15 and 24 hours after biliary obstruction compared with adenovirus control. Our results showed that HNF-6 expression is diminished in BEC and hepatocytes and that maintaining hepatic HNF-6 expression hinders the normal biliary proliferative response to bile duct injury. This suggests that diminished hepatic HNF-6 levels are required for repair in response to biliary injury and that it regulates expression of genes that possess differentiation-specific function that are inhibitory to proliferation. In conclusion, we propose a biologic role for diminished HNF-6 protein levels in bile duct disease.

In vivo regulation of murine CYP7A1 by HNF-6: a novel mechanism for diminished CYP7A1 expression in biliary obstruction.

Disruption of the enterohepatic bile acid circulation during biliary tract obstruction leads to profound perturbation of the cholesterol and bile acid metabolic pathways. Several families of nuclear receptor proteins have been shown to modulate this critical process by regulating hepatic cholesterol catabolism and bile acid synthesis through the transcriptional control of cholesterol 7-alpha hydroxylase (CYP7A1). Hepatocyte nuclear factor (HNF) 6 (also known as OC-1) is a member of the ONECUT family of transcription factors that activate numerous hepatic target genes essential to liver function. We have previously shown that hepatic expression of mouse HNF-6 messenger RNA (mRNA) and protein significantly decrease following bile duct ligation. Because CYP7A1 contains potential HNF-6 binding sites in its promoter region, we tested the hypothesis that HNF-6 transcriptionally regulates CYP7A1. Following bile duct ligation, we demonstrated that diminished HNF-6 mRNA levels correlate with a reduction in CYP7A1 mRNA expression. Increasing hepatic levels of HNF-6 either by infection with recombinant adenovirus vector expressing HNF-6 cDNA by growth hormone treatment leads to an induction of CYP7A1 mRNA. To directly evaluate if HNF-6 is a transcriptional activator for CYP7A1, we used deletional and mutational analyses of CYP7A1 promoter sequences and defined sequences -206/-194 to be critical for CYP7A1 transcriptional stimulation by HNF-6 in cotransfection assays. In conclusion, the HNF-6 protein is a component of the complex network of hepatic transcription factors that regulates the expression of hepatic genes essential for bile acid homeostasis and cholesterol/lipid metabolism in normal and pathological conditions.

Electron beam CT scan is a valuable and safe imaging tool for the pediatric surgical patient.

PURPOSE: Electron beam computed tomography (EBCT) is a relatively new technology that has been used primarily to detect coronary artery calcification in adult patients. EBCT has several potential advantages over traditional CT: (1) fast acquisition times resulting in less need for sedation, (2) decreased radiation exposure, and (3) robust software enabling real-time interactive 3-dimensional visualization of anatomic relationships. In this series of case reports, the authors describe their initial experience with the use of EBCT in pediatric noncardiac imaging. METHODS: Children with a variety of thoracic and abdominal disease processes were evaluated by EBCT. RESULTS: All patients underwent EBCT scanning without the need for sedation, and 3-dimensional images of the data sets were rendered in minutes after their acquisition. The diagnostic images provided equivalent spatial resolution to the multislice CT scanner but without motion artifacts and lower radiation exposure. CONCLUSIONS: EBCT is a safe, effective, and user- and patient-friendly alternative to traditional CT in the care of pediatric surgical diseases. The diagnostic yield of EBCT will continue to improve with new technologic advances and clinical experience.