Extreme pediatric obesity: weighing the health dangers.
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Adolescent↗
Biomedical subjects
Thomas H Inge
Publications and source records attributed to Thomas H Inge.
Bariatric surgery for morbidly obese adolescents: is there a rationale for early intervention?
Obesity is one of the most common metabolic disorders affecting the US population: 31% of adults and 16% of adolescents now meet the criteria for obesity. Similar to the rising prevalence of morbid obesity in adults, the prevalence of more severe obesity is also increasing in pediatric patients. The most effective treatment for morbid obesity is bariatric surgery, a procedure most commonly performed in the fifth and sixth decades of life. Although it is clear that rapid, profound weight loss can significantly improve multiple comorbid conditions in adults, including disordered carbohydrate metabolism, obstructive sleep apnea, and cardiovascular risk factors, it is not clear to what degree similar comorbidities are affected in adolescents undergoing surgical weight loss. In this paper, the indications, contraindications, and early surgical outcomes of gastric bypass surgery for morbidly obese adolescents are reviewed, and important directions for future research are discussed.
Adolescent↗
Bariatric surgery in adolescents: an update.
Bariatric surgery, although not a cure for obesity, can help selected extremely obese adolescents achieve significant weight loss and improvement of obesity-related comorbidities, in conjunction with continued dietary and behavioral interventions. This article summarizes the current guidelines for selection of adolescent candidates for bariatric surgery and discusses the types of bariatric procedures presently available for this age group. Data on the complications and outcomes of bariatric surgery in this special population are reviewed.
Adolescent↗
One-year outcomes of Roux-en-Y gastric bypass for morbidly obese adolescents: a multicenter study from the Pediatric Bariatric Study Group.
BACKGROUND/PURPOSE: Little is known about the metabolic outcomes of adolescent bariatric surgery. We report changes in weight, metabolic profile, and types of complications seen in a multicenter cohort. METHODS: One-year outcomes were included. For weight loss comparisons, a nonsurgical cohort (n = 12) was used. The primary outcome was weight change (n = 30) and secondary outcomes were metabolic variables (n = 24) and complications (n = 36). Data were analyzed using signed rank or paired t tests. RESULTS: Mean body mass index fell 37% (from 56.5 preoperatively to 35.8 kg/m2; P < .001) in surgical patients and 3% (from 47.2 to 46 kg/m2; P = NS) in nonsurgical patients. Surgical patients showed significant improvements in triglycerides (-65 mg/dL), total cholesterol (-28 mg/dL), fasting blood glucose (-12 mg/dL), and fasting insulin (-21 microM/mL]). Improvement in high-density lipoprotein cholesterol (-3.9 mg/dL) and low-density lipoprotein cholesterol (-8.8 mg/dL) was not statistically significant. Sixty-one percent of surgical patients had no complications. Of 15 patients with complications, 9 had minor complications with no long-term sequelae, 4 had at least 1 moderate complication with sequelae for at least 1 month and 2 had at least 1 severe medical complication with long-term consequences (including beriberi and death). There were no perioperative deaths or other severe surgical complications in this series. CONCLUSIONS: Postoperatively, adolescents lose significant weight and realize major metabolic improvements. The complication profile compares favorably to severely obese (body mass index >40 kg/m2) adults; however, small sample size precludes calculation of complication rates. Although there are considerable risks of bariatric surgery, early experience suggests that risks are offset by health benefits.
Adolescent↗
The effect of a right-sided aortic arch on outcome in children with esophageal atresia and tracheoesophageal fistula.
UNLABELLED: During repair of an esophageal atresia with tracheoesophageal fistula (EA/TEF), a right-sided aortic arch (RAA) presents a technical challenge. We reviewed our experience with EA/TEF focusing on the impact of RAA. METHODS: A retrospective review of patients with EA/TEF at our institution from 1990 to 2004 was performed. Of 61 patients, 53 had a left aortic arch (LAA) and 8 had RAA. RESULTS: The mean gestational age and birth weight were similar between patients with LAA and RAA. There were more vascular rings in patients with RAA than with LAA (37.5% vs 3.8%, P = .009). A preoperative echocardiogram correctly identified the location of the arch in all with LAA but only 62.5% of those with RAA. Operative complications occurred in 25% of patients with RAA and 11% of patients with LAA. CONCLUSIONS: Management of a child with RAA and EA/TEF is technically challenging. Preoperative identification of the great vessel anomalies may impact operative decision making. Therefore, careful diagnostic evaluation of a patient with an aortic arch that cannot be easily defined by ECHO should be considered before definitive repair.
Aorta, Thoracic↗
Nonoperative management of pectus carinatum.
BACKGROUND: Although surgery has been the mainstay of treatment of chondrogladiolar pectus carinatum (PC), several authors have advocated the benefits of nonoperative approaches to induce chest wall remodeling. Based on our initial success with compression bracing, we have integrated this modality into our treatment algorithm. METHOD: We reviewed the charts of all patients treated for PC at our pediatric hospital between 1997 and 2004. Patients were managed with observation, operative repair, and orthotic bracing that provides continuous anteroposterior sternal compression. The brace was worn for 14 to 16 hours per day until linear growth was complete or for a minimum of 2 years. RESULTS: One hundred patients were diagnosed with PC. Fifty-seven patients had no treatment and were monitored. Twenty-nine patients were fitted with a brace. Of these 29 patients, 3 were noncompliant, resulting in a compliance rate of 90%. Of the remaining brace patients, all have had positive outcomes with no observed complications. Seventeen patients underwent surgical repair. Their outcomes were also positive with no major complications. CONCLUSION: Our findings clearly demonstrate that compression bracing is a safe and effective treatment for children with chondrogladiolar PC. We currently offer this approach as a first-line treatment, reserving surgery for patients who are noncompliant and those who fail the nonoperative modality.
Adolescent↗
Adolescent obesity and bariatric surgery.
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Adolescent↗
Nutritional consequences of bariatric surgery.
PURPOSE OF REVIEW: Bariatric surgery is being increasingly used to help treat morbidly obese adults and adolescents. As a greater percentage of this population faces a lifetime of living with surgically altered gastrointestinal anatomy and physiology, increased awareness of the nutritional consequences is critical for all health care practitioners, as many of these patients may be lost to follow-up and can present with significant nutritional complications years after surgery. RECENT FINDINGS: Nutritional deficiencies can occur after bariatric surgery, although to a lesser degree after restrictive procedures. Risk may increase over time, perhaps due to poor compliance with supplementation, continued inadequate intake and/or ongoing malabsorption. Adolescent patients may be at greater risk due to poor compliance and longer life span. Nutritional monitoring and supplementation among bariatric programs has been widely variable and few prospective studies of outcomes exist. SUMMARY: Bariatric surgery can carry significant risk of nutritional complications. Compliance with dietary recommendations should be monitored and encouraged, with annual screening for selected deficiencies. Prospective longitudinal research is needed to identify the true prevalence and significance of nutritional deficiency in these patients and to determine optimum dietary recommendations.
Bariatric Surgery↗
Health-related quality of life and depressive symptoms in adolescents with extreme obesity presenting for bariatric surgery.
OBJECTIVE: We sought to document health-related quality of life (HRQoL) impairment and depressive symptomatology in adolescents with extreme obesity considering surgical weight loss. STUDY DESIGN: A retrospective review of clinical data was conducted for 33 consecutive extremely obese adolescents presenting for evaluation at a bariatric surgery program for adolescents. Adolescents completed the PedsQL and the Beck Depression Inventory. Mothers completed the parent-proxy PedsQL and the Child Behavior Checklist. RESULTS: HRQoL scores from both informants were markedly impaired relative to published norms on healthy youth. Moderate agreement was found for self-reported and parent-proxy HRQoL. Approximately 30% of youth met criteria for clinically significant depressive symptoms when based on self-report and 45% of youth when based on mother report. Only 21% of youth were currently engaged in some form of psychological treatment (eg, medication or therapy). CONCLUSIONS: The day-to-day life of adolescents with extreme obesity seeking bariatric surgery is globally and severely impaired. However, only some of these adolescents demonstrate clinically significant levels of depressive symptomatology. These data will be critical to the development of more informed patient selection criteria and more efficacious treatment paradigms for this vulnerable pediatric subgroup.
Adolescent↗
A critical appraisal of evidence supporting a bariatric surgical approach to weight management for adolescents.
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Adolescent↗
Managing bariatric patients in a children's hospital: radiologic considerations and limitations.
As the increasing prevalence of pediatric obesity and its associated risks gain national attention, adolescent bariatric surgery is gradually gaining acceptance as a viable weight loss tool for some severely obese adolescents. Obese patients often exceed the capacity limits of most radiological devices used for imaging. Because the radiological evaluation often plays a crucial role in the management of these patients, it is important for pediatric surgeons and radiologists to be aware of the special challenges and alternative algorithms for radiological evaluation. This review outlines and illustrates these considerations and limitations. Herein the authors discuss these topics within the context of characteristic bariatric patient profiles and the Roux-en-Y gastric bypass procedure, currently the authors' standard operative approach.
Adolescent↗
Sharp recanalization of an esophageal occlusion after repair of esophageal atresia and tracheoesophageal stricture.
Esophageal atresia with an associated tracheoesophageal fistula is a congenital anomaly requiring surgical correction. Recurrent stricture is the most common complication of surgical repair and is usually treated with mechanical dilation. Rarely, a recurrent completely obstructive stricture can cause obliteration of the anastomosis, preventing passage of a wire for dilation. This condition requires operative correction. In the case presented herein, the obliterated esophageal lumen from an obstructing stricture was operatively corrected with use of a novel transluminal technique. The obstruction was successfully crossed with a modified Chiba biopsy needle covered in a dilator through a gastrostomy. After subsequent balloon dilation, the lumen has remained patent for more than 3 years without significant complication.
Catheterization↗
Attitudes of bariatric surgeons concerning adolescent bariatric surgery (ABS).
BACKGROUND: As the number of adolescents with clinically severe obesity has grown, so too have the number of adolescents seeking bariatric surgery. METHODS: The membership of the ASBS was contacted by e-mail with a 14-question survey to ascertain plans for development of adolescent bariatric surgery (ABS) programs. Results were tabulated and expressed as a percentage of total respondents. RESULTS: Of the 92 respondents, most (84%) performed >50 adult bariatric procedures per year. Over half (53%) had performed ABS. Nearly half (45%) had performed <10 ABS cases within the last year, and 70% were planning ABS in the upcoming year. 42% reported that they have already or were in the process of developing an adolescent bariatric treatment program with pediatric specialists in their community. The vast majority (84%) of respondents was willing to participate in a multi-center collection of outcomes data, and 65% reported having dedicated personnel for clinical data collection. CONCLUSIONS: There is increasing interest in developing ABS programs. Despite the perceived need for such services, information is lacking in the adolescent age group to guide decisions regarding optimal patient selection, choice of operation, and postoperative management. Rigorous evaluation of the outcomes of this intervention with detailed prospective data collection is needed to support decision-making regarding use of bariatric surgery for adolescents with morbid obesity.
Adolescent↗
Surgical approach to adolescent obesity.
The obesity epidemic has resulted in the premature onset of traditionally adult diseases in children and adolescents. Bariatric surgery can be used to achieve significant weight loss and resolution of major and minor comorbidities of obesity. It is not known, however, whether weight loss or comorbidity resolution after adolescent bariatric surgery is sustainable over the lifetime, given the powerful biologic mechanisms that are thought to play an important role in development of severe obesity in these patients. There are also concerns about whether bariatric procedures may have unanticipated adverse nutritional consequences when applied in adolescence. Principles of adolescent medicine and evidence from adult bariatric surgical studies can be used to rationally guide the application of bariatric procedures to a group of young patients wither serious medical and psychological comorbidities of severe obesity. Given the immediacy of some of the medical and psychosocial complications, impaired quality of life, and the added health care costs of adolescent obesity, adolescent bariatric surgery programs should be developed to meet these needs. Adolescent bariatric surgery programs should have expertise that enables them to assess and meet the unique medical, cognitive, physiological, and psychosocial needs of the adolescent. Indications for operation during adolescence should be conservative until appropriately designed clinical studies have demonstrated the safety and efficacy of these techniques applied to adolescents.
Adolescent↗
Beriberi after gastric bypass surgery in adolescence.
We report three cases of dry beriberi in adolescents who underwent gastric bypass surgery for clinically severe obesity. The key to successful treatment of this problem lies in prompt recognition and thiamine supplementation.
Adolescent↗
A multidisciplinary approach to the adolescent bariatric surgical patient.
PURPOSE: Pediatric obesity is an epidemic in the United States. As of yet, no surgical programs specifically dedicated to the management of clinically severely obese adolescents exist. The purpose of this report was to describe the establishment and early experience of a multidisciplinary Comprehensive Weight Management Center (CWMC) in a free-standing children's hospital. METHODS: With input from an ethicist, gastroenterologist, pulmonologist, endocrinologist, and adolescent medicine physician, guidelines for patient selection, evaluation, and bariatric surgical management were developed and implemented. Roux-en-Y gastric bypass (RYGBP) surgery has been performed using open and laparoscopic techniques. RESULTS: The average age and body mas index (BMI) for 79 patients referred to the CWMC has been 16 years and 54 kg/m2, for boys and 17 years and 51 kg/m2 for girls. Twenty-five percent have been considered appropriate for RYGBP, 25% have not met criteria for surgery, and 50% are being evaluated. Ten patients who have undergone RYGBP had comorbidities of their obesity, including type 2 diabetes mellitus (DM), obstructive sleep apnea syndrome (OSAS), pulmonary embolism, hypertension, dyslipidemias, and depression. Clinically significant weight loss with resolution of comorbidities has occurred in all patients. Significant complications have included leak from the gastric remnant, DVT, partial roux limb obstruction, and micronutrient deficiency. CONCLUSIONS: RYGBP is an effective means to treat obesity-related morbidity in the adolescent. A multidisciplinary team of pediatric specialists is needed for optimal preoperative decision making and postoperative management. Results have been satisfactory and justify a clinical trial to confirm the safety and efficacy of bariatric surgery in the adolescent population.
Adolescent↗
WP744 is a novel anthracycline with enhanced activity against neuroblastoma.
BACKGROUND: Doxorubicin (Dox) is one of the most useful chemotherapeutic agents for patients with advanced neuroblastoma (NB). A series of Dox analogs with bulky substitutions at the C-4' at amino-sugar have been designed to impair interactions between the drug and P-glycoprotein (P-gp), a multidrug drug resistance (MDR) transporter. Two analogs, WP744 and WP769, were selected and their biological properties were compared with Dox and the daunorubicin-based bisintercalator WP631. These novel Dox analogs may have antitumor activity beyond MDR evasion. MATERIALS AND METHODS: MTT assays were used to determine the potency of three structurally altered Dox analogs against a panel of NB cell lines with and without amplification of the MYCN oncogene. Flow cytometry (FCM) was used to analyze apoptosis and cell death and phenotype cell lines for surface expression of the MDR protein P-gp. RESULTS: The 4'-O-benzylated Dox analogs WP744 and WP769 were 2 to 36 times more cytotoxic than Dox for the NB cell lines tested. The bis-intercalator WP631, despite its significantly greater affinity for DNA (>10,000-fold), was generally less potent against NB than Dox. In Tet21N cells, which conditionally express MYCN, greatly enhanced (nearly 6-fold) sensitivity to WP744 killing was seen when this oncogene was induced, while enhanced sensitivity to Dox was more modest (2-fold) under MYCN-induced conditions. Treatment with WP744 also resulted in enhanced apoptosis. Apoptosis, but not cell death, in response to either WP744 or Dox was inhibited by caspase inhibition, suggesting that cell death was not completely dependent upon apoptosis. P-gp expression was detectable on five NB cell lines. WP744 was more cytotoxic than Dox against both P-gp+ and P-gp- cells. CONCLUSIONS: These findings demonstrate that 4'-O-benzylation of the anthracycline molecule significantly enhances potency against NB independent of MYCN status, caspase activation, and MDR phenotype. However, WP744 demonstrated a unique synergy with MYCN for cell killing when this oncogene was specifically induced. WP744 may be more useful than conventional agents for the treatment of tumor clones that harbor defects in apoptotic pathways, in those with MYCN amplification, and in those with drug-resistant tumors.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Nuclear factor-kappa B and apoptosis inducing factor activation by doxorubicin analog WP744 in SH-SY5Y neuroblastoma cells.
BACKGROUND: Neuroblastoma (NB) is one of the most common extracranial tumors in children. The chemotherapeutic doxorubicin (Dox) remains a mainstay for treatment. However, the emergence of drug resistance seriously limits treatment efficacy. Numerous Dox analogues have been designed to more potently kill drug naive as well as drug-resistant NB. We have shown that the Dox analogue WP744 has enhanced the killing activity of NB compared to Dox, but the mechanism(s) of action is unclear. MATERIALS AND METHODS: MTT assays were used to characterize the relative potencies of Dox and WP744 against SH-SY5Y NB cells. Western blotting was used to assess activation of caspases-3, -9, anti-poly (ADP-ribose) polymerase, p53, p21, AIF, IkappaBalpha, Bcl-2, Bcl-X(L), and cyclin D1. Nuclear factor (NF-kappaB) activation was assessed by electrophoretic mobility shift assay. RESULTS: After WP744 treatment, enhanced apoptosis and cell death were seen, associated with cleavage of caspases-3, -9, and anti-poly (ADP-ribose) polymerase, an increase in p53 protein levels, and the induction of p21. WP744 also induced translocation of apoptosis-inducing factor from mitochondria to nuclei. Most remarkably, WP744 was 50-fold more potent than Dox in activating NF-kappaB. WP744 treatment also resulted in the down-regulation of expression of downstream targets of NF-kappaB. CONCLUSIONS: WP744 is a novel Dox analogue that triggers apoptosis and cell killing by activation of proapoptotic mediators in NB cells. Enhanced cytotoxicity of this novel drug compared with Dox may be related to more effective activation of NF-kappaB and apoptosis-inducing factor in tumor cells.
Anthracyclines↗