Peroral Endoscopic Myotomy (POEM) in Children: A State of the Art Review.

Esophageal achalasia is a relatively rare disease in children that has been treated with balloon dilatation, botulinum toxin injection, and Heller myotomy. Peroral endoscopic myotomy (POEM) is another treatment that has been successfully employed to treat adults with achalasia for over a decade and has been increasingly used in children. This State of the Art Review from the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Endoscopy Committee reviews the current literature in pediatric POEM including the technique, success rate, complications as well as training guidelines. Though there is limited data, POEM in children has shown encouraging success rates and with further study may become the mainstay of pediatric achalasia treatment.

Upper Gastrointestinal Endoscopy in Adolescents With Severe Obesity Before Vertical Sleeve Gastrectomy.

OBJECTIVES: Esophagogastroduodenoscopy (EGD) is often performed to evaluate for mucosal and anatomical abnormalities before vertical sleeve gastrectomy (SG). Little is known, however, about how prebariatric EGD in adolescents influences clinical management or outcome. Our aim was to assess if an abnormal prebariatric EGD resulted in interventions or modification of bariatric surgery. METHODS: We performed a retrospective cohort study of adolescents undergoing evaluation for bariatric surgery. We obtained demographic and anthropometric data in addition to EGD findings, biopsy pathology, gastrointestinal symptoms, and surgical outcomes. An EGD was considered abnormal if either abnormal gross findings or abnormal pathology was reported. Patients were followed until a 6-week postop visit. RESULTS: Of 134 patients presenting for evaluation, 94 (70%) underwent preoperative EGD. Fifty-one (54%) had a normal EGD and 43 (46%) had EGD abnormalities including 7 with an anatomical abnormality and 36 with mild mucosal abnormalities. Among patients with EGD abnormalities, 22% received medical intervention including proton pump inhibitor (PPI) administration (n = 10) and Helicobacter pylori eradication (n = 11). GI symptoms were the only predictor of EGD abnormalities (odds ratio [OR] 4.9: 95% confidence interval [CI] 1.6-15.0; P < 0.001). No factors predicted likelihood of a post-EGD intervention. An abnormal EGD did not correlate with any postoperative complications. CONCLUSIONS: In this cohort of adolescents undergoing evaluation for SG, 46% had an abnormal EGD, of which 22% received a medical intervention. Symptoms were the only predictor of EGD abnormalities. Abnormal EGD findings were not associated with modification of the surgery or any adverse outcome.

Pediatric Nonalcoholic Fatty Liver Disease in New York City: An Autopsy Study.

OBJECTIVE: To assess the prevalence and severity of nonalcoholic liver disease (NAFLD) in children in a diverse population sample in New York City. STUDY DESIGN: Liver specimens were examined from children 2-19 years old who died of unexpected causes within 48 hours of medical presentation and underwent autopsy in New York City from 2005 to 2010. Records were reviewed for age, sex, weight, height, and race. Two hepatopathologists evaluated each liver specimen to determine pathologic diagnosis. RESULTS: The final study cohort (n = 582) was 50% black, 33% Hispanic, 12% white, 3% Asian, and 2% other; 36% had a body mass index >85%. There were 26 cases of NAFLD (4.5%) of which 10 had nonalcoholic steatohepatitis (1.7%). There were no cases with severe fibrosis or cirrhosis. One percent (3/290) of black children had NAFLD and none had nonalcoholic steatohepatitis. White and Hispanic children had the highest percentages of NAFLD at 8.3% and 7.9%, respectively. In multiple logistic regression models, we observed that body mass index z-score (P < .001) was associated with NAFLD, and that white (P = .003) and Hispanic (P = .005) children had higher odds of having NAFLD compared with black children. CONCLUSIONS: This review of liver tissue demonstrates a lower prevalence and severity of NAFLD in black children compared with the general obese pediatric population. Hispanic children did not have a significantly increased rate of NAFLD compared with white children, most likely related to the large proportion of Caribbean Hispanic children in New York City.

Nonalcoholic fatty liver disease in children.

PURPOSE OF REVIEW: Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of liver disease in children from the developed world. The purpose of this review is to provide both a focused overview of pediatric NAFLD as well as a summary of the most recent advancements in the field. RECENT FINDINGS: Pediatric NAFLD is an underdiagnosed condition which can result in significant liver injury including cirrhosis. Although liver biopsy remains the standard for diagnosis and monitoring disease activity, several noninvasive biomarkers and imaging techniques hold significant promise. Dietary constituents, the intestinal bacterial flora, and sex hormones have been implicated as modulators of disease activity. NAFLD predisposition runs strongly in families and an allele in the PNPLA3 gene has shown a strong association with liver steatosis and hepatic inflammation. Treatment for pediatric NAFLD remains diet and exercise, but vitamin E may be a helpful adjunct. SUMMARY: Pediatric NAFLD shares many features with its adult counterpart but is a distinct entity which requires independent investigation. Our understanding of NAFLD in terms of epidemiology and risk factors has improved considerably but significantly more investigation is required to unravel its pathophysiology and identify novel therapeutic targets.

Toll-like receptor 4 and hepatic fibrogenesis.

Inflammation is strongly associated with chronic hepatic injury and the ensuing wound-healing process. Recent evidence from mouse models and human studies implicates Toll-like receptors (TLRs) as important regulators of the inflammatory response and a functional link between inflammation and fibrosis in the chronically injured liver. Here, we review mechanisms by which TLR4 and TLR4 ligands from the intestinal microbiota contribute to hepatic injury, inflammation, hepatic stellate cell activation, and fibrosis.

Effect of TSH on Non-Alcoholic Fatty Liver Disease (NAFLD) independent of obesity in children of predominantly Hispanic/Latino ancestry by causal mediation analysis.

BACKGROUND: Nonalcoholic Fatty Liver Disease (NAFLD) is a common co-morbidity of obesity. Elevated TSH levels (eTSH), also associated with obesity, may contribute to the dysmetabolic state that predisposes to NAFLD. OBJECTIVE: To assess the relationship between TSH levels and NAFLD in children with biopsy-proven NAFLD compared to controls. DESIGN AND METHODS: In this retrospective study of children with biopsy-proven NAFLD and age-matched controls, the association of eTSH with NAFLD was investigated and the role of TSH as a mediator between obesity and NAFLD was assessed. RESULTS: Sixty-six cases and 4067 controls (69.7 vs 59% Hispanic/Latino ancestry, p = 0.1) of the same age range seen in the same time duration at an urban Children's Hospital were studied. Children with NAFLD were more likely to be male (74.6 vs 39.4%, p < 0.001), have higher modified BMI-z scores (median 2.4 (IQR 1.7) vs 1.9 (IQR 1.7), p < 0.001), and abnormal metabolic parameters (TSH, ALT, HDL-C, non-HDL-C, and TG). Multivariate analyses controlling for age, sex and severity of obesity showed significant association between the 4th quartile of TSH and NAFLD. Causal mediation analysis demonstrates that TSH mediates 33.8% of the effect of modified BMI-z score on NAFLD. This comprises of 16.0% (OR = 1.1, p = 0.002) caused by the indirect effect of TSH and its interaction with modified BMI-z, and 17.7% (OR = 1.1, p = 0.05) as an autonomous effect of TSH on NAFLD. Overall, 33.8% of the effect can be eliminated by removing the mediator, TSH (p = 0.001). CONCLUSIONS: The association of eTSH and biopsy-proven NAFLD is demonstrated in children of Hispanic/Latino ancestry. Further, a causal mediation analysis implicates an effect of TSH on NAFLD, independent of obesity.

Use of Anesthesia for Imaging Studies and Interventional Procedures in Children.

Ongoing investigation from the Pediatric Anesthesia NeuroDevelopment Assessment (PANDA) study hopes to examine the long-term effect on cognitive and language development of a single anesthetic exposure in children undergoing inguinal hernia repair. The fifth PANDA Symposium, held in April 2016, continued the mission of previous symposia to examine evidence from basic science and clinical studies on potential neurotoxic effects of anesthetics on developing brain. At the 2016 Symposium, a panel of specialists from nonsurgical pediatric disciplines including anesthesiology, radiology, neurology, gastroenterology, oncology, cardiology, and critical care reviewed use of anesthesia in their practices, including how concern over possible neurodevelopmental effects of early childhood anesthetic exposure has changed discussion with patients and families regarding risks and benefits of imaging studies and interventional procedures involving sedation or anesthesia. This paper summarizes presentations from nonsurgical pediatric specialists at the 2016 PANDA Symposium.

Caring for children with NAFLD and navigating their care into adulthood.

NAFLD is the most common chronic liver disease in children and adults, with its prevalence closely associated with obesity and other features of the metabolic syndrome. As young adults with NAFLD transition from the paediatric care environment to adult services, establishing a coordinated model of transition to ensure ongoing and appropriate care is critical. Enabling a smooth transfer begins with an understanding of the key differences between paediatric and adult NAFLD as well as the psychosocial factors that affect older adolescents. This Review summarizes the literature on paediatric NAFLD from the past two decades with a focus on the differences in epidemiology, pathology, pathophysiology and treatment that are relevant to clinicians who transition paediatric patients to adult care. An integrated model, which employs a team of adult and paediatric providers who can address the psychosocial, cognitive and logistical challenges of transition, provides the best opportunity for a seamless and coordinated transfer to adult care.

Advances in pediatric nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) has emerged as the most common cause of pediatric liver disease in the developed world. Children have a form of NAFLD that is pathologically distinct from adults. Although NAFLD remains a pathologic diagnosis, biomarkers and imaging studies hold promise as noninvasive means of both establishing the diagnosis and following the disease course. Significant advancements have recently been made in genetics, pathophysiology, and the treatment of NAFLD. The purpose of this article is to provide a clinically relevant review of pediatric NAFLD with an emphasis on recent developments in the field.