The natural history of primary sclerosing cholangitis in 781 children: A multicenter, international collaboration.

There are limited data on the natural history of primary sclerosing cholangitis (PSC) in children. We aimed to describe the disease characteristics and long-term outcomes of pediatric PSC. We retrospectively collected all pediatric PSC cases from 36 participating institutions and conducted a survival analysis from the date of PSC diagnosis to dates of diagnosis of portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or death. We analyzed patients grouped by disease phenotype and laboratory studies at diagnosis to identify objective predictors of long-term outcome. We identified 781 patients, median age 12 years, with 4,277 person-years of follow-up; 33% with autoimmune hepatitis, 76% with inflammatory bowel disease, and 13% with small duct PSC. Portal hypertensive and biliary complications developed in 38% and 25%, respectively, after 10 years of disease. Once these complications developed, median survival with native liver was 2.8 and 3.5 years, respectively. Cholangiocarcinoma occurred in 1%. Overall event-free survival was 70% at 5 years and 53% at 10 years. Patient groups with the most elevated total bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis had the worst outcomes. In multivariate analysis PSC-inflammatory bowel disease and small duct phenotypes were associated with favorable prognosis (hazard ratios 0.6, 95% confidence interval 0.5-0.9, and 0.7, 95% confidence interval 0.5-0.96, respectively). Age, gender, and autoimmune hepatitis overlap did not impact long-term outcome. CONCLUSION: PSC has a chronic, progressive course in children, and nearly half of patients develop an adverse liver outcome after 10 years of disease; elevations in bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis can identify patients at highest risk; small duct PSC and PSC-inflammatory bowel disease are more favorable disease phenotypes. (Hepatology 2017;66:518-527).

Motility, digestive and nutritional problems in Esophageal Atresia.

Esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) is a rare congenital malformation. Digestive and nutritional problems remain frequent in children with EA both in early infancy and at long-term follow-up. These patients are at major risk of presenting with gastroesophageal reflux and its complications, such as anastomotic strictures. Esophageal dysmotility is constant, and can have important consequences on feeding and nutritional status. Patients with EA need a systematic follow-up with a multidisciplinary team.

Barrett esophagus and esophagojejunal anastomotic stenosis as complications of esophagogastric disconnection in children with esophageal atresia.

Total esophagogastric disconnection (TED) is an alternative surgical procedure in resistant gastroesophageal reflux disease. We report 2 severe, not yet described long-term complications of TED occurring in 4 children with a history of esophageal atresia. Three children presented with stenosis of the esophagojejunal anastomosis 5 months to 9 years after TED, requiring repeated dilations associated with mitomycin C application in one of them. Barrett esophagus was observed in 3 children 8 to 9 years after TED. Careful long-term clinical and endoscopic follow-up of children who underwent TED is required.

Four cancer cases after esophageal atresia repair: Time to start screening the upper gastrointestinal tract.

Esophageal atresia (EA) is one of the most common congenital digestive malformations and requires surgical correction early in life. Dedicated centers have reported survival rates up to 95%. The most frequent comorbidities after EA repair are dysphagia (72%) and gastroesophageal reflux (GER) (67%). Chronic GER after EA repair might lead to mucosal damage, esophageal stricturing, Barrett's esophagus and eventually esophageal adenocarcinoma. Several long-term follow-up studies found an increased risk of Barrett's esophagus and esophageal carcinoma in EA patients, both at a relatively young age. Given these findings, the recent ESPGHAN-NASPGHAN guideline recommends routine endoscopy in adults born with EA. We report a series of four EA patients who developed a carcinoma of the gastrointestinal tract: three esophageal carcinoma and one colorectal carcinoma in a colonic interposition. These cases emphasize the importance of lifelong screening of the upper gastrointestinal tract in EA patients.

Modulation of host defence against bacterial and viral infections by omega-3 polyunsaturated fatty acids.

OBJECTIVES: Although n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) are used widely in the treatment of chronic inflammatory diseases, their effect in infectious disease requires a particular attention. METHODS: The present article discusses their anti-inflammatory and immune properties involved in the host defence and presents a systematic review of the effects of their oral administration on the prevention and outcome of experimental and clinical infections. RESULTS: At a dose corresponding to an human dose of 500 mg/day, n-3 LC-PUFAs intake is beneficial against experimental infections caused by extracellular pathogens including Streptococcus pneumoniae, Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus by reducing inflammation, and reduces the incidence of pneumococcal infections in the elderly, but at 2-4-fold higher doses as occurs in some human intervention and/or during long-term it becomes detrimental in intestinal infections with Citrobacter rodentium or Helicobacter hepaticus by exacerbating anti-inflammatory response. They are also harmful against infections caused by intracellular pathogens as Mycobacterium tuberculosis, Salmonella, Influenza virus and Herpes simplex virus by affecting the immune cell response. CONCLUSION: The effects of n-3-LC-PUFAs on infections depend on the pathogen and the n-3 LC-PUFA dose and timing. Caution should be recommended for high-dose and long-term supplementation in humans.