Partial Biliary Diversion May Promote Long-Term Relief of Pruritus and Native Liver Survival in Children with Cholestatic Liver Diseases

Introduction Rare cholestatic liver diseases may cause debilitating pruritus in children. Partial biliary diversion (PBD) may relieve pruritus and postpone liver transplantation which is the only other alternative when conservative treatment fails. The aim was to report long-term outcome after PBD in a population of 26 million people during a 25-year period. Materials and Methods This is an international, multicenter retrospective study reviewing medical journals. Complications were graded according to the Clavien-Dindo classification system. Results Thirty-three patients, 14 males, underwent PBD at a median of 1.5 (0.3-13) years at four Nordic pediatric surgical centers. Progressive familial intrahepatic cholestasis was the most common underlying condition. Initially, all patients got external diversion, either cholecystojejunostomy (25 patients) or button placed in the gallbladder or a jejunal conduit. Early complications occurred in 14 (42%) patients, of which 3 were Clavien-Dindo grade 3. Long-term stoma-related complications were common (55%). Twenty secondary surgeries were performed due to stoma problems such as prolapse, stricture, and bleeding, or conversion to another form of PBD. Thirteen children have undergone liver transplantation, and two are listed for transplantation due to inefficient effect of PBD on pruritus. Serum levels of bile acids in the first week after PBD construction were significantly lower in patients with good relief of pruritus than in those with poor effect (13 [2-192] vs. 148 [5-383] mu mol/L; p =0.02). Conclusion PBD may ensure long-term satisfactory effect on intolerable pruritus and native liver survival in children with cholestatic liver disease. However, stoma-related problems and reoperations are common.Peer reviewe

ERNICA guidelines for the management of rectosigmoid Hirschsprung's disease

Background Hirschsprung's disease (HSCR) is a serious congenital bowel disorder with a prevalence of 1/5000. Currently, there is a lack of systematically developed guidelines to assist clinical decision-making regarding diagnostics and management. Aims This guideline aims to cover the diagnostics and management of rectosigmoid HSCR up to adulthood. It aims to describe the preferred approach of ERNICA, the European Reference Network for rare inherited and congenital digestive disorders. Methods Recommendations within key topics covering the care pathway for rectosigmoid HSCR were developed by an international workgroup of experts from 8 European countries within ERNICA European Reference Network from the disciplines of surgery, medicine, histopathology, microbiology, genetics, and patient organization representatives. Recommendation statements were based on a comprehensive review of the available literature and expert consensus. AGREE II and GRADE approaches were used during development. Evidence levels and levels of agreement are noted. Results Thirty-three statements within 9 key areas were generated. Most recommendations were based on expert opinion. Conclusion In rare or low-prevalence diseases such as HSCR, there remains limited availability of high-quality clinical evidence. Consensus-based guidelines for care are presented.Peer reviewe

ERNICA guidelines for the management of rectosigmoid Hirschsprung's disease

Background Hirschsprung's disease (HSCR) is a serious congenital bowel disorder with a prevalence of 1/5000. Currently, there is a lack of systematically developed guidelines to assist clinical decision-making regarding diagnostics and management. Aims This guideline aims to cover the diagnostics and management of rectosigmoid HSCR up to adulthood. It aims to describe the preferred approach of ERNICA, the European Reference Network for rare inherited and congenital digestive disorders. Methods Recommendations within key topics covering the care pathway for rectosigmoid HSCR were developed by an international workgroup of experts from 8 European countries within ERNICA European Reference Network from the disciplines of surgery, medicine, histopathology, microbiology, genetics, and patient organization representatives. Recommendation statements were based on a comprehensive review of the available literature and expert consensus. AGREE II and GRADE approaches were used during development. Evidence levels and levels of agreement are noted. Results Thirty-three statements within 9 key areas were generated. Most recommendations were based on expert opinion. Conclusion In rare or low-prevalence diseases such as HSCR, there remains limited availability of high-quality clinical evidence. Consensus-based guidelines for care are presented.Peer reviewe

Heterogeneity in γ-glutamyltransferase mRNA expression and glycan structures. Search for tumor-specific variants in human liver metastases and colon carcinoma cells

International audienceThe enzyme gamma-glutamyltransferase (GGT) is frequently overexpressed in cancer cells and tissues and has significant utility as a cancer marker. Significant heterogeneity of the enzyme has been described due to both transcriptional and post-translational variations. For possible use in diagnosis and follow-up of patients with colorectal cancer, a search was performed for specific mRNA subtypes and glycan structures of the enzyme in liver metastases. We found no differences in the distribution of three GGT mRNA subtypes (fetal liver, HepG2, placenta) in metastatic tissue and normal liver tissue. Furthermore, the three subtypes were present in leukocytes isolated from both normal individuals and cancer patients. Two colon carcinoma cell lines (Colo 205 and HCC 2998) also displayed the three forms and no consistent changes in mRNA composition were noted after butyrate-induced differentiation of the cells. Thus, neither of the GGT mRNA subforms appear to be tumor-specific, although some qualitative and quantitative variations were noted. Two distinct glycosylation features were detected for GGT in metastatic tissue in contrast to normal liver GGT; an extreme sialic acid heterogeneity and a significant increase in beta1,6GlcNAc branching. The GGT glycans from the two colon carcinoma cell lines also possessed these features. As butyrate treatment of the cells resulted in an increased sialic acid content and a reduced beta1,6GlcNAc branching, the described carbohydrate structures appear to be part of a tumor-related pattern. We were, however, unable to identify such GGT isoforms in serum from patients with advanced colorectal cancer. This indicates that their usefulness in diagnostic use is doubtful

A Nordic multicenter survey of long-term bowel function after transanal endorectal pull-through in 200 patients with rectosigmoid Hirschsprung disease

Objective: Transanal endorectal pull-through (ERPT) is the most popular technique to treat Hirschsprung disease (HD). Still, there is limited knowledge on long-term bowel function. This cross-sectional, multicenter study assessed long-term bowel function in a large HD population and examined predictors of poor outcome. Methods: Patients older than four years or their parents filled out a validated questionnaire on bowel function. Clinical details were recorded retrospectively from medical records. Results: 73/200 (37%) patients reported absolutely no impaired bowel function, meaning no constipation, fecal accidents, stoma, appendicostomy or need for enemas. Seven (4%) had a stoma, and 33 (17%) used antegrade or rectal colonic enemas. Most disarrangements of fecal control and constipation were significantly less common in older age group, but abnormal defecation frequency and social problems remained unchanged. Syndromic patients (n = 31) experienced frequent fecal accidents (46%) more often than nonsyndromic (14%, P <0.001). Having a syndrome (adjusted OR 5.6, 95% CI 2.1-15, P = 0.001) or a complete transanal ERPT (adjusted OR 2.4, 95% CI 1.1-5.7, P = 0.038) was significantly associated with poor outcome defined as having a stoma, an appendicostomy, daily fecal accidents or need of regular rectal wash outs. Conclusion: A significant number of HD patients experience bowel problems many years after definite surgery. Fecal control was significantly better in older than younger HD patients, but some continued to have considerable bowel problems also as adults. A total transanal ERPT was associated with poorer outcome. Long-term follow-up of HD patients is warranted. (C) 2017 Elsevier Inc. All rights reserved.Peer reviewe

A nordic multicenter study on contemporary outcomes of pediatric short bowel syndrome in 208 patients

Background &amp; aims: Despite advances in the management of short bowel syndrome related intestinal failure (SBS-IF), large-scale contemporary pediatric studies are scarce. The aim of this multicenter study was to assess key outcomes and clinical prognostic factors in a recent Nordic pediatric SBS-IF population. Methods: Patients with SBS-IF treated during 2010-2019, whose parenteral support (PS) started at age &lt;1 year and continued &gt;60 consecutive days were included and retrospectively reviewed. All six participating centers followed multidisciplinary SBS-IF management. Risk factors for PS dependency, intestinal failure associated liver disease (IFALD) and mortality were assessed with Cox regression and Kaplan Meier analyses. IFALD was defined with serum liver biochemistry levels. Results: Among 208 patients, SBS-IF resulted from NEC in 49%, gastroschisis w/wo atresia in 14%, small bowel atresia in 12%, volvulus in 11%, and other diagnoses in 14%. Median age-adjusted small bowel length was 43% (IQR 21-80%). After median follow up of 4.4 years (IQR 2.5-6.9), enteral autonomy was reached by 76%, none had undergone intestinal transplantation, and overall survival was 96%. Half of deaths (4/8) were caused by septic complications. Although biochemical cholestasis occurred only in 3% at latest follow-up and none of deaths were directly caused by IFALD, elevated liver biochemistry (HR 0.136; P = 0.017) and shorter remaining small bowel (HR 0.941; P = 0.040) predicted mortality. Shorter remaining small bowel and colon, and presence of end-ostomy were the main predictors of PS dependency, but not IFALD. Patients with NEC reached enteral autonomy more efficiently and had decreased incidence of IFALD compared to other etiologies. Conclusions: Although with current multidisciplinary management, prognosis of pediatric SBS is encouraging, septic complications and IFALD still associated with the remaining low mortality rate

Congenital diaphragmatic hernia in Scandinavia from 1995 to 1998: Predictors of mortality.

BACKGROUND/PURPOSE: There is a lack of large contemporary studies on the management of congenital diaphragmatic hernia (CDH), and the prediction of mortality remains difficult. The aim of this study was to investigate the influence of perinatal factors on mortality rate in a contemporary multicenter study. METHODS: The authors conducted a retrospective multicenter cohort study. Twelve of 13 Scandinavian pediatric surgical centers participated in the study. During a 4-year period (1995 through 1998) 195 children with CDH were included. The main endpoints were hospital mortality rate and total mortality rate (before 2001). Bivariate and multivariate survival analyses were performed using Kaplan-Meier plots, Log-rank test, and Cox regression. RESULTS: Overall hospital mortality rate was 30%. Among 168 neonates with symptoms within 24 hours (early presenters) 35% died before discharge. All 61 deaths occurred in 157 neonates with symptoms within the first 2 hours of life. Among early presenters, 27% had prenatal ultrasound diagnosis, 26% were delivered by cesarean section, and 21% had associated major malformations. Bivariate analysis of early presenters showed increased risk of death in neonates with prenatal diagnosis, associated anomalies, right-sided diaphragmatic hernia (RCDH), low 1-minute and 5-minute Apgar scores, low birth weight, short gestational age, and cesarean delivery. Neonates with prenatal diagnosis were characterized by significantly lower Apgar scores, lower birth weight, and increased frequency of associated anomalies than those diagnosed after birth. Multivariate analysis found that prenatal diagnosis (P =.004), 1-minute Apgar (P =.001), and RCDH (P =.042) were independent predictors of total mortality rate. CONCLUSIONS: In a series of 195 CDH patients, all 61 deaths occurred in the 157 neonates presenting with symptoms within the first 2 hours of life. Prenatal diagnosis, 1-minute Apgar score, and RCDH were significant independent predictors of total mortality. J Pediatr Surg 37:1269-1275. Copyright 2002, Elsevier Science (USA). All rights reserved