Brain imaging in children with neonatal cholestatic liver disease: A systematic review.

AIM: To determine if children with neonatal cholestatic liver disease had concurrent and later findings on brain imaging studies that could be attributed and the cholestasis to contribute to the understanding of the impaired neuropsychological development. METHODS: Ovid MEDLINE and EMBASE were searched on July 21, 2022, and updated on March 26, 2023. Studies with children under 18 years of age with neonatal cholestasis and a brain scan at the time of diagnosis or later in life were included. Excluded studies were non-English, non-human, reviews or conference abstracts. Data were extracted on demographics, brain imaging findings, treatment and outcome. The results were summarised by disease categories. Risk of bias was assessed using JBI critical appraisal tools. RESULTS: The search yielded 12 011 reports, of which 1261 underwent full text review and 89 were eligible for inclusion. Haemorrhage was the most common finding, especially in children with bile duct obstruction, including biliary atresia. Some findings were resolved after liver transplantation. CONCLUSION: Children with neonatal cholestasis had changes in brain imaging, which might play a role in impaired neuropsychological development, but longitudinal clinical research with structured assessment is needed to better qualify the aetiology of the impairment.

Cholestasis alters brain lipid and bile acid composition and compromises motor function in neonatal piglets.

Infants with neonatal cholestasis are prone to neurodevelopmental deficits, however, the underlying pathogenesis is unclear. Lipid malabsorption and accumulation of potentially neurotoxic molecules in the blood such as bile acids are important yet relatively unexplored pathways. Here, we developed a translational piglet model to understand how the molecular bile acid and lipid composition of the brain is affected by this disease and relates to motor function. Piglets (8-days old) had bile duct ligation or sham surgery and were fed a formula diet for 3 weeks. Alongside sensory-motor deficits observed in bile duct-ligated animals, we found a shift toward a more hydrophilic and conjugated bile acid profile in the brain. Additionally, comprehensive lipidomics of the cerebellum revealed a decrease in total lipids including phosphatidylinositols and phosphatidylserines and increases in lysophospholipid species. This was paralleled by elevated cerebellar expression of genes related to inflammation and tissue damage albeit without significant impact on the brain transcriptome. This study offers new insights into the developing brain's molecular response to neonatal cholestasis indicating that bile acids and lipids may contribute in mediating motor deficits.

Prolonged length of stay and many readmissions after appendectomy.

INTRODUCTION: The epidemiology of appendicitis seems to be changing; the proportion of complicated appendicitis cases is growing. The outcome of childhood appendectomy in Denmark has not previously been evaluated nationwide in Denmark. MATERIAL AND METHODS: Data on all Danish children treated for appendicitis were obtained from the National Patient Registry. Reoperation, readmittance or length of hospital stay (LOS) exceeding five days were considered nonsatisfactory outcomes. RESULTS: A total of 2,617 children, 55% boys and 45% girls, were operated at 32 hospitals. Their mean age was 11.1 years. Mortality was 0%. A laparoscopic procedure was used in 34% of the cases. The medians of the postoperative LOS were one day for both the open and laparoscopic appendectomy groups, the corresponding means were 2.5 and 2.0 days (p<0.05). 4.5% had one or more reoperations. 18% had a LOS>5 days or readmittance. The typical reasons were wound infection, need for prolonged antibiotics treatment and simple, prolonged recovery. CONCLUSION: The Danish practice for appendicitis has acceptable rates of reoperation, medians and means of LOS, and a rate of readmission which is comparable to that reported in other studies. However, a nonsatisfactory outcome after appendectomy in about 20% calls for improvement and further studies. FUNDING: Not relevant. TRIAL REGISTRATION: Not relevant.

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.

Outcomes of biliary atresia in the Nordic countries - a multicenter study of 158 patients during 2005-2016.

BACKGROUND/PURPOSE: Biliary atresia is the most common reason for newborn cholestasis and pediatric liver transplantation. Even after normalization of serum bilirubin after portoenterostomy, most patients require liver transplantation by adulthood due to expanding fibrosis. We addressed contemporary outcomes of biliary atresia in the Nordic countries. METHODS: Data on center and patients characteristics, diagnostic practices, surgical treatment, adjuvant medical therapy after portoenterostomy, follow-up and outcomes were collected from all the Nordic centers involved with biliary atresia care during 2005-2016. RESULTS: Of the 154 patients, 148 underwent portoenterostomy mostly by assigned surgical teams at median age of 64 (interquartile range 37-79) days, and 95 patients (64%) normalized their serum bilirubin concentration while living with native liver. Postoperative adjuvant medical therapy, including steroids, ursodeoxycholic acid and antibiotics was given to 137 (93%) patients. Clearance of jaundice associated with young age at surgery and favorable anatomic type of biliary atresia, whereas annual center caseload >3 patients and diagnostic protocol without routine liver biopsy predicted early performance of portoenterostomy. The cumulative 5-year native liver and overall survival estimate was 53% (95% CI 45-62) and 88% (95% CI 83-94), respectively. Portoenterostomy age <65days and annual center caseload >3 patients were predictive for long-term native liver survival, while normalization of serum bilirubin after portoenterostomy was the major predictor of both native liver and overall 5-year survival. CONCLUSIONS: The outcomes of biliary atresia in the Nordic countries compared well with previous European studies. Further improvement should be pursued by active measures to reduce patient age at portoenterostomy. RETROSPECTIVE PROGNOSIS STUDY: Level II.

Hepatobiliary scintigraphy for early diagnosis of biliary atresia.

INTRODUCTION: The aim of this study was to evaluate the validity of (99m)Technetium-trimethylbromo-iminodiacetic acid hepatobiliary scintigraphy (HS) for the diagnosis of biliary atresia (BA). METHODS: From January 2005 to December 2009, a total of 47 infants with conjugated hyperbilirubinaemia (> 20 micromol/l total bilirubin of which 20% is conjugated) underwent HS. BA was suspected if no tracer was visualised in the gut 24 hours post-injection. The results of the HSs were compared with the gold standard, laparotomy with antegrade cholangiography findings. RESULTS: Considering the final diagnosis based on the gold standard, the sensitivity, specificity, positive predictive value and negative predictive value (NPV) of the HS in the diagnosis of BA was 100%, 63.6%, 53.8%, and 100%, respectively. The accuracy was 74.5%. BA patients with non-draining HS had significantly higher levels of gamma-glutamyl transpeptidase (GGTP) than non-BA patients with non-draining HS (p = 0.019) or draining HS (p = 0.0001). CONCLUSIONS: HS plays an important role in the diagnostic strategy of infantile jaundice due to conjugated hyperbilirubinaemia. It is a non-invasive method that only seldomly calls for sedation. A high sensitivity and NPV prevent un-necessary surgery. Because of the low specificity of HS in diagnosing BA, it should be part of a multimodality imaging strategy when the result supports a clinical suspicion of BA. In cases with non-draining HS and normal GGTP blood levels, supplemental imaging modalities are especially needed. FUNDING: none. TRIAL REGISTRATION: not relevant.

[Acute, severe liver insufficiency caused by extrahepatic biliary atresia in a newborn]. / Akut, svær leverinsufficiens forårsaget af binyretumor hos nyfødt.

A newborn female was hospitalized due to metabolic acidosis and conjugated hyperbilirubinaemia. Extrahepatic biliary atresia (EHBA) was suspected why a (99m)Tc-mebrofenin cholescintigraphy was performed. It showed poor hepatocyte tracer uptake and no drainage to the gut. The hepatocyte dysfunction was caused by an obstructing adrenal gland neuroblastoma later visualised by ultrasound and MRI. The cholescintigraphy is a non-invasive modality to exclude or confirm the suspicion of EHBA. Furthermore neonatal conjugated hyperbilirubinaemia demands the use of a multimodality imaging strategy for differential diagnosis to EHBA.

[Cystectomy in Denmark 2000-2005]. / Cystektomi i Danmark 2000-2005.

INTRODUCTION: The organization and results after cystectomy in Denmark are unknown. MATERIALS AND METHODS: Based upon the Danish National Hospital Register and discharge notes, postoperative hospitalization, readmission within 30 days, re-operations and mortality after cystectomy in Denmark in the period January 1, 2000-December 31, 2005 were assessed. RESULTS: There were 995 cystectomies with a median postoperative hospital stay of 18.9 days (including readmissions) and hospital mortality of 3.7%. The operations were performed in seven departments without difference in outcome between departments. Morbidity was observed in 58%, 16.8% of which were re-operated for wound or urinary diversion complications. CONCLUSION: It is concluded that cystectomy should be performed in only five departments in Denmark, and the results suggest that an intensified multicenter collaboration should be initiated to improve outcome.