Surgical and Endoscopic Intervention for Chronic Pancreatitis in Children: The Kings College Hospital Experience

Paediatric chronic pancreatitis (CP) is a rare and debilitating pathology that often requires invasive diagnostics and therapeutic interventions either to address a primary cause such as a pancreaticobiliary malunion or to deal with secondary complications such as chronic pain. Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) are two endoscopic modalities that have an established diagnostic role in paediatric CP, and their therapeutic utilisation is increasing in popularity. Surgical decompression of the obstructed and dilated pancreatic duct plays a role in alleviating pancreatic duct hypertension, a common association in CP. Surgery equally has a role in certain anatomical abnormalities of the pancreaticobiliary draining system, or occasionally in some CP complications such as drainage of a symptomatic pancreatic pseudocyst

Ventral body wall closure: Mechanistic insights from mouse models and translation to human pathology

© 2024 The Author(s). Developmental Dynamics published by Wiley Periodicals LLC on behalf of American Association for Anatomy. This is an open access article distributed under the Creative Commons Attribution License, to view a copy of the license, see: https://creativecommons.org/licenses/by/4.0/The ventral body wall (VBW) that encloses the thoracic and abdominal cavities, arises by extensive cell movements and morphogenetic changes during embryonic development. These morphogenetic processes include embryonic folding generating the primary body wall; the initial ventral cover of the embryo, followed by directed mesodermal cell migrations, contributing to the secondary body wall. Clinical anomalies in VBW development affect approximately 1 in 3000 live births. However, the cell interactions and critical cellular behaviours that control VBW development remain little understood. Here, we describe the embryonic origins of the VBW, the cellular and morphogenetic processes, and key genes, that are essential for VBW development. We also provide a clinical overview of VBW anomalies, together with environmental and genetic influences, and discuss the insight gained from over 70 mouse models that exhibit VBW defects, and their relevance, with respect to human pathology. In doing so we propose a phenotypic framework for researchers in the field which takes into account the clinical picture. We also highlight cases where there is a current paucity of mouse models for particular clinical defects and key gaps in knowledge about embryonic VBW development that need to be addressed to further understand mechanisms of human VBW pathologies.Peer reviewe

Cardiac-associated biliary atresia (CABA): a prognostic subgroup

ObjectivesTo describe the range of concurrent cardiac malformations in biliary atresia (BA) while providing a functional framework of risk.MethodsDemographic and variables were collected from a prospectively maintained single-centre database. Infants were grouped according to a cardiac functional framework (A=acyanotic, B=cyanotic and C=insignificant shunt). Primary outcome was set as clearance of jaundice (bilirubin ≤20 μmol/L) following Kasai portoenterostomy (KPE). Native liver survival and overall actuarial survival were compared with a date-matched control infant with BA (n=77). P value &lt;0.05 was regarded as significant.Results524 infants with histologically confirmed BA were treated between January 1999 and December 2018, 37 (7%) had a concurrent cardiac anomaly (A: n=23 (62%), B: n=10 (27%), C: n=4 (11%)). Infants with biliary atresia splenic malformation (BASM) or cat-eye syndrome (CES) contributed over half of the cases (21/37; 57%).Overall, 20 (54%) infants cleared jaundice (vs 50/77 (65%) controls; p=0.2), but with higher mortality compared with the non-cardiac controls (15/37 (40%) vs 3/77 (4%); HR 15.5 (95% CI 5.5 to 43.4); p&lt;0.00001). Infants requiring cardiac intervention in the first year of life (n=15) were more likely to clear jaundice (6/7 vs 2/8; p=0.04) and had a trend towards higher survival (6/7 vs 3/8; p=0.1) when KPE followed cardiac surgery. Yet, the type of cardiac pathology did not impact clearance of jaundice or mortality.ConclusionWe propose the term cardiac-associated biliary atresia (CABA) as a high-risk group. We believe that restorative cardiac surgery should precede KPE wherever possible to improve outcome.</jats:sec

The diagnostic value of immunohistochemistry markers in Hirschsprung disease; a systematic review and meta-analysis

Background: immunohistochemistry (IHC) markers are employed to improve the diagnostic yield when testing for Hirschsprung disease (HSCR). Yet, a superior test has not been identified.Objectives: we aimed to determine the diagnostic test accuracy (DTA) of IHC markers.Methods: we conducted database search for studies reporting IHC staining on rectal biopsy investigating for HSCR. We constructed 2 × 2 contingency tables, and calculated DTA estimates in pooled and paired testing using random-effect model meta-analysis.Results: twenty eight IHC markers from 107 studies were used to investigate for HSCR in 10891 children. In pooled analysis; calretinin sensitivity and specificity were superior to acetylcholinesterase, S100, and peripherin [98 % (CI; 0.95–0.99) &amp; 99 % (CI; 0.97–0.99)], [94 % (CI; 0.86–0.97) &amp; 99 % (CI; 0.96–0.99)], [92 % (CI; 0.85–0.96) &amp; 97 % (CI; 0.89–0.99)] and [91.7 % (CI; 0.54–0.98) &amp; 94.8 % (CI; 0.59–0.99)], respectively. In paired analysis calretinin diagnostic odds ratio was superior to hematoxylin and eosin (H&amp;E), acetylcholinesterase and S100: [3349 (PI; 551.3–22667.2) vs 345.3 (PI; 54.9–2394.2)], [300.9 (PI; 13.3–4146.9) vs 34.6 (PI; 2.2–363.9)] and [696.9 (PI; 91.2–3401.7) vs 196.9 (PI; 29.8–890.5)], respectively. In biopsies labelled inadequate for H&amp;E testing, calretinin specificity to rule out HSCR reached 92 % (CI; 0.288–0.998).Conclusion: IHC provides additional diagnostic value over H&amp;E. Calretinin appears to be, currently, a superior IHC marker. The available literature is of variable quality, cautious interpretation of the findings should be considered.Level of Evidence: III.<br/

Cardiac-associated biliary atresia (CABA):A prognostic subgroup

Objectives: To describe the range of concurrent cardiac malformations in biliary atresia (BA) while providing a functional framework of risk. Methods: Demographic and variables were collected from a prospectively maintained single-centre database. Infants were grouped according to a cardiac functional framework (A=acyanotic, B=cyanotic and C=insignificant shunt). Primary outcome was set as clearance of jaundice (bilirubin ≤20 μmol/L) following Kasai portoenterostomy (KPE). Native liver survival and overall actuarial survival were compared with a date-matched control infant with BA (n=77). P value &lt;0.05 was regarded as significant. Results: 524 infants with histologically confirmed BA were treated between January 1999 and December 2018, 37 (7%) had a concurrent cardiac anomaly (A: n=23 (62%), B: n=10 (27%), C: n=4 (11%)). Infants with biliary atresia splenic malformation (BASM) or cat-eye syndrome (CES) contributed over half of the cases (21/37; 57%). Overall, 20 (54%) infants cleared jaundice (vs 50/77 (65%) controls; p=0.2), but with higher mortality compared with the non-cardiac controls (15/37 (40%) vs 3/77 (4%); HR 15.5 (95% CI 5.5 to 43.4); p&lt;0.00001). Infants requiring cardiac intervention in the first year of life (n=15) were more likely to clear jaundice (6/7 vs 2/8; p=0.04) and had a trend towards higher survival (6/7 vs 3/8; p=0.1) when KPE followed cardiac surgery. Yet, the type of cardiac pathology did not impact clearance of jaundice or mortality. Conclusion: We propose the term cardiac-associated biliary atresia (CABA) as a high-risk group. We believe that restorative cardiac surgery should precede KPE wherever possible to improve outcome. </p