A population-based cohort study on diagnosis and early management of anorectal malformation in the UK and Ireland

Background This study describes the presentation and initial management of anorectal malformation (ARM); evaluating the frequency, causes and consequences of late diagnosis. Methods A prospective, population cohort study was undertaken for newly diagnosed ARMs in the UK and Ireland from 01/10/2015 and 30/09/2016. Follow-up was completed at one year. Data are presented as n (%), appropriate statistical methods used. Factors associated with late diagnosis; defined as: detection of ARM either following discharge or more than 72 h after birth were assessed with univariable logistic regression. Results Twenty six centres reported on 174 cases, 158 of which were classified according to the type of malformation and 154 had completed surgical data. Overall, perineal fistula was the most commonly detected anomaly 43/158 (27%); of the 41 of these children undergoing surgery, 15 (37%) had a stoma formed. 21/154 (14%, CI95{9–20}) patients undergoing surgery experienced post-operative complications. Thirty-nine (22%) were diagnosed late and 12 (7%) were detected >30 days after birth. Factors associated with late diagnosis included female sex (OR 2.06; 1.0–4.26), having a visible perineal opening (OR 2.63; 1.21–5.67) and anomalies leading to visible meconium on the perineum (OR 18.74; 2.47–141.73). 56/174 (32%) had a diagnosis of VACTERL association (vertebral, anorectal, cardiac, tracheal, oesophageal, renal and limb); however, not all infants were investigated for commonly associated anomalies. 51/140 (36%) had a cardiac anomaly detected on echocardiogram. Conclusion There is room for improvement within the care for infants born with ARM in the UK and Ireland. Upskilling those performing neonatal examination to allow timely diagnosis, instruction of universal screening for associated anomalies and further analysis of the factors leading to clinically unnecessary stoma formation are warranted. Level of Evidence II (Prospective Cohort Study <80% follow-up)

Ultrasonographic features associated with previous torsion and the impact of surgery in managing neonatal ovarian cysts: a 20-year single-centre retrospective study

PURPOSE: To identify markers of previous ovarian torsion and outline the outcomes according to US appearance and operative management. METHODS: A retrospective single-centre review of neonatal ovarian cysts from January 2000 to January 2020. Data on postnatal cyst size and sonographic features and operative treatment were co-related with outcomes of ovarian loss and histology. RESULTS: 77 females were included with 22 simple and 56 complex cysts, one patient had bilateral cysts. 9/22 (41%) simple cysts regressed spontaneously in a median of 13 weeks (8-17). Complex cysts regressed spontaneously less frequently, 7/56(12%, P = 0.01), in 13 weeks (7-39). 38/56 (68%) complex and 12/22 (55%) simple cysts were treated operatively. 21/22 (95%) ovaries with initially simple cyst were salvaged compared to 20/56(36%) with initially complex cyst (P < 0.001). A fluid-debris level in 23/26 complex cysts was most associated with ovarian loss (P = 0.0006). Presence of viable ovarian stromal tissue was seen in 8/20 (40%) excised specimens during ovarian sparing procedures and in 5/30 (17%) oophorectomies for necrotic appearing ovaries. CONCLUSIONS: Fluid-debris level on US is significantly associated with ovarian loss likely due to previous torsion. Simple cysts are viable and often regress spontaneously. The finding of viable ovarian stromal tissue in resected specimens supports attempting ovarian preservation wherever possible

Liver secretin receptor predicts portoenterostomy outcomes and liver injury in biliary atresia

Biliary atresia (BA) is a chronic neonatal cholangiopathy characterized by fibroinflammatory bile duct damage. Reliable biomarkers for predicting native liver survival (NLS) following portoenterostomy (PE) surgery are lacking. Herein we explore the utility of 22 preidentified profibrotic molecules closely connected to ductular reaction (DR) and prevailing after successful PE (SPE), in predicting PE outcomes and liver injury. We used qPCR and immunohistochemistry in a BA cohort including liver samples obtained at PE (n = 53) and during postoperative follow-up after SPE (n = 25). Of the 13 genes over-expressed in relation to cholestatic age-matched controls at PE, only secretin receptor (SCTR) expression predicted cumulative 5-year NLS and clearance of jaundice. Patients in the highest SCTR expression tertile showed 34-55% lower NLS than other groups at 1-5 years after PE (P = 0.006-0.04 for each year). SCTR expression was also significantly lower [42 (24-63) vs 75 (39-107) fold, P = 0.015] among those who normalized their serum bilirubin after PE. Liver SCTR expression localized in cholangiocytes and correlated positively with liver fibrosis, DR, and transcriptional markers of fibrosis (ACTA2) and cholangiocytes (KRT7, KRT19) both at PE and after SPE. SCTR is a promising prognostic marker for PE outcomes and associates with liver injury in BA.Peer reviewe

Serum FGF19 predicts outcomes of Kasai portoenterostomy in biliary atresia

BACKGROUND AND AIMS: Outcomes after Kasai portoenterostomy (KPE) for biliary atresia remain highly variable for unclear reasons. As reliable early biomarkers predicting KPE outcomes are lacking, we studied the prognostic value of FGF19. APPROACH AND RESULTS: Serum and liver specimens, obtained from biliary atresia patients (N=87) at KPE or age-matched cholestatic controls (N=26) were included. Serum concentration of FGF19 and bile acids, liver mRNA expression of FGF19, and key regulators of bile acid synthesis were related to KPE outcomes and liver histopathology. Immunohistochemistry and in situ hybridization were used for the localization of liver FGF19 expression. Serum levels (223 vs. 61 pg/mL, p<0.001) and liver mRNA expression of FGF19 were significantly increased in biliary atresia. Patients with unsuccessful KPE (419 vs. 145 pg/mL, p=0.047), and those subsequently underwent liver transplantation (410 vs. 99 pg/mL, p=0.007) had significantly increased serum, but not liver, FGF19, which localized mainly in hepatocytes. In Cox hazard modeling serum FGF19 <109 pg/mL predicted native liver survival (HR: 4.31, p<0.001) also among patients operated <60 days of age (HR: 8.77, p=0.004) or after successful KPE (HR: 6.76, p=0.01). Serum FGF19 correlated positively with increased serum primary bile acids (R=0.41, p=0.004) and ductular reaction (R=0.39, p=0.004). CONCLUSIONS: Increased serum FGF19 at KPE predicted inferior long-term native liver survival in biliary atresia and was associated with unsuccessful KPE, elevated serum primary bile acids, and ductular reaction

Prognostic and Pathophysiologic Significance of IL-8 (CXCL8) in Biliary Atresia

Interleukin (IL)-8 (CXCL8), a chemokine involved in neutrophil recruitment, has been implicated in ductular reaction and liver fibrogenesis. We studied liver and serum IL-8 expression in a large biliary atresia (BA) cohort and explored its prognostic and pathophysiological potential. IL-8 expression was assessed in liver utilizing quantitative polymerase chain reaction (qPCR), immunohistochemistry and in situ hybridization and in serum using an enzyme-linked immunosorbent assay, among 115 BA patients, 10 disease controls and 68 normal controls. Results were correlated to portoenterostomy (PE) outcomes, biochemical and histological liver injury, transcriptional markers of fibrosis and cholangiocytes, and expression of other related cytokines. IL-8 was markedly overexpressed in liver and serum of BA patients at PE (n = 88) and in serum samples obtained during postoperative follow-up (n = 40). IL-8 expression in the liver was predominantly in cholangiocytes within areas of ductular reaction. Liver IL-8 mRNA expression correlated positively with its serum concentration, bile ductular proliferation, Metavir fibrosis stage, and transcriptional markers of activated myofibroblasts (ACTA2) and cholangiocytes (KRT19). Taken together, IL-8 may mediate liver injury in BA by promoting ductular reaction and associated liver fibrogenesis. Prognostic value of serum IL-8 to predict native liver survival was limited and confined to the postoperative period after PE

Portal Venous Deprivation in Patients with Portosystemic Shunts and Its Effect on Liver Tumors

To outline the use of radiological investigations in patients with congenital portosystemic shunts (CPS) and to assess the degree of portal venous deprivation in relation to the development of liver tumors

Tracheomegaly in infants with severe congenital diaphragmatic hernia treated with fetal endoluminal tracheal occlusion

Objective To measure and evaluate the effects of tracheal dimensions on survival and ventilation in a large series of infants with congenital diaphragmatic hernia (CDH) treated antenatally with fetal endoluminal tracheal occlusion (FETO). Study design Tracheal dimensions on chest radiograph (CR) were measured by 2 blinded radiologists. Survival, day 1 best oxygenation index and duration of ventilation, continuous positive airway pressure, and hospital stay were recorded. Survivors with a minimum 12-month follow-up were longitudinally compared for incidence of gastroesophageal reflux, chest infections, chest deformities, and hernia recurrence. Results Seventy infants with CDH (41 who underwent FETO) were treated between 2004 and 2010. Hernia repair was performed in 26 infants without FETO (8 with patch repair) and 35 infants with FETO (26 with patch repair; P =.0015). Infants with FETO had a wider trachea than those without FETO at T1 (P &lt;.0001) and between T1 and the carina (P &lt;.0001). Tracheal diameter was similar in survivors and nonsurvivors in the FETO group. Tracheal size was not correlated with day 1 best oxygenation index in the FETO group (R2 = 0.17) or the non-FETO group (R2 = 0.07). There were no between-group differences in duration of mechanical ventilation (P =.30), continuous positive airway pressure (P =.20), or hospital stay (P =.30). In the longitudinal study, tracheal widths were larger on the last CR than on preoperative CR in patients without FETO (T1, P =.02; widest point, P =.001; carina, P =.0001), and for patients with FETO at the widest point (P &lt;.0001) and at the carina (P &lt;.0001), but not at T1 (P =.12). There were no differences in clinical variables between the FETO and non-FETO groups. Conclusion FETO has a significant impact on tracheal size of infants with CDH; however, tracheal size does not affect survival or the requirement for early respiratory support. © 2014 Elsevier Inc. All rights reserved

Tracheomegaly in Infants with Severe Congenital Diaphragmatic Hernia Treated with Fetal Endoluminal Tracheal Occlusion

Objective To measure and evaluate the effects of tracheal dimensions on survival and ventilation in a large series of infants with congenital diaphragmatic hernia (CDH) treated antenatally with fetal endoluminal tracheal occlusion (FETO). Study design Tracheal dimensions on chest radiograph (CR) were measured by 2 blinded radiologists. Survival, day 1 best oxygenation index and duration of ventilation, continuous positive airway pressure, and hospital stay were recorded. Survivors with a minimum 12-month follow-up were longitudinally compared for incidence of gastroesophageal reflux, chest infections, chest deformities, and hernia recurrence. Results Seventy infants with CDH (41 who underwent FETO) were treated between 2004 and 2010. Hernia repair was performed in 26 infants without FETO (8 with patch repair) and 35 infants with FETO (26 with patch repair; P =.0015). Infants with FETO had a wider trachea than those without FETO at T1 (P &lt;.0001) and between T1 and the carina (P &lt;.0001). Tracheal diameter was similar in survivors and nonsurvivors in the FETO group. Tracheal size was not correlated with day 1 best oxygenation index in the FETO group (R2 = 0.17) or the non-FETO group (R2 = 0.07). There were no between-group differences in duration of mechanical ventilation (P =.30), continuous positive airway pressure (P =.20), or hospital stay (P =.30). In the longitudinal study, tracheal widths were larger on the last CR than on preoperative CR in patients without FETO (T1, P =.02; widest point, P =.001; carina, P =.0001), and for patients with FETO at the widest point (P &lt;.0001) and at the carina (P &lt;.0001), but not at T1 (P =.12). There were no differences in clinical variables between the FETO and non-FETO groups. Conclusion FETO has a significant impact on tracheal size of infants with CDH; however, tracheal size does not affect survival or the requirement for early respiratory support. © 2014 Elsevier Inc. All rights reserved

Complications of congenital portosystemic shunts: liver tumors are affected by shunt severity, but pulmonary and neurocognitive associations are not

Background and purpose: Congenital portosystemic shunts (CPSS) are associated with multisystem complications, with the most common being liver tumors. The purpose of this study is to investigate the incidence of complications of CPSS, and to determine the natural history of liver tumors and their relationship with shunt closure. Methods: Single-center retrospective cohort study of patients with CPSS referred from 1990 to 2020. Data on demographics, laboratory, radiological and histological investigations, clinical evolution, and surgery were reviewed. Mann-Whitney for continuous data and Fisher's exact test for categorical data were used. A p value of 0.05 was considered significant. Results: 54 patients were investigated for CPSS with a median age of 1.1 years (IQR 0.2-11.8 years) at presentation-7 intrahepatic shunts resolved spontaneously and were excluded. Type 1 (without intrahepatic portal flow) had a higher rate of all hepatic tumors than Type 2 (partial intrahepatic portal flow) [18/22(82%) vs. 9/25(36%); p = 0.003); and malignant tumors (6/22(27%) vs 1/25(4%); (p = 0.04). Following shunt closure, 4/11(36%) of patients experienced partial and 3/11(27%) complete tumor regression. Pulmonary hypertension and hepatopulmonary syndrome affected 4(9%), and 3(6%) patients, respectively. Pulmonary complications affected 1 patient with Type 1 and 6 with Type 2 shunts (p = 0.1). Neurocognitive anomalies were identified in 16/47(34%) patients, 8/22(35%) with Type 1 shunts and 8/25(32%) with Type 2 shunts (p = 0.76). 9/47 (19%) required special needs schooling. Conclusions: Severity of portal venous deprivation (Type 1 CPSS) increases the risk of hepatic tumors and surgical closure is associated with a reduction in size or complete resolution of benign tumors.</p

A Retrospective Multicenter Study of the Natural History of Fetal Ovarian Cysts

We investigated the natural history of fetal ovarian cysts to estimate the risk of torsion according to size