Key postnatal magnetic resonance characteristics for differentiating cystic biliary atresia from choledochal cyst.

OBJECTIVES: To analyze the ability of magnetic resonance (MR) to identify cystic biliary atresia (CBA) and choledochal cyst (CC). METHODS: Infants (≤ 1 year old) who were diagnosed with CBA or CC type I/IV from January 2010 to July 2023 were retrospectively reviewed. Imaging characteristics on MR were compared between the CBA and CC groups. Binary logistic regression and the area under the receiver operating characteristic curve (AUC) were analyzed for the identification of CBA. RESULTS: Sixty-three patients with CBA (median age, 30 days) and 172 patients with CC (median age, 60 days) were included. Gallbladder (GB) wall thickness (cutoff, 1.2 mm) showed 98.4% sensitivity and 100% specificity (AUC, 0.998). MR-triangular cord thickness (MR-TCT) (cutoff, 4.1 mm) showed 100% sensitivity and 95.9% specificity (AUC, 0.986). The bile duct loop visualization showed 96.8% sensitivity and 100% specificity (AUC, 0.984). Proximal bile duct (PBD) diameter (cutoff, 1.3 mm) showed 92.1% sensitivity and 95.3% specificity (AUC, 0.977). Cyst wall thickness (cutoff, 1 mm) showed 77.8% sensitivity and 95.3% specificity (AUC, 0.942). The combination of GB wall thickness > 1.2 mm and MR-TCT > 4.1 mm, GB wall thickness > 1.2 mm and loop visualization, GB wall thickness > 1.2 mm, and cyst wall thickness > 1 mm showed 100% sensitivity and 100% specificity (AUC, 1.000). CONCLUSIONS: Imaging characteristics on MR might be used to identify CBA and CC, and the combination of GB wall thickness and MR-TCT, or loop visualization, or cyst wall thickness, has a perfect diagnostic value. CLINICAL RELEVANCE STATEMENT: Early and accurate differentiation of CBA and CC is essential, but current methods rely on inherently subjective ultrasound. Biliary features on MRI allow for an objective, accurate diagnosis.

The association of immune-related genes and the potential role of IL10 with biliary atresia.

BACKGROUND: Biliary atresia (BA) is a severe immune-related disease that is characterized by biliary obstruction and cholestasis. The etiology of BA is unclear, our aim was to explore the relationship between biliary tract inflammation and immune-related genes. METHODS: We selected 14 SNPs in 13 immune-related genes and investigated their associations with BA by using a large case‒control cohort with a total of 503 cases and 1473 controls from southern China. RESULTS: SNP rs1518111 in interleukin10 (IL10) was identified as associated with BA (P = 5.79E-03; OR: 0.80; 95% CI: 0.68-0.94). The epistatic effects of the following pairwise interactions among these SNPs were associated with BA: signal transducer and activator of transcription 4 (STAT4) and chemokine (C-X-C motif) ligand 3 (CXCL3); STAT4 and damage-regulated autophagy modulator1 (DRAM1); CXCL3 and RAD51 paralog B (RAD51B); and interferon gamma (IFNG) and interleukin26 (IL26). Furthermore, we explored the potential role of IL-10 in the pathogenesis of the neonatal mouse model of BA. IL-10 effectively prevented biliary epithelial cell injury and biliary obstruction in murine BA as well as inhibit the activation of BA-related immune cells. CONCLUSIONS: In conclusion, this study provided strong evidence implicating IL10 as a susceptibility gene for BA in the southern Chinese population. IMPACT: This study provided strong evidence implicating IL10 as a susceptibility gene for BA in the southern Chinese population. This study could infer that IL-10 may play a protective role in BA mouse model. We found that four SNPs (rs7574865, rs352038, rs4622329, and rs4902562) have genetic interactions.

CD177+ cells produce neutrophil extracellular traps that promote biliary atresia.

BACKGROUND & AIMS: We have previously reported on the potential pathogenic role of neutrophils in biliary atresia (BA). Herein, we aimed to delineate the role of CD177+ neutrophils in the pathogenesis of BA. METHODS: Immune cells from the livers of mice with rhesus rotavirus-induced BA were analysed. Single-cell RNA-sequencing was performed to specifically analyse Gr-1+ (Ly6C/Ly6G+) cells in the liver. Gene expression profiles of CD177+ cells were analysed using the Smart-Seq RNA-sequencing method, and the pathogenesis of BA was examined in Cd177-/- mice. Neutrophil extracellular trap (NET) inhibitors were used to determine the role of CD177+ cell-derived NETs in BA-associated bile duct damage, and a pilot clinical study evaluated the potential effects of N-acetylcysteine on NET release in BA. RESULTS: Increased levels of Gr-1+ cells were observed in the livers of mice with rhesus rotavirus-induced BA. RNA-sequencing analysis revealed that CD177+ cells were the main population of Gr-1+ cells and expressed elevated levels of both interferon-stimulated and neutrophil degranulation genes. Cd177-/- BALB/c mice exhibited delayed disease onset and reduced morbidity and mortality. High numbers of mitochondria were detected in CD177+ cells derived from mice with BA; these cells were associated with increased levels of reactive oxygen species and increased NET formation, which induced the apoptosis of biliary epithelial cells in cocultures. In a pilot clinical study, the administration of N-acetylcysteine to patients with BA reduced CD177+ cell numbers and reactive oxygen species levels, indicating a potential beneficial effect. CONCLUSIONS: Our data indicate that CD177+ cells play an important role in the initiation of BA pathogenesis via NET formation. CLINICAL TRIAL REGISTRATION: The pilot study of N-acetylcysteine treatment in patients with BA was registered on the Chinese Clinical Trial Registry (ChiCTR2000040505). LAY SUMMARY: Neutrophils (a type of innate immune cell, i.e. an immune cell that doesn't target a specific antigen) are thought to play a role in the development of biliary atresia (a rare but potentially lethal condition of the bile ducts that occurs in infants). Herein, we found that neutrophils expressing a particular protein (CD177) played an important role in bile duct damage by releasing a special structure (NET) that can trap and kill pathogens but that can also cause severe tissue damage. A pilot study in patients with biliary atresia showed that inhibiting NETs could have a beneficial effect.

The Role of Neonatal Gr-1+ Myeloid Cells in a Murine Model of Rhesus-Rotavirus-Induced Biliary Atresia.

Activation of innate immunity together with cholangiocyte damage occurs in biliary atresia (BA). However, detailed information on the inflammatory cells involved is lacking. This study investigates both the pathophysiology of CD11b+Gr-1+ cells in a mouse model of BA and their presence in BA patients. CD11b+Gr-1+ cells were targeted by an anti-Ly6G antibody in murine BA induced by inoculation with rhesus rotavirus. Expression of the Ly6G homolog CD177+ was examined in biopsies from BA patients. The symptoms of BA were ameliorated, and survival was prolonged in those mice receiving 5 to 10 µg of antibody per mouse every 3 days for four times compared with the mice treated with virus alone. However, the mice later developed chronic BA with persistent low body weight and jaundice. Hepatic inflammatory cells were reduced compared with acute BA. Blockade of extrahepatic bile ducts occurred, whereas intrahepatic ductules were partially preserved, and a progressive increase in liver fibrosis was observed. High levels of CD11b+Gr-1+ cells were present in these mice. The administration of an anti-Ly6G antibody again in those chronic BA mice reduced jaundice and restored body weight. In BA patients CD177+ cells were highly expressed in the liver. Our data suggest that the chronic mouse BA model shares key characteristics with clinical BA and indicates the importance of CD11b+Gr-1+ cells in the initiation and progression of BA.

Single cell RNA-sequencing analysis reveals that N-acetylcysteine partially reverses hepatic immune dysfunction in biliary atresia.

Background & Aims: Our previous study indicated that CD177+ neutrophil activation has a vital role in the pathogenesis of biliary atresia (BA), which is partially ameliorated by N-acetylcysteine (NAC) treatment. Here, we evaluated the clinical efficacy of NAC treatment and profiled liver-resident immune cells via single cell RNA-sequencing (scRNA-seq) analysis to provide a comprehensive immune landscape of NAC-derived immune regulation. Methods: A pilot clinical study was conducted to evaluate the potential effects of intravenous NAC treatment on infants with BA, and a 3-month follow-up was carried out to assess treatment efficacy. scRNA-seq analysis of liver CD45+ immune cells in the control (n = 4), BA (n = 6), and BA + NAC (n = 6) groups was performed and the effects on innate cells, including neutrophil and monocyte-macrophage subsets, and lymphoid cells were evaluated. Results: Intravenous NAC treatment demonstrated beneficial efficacy for infants with BA by improving bilirubin metabolism and bile acid flow. Two hepatic neutrophil subsets of innate cells were identified by scRNA-seq analysis. NAC treatment suppressed oxidative phosphorylation and reactive oxygen species production in immature neutrophils, which were transcriptionally and functionally similar to CD177+ neutrophils. We also observed the suppression of hepatic monocyte-mediated inflammation, decreased levels of oxidative phosphorylation, and M1 polarisation in Kupffer-like macrophages by NAC. In lymphoid cells, enhancement of humoral immune responses and attenuation of cellular immune responses were observed after NAC treatment. Moreover, cell-cell interaction analysis showed that innate/adaptive proinflammatory responses were downregulated by NAC. Conclusions: Our clinical and scRNA-seq data demonstrated that intravenous NAC treatment partially reversed liver immune dysfunction, alleviated the proinflammatory responses in BA by targeting innate cells, and exhibited beneficial clinical efficacy. Impact and implications: BA is a serious liver disease that affects newborns and has no effective drug treatment. In this study, scRNA-seq showed that NAC treatment can partially reverse the immune dysfunction of neutrophil extracellular trap-releasing CD177+ neutrophils and Kupffer cells, and lower the inflammatory responses of other innate immune cells in BA. In consequence, intravenous NAC treatment improved the clinical outcomes of patients with BA in term of bilirubin metabolism.

Modified single-port versus multiport laparoscopic choledochal cysts excision and Roux-en-Y hepaticojejunostomy: a retrospective comparative cohort study.

Background: The feasibility, benefit, and safety of multiport laparoscopic choledochal cyst (CDC) excision and Roux-en-Y hepaticoenterostomy (MPCH) have been consistently confirmed. Single-port laparoscopic CDC excision and Roux-en-Y hepaticoenterostomy (SPCH) has advantages of less traumatic and more cosmetic beneficial, it has been reported in some case series, but it is technically challenging. We propose a modified technique to reduce technical difficulty in performing SPCH. The safety and feasibility of modified SPCH were compared with those of conventional multiport laparoscopic CDC excision. Methods: A total of 43 consecutive patients who diagnosed with CDC by preoperative magnetic resonance cholangiopancreatography (MRCP) and underwent SPCH (n=24) and MPCH (n=19) for choledochal cyst (CDC) by a single surgeon between January 1, 2018, and January 1, 2021, were enrolled. The baseline clinical characteristics, efficacy and safety outcomes of short-term were compared. Results: The baseline clinical characteristics of the MPCH and SPCH groups are comparable. Average postoperative length of hospital stay was shorter in the SPCH group than in the MPCH group, but the difference was not statistically significant (7.00 vs. 7.58 days; P>0.99). The operation time (281.75 vs. 277.3 min; P=0.58) and the amount of blood loss (9.33 vs. 16.68 mL; P=0.57) were similar in both groups. A significantly greater number of drainage tubes were placed in the MPCH group compared to the SPCH group (11 vs. 5; P=0.01). One patient suffered from hepaticoenterostomy anastomosis stricture in the SPCH group. Conclusions: The short-term outcome of modified SPCH is comparable with MPCH according to our study. It is easily adaptable treatment of CDC.

Timing of operation in children with a prenatal diagnosis of choledochal cyst: A single-center retrospective study.

BACKGROUND/PURPOSE: There is currently no consensus on the timing of operative correction for patients with a prenatal diagnosis of choledochal cyst (CDC). This study aims to retrospectively analyze patients with prenatally diagnosed CDCs to identify the optimal timing of operative correction and the importance of cyst size as a predictor of the appearance of symptoms related to the CDC. METHODS: We reviewed 125 patients with a prenatal diagnosis of CDC who were admitted to Guangzhou Women and Children's Medical Center from July 2015 to July 2020. After dividing the patients into a symptomatic group (n = 37) and an asymptomatic group (n = 88), according to whether they had any clinical symptoms at the time of their operation, we compared their clinical data and postoperative outcomes. The asymptomatic group was divided into a <1 month group; a ≥1 month and <4 months group; and a ≥4 months group according to their postnatal age at operation; postoperative complications of the three groups were then compared. We were also interested in the effect of cyst size (width and length) for predicting the development of symptoms related to the CDC. RESULTS: The time of onset of symptoms after birth was mainly concentrated in the first 3 months (48.6%). The median width and length of cysts measured by preoperative magnetic resonance cholangiopancreatography in the symptomatic group were greater than those in the asymptomatic group (43 mm vs 28 mm and 71 mm vs 45 mm, respectively; P < .05). The serum levels of the liver-related enzymes ALT, AST, and GGT, and the serum level of DBIL, were greater in the symptomatic group than in the asymptomatic group (P < .05). The operative time, intraoperative blood loss, and duration of postoperative hospital stay in the symptomatic group were greater than those in the asymptomatic group (P < .05). In the asymptomatic group, there were no statistically significant differences in the surgical data and postoperative complications between the <1 month group, the ≥1 month and <4 months group, and the ≥4 months group. The area under the receiver operating characteristic curve (AUROC) of the length of the cyst in predicting symptoms was 0.747, the best cut-off point was 5.2 cm, and the sensitivity and specificity were 78% and 70%, respectively. The AUROC of the width of the cyst was 0.704, the best cut-off point was 4.1 cm, and the sensitivity and specificity were 68% and 75%, respectively. CONCLUSION: We maintain that it is advantageous to receive surgical treatment in the asymptomatic period for patients with a prenatally diagnosed CDC. A cyst size of length >5.2 cm and width >4.1 cm suggested that clinical symptoms might appear, and that surgery should be carried out as soon as possible, even in the neonatal period.

Nomogram for Estimating the Risks of Intestinal Ischemia and Necrosis in Neonates With Midgut Volvulus: A Retrospective Study.

Background: Delayed diagnosis and inaccurate judgment of the severity of the disease may be the principal reasons for the poor prognosis associated with neonatal midgut volvulus. We aimed to develop a nomogram model that timely assesses the risks of intestinal ischemia and necrosis in the neonate with midgut volvulus. Materials and Methods: We retrospectively analyzed the clinical data from neonates with midgut volvulus who were admitted to Guangzhou Women and Children's Medical Center from January 2009 to December 2019. Univariate and multivariate analyses were used to obtain independent factors to build a predictive model. The independent factors were used to develop the nomogram model. Results: Heart rate, mean arterial pressure, serum C-reactive protein, serum sodium, serum albumin, and pH levels were independent predictors for intestinal ischemia and necrosis in patients with midgut volvulus. The area under the receiver operating characteristic curve (AUC) of the predictive model was 0.985 (95% confidence interval, 0.966-0.999; P < 0.001). The sensitivity was 90.48%, and the specificity was 93.10%. A nomogram model was established using the six independent predictors, with a C-index of 0.859 and a favorable consistency between the predicted and actual intestinal ischemia and necrosis rates according to the internal validation. Conclusion: The constructed nomogram model could be a superior tool for predicting intestinal ischemia and necrosis in neonates with midgut volvulus.

Long-term prophylactic intravenous antibiotics after Kasai portoenterostomy for biliary atresia do not reduce the risks of post-operative cholangitis, a retrospective study.

BACKGROUND: Postoperative cholangitis (PC) is the most common and serious complication of biliary atresia (BA) patients post-Kasai portoenterostomy (KPE). The duration of prophylactic intravenous antibiotics (IVA) after KPE varies with no clear consensus. We conducted a retrospective cohort study to explore the effects of IVA duration on preventing post-operative cholangitis and analyze the risk factors for cholangitis and short-term prognosis. METHODS: All patients diagnosed with BA and received KPE in Guangzhou Women and Children's Hospital in 2018, were included in this study. The patients received prophylactic IVA after KPE. Firstly, the patients were divided into two groups based on the presence or absence of PC (PC and NPC group). The correlation between PC and the IVA duration was analyzed, followed by a comparison of short-term prognosis, outcome, and other risk factors between the groups. Next, the patients were divided based on the median IVA duration of 11 days (long IVA and short IVA group), followed by a comparison of the incidence of PC, short-term prognosis, outcome, and other risk factors between the two groups. RESULTS: Totally 89 patients were included in this study. Amount them, eleven patients who were lost during follow-up, were excluded from the study. The prophylactic IVA duration of the PC (n=52) and NPC (n=25) groups was 12.6±8.5 and 13.0±4.5 days, respectively (P=0.79). Further, the jaundice clearance rate of the two groups was similar (PC: 31/52, NPC: 13/25, P=0.53). There was no difference in the incidence and frequency of cholangitis between the short (n=42) and long (n=35) IVA groups (27/42, 25/35, P=0.51), and the duration of IVA had no effect on jaundice clearance (24/42, 20/35, P=1.00). The short IVA group had a significantly shorter hospital stay than the long IVA group (16.2±5.1, 25.3±8.3, P=8.95×10-8). Patients undergoing KPE at an older age were at a higher risk of cholangitis (NPC: 60.6±19.7, PC: 72.3±17.8, P=0.01). CONCLUSIONS: A long duration of IVA after KPE for BA may not be necessary. Early diagnosed patients had timely surgery had a lower incidence of PC. Our findings may help in promoting the scientific use of antibiotics and reducing the LHS.

[Treatment strategy and prognosis analysis in children with type I esophageal atresia].

OBJECTIVE: To analyze the postoperative short-term and long-term outcomes in the management of type I esophageal atresia, and to explore the ideal operative strategy. METHODS: Clinical data of 22 patients with type I esophageal atresia treated from January 2005 to September 2012 were retrospectively reviewed. Of 22 patients, 6 patients gave up the treatment. Two underwent primary repair after birth. Of 14 patients undergoing cervical esophagostomy and gastrostomy, 8 patients received esophageal replacement. Postoperative short-term and long-term complications, nutritional state and neurodevelopment were studied on above 10 children with radical operations. RESULTS: Of 10 patients with radical operation, the short-term complications were hydrothorax in 1 case, anastomotic leakage in 4, dumping syndrome in 1, anastomotic stricture in 1. The long-term complications were esophageal stricture in 2 cases, and repeated respiratory infection in 3. These complications could be managed successfully. The postoperative follow-up duration ranged from 2 to 62 months. Two cases were lost during follow-up after 2 years. Weight-for-age was normal in 2 patients, mild malnutrition in 5 patients, and moderate malnutrition in 1 patients. Neurodevelopment is significantly delayed as compared to normal children. CONCLUSIONS: Operative strategy should be chosen according to the distance between proximal and distal esophagus in the treatment of type I esophageal atresia. The efficacy of radical operation is relative satisfactory in terms of short-term and long-term complications and the quality of life.