Development of a CT-based radiomics-clinical model to diagnose acute pancreatitis on nonobvious findings on CT in children with pancreaticobiliary maljunction.

OBJECTIVES: Since neither abdominal pain nor pancreatic enzyme elevation is specific for acute pancreatitis (AP), the diagnosis of AP in patients with pancreaticobiliary maljunction (PBM) may be challenging when the pancreas appears normal or nonobvious on CT. This study aimed to develop a quantitative radiomics-based nomogram of pancreatic CT for identifying AP in children with PBM who have nonobvious findings on CT. METHODS: PBM patients with a diagnosis of AP evaluated at the Children's Hospital of Soochow University from June 2015 to October 2022 were retrospectively reviewed. The radiological features and clinical factors associated with AP were evaluated. Based on the selected variables, multivariate logistic regression was used to construct clinical, radiomics, and combined models. RESULTS: Two clinical parameters and 6 radiomics characteristics were chosen based on their significant association with AP, as demonstrated in the training (area under curve [AUC]: 0.767, 0.892) and validation (AUC: 0.757, 0.836) datasets. The radiomics-clinical nomogram demonstrated superior performance in both the training (AUC, 0.938) and validation (AUC, 0.864) datasets, exhibiting satisfactory calibration (P > .05). CONCLUSIONS: Our radiomics-based nomogram is an accurate, noninvasive diagnostic technique that can identify AP in children with PBM even when CT presentation is not obvious. ADVANCES IN KNOWLEDGE: This study extracted imaging features of nonobvious pancreatitis. Then it developed and evaluated a combined model with these features.

A multicenter prospective study on the management of hepatoblastoma in children: a report from the Chinese Children's Cancer Group.

BACKGROUND: This study aimed to identify survival risk factors in Chinese children with hepatoblastoma (HB) and assess the effectiveness of the new treatment protocol proposed by the Chinese Children's Cancer Group (CCCG) in 2016. METHODS: A multicenter, prospective study that included 399 patients with HB from January 2015 to June 2020 was conducted. Patient demographics, treatment protocols, and other related information were collected. Cox regression models and Kaplan-Meier curve methods were used. RESULTS: The 4-year event-free survival (EFS) and overall survival (OS) were 76.9 and 93.5%, respectively. The 4-year EFS rates for the very-low-risk, low-risk, intermediate-risk, and high-risk groups were 100%, 91.6%, 81.7%, and 51.0%, respectively. The 4-year OS was 100%, 97.3%, 94.4%, and 86.8%, respectively. Cox regression analysis found that age, tumor rupture (R +), and extrahepatic tumor extension (E +) were independent prognostic factors. A total of 299 patients had complete remission, and 19 relapsed. Patients with declining alpha-fetoprotein (AFP) > 75% after the first two cycles of neoadjuvant chemotherapy had a better EFS and OS than those ≤ 75%. CONCLUSIONS: The survival outcome of HB children has dramatically improved since the implementation of CCCG-HB-2016 therapy. Age ≥ 8 years, R + , and E + were independent risk factors for prognosis. Patients with a declining AFP > 75% after the first two cycles of neoadjuvant chemotherapy had better EFS and OS.

Clinical presentations and outcomes of pancreaticobiliary maljunction in different pediatric age groups.

BACKGROUND: Pancreaticobiliary maljunction (PBM) is a congenital defect, with risk of developing various pancreaticobiliary and hepatic complications. The presentations of PBM in children and adults are believed to be different, but studies on PBM children of different age groups are limited. This study was to evaluate clinicopathologic characteristics and outcomes in PBM children of different ages. METHODS: A total of 166 pediatric patients with PBM were reviewed retrospectively. Clinicopathological, imaging, laboratory, surgical, and follow-up data were collected and analyzed. The patients were divided into three age groups, namely, group A (< 1 year, n = 31), group B (1-3 years, n = 63), and group C (> 3 years, n = 72). RESULTS: The major clinical manifestation was jaundice in group A and abdominal pain and vomiting in groups B and C. Acute pancreatitis was more often seen in group C than group A. The length of common channel was significantly longer in group C than group A, while the maximum diameter of common bile duct in group C was smaller than that in group A. Cholangitis and cholecystitis were more commonly performed in groups B and C, while hepatic fibrosis in group A. Whether preoperatively or postoperatively, group C was more likely to have elevated serum amylase, while groups A and B were more likely to present with abnormal liver function indicators, including the increase of aspartate transaminase, alanine transaminase, and gamma-glutamyl transpeptidase. CONCLUSION: Presentation of PBM varies among different pediatric age groups, thus suggesting that targeted management should be carried out according to these differences.

Using machine learning models to predict the surgical risk of children with pancreaticobiliary maljunction and biliary dilatation.

PURPOSE: To develop machine learning (ML) models to predict the surgical risk of children with pancreaticobiliary maljunction (PBM) and biliary dilatation. METHODS: The subjects of this study were 157 pediatric patients who underwent surgery for PBM with biliary dilatation between January, 2015 and August, 2022. Using preoperative data, four ML models were developed, including logistic regression (LR), random forest (RF), support vector machine classifier (SVC), and extreme gradient boosting (XGBoost). The performance of each model was assessed via the area under the receiver operator characteristic curve (AUC). Model interpretations were generated by Shapley Additive Explanations. A nomogram was used to validate the best-performing model. RESULTS: Sixty-eight patients (43.3%) were classified as the high-risk surgery group. The XGBoost model (AUC = 0.822) outperformed the LR (AUC = 0.798), RF (AUC = 0.802) and SVC (AUC = 0.804) models. In all four models, enhancement of the choledochal cystic wall and an abnormal position of the right hepatic artery were the two most important features. Moreover, the diameter of the choledochal cyst, bile duct variation, and serum amylase were selected as key predictive factors by all four models. CONCLUSIONS: Using preoperative data, the ML models, especially XGBoost, have the potential to predict the surgical risk of children with PBM and biliary dilatation. The nomogram may provide surgeons early warning to avoid intraoperative iatrogenic injury.

Identification and validation of radiomic features from computed tomography for preoperative classification of neuroblastic tumors in children.

BACKGROUND: To identify radiomic features that can predict the pathological type of neuroblastic tumor in children. METHODS: Data on neuroblastic tumors in 104 children were retrospectively analyzed. There were 14 cases of ganglioneuroma, 24 cases of ganglioneuroblastoma, and 65 cases of neuroblastoma. Stratified sampling was used to randomly allocate the cases into the training and validation sets in a ratio of 3:1. The maximum relevance-minimum redundancy algorithm was used to identify the top 10 of two clinical features and 851 radiomic features in portal venous-phase contrast-enhanced computed tomography images. Least absolute shrinkage and selection operator regression was used to classify tumors in two binary steps: first as ganglioneuroma compared to the other two types, then as ganglioneuroblastoma compared to neuroblastoma. RESULTS: Based on 10 clinical-radiomic features, the classifier identified ganglioneuroma compared to the other two tumor types in the validation dataset with sensitivity of 100.0%, specificity of 81.8%, and an area under the receiver operating characteristic curve (AUC) of 0.875. The classifier identified ganglioneuroblastoma versus neuroblastoma with a sensitivity of 83.3%, a specificity of 87.5%, and an AUC of 0.854. The overall accuracy of the classifier across all three types of tumors was 80.8%. CONCLUSION: Radiomic features can help predict the pathological type of neuroblastic tumors in children.

Prediction of post-operative acute pancreatitis in children with pancreaticobiliary maljunction using machine learning model.

PURPOSE: This study aimed to develop a prediction model to identify risk factors for post-operative acute pancreatitis (POAP) in children with pancreaticobiliary maljunction (PBM) by pre-operative analysis of patient variables. METHODS: Logistic regression (LR), support vector machine (SVM), and extreme gradient boosting (XGBoost) models were established using the prospectively collected databases of patients with PBM undergoing surgery which was reviewed in the period comprised between August 2015 and August 2022, at the Children's Hospital of Soochow University. Primarily, the area beneath the receiver-operating curves (AUC), accuracy, sensitivity, and specificity were used to evaluate the model performance. The model was finally validated using the nomogram and clinical impact curve. RESULTS: In total, 111 children with PBM met the inclusion criteria, and 21 children suffered POAP. In the validation dataset, LR models showed the highest performance. The risk nomogram and clinical effect curve demonstrated that the LR model was highly predictive. CONCLUSION: The prediction model based on the LR with a nomogram could be used to predict the risk of POAP in patients with PBM. Protein plugs, age, white blood cell count, and common bile duct diameter were the most relevant contributing factors to the models.

Systematic screen of potential circular RNA biomarkers of Hirschsprung's disease.

BACKGROUND: Hirschsprung's disease (HSCR) is a developmental disorder of the enteric nervous system in which enteric ganglia are missing along a portion of the intestine. Aberrant expression of several circular RNAs (circRNAs) has been identified in the disease, but the full range of dysregulated circRNAs and their potential roles in its pathogenesis remain unclear. We used microarray profiling to systematically screen for circRNAs that were differentially expressed in HSCR, and we comprehensively analyzed the potential circRNA-miRNA-mRNA regulatory network to identify molecular mechanisms involved in the disorder. METHODS: We identified circRNAs that were differentially expressed between diseased tissue and paired normal intestinal tissues from patients with HSCR. The most strongly upregulated circRNAs were then validated by quantitative reverse-transcription-PCR (RT-PCR). We also constructed a circRNA-miRNA-mRNA interaction network to determine functional interactions between miRNAs and mRNAs. RESULTS: We identified 17 circRNAs that were upregulated and 10 that were downregulated in HSCR tissue compared with normal tissues. The five circRNAs that showed the greatest upregulation were verified by RT-PCR: hsa_circRNA_092493, hsa_circRNA_101965, hsa_circRNA_103118, hsa_circRNA_103279, and hsa_circRNA_104214. These five circRNAs were successfully adopted to diagnose HSCR based on receiver operating characteristic curves, and they were used to generate a circRNA-miRNA-mRNA network. The network revealed a potential function of the circRNAs as molecular sponges targeting miRNAs and mRNAs in HSCR. CONCLUSIONS: This first-ever systematic dissection of the circRNA profile in HSCR may provide useful insights into improving diagnosis and therapy.

Machine learning-based quantitative analysis of barium enema and clinical features for early diagnosis of short-segment Hirschsprung disease in neonate.

OBJECTIVE: To develop a mathematical model based on a combination of clinical and radiologic features (barium enema) for early diagnosis of short-segment Hirschsprung disease (SHSCR) in neonate. METHODS: The analysis included 54 neonates with biopsy-confirmed SHSCR (the cases) and 59 neonates undergoing barium enema for abdominal symptoms but no Hirschsprung disease (the control). Colon shape features extracted from barium enema images and clinical features were used to develop diagnostic models using support vector machine (SVM) and L2-regularized logistic regression (LR). The training cohort included 32 cases and 37 controls; testing cohort consisted 22 cases and 22 controls. Results were compared to interpretation by 2 radiologists. RESULTS: In the analysis by radiologists, 87 out of 113 cases were correctly classified. Six SHSCR cases were mis-classified into the non-HSCR group. In the remaining 20 cases, radiologists were unable to make a decision. Both the SVM and LR classifiers contained five clinical features and four shape features. The performance of the two classifiers was similar. The best model had 86.36% accuracy, 81.82% sensitivity, and 90.91% specificity. The AUC was 0.9132 for the best-performing SVM classifier and 0.9318 for the best-performing LR classifier. CONCLUSION: A combination of clinical features and colon shape features extracted from barium enemas can be used to improve early diagnosis of SHSCR in neonate.

Gene expression profiling reveals upregulated FUT1 and MYBPC1 in children with pancreaticobiliary maljunction.

Pancreaticobiliary maljunction (PBM) is associated with high risk of epithelial atypical growth and malignant transformation of the bile duct or gallbladder. However, overall changes in genetic expression have not been examined in children with PBM. Genome-wide expression was analyzed using peripheral blood samples from 10 children with PBM and 15 pediatric controls. Differentially expressed genes (DEGs) were identified using microarray. Bioinformatics analysis was conducted using Gene Ontology and KEGG analyses. The top 5 in the up-regulated genes in PBM were verified with qRT-PCR. Receiver operator characteristic curve analysis was conducted to evaluate the predictive accuracy of selected genes for PBM. The microarray experiments identified a total of 876 DEGs in PBM, among which 530 were up-regulated and the remaining 346 were down-regulated. Verification of the top 5 up-regulated genes (TYMS, MYBPC1, FUT1, XAGE2, and GREB1L) by qRT-PCR confirmed the up-regulation of MYBPC1 and FUT1. Receiver operating characteristic curve analysis suggested that FUT1 and MYBPC1 up-regulation could be used to predict PBM, with the area under the curve of 0.873 (95%CI=0.735-1.000) and 0.960 (95%CI=0.891-1.000), respectively. FUT1 and MYBPC1 were up-regulated in children with PBM, and could be used as potential biomarkers for PBM.

Forecasting and predicting intussusception in children younger than 48 months in Suzhou using a seasonal autoregressive integrated moving average model.

OBJECTIVE: The aims of this study were to highlight some epidemiological aspects of intussusception cases younger than 48 months and to develop a forecasting model for the occurrence of intussusception in children younger than 48 months in Suzhou. DESIGN: A retrospective study of intussusception cases that occurred between January 2007 and December 2017. SETTING: Retrospective chart reviews of intussusception paediatric patients in a large Children's hospital in South-East China were performed. PARTICIPANTS: The hospital records of 13 887 intussusception cases in patients younger than 48 months were included in this study. INTERVENTIONS: The modelling process was conducted using the appropriate module in SPSS V.23.0. METHODS: The Box-Jenkins approach was used to fit a seasonal autoregressive integrated moving average (ARIMA) model to the monthly recorded intussusception cases in patients younger than 48 months in Suzhou from 2007 to 2016. RESULTS: Epidemiological analysis revealed that intussusception younger than 48 months was reported continuously throughout the year, with peaks in the late spring and early summer months. The most affected age group was younger than 36 months. The time-series analysis showed that an ARIMA (1,0,1 1,1,1)12 model offered the best fit for surveillance data of intussusception younger than 48 months. This model was used to predict intussusception younger than 48 months for the year 2017, and the fitted data showed considerable agreement with the actual data. CONCLUSION: ARIMA models are useful for monitoring intussusception in patients younger than 48 months and provide an estimate of the variability to be expected in future cases in Suzhou. The models are helpful for predicting intussusception cases in Suzhou and could be useful for developing early warning systems. They may also play a key role in early detection, timely treatment and prevention of serious complications in cases of intussusception.

Gene expression profiling reveals upregulated FUT1 and MYBPC1 in children with pancreaticobiliary maljunction

Pancreaticobiliary maljunction (PBM) is associated with high risk of epithelial atypical growth and malignant transformation of the bile duct or gallbladder. However, overall changes in genetic expression have not been examined in children with PBM. Genome-wide expression was analyzed using peripheral blood samples from 10 children with PBM and 15 pediatric controls. Differentially expressed genes (DEGs) were identified using microarray. Bioinformatics analysis was conducted using Gene Ontology and KEGG analyses. The top 5 in the up-regulated genes in PBM were verified with qRT-PCR. Receiver operator characteristic curve analysis was conducted to evaluate the predictive accuracy of selected genes for PBM. The microarray experiments identified a total of 876 DEGs in PBM, among which 530 were up-regulated and the remaining 346 were down-regulated. Verification of the top 5 up-regulated genes (TYMS, MYBPC1, FUT1, XAGE2, and GREB1L) by qRT-PCR confirmed the up-regulation of MYBPC1 and FUT1. Receiver operating characteristic curve analysis suggested that FUT1 and MYBPC1 up-regulation could be used to predict PBM, with the area under the curve of 0.873 (95%CI=0.735−1.000) and 0.960 (95%CI=0.891−1.000), respectively. FUT1 and MYBPC1 were up-regulated in children with PBM, and could be used as potential biomarkers for PBM.

Factors affecting the operating time for complete cyst excision and Roux-en-Y hepaticojejunostomy in paediatric cases of congenital choledochal malformation: a retrospective case study in Southeast China.

OBJECTIVE: The aim of this study was to evaluate factors affecting the operating time for complete cyst excision and Roux-en-Y hepaticojejunostomy in paediatric cases of congenital choledochal malformation (CCM). DESIGN: A 3-year retrospective study was undertaken between January 2013 and December 2015 in four centres in China. SETTING: This involved a retrospective chart review of paediatric patients with CCM in four large hospitals in Southeast China. PARTICIPANTS: Sixty-five paediatric patients with CCM were included in this study. We derived all available information on patient demographics, clinical characteristics, preoperative complications and surgical methods from the charts of all these patients. INTERVENTIONS: Univariate and multivariate logistic regression analyses were used to evaluate factors significantly affecting the operating time for complete cyst excision and Roux-en-Y hepaticojejunostomy in paediatric cases of CCM. RESULTS: Twenty-three of the 65 case surgeries were performed using laparoscopic technique, and 42 surgeries were performed by conventional open surgery. The median operating time was 215 min (range 120-430 min). The morphological subtype of CCM and the presence of cholecystitis or cholangitis were the only factors found to affect the operating time (p<0.05). Logistic regression analysis confirmed cholangitis as an independent risk factor. CONCLUSIONS: The morphological subtype of CMM and the presence of cholecystitis or cholangitis are factors affecting the operating time for complete cyst excision and Roux-en-Y hepaticojejunostomy in paediatric cases of CCM, whereas cholangitis is an independent risk factor.

Molecular imaging of Toll-like receptor 4 detects ischemia-reperfusion injury during intussusception.

We investigated the expression of Toll-like receptor 4 (TLR4) in the acute phase of intestinal I/R injury during intussusception and evaluated whether anti-TLR4 antibody-conjugated lead sulfide quantum dots (TLR4-PbS QDs) could be used to detect and monitor the injury. We first established a mouse model of I/R injury during intussusception. TLR-PbS QDs were then intravenously administered to intestinal I/R injured mice and visualized using whole-body fluorescence imaging in the second near-infrared window (NIR-II). Immunohistochemical analysis of intestinal tissue from the mice revealed that TLR4 expression was higher in the I/R injury group than the control and TAK-242 groups (5.189 ± 2.482, 1.186 ± 1.171, and 2.400 ± 0.857, respectively, P < 0.05). NIR-II fluorescence intensity was also higher in the I/R injury group than in the control and TAK-242 groups (86.415 ± 10.955, 38.975 ± 8.619, and 71.977 ± 3.838, respectively; P < 0.05). Thus, anti-TLR4-PbS QDs bound to TLR4 on the cell membranes of intestinal epithelial cells with high specificity in vitro and in vivo. These results indicate that TLR4 promotes intestinal I/R injury during intussusception and that the injury can be noninvasively imaged using TLR4-PbS QDs.

Factors Interfering with Delineation on MRCP of Pancreaticobiliary Maljunction in Paediatric Patients.

BACKGROUND: The aim of this study was to assess factors for delineating the pancreaticobiliary junction in the presence of pediatric congenital choledochal cysts (CCC) using Magnetic resonance cholangiopancreatography (MRCP). METHODS: Retrospective review of medical records for 48 patients with CCC was conducted, including demographics, biliary amylase and MRCP findings if available. With univariate and multivariate logistic regression, we measured significant factors affecting pancreaticobiliary maljunction(PBM) diagnoses by MRCP. RESULTS: Of the subjects enrolled with CCC. Twenty-eight cases had PBM according to MRCP. Univariate analysis confirmed that age, cyst diameter > 30 mm and cysts that descended to the introitus pelvis affected junctional delineation and detection of PBM (P<0.05). Stepwise logistic regression analysis confirmed large cysts in the introitus pelvis predicted pancreaticobiliary junctional delineation in MRCP and these data agreed with the literature. A correlation between cyst diameter and the length of the common channel was found as was cyst diameter and biliary amylase although there were no significant differences between them. CONCLUSIONS: Age, cyst diameter >30 mm and descending cysts into the introitus pelvis affected junctional delineation of the pancreatic and bile duct in PBM with MRCP. Large cyst descension into the introitus pelvis was an independent factors affecting PBM detection.

Altered expression levels of occludin, claudin-1 and myosin light chain kinase in the common bile duct of pediatric patients with pancreaticobiliary maljunction.

BACKGROUND: In pancreaticobiliary maljunction (PBM), the sphincter of Oddi can not control bile and pancreatic juice flow, which may lead to two-way reflux of bile and pancreatic juice, thus causing chronic inflammation, thickening, fibrosis and metaplasia of the common bile duct wall. These pathophysiological changes have been linked to disruption of the epithelium barrier in the common bile duct. We hypothesized that the expression of tight junction-associated proteins may be dysregulated in the common bile duct in PBM. In the current study, we sought to analyze the expression of tight junction-associated proteins in the common bile duct epithelium of pediatric patients with PBM. METHODS: Specimens of the common bile duct were collected from 12 pediatric patients with PBM and 10 non-PBM controls. The expression of the tight junction-associated proteins occludin and claudin-1 in the epithelium was examined by immunohistochemistry. The Image-Pro Plus v. 6.0 image analysis software was used to calculate the mean qualifying score (MQS) of imunostained sections of common bile duct epithelium. Total protein extracts of common bile duct were analyzed by Western blotting assays to examine expression of occludin, claudin-1 and myosin light chain kinase (MLCK). Spearman correlation analysis was used to analyze the relation between MLCK and occludin, MLCK and claudin-1. RESULTS: Immunostained sections of the common bile duct epithelium showed significantly higher MQS in pediatric patients than controls for occludin (44.11 ± 13.82 vs. 11.30 ± 9.58, P = 0.0034) and claudin-1 (63.44 ± 23.59 vs. 46.10 ± 7.84, P = 0.0384). Western blotting also showed significantly higher expression of occludin, claudin-1 and MLCK in the common bile duct of patients than of controls (P = 0.0023, 0.0015, 0.0488). Spearman correlation analysis showed that MLCK expression correlated positively with the expression of occludin (r s = 0.61538, P = 0.0032) and claudin-1 (r s = 0.7972, P = 0.0019). CONCLUSIONS: Occludin and claudin-1 are up-regulated in the common bile duct epithelium of pediatric PBM patients. MLCK may be involved in the process of up-regulation of the tight junction-associated proteins in PBM.

Anatomical and Morphological Features of the Fetal Human Pancreaticobiliary Ductal Union.

To investigate pancreaticobiliary ductal anatomy during developmental stages, gallbladders, common bile ducts, pancreatic ducts and their interface with the duodenum were studied in 36 human fetuses between 4-6 weeks postconceptual age were studied. For histological examination, sections were cut continuously from the paraffin-embedded tissue block and stained with hematoxylin and eosin. The expression of proliferating cell nuclear antigen in the gallbladder was examined with immunohistochemistry. Among 36 cases, three shapes of the greater duodenal papilla were found: hemispheroid (58.1%), circular cylinder (25%), and flat shape (16.9%). For the location of the greater duodenal papillas, more than half (69.4%) of the cases were in the middle descendant duodenum. Seven cases (19.4%) were in the lower descendant duodenum. Three cases (8.3%) were in the upper descendant duodenum, and one (2.9%) was in the distal descending part of duodenum. There were four types of the pancreaticobiliary ductal union: "Y" in 24 cases(66.7%), "U" in 4 cases (11.1%),"V" in 7 cases (19.4%), and pancreaticobiliary maljunction in 1 case (2.8%). For patients with congenital bile duct dilation and Biliary cancer, the positive cells of proliferating cell nuclear antigen were increased significantly (P < 0.05). Different types in pancreaticobiliary ductal union investigated in this study may provide clues for pathogenesis and clinical treatment of pancreaticobiliary maljunction.

The role of 64-slice CT following perfusion with iohexol via the hepatopancreatic ampulla in assessing pancreaticobiliary junctions.

The aim of this study was to delineate the structure of the pancreatic and biliary ducts in premature infants using a novel imaging method. The duodenal papillae of 30 premature infant cadavers were dissected. The pancreatic and biliary ducts were visualized using 64-detector multislice spiral computed tomography (MSCT). Contrast agent was injected into the duodenal papilla via the hepatopancreatic ampulla of Vater. MSCT scanning revealed both the pancreatic and biliary ducts as well as the common channel in 18 cases. The bile duct was visualized in the remaining 12 cases. Four patterns of the pancreaticobiliary ductal junction were noted: Y-type (73.3%), U-type (13.3%), V-type (6.7%), and II-type (6.7%). The results showed that MSCT and three-dimensional reconstruction can be used to visualize the junction pattern and common channel of the pancreatic and biliary ducts, and the structure of the surrounding tissue, in premature infants.

Liver, biliary and pancreatic injuries in pancreaticobiliary maljunction model in cats.

BACKGROUND: Pancreaticobiliary maljunction is a high risk factor of pancreatitis and biliary tract cancer. How this maljunction affects the liver remains obscure. This study aimed to examine the effects of pancreaticobiliary maljunction on the liver, pancreas and gallbladder in a cat model. METHODS: A model of choledocho-pancreatic side-to-side ductal anastomosis was created in ten cats. Before the procedure, a small piece of tissue from the liver, pancreas and gallbladder was collected as a control. The common channel formation was checked by cholecystography. The livers, pancreases and gallbladders of these cats were harvested for histological examination. The expression of proliferating cell nuclear antigen in the gallbladder was examined with immunohistochemistry. RESULTS: Seven of the 10 cats survived for 6 months after surgery. The color of the liver was darker in the PBM model than the control specimen, with nodules on the surface. Histological examination showed ballooning changes and inflammatory infiltrations and the histopathological score increased significantly (P<0.05). Also, mitochondria swelling and lipid droplet in cytoplasm were observed under an electron microscope. The pancreas also appeared darker in the PBM model than the control specimen and dilated pancreatic ducts were found in three cats. Histopathological examination revealed vascular proliferation and inflammatory infiltration with numerous neutrophils. Gallbladder epithelial cells were featured by expanded endoplasmic reticulum, increased intercellular space and cellular nucleus deformation. The positive cells of proliferating cell nuclear antigen were increased significantly (P<0.05). CONCLUSION: The present study demonstrated that pancreaticobiliary maljunction can lead to the injuries of the liver, pancreas and gallbladder.

The compromised inflammatory response to bacterial components after pediatric cardiac surgery is associated with cardiopulmonary bypass-suppressed Toll-like receptor signal transduction pathways.

PURPOSE: Cardiopulmonary bypass (CPB) during pediatric cardiac surgery often elicits a systemic inflammatory response followed by a compromised immune response, which has been attributed to the morbidity of postoperative infection; however, the underlying mechanism(s) has not yet been fully elucidated. We hypothesized that CPB inhibits the activation of Toll-like receptor (TLR) signal transduction pathways, thereby causing an immunosuppressive state after pediatric cardiac surgery. METHODS: We examined 20 children with congenital heart disease undergoing pediatric cardiac surgery. RESULTS: Cardiopulmonary bypass differentially affected lipopolysaccharide (LPS)- or bacterial lipoprotein (BLP)-stimulated ex vivo production of proinflammatory and anti-inflammatory cytokines, with significantly diminished tumor necrosis factor α, interleukin (IL) 1ß, IL-6, and IL-8, but substantially enhanced IL-10 production. Consistent with the reduced inflammatory response, CPB strongly inhibited LPS- or BLP-activated TLR signal transduction pathways in monocytes with down-regulated expression of CD14, TLR4, and TLR2 and with suppressed phosphorylation of nuclear factor κB p65, p38, and extracellular signal-regulated kinase 1/2. CONCLUSIONS: These results indicate that CPB during pediatric cardiac surgery causes substantially reduced production of inflammatory cytokines in response to bacterial component LPS or BLP stimulation, which is associated with CPB-induced suppression of TLR-mediated signal transduction pathways. This reduced inflammatory response after CPB in children with congenital heart disease may predispose them to an increased risk of postoperative infection.

Laparotomy and laparoscopy diversely affect macrophage-associated antimicrobial activity in a murine model.

BACKGROUND: Surgical intervention-related trauma contributes largely to the development of postoperative immunosuppression, with reduced resistance to secondary bacterial infection. This study compared the impact of laparotomy versus laparoscopy on macrophage-associated bactericidal ability and examined whether laparotomy renders the host more susceptible to microbial infection. RESULTS: BALB/c mice were randomized into control, laparotomy, and laparoscopy groups. Laparotomy, but not laparoscopy, significantly downregulated CR3 expression on macrophages, diminished macrophage-induced uptake and phagocytosis of E. coli and S. aureus, and impaired macrophage-mediated intracellular bacterial killing. Consistent with this, mice that underwent laparotomy displayed substantially higher bacterial counts in the blood and visceral organs as well as a significantly enhanced mortality rate following bacterial infection, whereas mice subjected to laparoscopy did not show any defects in their bacterial clearance. CONCLUSION: Laparotomy has an adverse effect on host innate immunity against microbial infection by impairing macrophage-mediated phagocytosis and killing of the invaded bacteria. By contrast, laparoscopy appears to preserve macrophage-associated bactericidal ability, thus alleviating the development of postoperative immunosuppression.