Biliary atresia (BA) is the most severe form of obstructive cholangiopathy occurring in infants. Definitive diagnosis of BA usually relies on operative findings together with supporting pathological patterns found in the extrahepatic bile duct. In infancy, overlapping clinical patterns of cholestasis can be found in other diseases including biliary hypoplasia and progressive familial intrahepatic cholestasis. In addition, BA has been reported as a phenotype in some rare genetic syndromes. Unlike BA, other cholangiopathic phenotypes have their own established genetic markers. In this study, we used these markers to look for other cholestasis entities in cases diagnosed with BA. DNA from 20 cases of BA, diagnosed by operative findings and histopathology, were subjected to a study of 19 genes associated with infantile cholestasis syndromes, using whole exome sequencing. Variant selection focused on those with allele frequencies in dbSNP150 of less than 0.01. All selected variants were verified by polymerase chain reaction-direct sequencing. Of the 20 cases studied, 13 rare variants were detected in 9 genes: 4 in (Alagille syndrome), 2 in (progressive familial intrahepatic cholestasis [PFIC] type 6), and one each in (Dubin-Johnson syndrome), (PFIC type 2), (Crigler-Najjar syndrome), (Kabuki syndrome), (Mitchell-Riley syndrome), (Fanconi anemia), and (Zimmermann-Laband syndrome). Genetic lesions associated with various cholestatic syndromes detected in cases diagnosed with BA raised the hypothesis that severe inflammatory cholangiopathy in BA may not be a distinct disease entity, but a shared pathology among several infantile cholestatic syndromes.

Background: This case-control study aimed to determine if there were any associations between the two single nucleotide polymorphisms (SNPs) in Gc, rs7041 (Asp416Glu) and rs4588 (Thr420Lys) and 3 common cancers (breast, lung and colorectal) in Thai patients. Materials and Methods: Two hundred and eighty two colorectal, 101 breast and 113 lung cancer patients were recruited from one institute during 2011-2013. The controls were age-matched volunteers who had a negative history of index cancers. In addition, vitamin D levels were compared among different genotypes in the 2 SNPs. Results: The minor allele frequencies of rs7041 (G) and rs4588 (A) were 0.32 and 0.24, respectively. Under the dominant model, the study found significant associations between minor-allele genotypes of the SNP rs7041 (TG/GG) and lung cancer (odds ratio [OR] 1.78, 95% CI 1.05-3.03). When subgroup analysis was performed according to sex and age at diagnosis, the study found that the minorallele genotypes of rs7041 (TG/GG) were significantly associated with colorectal cancer in patients whose age at diagnosis was more than 60 years (OR 1.67, 95%CI 1.06-2.61) and the minor-allele genotypes of rs4588 (CA/AA) were significantly associated with colorectal cancer in males aged 60 years or less (OR 2.34, 95%CI 1.25-4.37). When SNP combinations (rs7041-rs4588) were examined, the TT-CA combination had a significant protective

Background: There is an established link between obesity related metabolic derangement and colorectal cancer development. Recently, we developed a metabolic-colorectal cancer risk score. In this follow-up study, we studied its association with colorectal neoplasm by measuring two major metabolic syndrome biomarkers, leptin and adiponectin. Objectives: To evaluate the serum levels of leptin and adiponectin in patients with colorectal polyps and colorectal cancer and to determine any correlation with metabolic risk score. Results: In total, 130 individuals were studied: 30 controls without colonic pathology, 18 with colonic adenoma (CAP), and 82 with colorectal adenocarcinoma (CRC, 17 cases of T1-2 and 65 cases of T3-4). The metabolic risk scores in CAP and T1-2 CRC were higher than those in the controls and T3-4 CRC cases. There were no statistically significant differences in leptin levels among CAPs, CRCs, and controls. Both leptin and adiponectin levels reflected differences in body mass index and metabolic risk scores. Cases in the CAP group and early T-stage CRC groups had lower adiponectin levels (14.03 and 13.01 mg/ml, respectively) than the no polyps group (19.5mg/ml, p = 0.03). The average serum adiponectin level in the invasive cancer group (18.5 ng/ml) was comparable with that of the control group. Conclusions: The level of serum adiponectin was positively correlated with the metabolic risk score. Decreased serum adiponectin was significantly associated with the development of colorectal adenoma and early stage colorectal carcinoma.

Abstract. Wilms' tumor 1 gene (WT1) is known to be a tumor suppressor gene in the subset of nephroblastomas that harbors WT1 mutations. However, its role in nephroblastomas without mutations remains unclear. This study aimed to evaluate the expression of WT1 and its potential oncogenic role in pediatric nephroblastoma with wild-type WT1. A total of 24 nephroblastomas were studied for WT1 mRNA expression by quantitative reverse-transcription polymerase chain reaction. The expression levels were compared between nephro-blastomas with and without WT1 mutations, as well as to normal kidney tissue, other pediatric renal tumors and neuroblastomas. Immunohistochemistry was used to evaluate expression patterns at the tissue level. Post-transcriptional inhibition of WT1 was performed in primary cultures of wildtype nephroblastoma using WT1 siRNA. The average WT1 expression level in nephroblastoma tissue was significantly higher than that in normal kidney tissue and neuroblastomas. Expression at the mRNA level was not different between nephroblastomas with WT1 mutations (4 cases) and those with wild-type WT1 (20 cases). However, while WT1 immunoreactivity was positive in all of the nephroblastoma components in the tumors with wild-type WT1, the protein expression was weaker and limited to stromal components in the tumors with mutated WT1, where it co-localized with β-catenin nuclear accumulation. The post-transcriptional inhibition of WT1 resulted in growth retardation and a significantly increased apoptotic fraction. Our study found overexpression of the WT1 gene in pediatric nephroblastomas with wild-type WT1.Moreover, the study suggests an oncogenic role of WT1 in this tumor subset.

The overall outcomes of GIST can be predicted by risk-categorization. Surgery alone may not be a curative treatment for GIST. Response to targeted therapy is a crucial survival determinant in these patients.