Common Bile Duct Dilatations in Asymptomatic Neonates: Incidence and Prognosis

Background. This retrospective study reviewed 213 asymptomatic neonates with common bile duct (CBD) dilatations diagnosed via ultrasound to evaluate their incidence and outcomes. Materials and Methods. From August 2001 to July 2010, 18,230 abdominal ultrasound scans were performed as newborn screening. There were 213 (1.17%) cases of CBD dilatation. Dilatation of neonatal CBD was defined when its diameter was ≥2 mm. The neonates’ birth history, CBD size, and follow-up results were analyzed. Results. In the 213 infants, four cystic dilatations (1.88%, 4/213) that were eventually diagnosed as choledochal cysts (CC). Among 209 neonates with fusiform dilatations (size 2.0–6.7 mm), 77 had ultrasound follow-up and 87% of them resolved spontaneously which were diagnosed as transient CBD dilatation (TCBDD). Eighty percent of TCBDDs resolved within 6 months. Patients with initial CBD size ≥3 mm had significantly lower resolution rate and neonates whose mothers are older than 35 years took longer time to resolve. Conclusion. The incidence of CBD dilatation in asymptomatic neonates was 1.17%. Eighty percent of TCBDDs resolved within 6 months. Regular ultrasound follow-up every 6 months may be appropriate for asymptomatic neonates with fusiform CBD dilatations to ensure resolution or progression

Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels

Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 × 10-8) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 × 10-9), NCOA2 (P = 1.6 × 10-8), and NID2-PTGDR (P = 4.2 × 10-8), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 × 10-10). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log10Bayes Factor ≥6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 × 10-5) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets

A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure

Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene-smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene-smoking interaction analysis and 38 were newly identified (P <5 x 10(-8), false discovery rate <0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.Peer reviewe

Biliary Cysts in Children — Long-term Follow-up in Taiwan

This study analyzed the clinical presentation, postoperative morbidity and mortality and incidence of associated extrahepatic biliary atresia in children with biliary cysts in Taiwan. Methods: We retrospectively reviewed the records of 158 pediatric patients with biliary cysts seen between June 1981 and July 2004, with follow-up ranging from 12 months to 22 years (mean, 11.2 ± 6.1 years). Patients were divided into three groups: biliary atresia-associated biliary cyst (BABC, 21 patients), non-biliary atresia-associated choledochal cyst (NBACC) in infancy (37 patients), and late NBACC (> 1 year of age, 100 patients). Results: BABC accounted for 36.2% of the infantile biliary cysts in this study. Extrahepatic cysts in late NBACC had a greater mean diameter than those in infantile NBACC and BABC (21.5 mm vs. 16.0 mm vs. 7.9 mm, p < 0.001). Cholangitis was the most serious complication within 3 months postoperatively in all three groups, resulting in four deaths (two in the infantile NBACC group and one each in the other two groups). Liver cirrhosis developed during long-term follow-up in nine of the 21 patients with BABC, four of whom died. Three of these nine patients underwent liver transplantation and remained well during follow-up. Chronic complications in NBACC occurred mainly in late IVa cases, with persistent intrahepatic dilatation developing in 12 of 35 patients and intrahepatic stones in five. Elevation of serum alanine aminotransferase (ALT) was found preoperatively in 85% of late NBACC and 35% of infantile NBACC cases. Postoperative normalization of ALT occurred after a mean of 152 ± 23 days and 158 ± 67 days in late NBACC and infantile NBACC, respectively. Higher ALT levels before operation were associated with a longer period until normalization. Conclusion: The possibility of BABC must be included in the differential diagnosis when a small extrahepatic cyst (< 8 mm in diameter) with prolonged jaundice is found in infancy. Postoperative follow-up is essential for patients with NBACC due to their frequently prolonged elevation of serum ALT and possibility of residual intrahepatic dilatation. Cholangitis was the major cause of death within 3 months postoperatively in this study

Gastrointestinal Polyps in Children

Gastrointestinal polyps are common in children. The purpose of this study was to review the clinical manifestations, diagnostic procedures, endoscopic findings, management, pathology, and recurrence of gastrointestinal polyps in children at Mackay Memorial Hospital. Methods: We retrospectively reviewed the charts of 50 children with a diagnosis of gastrointestinal polyps managed at Mackay Memorial Hospital between January 1984 and April 2007. Demographic data; clinical features; polyp size, number and location; endoscopic findings; management; pathology; and information on recurrences were extracted from the clinical records. Results: The distribution of polyps in the 50 patients included gastric (4 patients), duodenal (2), ileocecal (4) and colorectal polyps (40). All patients with gastric polyps presented with vomiting, and three of the four patients with ileocecal polyps presented with intussusception. The mean age of the 40 patients with colorectal polyps was 6.8 years. The majority of those polyps were in the rectosigmoid colon; 36 patients presented with hematochezia. Solitary polyps were identified in 33 patients and multiple polyps were identified in seven patients. Most of the colorectal polyps were less than 2 cm in diameter. Histologically, the most frequent type was juvenile polyp. Conclusion: Gastrointestinal polyps in children are usually benign. Pediatricians treating a child with a gastrointestinal polyp should pay attention to the immediate complications of the polyps, such as intussusception or bleeding, the extraintestinal manifestations and long-term risk for malignancy