Clinicopathological features of choledocholithiasis patients with high aminotransferase levels without cholangitis: Prospective comparative study.

Common bile duct (CBD) stones are generally associated with greater elevations of alkaline phosphatase and gamma-glutamyl transpeptidase levels than aspartate aminotransferase and alanine aminotransferase levels. However, some patients with CBD stones show markedly increased aminotransferase levels, sometimes leading to the misdiagnosis of liver disease. Therefore, the aim of this study was to investigate the clinicopathologic features of patients with CBD stones and high aminotransferase levels.This prospective cohort study included 882 patients diagnosed with CBD stones using endoscopic retrograde cholangiopancreatography (ERCP). Among these patients, 38 (4.3%) exhibited aminotransferase levels above 400 IU/L without cholangitis (gallstone hepatitis [GSH] group), and 116 (13.2%) exhibited normal aminotransferase levels (control group). We compared groups in terms of clinical features, laboratory test results, radiologic images, and ERCP findings such as CBD diameter, CBD stone diameter and number, and periampullary diverticulum. Liver biopsy was performed for patients in the GSH group.GSH patients were younger and more likely to have gallbladder stones than control patients, implying a higher incidence of gallbladder stone migration. Also, GSH patients experienced more severe, short-lasting abdominal pain. ERCP showed narrower CBDs in GSH patients than in control patients. Histological analysis of liver tissue from GSH patients showed no abnormalities except for mild inflammation.Compared with control patients, GSH patients were younger and showed more severe, short-lasting abdominal pain, which could be due to a sudden increase of CBD pressure resulting from the migration of gallstones through narrower CBDs. These clinical features could be helpful not only for the differential diagnosis of liver disease but also for investigating the underlying mechanisms of liver damage in obstructive jaundice. Moreover, we propose a new definition of "gallstone hepatitis" based on the specific clinicopathologic characteristics observed in our patients.

Establishing benchmarks for the management of elevated liver enzymes and/or dilated biliary trees in an urban safety net hospital: analysis of 915 subjects.

BACKGROUND: The push for public reporting of outcomes necessitates relevant benchmarks for disease states across different settings. This study establishes benchmarks for choledocholithiasis management in a safety net hospital setting. METHODS: We reviewed all patients admitted to our acute care surgery service with biochemical evidence of choledocholithiasis who underwent same-admission cholecystectomy (CCY) between July 2012 and December 2013. RESULTS: During this 18-month period, 915 patients were admitted with biochemical evidence of choledocholithiasis. Descriptive statistics for the cohort are provided, which include a 51% rate of obesity and 95% rate of pathologic cholecystitis. Conversion rates of 4% and complication rates of 6% were found. The majority had a CCY without biliary imaging (n = 630, 68.9%). CONCLUSIONS: Relevant benchmarks are characterized, and results of a practice pattern of omitting pre- or intraoperative biliary tree imaging are described. These findings serve as a first benchmark of choledocholithiasis management for urban safety net hospitals.

An analysis of omitting biliary tract imaging in 668 subjects admitted to an acute care surgery service with biochemical evidence of choledocholithiasis.

BACKGROUND: No consensus exists for the timing and utility of biliary imaging in patients with preoperative concern for choledocholithiasis. METHODS: Admissions to an acute care surgery service with evidence of choledocholithiasis undergoing same-admission cholecystectomy without preoperative or intraoperative imaging were identified. One-way analysis of variance on the log-transformed outcomes, with the Tukey-Kramer multiple comparison procedure, were used to compare means between groups. RESULTS: A total of 668 patients with elevated but downtrending liver enzymes underwent cholecystectomy without preoperative or intraoperative imaging. Thirty-eight patients (5.7%) had postoperative biliary imaging, of whom 22 (3.3%) had definite choledocholithiasis. One case of postoperative cholangitis occurred which required readmission and endoscopic retrograde cholangiopancreatography with no long-term morbidity. Presenting liver enzymes were significantly higher in the group found to have retained stones postoperatively than those without retained stones. CONCLUSIONS: Patients presenting with biochemical evidence of choledocholithiasis who downtrend preoperatively can be safely managed by cholecystectomy with omission of biliary tract imaging.

Changes of activity and isoforms of alkaline sphingomyelinase (nucleotide pyrophosphatase phosphodiesterase 7) in bile from patients undergoing endoscopic retrograde cholangiopancreatography.

BACKGROUND: Alkaline sphingomyelinase (NPP7) is an ecto-enzyme expressed in intestinal mucosa, which hydrolyses sphingomyelin (SM) to ceramide and inactivates platelet activating factor. It is also expressed in human liver and released in the bile. The enzyme may have anti-tumour and anti-inflammatory effects in colon and its levels are decreased in patients with colon cancer and ulcerative colitis. Active NPP7 is translated from a transcript of 1.4 kb, whereas an inactive form from a 1.2 kb mRNA was found in colon and liver cancer cell lines. While the roles of NPP7 in colon cancer have been intensively studied, less is known about the function and implications of NPP7 in the bile. The present study examines the changes of NPP7 in bile of patients with various hepatobiliary diseases. METHODS: Bile samples were obtained at endoscopic retrograde cholangiopancreatography (ERCP) in 59 patients with gallstone, other benign disease, tumour, and primary sclerosing cholangitis (PSC). The NPP7 activity was determined. The appearance of the 1.4 and 1.2 kb products in the bile was examined by Western blot. The results were correlated to the diseases and also plasma bilirubin and alkaline phosphatase. RESULTS: NPP7 activity in the tumour group was significantly lower than in the gallstone group (p < 0.05). The activity in the tumour plus PSC group was also lower than in gallstone plus other benign disease group (p < 0.05). Within the tumour group NPP7 activity was lowest in cholangiocarcinoma patients, being only 19% of that in gallstone patients. Bilirubin correlated inversely to NPP7 and was higher in the tumour than in the gallstone group. Western blot identified both the 1.4 kb and the 1.2 kb products in most bile samples. The density ratio for the 1.4/1.2 kb products correlated to NPP7 activity significantly. Two patients (one PSC and one cholangiocarcinoma) lacking NPP7 activity had only the 1.2 kb form in bile. CONCLUSION: NPP7 activity and the ratio of 1.4/1.2 kb products in bile are significantly decreased in malignancy, particularly in cholangiocarcinoma. The implications of the finding in diagnosis of cholangiocarcinoma and 1.2 kb product in hepatobiliary diseases require further investigation.

Serum gamma glutamyl transferase and alkaline phosphatase in acute cholecystitis.

BACKGROUND: The serum level of gamma glutaryl transferase and alkaline phosphatase is raised in acute calculus cholecystitis and common bile duct stone. However, the rise in serum level of these enzymes in acute cholecystitis implies stone in the common bile duct is not well studied. Thus, it may lead to retained CBD stone on one side and unnecessary CBD exploration on the other during emergency laparoscopic cholecystectomy. The objective of the study is to predict presence of CBD stone by assessing serum level of gamma-glutamyltransferase (gamma-GT)and alkaline phosphatase. METHODS: A prospective study was designed which included 40 patients with clinically diagnosed and radiologically confirmed acute cholecystitis and 40 patients who had choledocholithiasis with or without cholangitis. Their serumgamma glutaryl transferase and alkaline phosphatase were analyzed. RESULTS: Both acute cholecystitis and CBD pathology had significant increase in alkaline phosphatase (p-value: 0.05). However, in acute cholecystitis there was 1.69±0.118 fold increase and in CBD pathology there was 2.5±0.57 fold increase in alkaline phosphatase than normal.(130 IU /L). There was no statistically significant difference ingamma- GT in both acute cholecystitis and CBD pathology(p-value: 0.390). However it increases by 2.8±0.47fold in acute cholecystitis and by 2.2±0.16 in CBD pathology(p value: 0.627). CONCLUSIONS: Although there is rise in serumγ-GT and alkaline phosphatase level in acute cholecystitis and CBD stone,only more than 2.5 fold rise in serum alkaline phosphatase level predicts CBD stone.

Uridine diphosphate glucuronosyl transferase 1A1 promoter polymorphism is associated with choledocholithiasis in Taiwanese patients.

BACKGROUND AND AIMS: The gene product of the uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) is crucial to bilirubin metabolism. Mutations in this gene subsequently result in disease presented with unconjugated hyperbilirubinemia. A previous study showed that a TA-repeat polymorphism in the promoter region of this gene might play a role in the metabolism of bilirubin. Whether this polymorphism might predispose choledocholithiasis is unclear. METHODS: We recruited 32 patients who were diagnosed with pigment choledocholithiasis (common bile duct stones) by endoscopic retrograde cholangiopancreatography (ERCP) morphology and 107 population controls. The TA-repeat in the UGT1A1 promoter was genotyped. RESULTS: We found that among the 32 patients, 15 (46.9%) were wild type (A[TA](6)TAA homozygous); 15 (46.9%) were a heterozygous variation (A[TA[(6)TAA/A[TA](7)TAA) and 2 (6.2%) were a homozygous variation (A[TA](7)TAA). Among the controls, 81 (75.7%) were wild type, 23 (21.5%) were a heterozygous variation and 3 (2.8%) were a homozygous variation. The genotype distribution was significantly different between patients and controls. CONCLUSIONS: The results suggest that the UGT1A1 promoter TA-repeat polymorphism is associated with choledocholithiasis in Taiwanese patients.

Amylase levels in bile in patients with a morphologically normal pancreaticobiliary ductal arrangement.

BACKGROUND: We investigated the presence of occult pancreaticobiliary reflux in patients with a morphologically normal pancreaticobiliary ductal arrangement by measuring biliary amylase levels and compared histopathological findings of the gallbladder between groups with high and low biliary amylase levels. METHODS: In 178 patients with a normal pancreaticobiliary ductal arrangement who had undergone endoscopic retrograde cholangiopancreatography (ERCP), we sampled bile from the bile duct and measured amylase levels. Then we compared clinical features and histological findings of the gallbladder between high (HALG) and low amylase level groups (LALG). RESULTS: A high biliary amylase level was observed in 25.8% (46/178) of the patients. The prevalence of a high biliary amylase level was high in patients with gallbladder carcinoma (40%) and in those with choledocholithiasis (28.4%). The level of amylase in bile was high in patients with gallbladder carcinoma, adenomyomatosis of the gallbladder, and chronic cholecystitis. A strong correlation between the levels of amylase and lipase in bile and the dominance of amylase of pancreatic origin in bile were confirmed by isozyme analysis. Thickening of the gallbladder mucosa was a significant manifestation in HALG. Histological examination of the gallbladder mucosa showed that incidences of metaplastic change and atypical epithelium and Ki67-LI in were higher in HALG than in LALG. CONCLUSIONS: Occult pancreaticobiliary reflux is observed in a considerable number of ERCP candidates. Those who show an extremely high biliary amylase level, at least, may be at high risk for biliary malignancies.

[Clinical features of patients with choledocholithiasis showing high levels of aminotransferases].

BACKGROUND/AIMS: We aimed to determine the clinical features of patients with common bile duct (CBD) stones with high serum levels of AST or ALT. METHODS: A retrospective review of 93 patients with CBD stones was done. Clinical characteristics, diameters of CBD, and prior diagnosis before endoscopic retrograde cholangiopancreatography (ERCP) were assessed between two groups (group 1 with serum AST or ALT levels > or =400 IU/L and group 2 with AST and ALT < or =100 IU/L). RESULTS: Nineteen patients in group 1 and 17 patients in group 2 were enrolled. The most common presenting symptom was abdominal pain in both groups. Patients in group 1 was about 14 years younger than group 2 (p=0.003). The duration of symptoms in group 1 and group 2 were 4.1 and 36.8 days, respectively (p=0.005). The diameter of CBD was smaller in group 1 (11.4 mm) than in group 2 (16.3 mm) (p=0.001). Most patients were diagnosed as CBD stones by abdominal ultrasound or computed tomography before ERCP, except two patients in group 1 who were diagnosed as hepatitis initially. All of the patients were recovered by stone removal through ERCP and antibiotics treatment. There were inverse correlations between the diameter of CBD and AST or ALT levels (r=-0.517, p=0.002 and r=-0.504, p=0.002, respectively). CONCLUSIONS: CBD stones with high levels of AST or ALT are frequently observed in younger patients with shorter duration of symptoms and a smaller diameter of CBD. ERCP seems to be a valuable method in the diagnosis and treatment of these patients.

Marked elevation in serum transaminases: an atypical presentation of choledocholithiasis.

BACKGROUND: Choledocholithiasis causes elevations in levels of alkaline phosphatase out of proportion to aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Isolated marked elevation in AST and ALT levels over 1,000 IU/L has been reported infrequently in patients with choledocholithiasis. METHODS: The charts of 18 patients who presented between 1971 and 2002 with documented choledocholithiasis and AST or ALT levels greater than 1,000 IU/L were retrospectively reviewed. An extensive work-up for coexisting disease processes to account for the abnormal AST and ALT levels was negative. RESULTS: Eighteen patients (16 women, 16 Hispanics, age 38 +/- 3 yr) presented with symptoms of choledocholithiasis and marked transaminase elevation. Peak levels of AST and ALT were 1,062 +/- 129 and 1,119 +/- 90, respectively. Following successful management of gallstone disease, AST and ALT levels fell rapidly to 129 +/- 22 and 268 +/- 61, respectively, within 3-14 days. There was also a concomitant improvement in the levels of bilirubin and alkaline phosphatase. CONCLUSIONS: In the absence of other hepatobiliary or pancreatic disease, choledocholithiasis can result in elevations in AST and/or ALT greater than 1,000 IU/L. These levels fall markedly once the gallstone disease is appropriately managed.