Promoter methylation of INK4a/ARF as detected in bile-significance for the differential diagnosis in biliary disease.
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PURPOSE: There is a need to enhance endobiliary cytotechniques by molecular marker lesions. This is of special significance for patients with primary sclerosing cholangitis, a disease predisposing for the development of cholangiocarcinoma. The INK4a/ADP ribosylation factor (ARF) locus encodes two tumor suppressor genes: p16INK4a and p14ARF. p16INK4a has been shown to be of major significance in cholangiocarcinoma. EXPERIMENTAL DESIGN: In an effort to evaluate the potential diagnostic role of p16INK4a and p14ARF promoter methylation in biliary disease, endoscopical obtained bile specimens of 71 patients were analyzed (26 choledocholithiasis, 6 with normal results, 23 bile duct carcinoma, 5 gall bladder carcinoma). Eleven patients with primary sclerosing cholangitis were enrolled. RESULTS: Merely 6% of specimens (2 of 32) obtained from patients without evidence for malignant biliary disease but 53.5% of malignancies (15 of 28) showed p16 promoter methylation (p14: 3 and 46.2%, respectively). The concordance of methylation rates detected in either bile or tissue specimens was high. In primary sclerosing cholangitis, a similar prevalence of methylation was detected as in malignant disease. CONCLUSIONS: This study demonstrates: (a) a high frequency and specificity of INK4a/ARF methylation in malignant biliary disease compared with mere cholangitis; and (b) the capability to detect these alterations reliably in endoscopically obtained bile. Thus, INK4a/ARF's promoter methylation status represents a candidate marker for the endoscopic diagnosis of biliary disease. (+info)
Cholecysto-choledochostomy plus construction of subcutaneous cholecystic tunnel in treatment of choledocholith.
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OBJECTIVE: To avoid the pitfalls of choledochotomy with T-tube drainage in the treatment of choledocholith. METHODS: A novel operation was designed as cholecysto-choledochostomy plus construction of subcutaneous cholecystic tunnel. After the common bile duct was cut open and stones were removed, the gallbladder was appropriately dissociated and the cholecystic ampulla was incised. Then, the incision of the cholecystic ampulla was anastomosed to the opened common bile duct, and the cholecystic fundus was fixed out of the abdominal muscular stratum. RESULTS: Twenty-one patients with choledocholith underwent this operation successfully and recovered well without postoperative complications. One of them was diagnosed as having recurrent stones in 2 years and 3 months after operation. Consequently, the subcutaneous cholecystic tunnel was opened under local anesthesia to remove successfully the stones with choledochoscope. CONCLUSION: This operation provides a convenient way to remove postoperative recurrent stones with choledochoscope and avoid receliotomy. (+info)
Prospective evaluation of magnetic resonance cholangiography in patients with suspected common bile duct stones before laparoscopic cholecystectomy.
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OBJECTIVE: To evaluate the predictive value of magnetic resonance cholangiography (MRC) in selected patients before laparoscopic cholecystectomy (LC). METHODS: Patients with risk factors for common bile duct (CBD) stones scheduled for elective LC from March 1999 to May 2001, underwent MRC followed by endoscopic retrograde cholangiography (ERC) to detect the stones and the accuracy of MRC. Selection of suspected patients was based on clinical, ultrasonographic, and laboratory criteria. RESULTS: During a 26-month period, a total of 267 patients were studied. Seventy-eight MRC identified patients were found to have CBD stones by ERC or laparoscopic cholangiography in the study. Seven of 78 patients were misdiagnosed as having CBD stones by MRC. In this study, MRC had a sensitivity of 100%, a specificity of 96.3%, a positive predictive value of 91.8%, and a negative predictive value of 100% for the detection of common bile duct stones. CONCLUSIONS: With the use of LC, ERC is frequently performed before LC to detect CBD stones; but it is invasive with a well-documented complication rate. MRC is a simple non-invasive method for preoperative screening for CBD stones in at-risk patients. In this study if ERC had been limited to patients with a positive MRC, it would have reduced the need for ERC by 68.2%, and the complications of preoperative examination would be minimized significantly. (+info)
Platelet activation and the protective effect of aprotinin in hepatolithiasis patients.
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OBJECTIVE: To explore platelet activation and the protective effect of aprotinin in patients with hepatolithiasis. METHODS: The count of platelets and levels of CD62P and CD63 were measured by flow cytometry in 38 patients with hepatolithiasis. Several measurements were carried out after treatment with aprotinin. RESULTS: The levels of CD62P, CD63 in patients with hepatolithiasis were higher than those in patients with cholecystolithiasis (P<0.05), but the count of platelets was lower (P<0.05). After operation, the levels of CD62P, CD63 were significantly increased in patients with hepatolithiasis, but the count of platelets was lower (P<0.05). Postoperative levels of CD62P, CD63 were significantly lower in patients treated with aprotinin than in normal controls (P<0.05); but there was no significant change in the count of platelets in the two groups. CONCLUSION: Platelet activation occurs in patients with hepatolithiasis, and may be inhibited by aprotinin. (+info)
Management of choledocholithiasis: comparison between laparoscopic common bile duct exploration and intraoperative endoscopic sphincterotomy.
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AIM: Choledocholithiasis is present in 5 to 10 percent of patients who have cholelithiasis. In the area of laparoscopic cholecystectomy (LC), laparoscopic common bile duct exploration (LCBDE) and intraoperative endoscopic sphincterotomy (IOES) have been used to treat choledocholithiasis. The purpose of this study was to compare the clinical outcomes and hospital costs of LCBDE with IOES. METHODS: Between November 1999 and October 2002, patients with choledocholithiasis undergoing LC plus LCBDE (Group A, n=45) were retrospectively compared to those undergoing LC plus IOES (Group B, n=57) at a single institution. RESULTS: Ductal stone clearance rates were equivalent for the two groups (88% versus 89%, P=0.436). The conversion rate was higher for Group B (8.8% versus 4.4%, P=0.381), as was the morbidity (12.3% versus 6.7%, P=0.336). There were no other significant differences between the two groups. The complications were mainly related to endoscopic sphincterotomy (ES), and the hospital costs were significantly increased in this subset of Group B (median, 23,910 versus 14,955 RMB yuan, P=0.03). Although hospital stay was longer in Group A (median, 7 versus 6 days, P=0.041), the patients in Group A had a significantly decreased cost of hospitalization compared with those in Group B (median, 11,362 versus 15,466 RMB yuan, P=0.000). CONCLUSION: The results demonstrate equivalent ductal stone clearance rates for the two groups. LCBDE management appears safer, and is associated with a significantly decreased hospital cost. The findings suggest LCBDE for choledocholithiasis is a better option. (+info)
Rapid detection of K-ras mutations in bile by peptide nucleic acid-mediated PCR clamping and melting curve analysis: comparison with restriction fragment length polymorphism analysis.
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BACKGROUND: Current methods for detection of K-ras gene mutations are time-consuming. We aimed to develop a one-step PCR technique using fluorescent hybridization probes and competing peptide nucleic acid oligomers to detect K-ras mutations in bile and to compare the efficacy with restriction fragment length polymorphism (RFLP) analysis. METHODS: Bile samples were obtained from 116 patients with biliary obstruction, including gallstones (n = 64), benign biliary strictures (n = 6), pancreatic cancer (n = 20), and cholangiocarcinoma (n = 26). The DNA was extracted and subjected to K-ras mutation analysis by real-time PCR and RFLP analysis. Mutations were confirmed by direct sequencing. The sensitivity and specificity were calculated according to the clinical results. RESULTS: The analysis time for real-time PCR was <1 h, whereas RFLP analysis took more than 2 days. With the sensor probe designed for the GAT (G12D) mutant in codon 12 of the K-ras gene, the real-time PCR method also detected the GTT (G12V) mutant. In contrast, a specific sensor probe for the TGT (G12C) mutant detected GAT (G12D), AGT (G12S), and GTT (G12V) mutants in addition to the TGT mutant. The real-time PCR assay allowed the detection of mutation in a 3000-fold excess of wild-type bile DNA. In bile, K-ras codon 12 mutations were detected in 16 of 46 malignant cases by real-time PCR with the TGT probe and 15 by RFLP analysis. All benign cases were wild type. CONCLUSION: Real-time PCR with a cysteine-specific (TGT) sensor probe can rapidly detect K-ras gene mutations in bile and diagnose malignant biliary obstruction with high specificity. (+info)
NIH state-of-the-science statement on endoscopic retrograde cholangiopancreatography (ERCP) for diagnosis and therapy.
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OBJECTIVE: To provide health care providers, patients, and the general public with a responsible assessment of currently available data regarding the use of endoscopic retrograde cholangiopancreatography (ERCP) for diagnosis and therapy. PARTICIPANTS: A non-Federal, non-advocate, 13-member panel representing the fields of gastroenterology, hepatology, clinical epidemiology, oncology, biostatistics, surgery, health services research, radiology, internal medicine, and the public. In addition, experts in these same fields presented data to the panel and to a conference audience of approximately 300. EVIDENCE: Presentations by experts; a systematic review of the medical literature provided by the Agency for Healthcare Research and Quality; and an extensive bibliography of ERCP research papers, prepared by the National Library of Medicine. Scientific evidence was given precedence over clinical anecdotal experience. CONFERENCE PROCESS: Answering predefined questions, the panel drafted a statement based on the scientific evidence presented in open forum and the scientific literature. The draft statement was read in its entirety on the final day of the conference and circulated to the experts and the audience for comment. The panel then met in executive session to consider these comments and released a revised statement at the end of the conference. The statement was made available on the World Wide Web at http://consensus.nih.gov immediately after the conference. This statement is an independent report of the panel and is not a policy statement of the NIH or the Federal Government. CONCLUSIONS: In the diagnosis of choledocholithiasis, magnetic resonance cholangiopancreatography (MRCP), endoscopic ultrasound (EUS), and ERCP have comparable sensitivity and specificity. Patients undergoing cholecystectomy do not require ERCP preoperatively if there is low probability of having choledocholithiasis. Laparoscopic common bile duct exploration and postoperative ERCP are both safe and reliable in clearing common bile duct stones. ERCP with endoscopic sphincterotomy (ES) and stone removal is a valuable therapeutic modality in choledocholithiasis with jaundice, dilated common bile duct, acute pancreatitis, or cholangitis. In patients with pancreatic or biliary cancer, the principal advantage of ERCP is palliation of biliary obstruction when surgery is not elected. In patients who have pancreatic or biliary cancer and who are surgical candidates, there is no established role for preoperative biliary drainage by ERCP. Tissue sampling for patients with pancreatic or biliary cancer not undergoing surgery may be achieved by ERCP, but this is not always diagnostic. ERCP is the best means to diagnose ampullary cancers. ERCP has no role in the diagnosis of acute pancreatitis except when biliary pancreatitis is suspected. In patients with severe biliary pancreatitis, early intervention with ERCP reduces morbidity and mortality compared with delayed ERCP. ERCP with appropriate therapy is beneficial in selected patients who have either recurrent pancreatitis or pancreatic pseudocysts. Patients with type I sphincter of Oddi dysfunction (SOD) respond to endoscopic sphincterotomy (ES). Patients with type II SOD should not undergo diagnostic ERCP alone. If sphincter of Oddi manometer pressures are >40 mmHg, ES is beneficial in some patients. Avoidance of unnecessary ERCP is the best way to reduce the number of complications. ERCP should be avoided if there is a low likelihood of biliary stone or stricture, especially in women with recurrent pain, a normal bilirubin, and no other objective sign of biliary disease. Endoscopists performing ERCP should have appropriate training and expertise before performing advanced procedures. With newer diagnostic imaging technologies emerging, ERCP is evolving into a predominantly therapeutic procedure. (+info)
Acute cholecystitis and severe ischemic cardiac disease: is laparoscopy indicated?
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BACKGROUND AND OBJECTIVES: Laparoscopy in patients with poor cardiac function has been the subject of controversy and is considered by many surgeons a relative contraindication. METHODS: We report the case of a patient who presented with acute cholecystitis and choledocholithiasis concurrent with unstable angina. Our experience in laparoscopic management of patients with calculous biliary disease and severe coronary artery disease is examined. RESULTS: The patient was managed by coronary angioplasty and stenting immediately followed by laparoscopic cholecystectomy and common bile duct exploration under close invasive hemodynamic monitoring and low-pressure pneumoperitoneum. Between 1996 and 2001, 39 patients with coronary artery disease and an ASA class of III or IV underwent laparoscopic cholecystectomy. Eight of these patients (20.5%) had common bile duct stones necessitating laparoscopic common bile duct exploration. No conversions were necessary, and no major morbidity or mortalities occurred. CONCLUSIONS: Laparoscopic cholecystectomy and common bile duct exploration can be safely performed in patients with severe ischemic cardiac disease under close hemodynamic monitoring and a low-pressure pneumoperitoneum (10 to 12 mm Hg). (+info)