Use of computer program for diagnosing jaundice in district hospitals and specialized liver unit.
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A computer-assisted model for diagnosing jaundice has been adapted for use on the University of London C.D.C. 7600 computer via an on-line terminal at King's College Hospital to provide a rapid turn-round time. The model was used prospectively in the diagnosis of 219 patients--135 seen in a specialized liver unit and 84 seen in one of four district hospitals in south-east London--with an overall accuracy in distinguishing among 11 different causes of jaundice of 69% and 62% respectively. These figures rose to 77% and 88% respectively when only those patients in whom the final diagnosis reached a "certain" probability were considered. When used to distinguish between a medical and a surgical cause of jaundice the accuracy was 86% in the liver unit and 77% in the district hospitals, rising to 95% in both series for those with a diagnosis of certain probability. The proposed improvements to the model--namely, the use of two deparate data bases and more diagnoses within the matrix--should be improve the accuracy even further. In practice the rapid feedback to the clinicians looking after patients provided help in managing difficult cases. (+info)
Recognition of intrabiliary hepatic metastases from colorectal adenocarcinoma.
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Intrinsic involvement of bile ducts, by metastatic colorectal adenocarcinoma growing from within or invading the lumen of bile ducts, is not a well recognized pattern of tumor growth. Clinical, radiographic, operative, and histopathologic aspects of 15 patients with intrabiliary colorectal metastases were described. Fourteen patients were explored for possible hepatic resection. Two had jaundice, two radiographic evidence of an intrabiliary filling defect, 10 intraoperative evidence of intrabiliary tumor, and six microscopic evidence of intrabiliary tumor. Eleven patients underwent hepatic resection. Five of the resected patients developed hepatic recurrence. Four patients were explored for possible repeat resection. One had jaundice, one radiographic evidence of an intrabiliary filling defect, all had intraoperative evidence of intrabiliary tumor, and three microscopic evidence of intrabiliary tumor. Three patients underwent repeat hepatic resection. All patients with preoperative jaundice and radiographic evidence of an intrabiliary filling defect were unresectable. Overall, actuarial five-year survival is 33% for those patients resected versus 0% for those not resected. Intraoperative recognition of intrabiliary tumor at exploration for hepatic resection was more common than clinical, radiographic, or histopathologic recognition. More diligent examination of resected liver tissue by the surgeon and pathologist may increase identification of bile duct involvement and aid in achieving adequate tumor clearance. (+info)
Frequency of p16(INK4A) alterations and K-ras mutations in intrahepatic cholangiocarcinoma of the liver.
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BACKGROUND: Inactivation of the tumour suppressor gene p16 (CDKN2/MTS-1/INK4A) and K-ras mutations are among the most frequent genetic alterations in human malignancies. AIMS: To investigate the tumour suppressor gene p16 and its possible association with K-ras mutations in intrahepatic cholangiocarcinomas of the liver. METHODS: The status of p16 was evaluated in 41 cholangiocarcinomas by methylation specific polymerase chain reaction, microsatellite analysis, DNA sequencing, and immunohistochemical staining. K-ras mutations were determined by direct DNA sequencing analyses after microdissection. The results obtained were correlated with histopathological variables and patient survival. RESULTS: Hypermethylation of the 5' CpG island of the p16 gene was found in 34 of 41 (83%) carcinomas. Homozygous deletion at the p16 region was present in two (5%), and loss of heterozygosity (LOH) in eight cases (20%). We failed to detect p16 gene missense mutations. K-ras mutations were found in 22 of 41 (54%) cholangiocarcinomas and in two cases of tumour surrounding non-neoplastic liver tissue. All 22 cancers with K-ras mutations also exhibited methylated p16. We failed to observe a correlation between K-ras or p16 status and histopathological factors or prognosis of patients. CONCLUSION: These data suggest that inactivation of the p16 gene is a frequent event in cholangiocarcinoma. The most common somatic alteration is promotor methylation of the p16 gene which is closely associated with K-ras mutations. We failed to establish p16 or K-ras status as independent prognostic factors in these tumours. (+info)
Changing strategies in diagnosis and management of hilar cholangiocarcinoma.
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Hilar cholangiocarcinoma is one of the most difficult tumors to stage and treat. This study aims to evaluate (1) the best diagnostic imaging, (2) the usefulness of preoperative biliary drainage, (3) the resectability rate, and (4) the results of palliative treatments and surgical resection. Seventy-six patients with hilar cholangiocarcinoma with a mean age of 64 +/- 11 years were treated at our institution from 1989 to 1999. Patients were studied preoperatively using ultrasound, computed tomography (CT), and percutaneous cholangiography or magnetic resonance cholangiography. Forty-eight patients (63%) underwent palliative treatment. Twenty-eight patients underwent surgical curative therapy; 20 resections and 8 orthotopic liver transplantations (OLTs). Percutaneous transhepatic cholangiography was performed in 18 of 28 patients (64%), and magnetic resonance cholangiography in 5 patients; both methods were equally effective in establishing tumoral invasion of the biliary ducts. Five patients did not undergo either diagnostic modality. Excluding the patients who underwent OLT, no significant differences were found in surgical mortality (1 v 2 patients) or postoperative morbidity (100% v 66%) for patients with and without preoperative biliary drainage. The postoperative mortality rate was 11% (3 of 28 patients). The overall resectability rate was 37%. Mean survival in the surgical and palliative groups was 35 and 6 months, respectively (P <.0001). Patients who underwent OLT had a better 5-year survival rate than those treated by tumor resection (36% v 21%; P =.02). Combined chemotherapy and radiotherapy apparently did not provide a significant survival benefit. Helical CT and magnetic resonance cholangiography are useful techniques to delineate tumor extent and rule out vascular invasion and lymph node or liver metastases. No clear conclusions regarding preoperative drainage can be drawn from this study. A high resectability rate (37%) is feasible with major hepatectomy. (+info)
Treatment options for other hepatic malignancies.
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1. Resection rates for cholangiocarcinoma (unrelated to primary sclerosing cholangitis) have increased to 54% to 79%, and the subsequent 5-year survival rates are 24% to 31%. 2. Multimodality approaches involving various combinations of chemotherapy, irradiation, and surgery increasingly are being used to treat cholangiocarcinoma. 3. The role of liver transplantation in the management of cholangiocarcinoma is limited by the perception that it is inappropriate to use scarce organs when 5-year survival rates are 25%. 4. Liver transplantation is an important intervention in patients with tumors that remain unresectable after chemotherapy. The role of liver transplantation in patients with extrahepatic disease that responds to chemotherapy is controversial. Careful timing of surgery is required to avoid secondary drug resistance. 5. Liver transplantation has been successfully applied to a range of rare hepatic malignancies, but small numbers preclude strong recommendations on the appropriateness of this practice. (+info)
Early detection and treatment of cholangiocarcinoma.
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1. The major identified risk factor for the development of cholangiocarcinoma in Western countries is primary sclerosing cholangitis (PSC). 2. The diagnosis of cholangiocarcinoma in PSC requires a high index of suspicion because endoscopic brush cytology and/or biopsies and imaging studies are often negative for malignancy. Positron emission tomography is a promising imaging modality for the diagnosis of cholangiocarcinoma, even in patients with PSC. 3. A serum carbohydrate antigen 19-9 value greater than 100 U/mL has a sensitivity and specificity for cholangiocarcinoma of approximately 75% and 80%, respectively. 4. Liver transplantation is a viable therapeutic option for selected patients with early-stage cholangiocarcinoma. Outcomes are optimized by using preoperative radiation and chemotherapy and ensuring the absence of metastases by an exploratory laparotomy. (+info)
Aberrant cyclooxygenase isozyme expression in human intrahepatic cholangiocarcinoma.
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METHODS: Cellular localisation of the cyclooxygenase (COX) isozymes COX-1 and COX-2 was analysed in 24 cholangiocarcinomas, including 17 matched tissues originating from non-tumorous liver tissue adjacent to tumours and seven biopsies of normal human liver, by immunohistochemistry using isozyme selective antibodies. RESULTS: In normal liver, constitutive expression of COX-2 protein was a characteristic feature of hepatocytes whereas no COX-2 immunosignal was detectable in normal bile duct epithelium, Kupffer, and endothelial cells. In cholangiocarcinoma cells, COX-2 protein was strongly expressed at high frequency. The intensity, percentage of positive cells, and pattern of COX-2 expression were found to be independent of the stage of tumour differentiation. In hepatocytes of matched non-tumorous tissue, COX-2 expression was unaltered. In contrast, strong COX-1 expression was frequently localised to Kupffer cells, endothelial cells, and occasionally to hepatocytes, but not to bile duct epithelial cells. In approximately half of moderately and poorly differentiated but not well differentiated cholangiocarcinomas, weak to moderate COX-1 staining was found in tumour cells while COX-1 expression in Kupffer cells was much more pronounced. CONCLUSION: Aberrant COX-2 expression occurs during the early stage while COX-1 over expression seems to be related to later stages of cholangiocarcinogenesis. (+info)
Expression of p53 and PCNA in cholangiocarcinoma and primary sclerosing cholangitis.
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The aim of this study was to identify the pattern and significance of expression of p53 and PCNA in cholangiocarcinoma and primary sclerosing cholangitis. Histological sections from 18 patients with cholangiocarcinoma (3 of the cases were associated with primary sclerosing cholangitis), 10 patients with primary sclerosing cholangitis without cholangiocarcinoma, and 7 patients with cirrhosis without cholangiocarcinoma or primary sclerosing cholangitis were stained immunohistochemically for p53 and PCNA. Samples from 17 patients with cholangiocarcinoma (94%) stained positively for p53. Among these 17 cases, nontumorous bile duct epithelium was positive in 7 (including 3 cases with primary sclerosing cholangitis and 2 with carcinoma in situ), and were positive proliferating bile ductules in 4 cases. The single p53-negative cholangiocarcinoma did not show p53 positivity in either the bile duct epithelium or the proliferating bile ductules. Bile ductal and ductular cells in all 10 patients with primary sclerosing cholangitis without cholangiocarcinoma and in the 7 controls were not reactive for p53. All 18 samples from patients with cholangiocarcinoma (100%) were positive for PCNA protein. Bile duct epithelium was positive for PCNA in nine cases (90%) of primary sclerosing cholangitis without cholangiocarcinoma and in six (85%) controls. Our study showed a high rate of p53 expression (94%) in cholangiocarcinoma. The adjacent uninvolved bile duct epithelium was also immunoreactive for p53 in 7 of 17 patients (41%). These findings suggest an early p53 mutation in bile ductal cells in cholangiocarcinogenesis. Expression of p53 may potentially be used to identify or screen, by bile duct brushings, cases of primary sclerosing cholangitis suspected of harboring cholangiocarcinoma. Expression of PCNA was a universal feature in cholangiocarcinoma. (+info)