Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cholangiocarcinoma is a rare tumor. Many cases are localized while metastatic disease within the liver and abdomen do occur. There is as yet no standard therapy for advanced bile duct tumors. Radiotherapy and chemotherapy are not curative modalities in this condition but are being assessed adjuvantly following surgery, and as palliative treatment in an attempt to either extend progression-free and overall survival or to palliate symptoms. Advances may be made by: (i) The combined use of radiation and chemotherapy, (ii) High dose conformal radiotherapy, (iii) Novel chemotherapeutic agents. Patients should be given the opportunity to participate in clinical trials.
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PMID:Cholangiocarcinoma and the role of radiation and chemotherapy. 1126 97

Cholangiocarcinoma (CCA) is a lethal disease, afflicting many thousands the world over. Human CCA develops through a multi-step progression model, preceded by the onset of dysplasia in the cholangiolar ductal epithelium. An animal model of multi-step carcinogenesis in the biliary tree will enable the study of genetic changes in human CCA, and provide an avenue for chemoprevention strategies. We describe an oral thioacetamide (TAA)-induced model of rat CCA that recapitulates the histologic progression of human CCA. Male Sprague-Dawley (SD) rats (n = 170), weighing 350 +/- 20 g, were used in this study. Drinking water with TAA 300 mg/l was administered orally, and the liver was harvested and examined histologically at weekly intervals, beginning at 5 weeks after initiation of TAA. Harvested tissues were formalin-fixed and paraffin embedded for morphologic and immunohistochemical studies. Multifocal bile ductular proliferation with intestinal metaplasia (presence of goblet cells) and increasing histologic atypia (biliary dysplasia) was observed by the 9th week of TAA administration. Biliary cytokeratin (CK19)-expressing invasive intestinal-type CCA with stromal desmoplasia was evident at the 16th week, and by the 22nd week, the yield rate for CCAs had increased to 100%. Invasive CCAs preceded the development of hepatic cirrhosis by at least 4 weeks; the earliest incidence of hepatic fibrosis was observed beginning at 20 weeks post-TAA administration. The progression from normal cholangioles to biliary dysplasia to invasive CCA was accompanied by up-regulation of the proto-oncogenes c-met and c-erbB-2, tyrosine kinase receptors over-expressed in human CCAs. The study was terminated at 6 months, at which time no systemic metastases or deaths were observed. Oral administration of TAA in drinking water to male SD rats provides a reproducible animal model for development of CCA with a high yield rate. In particular, the presence of biliary dysplasia beginning at the 9th week, which progresses to invasive CCA, mimics the multi-step model of human CCA. The TAA rat model may serve as a powerful pre-clinical platform for therapeutic and chemoprevention strategies for human CCA.
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PMID:Thioacetamide-induced intestinal-type cholangiocarcinoma in rat: an animal model recapitulating the multi-stage progression of human cholangiocarcinoma. 1465 42

Intra-hepatic cholangiocarcinoma (IHCC) is a rare tumor which arises from the epithelial cells of the intra-hepatic bile ducts; it may develop in a healthy liver and bile ducts or in bile ducts with malignant predisposition (Caroli's syndrome, primary sclerosing cholangitis). It has the worst prognosis of any tumor arising in the liver. Unlike hepatocellular carcinoma, no predisposing factors or high-risk populations have been demonstrated for cholangiocarcinoma other than intraphepatic choledocholithiasis such as is seen in east Asian populations. The most common clinical sign is a palpable tumor mass emphasizing that the tumor is usually detected at an advanced stage. CT scanning yields much clinical information but ultrasound-guided needle biopsy is necessary for diagnosis. Aggressive surgical resection is the only treatment modality which has afforded even slight prolongation of survival; hepatic resection must be large with uninvolved resection margins. When an IHCC is deemed resectable (localized tumor without hepatic metastases or intrahepatic or extrahepatic lymph node spread), pre-operative tumor embolization may be useful; when jaundice is present, percutaneous drainage of the dilated biliary system of the liver to be spared may also be necessary. Neither adjuvant nor neo-adjuvant chemotherapy or radiotherapy have shown proof of efficacity. Cholangiocarcinoma complicates sclerosing cholangitis in 10-15% of cases and is very difficult to diagnose. IHCC may also develop in Caroli's syndrome, where it is commonly found incidentally on pathologic examination of a resection specimen after surgery for a complication of the disease.
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PMID:[Intra-hepatic cholangiocarcinoma]. 1549 65

Cholangiocarcinoma is a relatively uncommon malignancy, that presents late in the vast majority of cases. Overall survival rates are extremely poor and treatment options remain limited in patients with inoperable, recurrent or metastatic disease. Systemic chemotherapy has historically had little impact on the natural history of this disease, owing to both the absence of agents with substantial activity and the overall morbidity of treatment in this patient population. Response rates with 5-fluorouracil have been 10% at best, with a median survival of 6 months. However, there has been interest in the use of newer cytotoxic drugs and combination regimens in advanced cholangiocarcinoma, and Phase II trials have reported much improved results. This review examines this data and assesses whether a new standard of care for advanced cholangiocarcinoma can be found.
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PMID:Chemotherapy for advanced cholangiocarcinoma: what is standard treatment? 1692 17

Cholangiocarcinoma is one of the most aggressive malignancies. Patients with advanced or metastatic disease have a particularly dismal prognosis. The role of chemotherapy remains a matter of debate. A number of recent trials have shown that capecitabine in combination with other agents seems to be active as first-line treatment in advanced biliary cancer. Clinical data regarding the activity of capecitabine in pretreated patients are limited. In this report we describe a patient with previously treated, metastatic cholangiocarcinoma who developed stabilization of the disease for 7 months following chemotherapy with capecitabine. The patient had previously received 2 lines of chemotherapy. Capecitabine was tolerated fairly well without serious adverse events. We consider this observation to be important given the absence of active, non-surgical treatments in unresectable tumors.
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PMID:Capecitabine in pretreated metastatic cholangiocarcinoma. A case report and review of the literature. 1760 Aug 85

Cholangiocarcinoma is the second most common primary malignant hepatobiliary neoplasm, accounting for approximately 15% of liver cancers. Diagnosis of cholangiocarcinoma is challenging and the prognosis is uniformly poor, with recurrence rates of 60%-90% after surgical resection. A wide spectrum of neoplastic and nonneoplastic conditions of the biliary tract may masquerade as cholangiocarcinoma, adding to the complexity of management in patients suspected to have cholangiocarcinoma. Mimics of cholangiocarcinoma constitute a heterogeneous group of entities that includes primary sclerosing cholangitis, recurrent pyogenic cholangitis, acquired immunodeficiency syndrome cholangiopathy, autoimmune pancreatitis, inflammatory pseudotumor, Mirizzi syndrome, xanthogranulomatous cholangitis, sarcoidosis, chemotherapy-induced sclerosis, hepatocellular carcinoma, metastases, melanoma, lymphoma, leukemia, and carcinoid tumors. These entities demonstrate characteristic histomorphology and variable clinicobiologic behaviors. The imaging findings of these disparate entities are protean and may be indistinguishable from those of cholangiocarcinoma. In most cases, a definitive diagnosis can be established only with histopathologic examination of a biopsy specimen.
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PMID:Mimics of cholangiocarcinoma: spectrum of disease. 1863 32

Cholangiocarcinoma is a rare malignancy associated with poor prognosis and high mortality. Surgical resection is the only chance for cure depending on careful patient selection. There are no well-conducted studies regarding the role of adjuvant chemotherapy. Preliminary data suggest that liver transplantation could offer long-term survival in selected patients when combined with neoadjuvant chemoradiotherapy. The literature regarding treatment results with specific regimens in the adjuvant setting is limited and no general recommendation can be given. In patients with locally advanced or metastatic disease, most studies are small, non-randomized phase II trials, and many studies comprise a mix of bile duct cancers, gallbladder cancer, and either pancreatic or hepatocellular cancers. In metastatic cancer, phase II studies with several cytotoxics, including gemcitabine, the platinums, and the fluoropyrimidines, have shown a modest and often short-lasting activity. No single chemotherapy agent or combination regimen can therefore be recommended as a standard of care at present. In this review, we give an overview of chemotherapy in the adjuvant, neoadjuvant, and advanced settings.
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PMID:The role of chemotherapy in biliary tract carcinoma. 1877 46

Cholangiocarcinoma (CC) arises from the biliary epithelium and in most cases represents adenocarcinoma. Pathomorphological evaluation is of decisive impact for the prognosis and management of CC. Morphological subtyping (histotype; hilar vs peripheral type), TNM classification, lymphatic spread, and resection margin status are of prognostic relevance. Distinction from hepatic metastases may be aided by immunohistology and clinico-pathological correlation. There is convincing evidence of the development of CC via premalignant lesions, especially biliary intraepithelial neoplasia, although further knowledge about the biology and diagnostic definition of these lesions has to be accumulated. Currently, there are no established molecular markers of prognosis or therapeutic target structures to be evaluated at the tissue level. Future progress is needed and expected in novel differential diagnostic and predictive markers, in uniform definition of resection margin status and further understanding of molecular and morphological changes in the development of CC.
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PMID:Pathological aspects of cholangiocarcinoma. 1877 61

Cholangiocarcinoma is suspected based on signs of biliary obstruction, abnormal liver function tests, elevated tumor markers (carbohydrate antigen 19-9 and carcinoembryonic antigen), and ultrasonography showing a bile stricture or a mass, especially in intrahepatic cholangiocarcinoma. Magnetic resonance imaging (MRI) or computed tomography (CT) is performed for the diagnosis and staging of cholangiocarcinomas. However, differentiation of an intraductal cholangiocarcinoma from a hypovascular metastasis is limited at imaging. Therefore, reasonable exclusion of an extrahepatic primary tumor should be performed. Differentiating between benign and malignant bile duct stricture is also difficult, except when metastases are observed. The sensitivity of fluorodeoxyglucose positron emission tomography is limited in small, infiltrative, and mucinous cholangiocarcinomas. When the diagnosis of a biliary stenosis remains indeterminate at MRI or CT, endoscopic imaging (endoscopic or intraductal ultrasound, cholangioscopy, or optical coherence tomography) and tissue sampling should be carried out. Tissue sampling has a high specificity for diagnosing malignant biliary strictures, but sensitivity is low. The diagnosis of cholangiocarcinoma is particularly challenging in patients with primary sclerosing cholangitis. These patients should be followed with yearly tumor markers, CT, or MRI. In the case of dominant stricture, histological or cytological confirmation of cholangiocarcinoma should be obtained. More studies are needed to compare the accuracy of the various imaging methods, especially the new intraductal methods, and the imaging features of malignancy should be standardized.
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PMID:Diagnosis of cholangiocarcinoma. 1877 62

Cutaneous metastases rarely develop in patients with internal malignancy. Cholangiocarcinoma, a malignant cancer of the bile duct, is a relatively rare adenocarcinoma and has a poor prognosis. Few reports have mentioned cutaneous metastases of cholangiocarcinoma, and the most of them were due to direct tumor seeding by percutaneous procedures. Herein, we report a case of cholangiocarcinoma with distant cutaneous metastases in a 60-year-old man.
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PMID:[Cholangiocarcinoma with distant cutaneous metastases]. 1993 17


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