The Study On Diagnosis Method Of Cholangiocarcinoma Before Operation

There is few atypical sign in early stage cholangiocarcinoma(CCA). Most cases were diagnosed in their lately stage, with lower rate of operation and a bad prognosis. Now, there is no proper diagnosis method with high sensitivity and specialty. Clinical doctors tried hardly to establish a simple protocol to determine the nature of bile duct diseases. Endoscopic Retrograde Cholangiopancreatography(ERCP),CT scan, Magnetic Resonance Image, Magnetic Resonance Cholangiopancreatography, and Percutanous Transhepatic Cholangiography, all these methods are employed to diagnose CCA, which hold heavy economic burden to the patients. A positive histological sample plays an important role in diagnosis of CCA. Doctors focus on method with high sensitivity and specialty and lower rate of sequelae. We discuss the diagnosis value of bile duct brush, the brush-off cells, and the tumor markers in bile for clinical work.Part One:The value of bile duct brush, the brush-off cells, and the oncogenes in bile choler for diagnosis of cholangiocarcinoma Objective: To evaluate the usefulness of bile duct brush cytology, the exfoliative bile cells, and the mutation or expression of oncogene from bile samples in diagnosis of Cholangiocarcinoma(CCA) .Methods: By ERCP method, we extracted bile brush cytology and the exfoliative bile cells from bile ducts in 41 cases of CCA, 32 cases of benign bile duct stricture. PCR-SSCP was used to detect the mutation of K-ras gene. Immunological histological method was employed to assay the expression status of p53.Results: By the bile duct brush cytology method with pathological diagnosis, the sensitivity for the diagnosis of CCA was 53.7%. By the exfoliative bile cells pathological diagnosis method, the sensitivity for the diagnosis of CCA was 29.3%. There is significant difference between the 2 above methods, but no difference in veracity of diagnosis. The positive rate of duct brush cytology is much higher in portal CCA group than in middle to down-stream CCA group(68.0% vs 31.3%,P<0.05). Combining the 2 methods will promote the sensitivity for the diagnosis of CCA to 82.9%.The mutation rate is 63.4%(26/41)of K-ras, and positive expression rate is 63.4%(26/41)of p53, with no difference(P>0.05)in CCA group. No mutation was detected in benign bile duct stricture. There are no relativity between K-ras mutation and p53 expression with position, histological type and clinical stage. The positive rate of p53 expression is much higher in portal CCA group than in middle to down-stream CCA group(76.0% vs 43.6%,P<0.05).Conclusion: Combining ERCP with brush cytology and exfoliative bile cell assay will help for diagnosing CCA. Detection of mutation in K-ras and expression in p53 are effective in the differential diagnosis of CCA and benign bile duct stricture, both methods have higher sensitivity and veracity. Brush cytology and detection of p53 expression are relative to the position of CCA.Part two:The Study of tumor makers in the bile for differential diagnosis of cholangiocarcinoma and benign bile duct strictureObjective: To evaluate the value of combining detecting tumor markers in the bile for differential diagnosis of CCA and benign bile duct stricture.Methods: Bile samples were extracted from bile ducts by ERCP method in 39 cases with CCA, 34 cases with benign bile duct stricture and 30 cases with no hepatopancreatobiliary disease. Radioimmunoassy (RIA) and Immunoradiomassay (IRMA) were used to detect the content of CA19—9,CA125 and CEA in bile and in serum.Results: The cut-off value in bile is: CEA 53ng/ml ,CA12541 U/ml, CA19—91120 U/ml. In bile, the sensitivity for the diagnosis of CCA was 91.44% of CA19-9, 66.92% of CA125 and 78.31% of CEA. The specificity was 66.52% of CA19—9100% of CA125 and 74.82% of CEA, respectively. In serum, the sensitivity for the diagnosis of CCA was 78.97% of CA19-9, 33.53% of CA125 and 58.46% of CEA. The specificity was 81.18% of CA19—9,100% of CA125 and 77.06% of CEA, respectively. There is significant difference between the assay the value of these 3 tumor markers in bile and in serum(P<0.05)。Conclusion: Detecting of CA19—9,CA125 and CEA in bile is effective in the differential diagnosis of CCA and benign bile duct stricture, better than detecting these markers in serum. Assay of CA19-9 is more sensitive than CA125 and CEA in bile, which will be a good method for differential diagnosis of CCA and benign bile duct stricture. Assay of all these 3 markers in bile will promote the sensitivity, specialty and veracity.