Relationship between serum MMP-9 level and prognosis after radical resection for Hilar cholangiocarcinoma patients

Abstract Purpose: To analyze the preoperative serum matrix metalloproteinase-9 (MMP-9) levels and prognosis of patients with hilar cholangiocarcinoma (HC) undergoing radical resection. Methods: Preoperative serum MMP-9 levels in patients with HC undergoing radical resection were detected by enzyme-linked immunosorbent assay (ELISA). The ROC curve assay was used to analyze the preoperative serum MMP-9 level to determine the most valuable cut-off point. The relationship between MMP-9 and clinicopathological features of HC patients was analyzed. Kaplan-Meier method was used to analyze the prognostic factors, and COX regression model was used to analyze the independent risk factors affecting prognosis. Results: Preoperative serum MMP-9 levels were significantly elevated in the death patients compared with the survival patients. The most valuable cut-off point for preoperative serum MMP-9 for prognosis was 201.93 ng/mL. Preoperative serum MMP-9 was associated with Bismuth-Corlette classification) and lymph node metastasis. Kaplan-Meier analysis showed that MMP-9, Bismuth-Corlette classification, Lymph node metastasis, Portal vein invasion, Hepatic artery invasion, Liver invasion, Incised margin, and Preoperative biliary drainage were related to prognosis. Cox regression model confirmed that hepatic artery invasion, liver invasion, incised margin, and MMP-9 have the potential to independence predicate prognosis in HC patients. Conclusion: Preoperative serum MMP-9 has high predictive value for prognosis and is an independent influencing factor for the prognosis of patients with hilar cholangiocarcinoma.

Sobrevida de pacientes com estenose biliar maligna baseada no escovado endoscópico e na bilirrubinemia / Survival of patients with malignant biliary stricture based on endoscopic brushing and on bilirubinemia

RACIONAL: As principais causas de estenose biliar maligna são câncer de pâncreas e colangiocarcinoma. A definição do prognóstico dos pacientes no momento da pancreatocolangiografia retrógrada endoscópica é importante na escolha da conduta mais adequada. OBJETIVO: Avaliar a importância do escovado endoscópico e da bilirrubinemia na determinação da sobrevida dos pacientes com estenose biliar maligna. MÉTODOS: Os pacientes com estenose biliar diagnosticados durante pancreatocolangiografia retrógrada endoscópica foram submetidos a duplo escovado. Amostras de sangue de todos eles foram obtidas para dosagem das bilirrubinas. Os pacientes foram acompanhados para determinar o diagnóstico final e a sobrevida. RESULTADOS: Diagnóstico final de doença maligna foi obtido em 40 pacientes de um total de 50 casos de estenose biliar. Os níveis séricos elevados das bilirrubinas ou a citologia por escovado positiva para malignidade estava relacionada a menor sobrevida. CONCLUSÃO: Os dados desta pesquisa demonstram a possibilidade de determinar o prognóstico em casos de estenoses biliares malignas através do resultado do escovado endoscópico ou da bilirrubinemia.

Hemoglobin typing in cholangiocarcinoma.

Prevalence of thalassemias and/or hemoglobinopathies, particularly hemoglobin E, and cholangiocarcinoma were found more prominently in the lower part of the Northeast of Thailand as compared with the upper part of this region or any other area of the country. The aim of this study was to evaluate if there was coincident distribution or some relationship. Hemoglobin typing by the cellulose acetate method was performed in 111 cases of cholangiocarcinoma, mainly diagnosed by ultrasonography, compared with 146 normal controls. It was found that hemoglobin E trait and beta-thalassemia trait were significantly higher in the former group.

Serum beta-N-acetylhexosaminidase, carcinoembryonic antigen & sialic acid in benign & malignant extrahepatic biliary obstruction.

Study of tumour markers to differentiate benign and malignant extra hepatic biliary obstructions showed that levels fo serum beta-N-acetylhexosaminidase and lipid associated sialic acid were not different in the two groups. The levels of carcinoembryonic antigen (CEA) and total sialic acid (TSA), on the other hand, were significantly higher in patients with the malignant biliary obstruction. At a cut-off value of 6.4 ng/ml (mean + 2SD) CEA had 66.7 per cent true positivity in malignancy 100 per cent true negativity in control and 78 per cent true negativity in the benign group. Similarly, TSA at a cut off value of 60 mg/dl had 61 per cent true positivity in malignancy, 90 per cent true negativity in controls and 70 per cent true negativity in the benign group. These two tumour markers appear to have similar diagnostic potential for malignant extrahepatic biliary obstruction. Surgical management of the malignant obstruction did not result in a decline in the elevated levels of these two markers during the post-surgical period of 7 days.

Serum unconjugated primary and secondary bile acids in patients with cholangiocarcinoma and hepatocellular carcinoma.

Serum unconjugated primary bile acids (cholic acid, chenodeoxycholic acid), secondary bile acids (lithocholic acid, deoxycholic acid), conjugated primary bile acids (glycocholic acid, glycohenodeoxycholic acid, taurocholic acid, taurochenodeoxycholic acid) and total bile acids were measured in 25 and 75 male patients with cholangiocarcinoma and hepatocellular carcinoma respectively. Twenty-one healthy male volunteers served as controls. Other biochemical parameters, i.e. bilirubin, transaminases, albumin, globulin and cholesterol were also studied. Conjugated bile acids and total bile acids were elevated in both patient groups when compared with those of controls. The presence of unconjugated primary bile acids and secondary bile acids was noted in the patient groups, whereas, they were not detectable in controls. The appearance of these serum bile acids may be useful as a marker for early diagnosis of cholangiocarcinoma and hepatocellular carcinoma in people at-risk such as those who have chronic infection with Opisthorchis viverrini. Differentiation between the two types of tumor may be possible by using other parameters such as alpha-fetoprotein or other tumor markers newly discovered. An increase of the trihydroxy bile acids: dihydroxy bile acids and glycine conjugated bile acids: taurine conjugated bile acids ratios was shown in the patient groups. The latter may be due to the proportion of the increase of taurine conjugates being greater than the increase of glycine conjugates. The other biochemical parameters were significantly elevated in the patient groups except for albumin which was significantly decreased. The sensitivity of the tests for cholic acid, chenodeoxycholic acid, alkaline phosphatase and gamma glutamyl transferase was high.

Serum protease inhibitors in opisthorchiasis, hepatoma, cholangiocarcinoma, and other liver diseases.

Serum alpha 1-antitrypsin, alpha 1-antichymotrypsin and alpha 2-macroglobulin increased significantly in patients suffering from liver diseases: hepatoma, amoebic liver abscess, hepatitis, hepatic cirrhosis, cholangiocarcinoma, carcinoma of the head of pancreas including liver fluke infection (opisthorchiasis). Marked increase of alpha 1-antitrypsin and alpha 1-antichymotrypsin were found in cholangiocarcinoma, carcinoma of the head of pancreas, amoebic liver abscess, hepatic cirrhosis and hepatoma. alpha 2-macroglobulin increased markedly in hepatic cirrhosis. The concentrations of protease inhibitors found in opisthorchiasis were only moderately elevated.