The Study On Clinical Analysis Of Hilar Cholangiocarcinoma With Nerve Invasion And The Relationship Of Expression Of MMP-13 And TIMP-1

Hilar cholangiocarcinoma was famous for the lower rate of early diagnosis, higher rate of metastasis and the poor survival rate. With the improvement of surgical treatment for hilar cholangiocarcinoma, the 5-year survival rate of the patients has been prolonged than before obviously. However, the recurrence and metastasis of hilar cholangiocarcinoma are still a main problem faced by surgeons.Through a retrospective analysis of pathologic types and clinical data of hilar cholangiocarcinoma in 311 patients (hilar cholangiocarcinoma with nerve invasion in 89 and hilar cholangiocarcinoma without nerve invasion in 222) from January 1993 to December 2004 in the Department of Hepatobiliary Surgery in China PLA General Hospital, we investigated the relationship among the metastasis manners, pathologic types, operation methods and possible important related factors for long survival.Matrix metalloproteinase-13 (MMP-13) can degrade the extracellcular matrix or the basement membrane. It has an essential role in tumor invasion and metastasis. To evaluate the roles of MMP-13 and its inhibitor: tissue inhibitors of metalloproteinase-1 (TIMP-1) in tumor invasion and metastasis or as a prognostic factor in patients of hilar cholangiocarcinoma with nerve invasion. In our experiments, we have investigated the expression of MMP-13 and TIMP-1 in patients with hilar cholangiocarcinoma. Tissues of fresh and paraffin sections obtained from 40 patients with hilar cholangiocarcinoma from April 2004 to December 2005 were used for analysis. The expression of MMP-13 and TIMP-1 were examined by immunohistochemistry and Western Blot methods. The Image-pro Plus Analysis Software was used to semi-quantitatively measure the expression of MMP-13 and TIMP-1.The main results of the two parts study are as following:1. Nerve invasion is one of the most important metastasis manners of hilar cholangiocarcinoma as well as lymph metastasis, blood vessel metastasis. And there is no significant difference between them.2. In the positive group (nerve invasion), low differentiation has the most proportion. In the negative group (no nerve invasion), high differentiation has the most proportion.3. Radical resection plays an important role for curative effect and could obtain longer term survival rate in patients with hilar cholangiocarcinoma whether it with nerve invasion than palliative resection.4. The 1-, 3- and 5-year survival rates of the positive group (nerve invasion) were 65.59%, 22.71% and 14.83%, respectively, while those of the negative group (no nerve invasion) were 80.62%, 35.14% and 24.98%, there is a remarkable difference between them.5. The expression of MMP-13 and TIMP-1 are strongly associated with nerve invasion of hilar cholangiocarcinoma.Through above-mentioned study and results, we have these conclusions:1. Nerve invasion is one of the most important metastasis manners of hilar cholangiocarcinoma.2. The main treatment of hilar cholangiocarcinoma is operation, and radical resection plays an important role for curative effect and long term survival rate in patients with hilar cholangiocarcinoma whether it with nerve invasion.3. MMP-13 has an important role in nerve invasion of hilar cholangiocarcinoma, while TIMP-1 shows strong inhibit effect in nerve invasion of hilar cholangiocarcinoma.4. The expression of MMP-13 and TIMP-1, and the ratio of MMP-13 / TIMP-1 may be a prognostic indicator for patients of hilar cholangiocarcinoma with nerve invasion.