RISULTATI E FATTORI PROGNOSTICI DEL COLANGIOCARCINOMA INTRAEPATICO E PERI-ILARE DOPO TRATTAMENTO CHIRURGICO

Introduction: Prognosis of perihilar and intrahepatic cholangiocarcinoma is dismal. Curative resection is the only chance of survival. Prognostic factors of survival after surgery, onset and treatment of recurrence and the reports of results during the years is still under debate in literature. Matherial and Methods: Prospectively data of 95 patients with perihilar (PCC) and 84 with intrahepatic cholangiocarcinoma (ICC) submitted to surgical resection in Division of General Surgery of the University of Verona Medical School between September 1990 and September 2012 were evaluate. Results: for PCC patients, Preoperative serum level of Ca 19.9 and CEA, major hepatectomy, caudate lobe resection, portal vein resection and reconstruction, and lymph node dissection, absence of satellite nodules, N0 status and lower TMN stage resulted as prognostic factors for longer survival at univariate analisys. The multivariate analysis confirmed the serum value of Ca 19.9 lower than 500 U/L, and the absebnce of positive lymphnodal involvement as factor strongly related to survival. Median follow up was of 29 months (range 4-107). Median overall survival was 28.8 months; cumulative proportion survival at 3 and 5 years were 43.2% and 23.9% respectively. For ICC patients, at univariate analysis, the CEA > 5 ng/dL, the presence of lymph node metastases, macroscopic vascular invasion, the presence of intrahepatic metastases, an higher grade of differentiation, an higher TNM stage and positive resection margins (R +) were significantly related to survival. Cox’s regression multivariate model identified the high serum value of CEA, the presence of intrahepatic metastases and the radicality as being significantly related to survival with hazard ratios (HR) of 9.8, 2.2 and 2.3 , respectively. The overall median survival time was 31.8 months, with 3- and 5-year actuarial survival rates of 44.5% and 26.8%, respectively. For all patients, the 1- and 5-year disease-free survival was 69.4% and 21.1%. In patients with PCC, recurrences were more frequently extrahepatic (71%). High lymph-node ratio, multifocality, portal resection/reconstruction, perineural invasion and elevated serum level of CEA were significantly associated with recurrence. Nine (19.1%) patients were submitted to surgery, 29 patients were submitted to chemo or radiotherapy (61.8%), 9 patients (19.1%) received best supportive care. In patients affected by ICC recurrences occurred more frequently into the liver (52%). High level of Ca 19.9, a tumor size higher than 30 mm, R1 resection, multifocality and histological grading are factors correlated to recurrence. Six (19.6%) patients underwent surgical resection of recurrence, chemotherapy was performed in 14 patients (45.2%) and the remnant 11 patients received best supportive care. When recurrence was surgically treated patients showed a longer survival after recurrence than patients submitted to chemo or radiotherapy (1- and 3-year survival of 64.8% and 25.9% vs. 60.3% and 18.8% respectively, p=0.005). Among patients affected by PCC, 29 were submitted before 2005 and 55 after 2005. The 5-year overall survival was significantly increased before and after 2005 (12.5% and 39.4%, respectively, p=0.01). In patients submitted to surgery after 2005 respect than in those treated before 2005, it is shown a lower recurrence rate (51.7% vs. 78.9%, p=0.07) and a higher 3-year disease-free survival (49.6% vs. 26.3%, respectively, p=0.01). Remarkably, in patients submitted to surgery after 2005 with radical resection and with no positive lymph-nodes metastases, the 5-year survival was 73.8%, compared to 13.6% of the same patients submitted to surgery before 2005. In patients affected by ICC, 25 were submitted to surgery before and 58 after 1st January, 2005. Patients were older after 2005. Tumor seemed to be more advanced after 2005: indeed, the tumors were bigger in size and with more macrovascular involvement rate in patients submitted to surgery after 2005 than in patients submitted before 2005. So, the surgery resulted more aggressive after 2005, with more major hepatectomy and more lymph node harvested than before, even if with no difference in complication rate between the two periods. R0 resections were more performed after 2005 than before. Nevertheless, these results did not allow a survival gain in patients before and after 2005 (p=0.48). Conclusions: in patients with PCC we demonstrated that an low preoperative serum level of Ca 19.9 and CEA, major hepatectomy, caudate lobe resection, portal vein resection and reconstruction, and large lymph node dissection with more than 10 lymph nodes were positive prognostic factors for longer survival. Besides, perioperative and surgical thecniques for the treatment of PCC has been evolved during the years. In our institution, patients treated for PCC in the last 10 years gained a significantly better overall survival rates compared to patients treated before, especially if radical resections were performed with no lymph node involved. Regarding patients with ICC, CEA > 5 ng/dL, the presence of lymph node metastases, macroscopic vascular invasion, the presence of intrahepatic metastases, an higher grade of differentiation, an higher TNM stage and positive resection margins (R +) were significantly related to survival. MF type demonstrated to have better prognosis than other types of ICC. Recurrence is confirmed to be a major prognostic factor. When feasible, aggressive surgical resection of recurrence can improve the prognosis in these patients, especially in patients with ICC. In patients with PCC, in which recurrence is more often unresectable, aggressive adjuvant treatment protocol could improve survival reducing the frequency of recurrences.