Clinical efficacy of radical resection for stage T3 gallbladder cancer and prognostic analysis

Abstract

Objective To investigate the clinical efficacy of radical resection for stage T3 gallbladder cancer and prognostic factors. Methods The retrospective case-control study was conducted. The clinico-pathological data of 87 patients with T3 gallbladder cancer who were admitted to Tianjin Medical University Cancer Institute and Hospital from January 2005 to June 2016 were collected. There were 44 males and 43 females, aged 29-79 years, with a median age of 61 years. According to the different preoperative pathological classification and intraoperative exploration of gallbladder cancer, corresponding surgeries were performed. Observation indicators: (1) surgical and postoperative conditions; (2) clinical efficacy of stage T3 gallbladder cancer and prognostic factors analysis; (3) clinical efficacy of stage T3 gallbladder adenocarcinoma and prognostic factors analysis; (4) clinical efficacy of stage T3 gallbladder adenosquamous carcinoma and prognostic factors analysis. Follow-up by outpatient examination or telephone interview was performed to detect the postoperative survival of patients up to June 2018. Measurement data with skewed distribution were represented as M (range), and count data were described as absolute numbers. Survival curve, survival time and survival rate were drawn and calculated by the Kaplan-Meier method. Survival analysis was performed by the Log-rank test. Univariate analysis was performed using the Log-rank test and multivariate analysis using the COX proportional hazard model. Results (1) Surgical and postoperative conditions: all the 87 patients underwent radical resection of gallbladder cancer, including 29 cases of hepatic wedge resection and 58 cases of extended hepatectomy. Of the 87 patients, 42 underwent standard lymph node dissection and 45 underwent enlarged lymph node dissection. There were 27 cases receiving extrahepatic bile duct reconstruction. The postoperative pathological results of 87 patients showed that 64 were diagnosed with gallbladder adenocarcinoma and 23 were diagnosed with gallbladder adenosquamous carcinoma. There were 59 cases comorbid with liver invasion and 3 cases comorbid with vascular invasion. The marginal histopathological examination showed negative margin in 63 cases and positive margin in 24 cases. The degree of tumor differentiation: there were 23 patients with highly differentiated tumor and 64 with poorly differentiated tumor. Of the 87 patients, 43 received postoperative adjuvant therapy and 44 didn′t receive adjuvant therapy. (2) Clinical efficacy of stage T3 gallbladder cancer and prognostic factors analysis. ① All the 87 patients were followed up for 1.8-128.0 months, with a median follow-up time of 26.3 months. All the 87 patients had survived for 1.1-82.7 months, with a median time of 20.1 months. The 2-year overall survival rate of patients was 59.8%, and the 2-year disease-free survival rate was 49.4%. ② Univariate analysis showed that preoperative alkaline phosphatase (ALP) level, tumor diameter, pathological type of tumor, lymph node metastasis, and range of hepatectomy were associated factors for the postoperative 2-year overall survival rate of patients (χ2=5.451, 4.900, 8.256, 4.419, 5.858, P 0.05), but a significant difference in the postoperative 2-year disease-free survival rate between them (56.3% vs. 30.4%, χ2=5.828, P<0.05). (3) Clinical efficacy of stage T3 gallbladder adenocarcinoma and prognostic factors analysis. ① Sixty-four patients with gallbladder adenocarcinoma had the median survival time of 23.1 months, with a range from 3.2 to 82.7 months. The postoperative 2-year overall survival rate was 68.8%, and the postoperative 2-year disease-free survival rate was 56.3%. ② For the 64 patients with T3 stage gallbladder adenocarcinoma, univariate analysis showed that preoperative CA19-9 level and range of lymph node dissection were associated factors for the postoperative 2-year overall survival rate (χ2=4.012, 8.837, P<0.05). The range of lymph node dissection was an associated factor for the postoperative 2-year disease-free survival rate (χ2=6.361, P<0.05). Multivariate analysis showed that range of lymph node dissection was an independant factor for both the postoperative 2-year overall survival rate and postoperative 2-year disease-free survival rate (HR=0.244, 0.382, 95%CI: 0.088-0.674, 0.176-0.831, P<0.05). ③ Survival analysis: range of lymph node dissection was an associated factor for both the postoperative 2-year overall survival rate and postoperative 2-year disease-free survival rate of patients. Of the 64 patients with T3 stage gallbladder adenocarcinoma, the postoperative 2-year overall survival rate and disease-free survival rate of patients undergoing enlarged lymph node dissection were 84.8% and 69.7%, versus 51.6% and 41.9% of the patients undergoing standard lymph node dissection (χ2=8.837, 6.361, P<0.05). (4)Clinical efficacy of stage T3 gallbladder adenosquamous carcinoma and prognostic factors analysis. ① Twenty-three patients with gallbladder adenosquamous carcinoma had the median survival time of 13.2 months, with a range from 1.1 to 70.3 months. The postoperative 2-year overall survival rate was 34.8%, and the postoperative 2-year disease-free survival rate was 30.4%. ② For the 23 patients with T3 stage gallbladder adenosquamous carcinoma, univariate analysis showed that preoperative ALP level, lymph node metastasis, range of hepatectomy, and extrahepatic bile duct reconstruction were associated factors for the postoperative 2-year overall survival rate of patients (χ2=5.288, 4.574, 12.960, 4.106, P<0.05). The lymph node metastasis and range of hepatectomy were associated factors for the postoperative 2-year disease-free survival rate of patients (χ2=7.364, 10.582, P<0.05). Multivariate analysis showed that range of hepatectomy was an independant factor for both the postoperative 2-year overall survival rate and postoperative 2-year disease-free survival rate (HR=0.102, 0.153, 95%CI: 0.012-0.880, 0.033-0.718, P<0.05). ③ Survival analysis: range of hepatectomy was an independant factor for both the postoperative 2-year overall survival rate and postoperative 2-year disease-free survival rate of patients. Of the 23 patients with T3 stage gallbladder adenosquamous carcinoma, the postoperative 2-year overall survival rate and postoperative 2-year disease-free survival rate of patients undergoing extended hepatectomy were 87.5% and 75.0%, versus 6.7% and 6.7% of the patients undergoing hepatic wedge resection (χ2=12.960, 10.528, P<0.05). Conclusions Lymph node metastasis is an independent factor influencing the postoperative 2-year overall survival rate and postoperative 2-year disease-free survival rate of patients with T3 stage gallbladder cancer. The range of lymph node dissection is an independent factor for the postoperative 2-year overall survival rate and postoperative 2-year disease-free survival rate of patients with stage T3 gallbladder adenocarcinoma. Range of hepatectomy is an independent factor for the postoperative 2-year overall survival rate and postoperative 2-year disease-free survival rate of patients with stage T3 gallbladder adenosquamous carcinoma. Patients with gallbladder adenocarcinoma should undergo enlarged lymph node dissection, and patients with gallbladder adenosquamous carcinoma need to undergo extended hepatectomy. Key words: Biliary neoplasms; Gallbladder cancer, stage T3; Gallbladder adenocarcinoma; Gallbladder adenosquamous carcinoma; Lymph node dissection; Prognostic analysis