摘要
目的:探讨T3期胆囊癌根治术的临床疗效及预后影响因素。方法:采用回顾性病例对照研究方法。收集2005年1月至2016年6月天津医科大学肿瘤医院收治的87例T3期胆囊癌患者的临床病理资料;男44例,女43例;中位年龄为61岁,年龄范围为29~79岁。根据患者术前病理学分型及术中探查情况施行相应手术。观察指标:(1)手术和术后情况。(2)T3期胆囊癌临床疗效及预后影响因素分析。(3)T3期胆囊腺癌临床疗效及预后影响因素分析。(4)T3期胆囊腺鳞癌临床疗效及预后影响因素分析。采用门诊或电话方式进行随访,了解患者术后生存情况。随访时间截至2018年6月。偏态分布的计量资料以M(范围)表示,计数资料以绝对数表示。采用Kaplan-Meier法绘制生存曲线,计算生存时间和生存率;Log-rank检验进行生存情况分析。单因素分析采用Log-rank检验,多因素分析采用COX比例风险模型。结果:(1)手术和术后情况。87例患者均行胆囊癌根治术,其中行肝楔形切除29例,行扩大肝切除58例;行标准淋巴结清扫42例,行扩大淋巴结清扫45例;行肝外胆管重建27例。87例患者术后病理学检查结果显示:胆囊腺癌64例,胆囊腺鳞癌23例;合并肝脏侵犯59例,合并血管侵犯3例;切缘组织病理学检查阴性63例,阳性24例。肿瘤分化程度为高分化23例,低分化64例。87例患者行术后辅助化疗43例,未行术后辅助化疗44例。(2)T3期胆囊癌临床疗效及预后影响因素分析。①87例患者均获得随访,随访时间为1.8~128.0个月,中位随访时间为26.3个月。87例患者生存时间为1.1~82.7个月,中位生存时间为20.1个月。患者术后2年总体生存率为59.8%,术后2年无病生存率为49.4%。②单因素分析结果显示:术前碱性磷酸酶(ALP)水平、肿瘤直径、肿瘤病理学类型、淋巴结转移、肝切除范围是影响患者术后2年总体生存率的相关因素(x^2=5.451,4.900,8.256,4.419,5.858,P<0.05)。肿瘤病理学类型、淋巴结转移、肝切除范围是影响患者术后2年无病生存率的相关因素(x^2=5.828,6.968,4.077,P<0.05)。多因素分析结果显示:术前ALP水平、肿瘤直径、淋巴结转移是患者术后2年总体生存率的独立影响因素(风险比=2.539,2.619,2.201,95%可信区间为1.174~5.491,1.209~5.673,1.104~4.391,P<0.05)。肿瘤病理学类型、淋巴结转移是患者术后2年无病生存率的独立影响因素(风险比=2.254,2.296,95%可信区间为1.170~4.344,1.206~4.374,P<0.05)。③生存情况分析:肿瘤病理学类型是影响患者术后2年总体生存率和2年无病生存率的相关因素。87例患者中,64例胆囊腺癌和23例胆囊腺鳞癌患者术后2年总体生存率分别为68.8%和34.8%,两者比较,差异无统计学意义(xx=8.256,P>0.05);术后2年无病生存率分别为56.3%和30.4%,两者比较,差异有统计学意义(x^2=5.828,P<0.05)。(3)T3期胆囊腺癌临床疗效及预后影响因素分析。①64例胆囊腺癌患者术后生存时间为3.2~82.7个月,中位生存时间为23.1个月。患者术后2年总体生存率为68.8%,术后2年无病生存率为56.3%。②64例胆囊腺癌患者单因素分析结果显示:术前CA19-9水平、淋巴结清扫范围是影响患者术后2年总体生存率的相关因素(x^2=4.012,8.837,P<0.05)。淋巴结清扫范围是影响患者术后2年无病生存率的相关因素(xx=6.361,P<0.05)。多因素分析结果显示:淋巴结清扫范围是患者术后2年总体生存率和2年无病生存率的独立影响因素(风险比=0.244,0.382,95%可信区间为0.088~0.674,0.176~0.831,P<0.05)。③生存情况分析:淋巴结清扫范围是患者术后2年总体生存率和2年无病生存率的独立影响因素。64例T3期胆囊腺癌患者中,行标准淋巴结清扫和扩大淋巴结清扫患者术后2年总体生存率分别为51.6%和84.8%,两者比较,差异有统计学意义(xx=8.837,P<0.05);术后2年无病生存率分别为41.9%和69.7%,两者比较,差异有统计学意义(x^2=6.361,P<0.05)。(4)T3期胆囊腺鳞癌临床疗效及预后影响因素分析。①23例胆囊腺鳞癌患者术后生存时间为1.1~70.3个月,中位生存时间为13.2个月。患者术后2年总体生存率为34.8%,术后2年无病生存率为30.4%。②23例胆囊腺鳞癌患者单因素分析结果显示:术前ALP水平、淋巴结转移、肝切除范围、肝外胆管重建是影响患者术后2年总体生存率的相关因素(x^2=5.288,4.574,12.960,4.106,P<0.05)。淋巴结转移、肝切除范围是影响患者术后2年无病生存率的相关因素(x^2=7.364,10.582,P<0.05)。多因素分析结果显示:肝切除范围是患者术后2年总体生存率和2年无病生存率的独立影响因素(风险比=0.102,0.153,95%可信区间为0.012~0.880,0.033~0.718,P<0.05)。③生存情况分析:肝切除范围是患者术后2年总体生存率和2年无病生存率的独立影响因素。23例T3期胆囊腺鳞癌患者中,行肝楔形切除和扩大肝切除患者术后2年总体生存率分别为6.7%和87.5%,两者比较,差异有统计学意义(x^2=12.960,P<0.05);术后2年无病生存率分别为6.7%和75.0%,两者比较,差异有统计学意义(x^2=10.582,P<0.05)。结论:淋巴结转移是T3期胆囊癌患者术后2年总体生存率和2年无病生存率的独立影响因素。淋巴结清扫范围是T3期胆囊腺癌患者术后2年总体生存率和2年无病生存率的独立影响因素。肝切除范围是T3期胆囊腺鳞癌患者术后2年总体生存率和2年无病生存率的独立影响因素。胆囊腺癌患者应行扩大淋巴结清扫,胆囊腺鳞癌患者应行扩大肝切除。
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 (x^2=5.451, 4.900, 8.256, 4.419, 5.858, P<0.05), and pathological type of tumor, lymph node metastasis, and range of hepatectomy were associated factors for the postoperative 2-year disease-free survival rate of patients (x2=5.828, 6.968, 4.077, P<0.05). Multivariate analysis showed that preoperative ALP level, tumor diameter, and lymph node metastasis were independent factors influencing the postoperative 2-year overall survival rate of patients [hazard ratio (HR)=2.539, 2.619, 2.201, 95% confidence interval (CI):1.174-5.491, 1.209-5.673, 1.104-4.391, P<0.05)];pathological type of tumor and lymph node metastasis were independent factors influencing the postoperative 2-year disease-free survival rate of patients (HR=2.254, 2.296, 95%CI: 1.170-4.344,1.206-4.374, P<0.05).③ Survival analysis: pathological type of tumor was an associated factor for the postoperative 2-year overall survival rate and 2-year disease-free survival rate of patients. Of the 87 patients with T3 gallbladder cancer, there was no significant difference in the postoperative 2-year overall survival rate between the 64 patients with gallbladder adenocarcinoma and 23 with gallbladder adenosquamous carcinoma (68.8% vs. 34.8%, x^2=8.256, P>0.05), but a significant difference in the postoperative 2-year disease-free survival rate between them (56.3% vs. 30.4%, x^2=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 (x^2=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 (x^2=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 (x^2=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 (x^2=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 (x^2=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 (x^2=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.
作者
何红莹
李广涛
李青利
马小忱
张扬帆
陈璐
房锋
宋天强
He Hongying;Li Guangtao;Li Qingli;Ma Xiaochen;Zhang Yangfan;Chen Lu;Fang Feng;Song Tianqiang(Departm ent of Hepatobiliary Oncology,Tianjin Medical University Cancer Institute and Hospital,National Clinical Research Center for Cancer,Key Laboratory of Cancer Prevention and Therapy of Tianjin ,Tianjin 's Clinical Research Center for Cancer,Tianjin 300060,China)
出处
《中华消化外科杂志》
CAS
CSCD
北大核心
2019年第10期966-978,共13页
Chinese Journal of Digestive Surgery
关键词
胆道肿瘤
T3期胆囊癌
胆囊腺癌
胆囊腺鳞癌
淋巴结转移
预后分析
Biliary neoplasms
Gallbladder cancer, stage T3
Gallbladder adenocarcinoma
Gallbladder adenosquamous carcinoma
Lymph node dissection
Prognostic analysis
