胆管细胞性肝癌外科治疗的预后因素分析

Prognostic factors after surgical resection for intrahepatic cholangiocarcinoma

目的探讨影响胆管细胞性肝癌外科治疗预后的因素。方法回顾性分析2000年1月至2010年1月天津医科大学附属肿瘤医院行外科治疗的99例胆管细胞性肝癌患者的临床资料。所有患者行常规淋巴结清扫，清扫范围包括肝门及第12、13和8组淋巴结。根据肿瘤的大小、位置、数目及肝功能状况确定肝切除的范围。患者术后半年内每个月门诊复查，半年后每3个月复查1次，2年后每半年复查1次，对怀疑有复发或疾病进展者每月复查1次。对未能按时就诊的患者进行电话随访。随访时间截至患者死亡或2013年3月。生存分析采用Log—rank检验。经过单因素分析有统计学意义的变量进一步采用COX逐步回归模型进行预后多因素分析。结果99例胆管细胞性肝癌患者中，40例行半肝切除术，27例行扩大半肝切除术，20例行肝段切除术，12例行半肝切除＋楔形切除术。99例患者均获得随访，中位随访时间为33个月（21．1～44．9个月）。患者术后1、3、5年的无复发生存率及总生存率分别为64．6％、29．2％、22．7％和78．8％、46．4％、30．3％。单因素分析结果表明：病毒性肝炎、术前CAl9—9、TNM分期、淋巴结转移、微血管侵犯、结节数目和R。切除是影响患者无复发生存率的危险因素（Log—rank值=5．048，5．982，20．128，13．148，29．632，32．488，50．574，P〈0．05）；术前CAl9—9、TNM分期、淋巴结转移、微血管侵犯、结节数目和R。切除是影响患者总生存率的危险因素（Log—rank值=4．302，17．267，11．756，23．840，36．411，47．126，P〈0．05）。进一步分析发现：TNM分期患者（I期20例、Ⅱ期44例、Ⅲ期8例、Ⅳ期27例）中，各期患者的无复发生存时间和总生存时间比较，差异均有统计学意义（Log—rank值=20．128，17．267，P〈0．05）。I期与Ⅲ、Ⅳ期和Ⅱ期与Ⅳ期患者无复发生存时间比较，差异有统计学意义（Log—rank值=10．807，19．368，6．347，P〈0．05）；I期与Ⅱ、Ⅲ、Ⅳ期和Ⅱ期与Ⅳ期患者总生存时间比较，差异有统计学意义（Log-rank值=6．119，4．015，16．282，4．929，P〈0．05）；其余各期患者比较，差异无统计学意义（P〉0．05）。多因素分析结果表明：TNMm期和Ⅳ期、微血管侵犯、多结节和Rn切除是影响无复发生存时间独立危险因素（RR=1．413，3．073，2．737，3．916，95％可信区间：1．119～1．784，1．837～5．140，1．338～4．207，1．849～8．291，P〈0．05）；淋巴结转移、微血管侵犯、多结节和R。切除是影响总生存时间的独立危险因素（RR=2．025，2．948，0．327，3．494，95％可信区间：1．215～3．374，1．774～4．900，0．183～0．583，1．670～7．310，P〈0．05）。结论TNMHI期和Ⅳ期、淋巴结转移、微血管侵犯、多结节、非R0切除导致胆管细胞性肝癌患者术后无复发生存时间和总生存时间明显缩短，是预后不良的主要影响因素。R0切除是改善胆管癌患者预后的最大希望。

Objective To identify the prognostic factors for patients with intrahepatic cholangiocarcinoma. Methods The clinical data of 99 patients with intrahepatic cholangiocarcinoma who received surgical treatment at the Cancer Hospital of Tianjin Medical University from January 2000 to January 2010 were analyzed retrospectively. Lymph nodes at the hepatic portal and group 12, 13 and 8 lymph nodes were resected. The range of hepatectomy was decided according to the size, location, number of tumor and the hepatic function. Patients were followed up every month within the first 6 months after operation, every 3 months at 6 months later, and they were followed up every half year at 2 years later. Patients who were suspected as with tumor recurrence or progression were followed up every month. All the patients were followed up till death or March of 2013. The survival was analyzed using theLog-rank test, and multivariate analysis was done using the COX regression model. Results Forty patients received hemi-hepatectomy, 27 received extended hemi-hepatectomy, 20 received segmentectomy, and 12 received hemi-hepatectomy ＋ wedge resection. All the patients were followed up and the median time of follow-up was 33 months （range 21.1-44.9 months）. The 1-, 3-, 5-year recurrence-free survival rates and total survival rates of the 99 patients were 64.6%, 29.2%, 22.7% and 78.8%, 46.4% and 30.3%, respectively. The results of univariate analysis showed that hepatitis B or C virus infection, preoperative CA19-9 level, TNM staging, lymph node metastasis, microvascular invasion, number of nodules and R0 resection were risk factors influencing the recurrence-free survival time （ Log-rank value = 5. 048, 5. 982, 20. 128, 13. 148, 29.632, 32. 488, 50.574, P 〈 0.05）. The peroperative CA19-9 level, TNM staging, lymph node metastasis, microvascular invasion, number of nodules and R0 resection were risk factors influencing the total survival rate （ Log-rank value = 4. 302, 17. 267, 11. 756, 23. 840, 36. 411,47. 126, P 〈0.05）. There were significant differences in the recurrence-free survival time and total survival time between patients in different TNM stages （20 patients in stage Ⅰ , 44 in stage Ⅱ8 in stage Ⅲ and 27 in stage Ⅳ ） （ Log-rank value = 20. 128, 17. 267, P 〈 0.05 ）. There were significant difference in the recurrence-free survival time between patients in stage I and Ⅲ, patients in stage Ⅰ and IV, and between patients in stage Ⅱ and Ⅳ （ Log-rank value = 10. 807, 19. 368, 6. 347, P 〈 0.05 ）. There were significant differ- ence in the total survival time between patients in stage I and II , patients in stage I and Ⅲ, patients in stage Ⅰ and IV and between patients in stage Ⅱ and Ⅳ （Log-rank value =6. 119, 4.015, 16.282, 4.929, P〈0.05）. There was no significant difference in the survival time between patients in other TNM stages （P 〉 0.05 ）. The results of multivariate analysis showed that TNM stage Ⅲ and IV, microvascular invasion, multiple nodules and R0 resection were independent risk factors influencing the recurrence-free survival time （RR = 1. 413, 3. 073,2. 737, 3. 916, 95% confidence interval： 1. 119-1. 784, 1. 837-5. 140, 1. 338-4. 207, 1. 849-8. 291, P 〈0.05） ; lymph node metastasis, microvascular invasion, multiple tumors and R0 resection were the independent risk factors influencing the total survival time （RR =2. 025, 2. 948, 0. 327, 3.494, 95% confidence interval： 1. 215-3. 374, 1. 774-4. 900, 0. 183-0. 583, 1. 670-7. 310, P 〈 0.05）. Conclusions TNM stage m and IV, lymph node metastasis, microvascular invasion, multiple nodules, non-R0 resection shorten the recurrence-free survival time and total survival time of patients who received surgical resection for intrahepatic cholangiocarcinoma, and they are the main factors influencing the prognosis. Ro resection could improve the survival of patients with intrahepatic eholangiocareinoma.