肝内胆管细胞癌根治性切除术后临床预后影响因素的研究
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摘要
目的探讨肝内胆管细胞癌(ICC)行根治性切除(R0切除)术后的独立预后影响因素。方法回顾性分析中山大学附属第一医院自2002年1月至2018年8月行R0切除并经病理确诊的237例ICC患者的临床病理及随访资料,采用Kaplan-Meier法构建生存曲线;单因素及多因素COX回归分析筛选影响患者生存预后的独立因素。一致性指数(C-index)、时间依赖性受试者工作特征曲线(ROC曲线)、曲线下面积(AUC)及校准曲线用于评价COX回归模型的预测效能。结果237例ICC患者的中位生存期为19.93个月(95%CI=14.31～26.21),术后1、2、3年生存率分别为62.3%、45.0%及35.6%。单因素及多因素回归分析显示谷氨酰转移酶(GGT)>53 U/L(P=0.001)、CA125>17.4 U/ml(P<0.001)、淋巴结转移(P=0.039)、肿瘤分化不良(P<0.001)是ICC患者行R0切除术后预后不良的独立危险因素。按照删除概率P>0.1的标准,纳入癌胚抗原(CEA)(P=0.092)后的预后模型C-index为0.74(95%CI=0.68～0.78),不同随访时间点对应的AUC值均在0.8左右,模型具有良好的预测效能。结论 GGT、CEA、CA125、淋巴结转移情况及肿瘤分化程度可作为ICC患者R0切除术后临床预后的预测指标。
Objective To identify the independent prognostic factors of intrahepatic cholangiocarcinoma(ICC) patients after receiving curative(R0) resection. Methods From January 2002 to August 2018, the clinicopathological and prognosis data of two hundred and thirty-seven patients with the pathological diagnosis of ICC in the First Affiliated Hospital of Sun Yat-sen University who underwent curative resection were analyzed retrospectively. The survival curve was constructed by Kaplan-Meier method. Univariate and multivariate COX regression analysis were used to screen independent factors affecting survival and prognosis of patients. C-index, ROC curve, AUC curve and calibration curve were used to evaluate the predictive effectiveness of COX regression model. Results The median survival time of ICC patients was 19.93 months(95%CI=14.31-26.21), and the 1-, 2-, and 3-year survival rates were 62.3%, 45.0%, and 35.6%, respectively. Univariate and multivariate regression analysis demonstrated that gamma-glutamyl transpeptidase(GGT) >53 U/L(P=0.001), CA125>17.4 U/ml(P<0.001), lymph node metastasis(P=0.039) and poor tumor differentiation(P<0.001) were the adverse factors of prognosis after R0 resection in ICC patients. According to the criteria for deleting probability: P>0.1, the C-index of the prognostic model containing CEA(P=0.092) was 0.74(95%CI=0.68-0.78). The AUC values corresponding to different follow-up time points were all around 0.8, and the model had good prediction efficiency. Conclusion GGT, CEA, CA125, lymph node metastasis and poor tumor differentiation are prognostic predictors of ICC patients after receiving R0 resection.
Objective To identify the independent prognostic factors of intrahepatic cholangiocarcinoma(ICC) patients after receiving curative(R0) resection. Methods From January 2002 to August 2018, the clinicopathological and prognosis data of two hundred and thirty-seven patients with the pathological diagnosis of ICC in the First Affiliated Hospital of Sun Yat-sen University who underwent curative resection were analyzed retrospectively. The survival curve was constructed by Kaplan-Meier method. Univariate and multivariate COX regression analysis were used to screen independent factors affecting survival and prognosis of patients. C-index, ROC curve, AUC curve and calibration curve were used to evaluate the predictive effectiveness of COX regression model. Results The median survival time of ICC patients was 19.93 months(95%CI=14.31-26.21), and the 1-, 2-, and 3-year survival rates were 62.3%, 45.0%, and 35.6%, respectively. Univariate and multivariate regression analysis demonstrated that gamma-glutamyl transpeptidase(GGT) >53 U/L(P=0.001), CA125>17.4 U/ml(P<0.001), lymph node metastasis(P=0.039) and poor tumor differentiation(P<0.001) were the adverse factors of prognosis after R0 resection in ICC patients. According to the criteria for deleting probability: P>0.1, the C-index of the prognostic model containing CEA(P=0.092) was 0.74(95%CI=0.68-0.78). The AUC values corresponding to different follow-up time points were all around 0.8, and the model had good prediction efficiency. Conclusion GGT, CEA, CA125, lymph node metastasis and poor tumor differentiation are prognostic predictors of ICC patients after receiving R0 resection.
引文
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[25]Loosen SH,Roderburg C,Kauertz KL,et al.CEA but not CA19-9 is an independent prognostic factor in patients undergoing resection of cholangiocarcinoma[J].Sci Rep,2017,7(1):16975.
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[27]Addeo P,Jedidi I,Locicero A,et al.Prognostic impact of tumor multinodularity in intrahepatic cholangiocarcinoma[J].JGastrointest Surg,2018 Nov 26.[Epub ahead of print]
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[3]Endo I,Gonen M,Yopp AC,et al.Intrahepatic cholangiocarcinoma:rising frequency,improved survival,and determinants of outcome after resection[J].Ann Surg,2008,248(1):84-96.
[4]Rizvi S,Khan SA,Hallemeier CL,et al.Cholangiocarcinomaevolving concepts and therapeutic strategies[J].Nat Rev Clin Oncol,2018,15(2):95-111.
[5]Wang Y,Li J,Xia Y,et al.Prognostic nomogram for intrahepatic cholangiocarcinoma after partial hepatectomy[J].J Clin Onco,2013,31(9):1188-1195.
[6]Edge SB,Compton CC.The American Joint Committee on Cancer:the 7th edition of the AJCC cancer staging manual and the future of TNM[J].Ann Surg Oncol,2010,17(6):1471-1474.
[7]Chun YS,Pawlik TM,Vauthey JN.8th edition of the AJCC Cancer Staging Manual:pancreas and hepatobiliary cancers[J].Ann Surg Oncol,2018,25(4):845-847.
[8]Okabayashi T,Yamamoto J,Kosuge T,et al.A new staging system for mass-forming intrahepatic cholangiocarcinoma:analysis of preoperative and postoperative variables[J].Cancer,2001,92(9):2374-2383.
[9]Nathan H,Aloia TA,Vauthey JN,et al.A proposed staging system for intrahepatic cholangiocarcinoma[J].Ann Surg Oncol,2009,16(1):14-22.
[10]de Jong MC,Nathan H,Sotiropoulos GC,et al.Intrahepatic cholangiocarcinoma:an international multi-institutional analysis of prognostic factors and lymph node assessment[J].J Clin Oncol,2011,29(23):3140-3145.
[11]Weber SM,Ribero D,O'Reilly EM,et al.Intrahepatic cholangiocarcinoma:expert consensus statement[J].HPB(Oxford),2015,17(8):669-680.
[12]Kim DH,Choi DW,Choi SH,et al.Is there a role for systematic hepatic pedicle lymphadenectomy in intrahepatic cholangiocarcinoma?Areview of 17 years of experience in a tertiary institution[J].Surgery,2015,157(4):666-675.
[13]Choi SB,Kim KS,Choi JY,et al.The prognosis and survival outcome of intrahepatic cholangiocarcinoma following surgical resection:association of lymph node metastasis and lymph node dissection with survival[J].Ann Surg Oncol,2009,16(11):3048-3056.
[14]Chen T,Zhang MG,Xu HX,et al.Preoperative serum CA125levels predict the prognosis in hyperbilirubinemia patients with resectable pancreatic ductal adenocarcinoma[J].Medicine(Baltimore),2015,94(19):e751.
[15]Higashi M,Yamada N,Yokoyama S,et al.Pathobiological implications of MUC16/CA125 expression in intrahepatic cholangiocarcinoma-mass forming type[J].Pathobiology,2012,79(2):101-106.
[16]Hu HJ,Mao H,Tan YQ,et al.Clinical value of preoperative serum CA 19-9 and CA 125 levels in predicting the resectability of hilar cholangiocarcinoma[J].Springerplus,2016,5:551.
[17]Li T,Qin LX,Zhou J,et al.Staging,prognostic factors and adjuvant therapy of intrahepatic cholangiocarcinoma after curative resection[J].Liver Int,2014,34(6):953-960.
[18]Zhang C,Wang H,Ning Z,et al.Serum liver enzymes serve as prognostic factors in patients with intrahepatic cholangiocarcinoma[J].Onco Targets Ther,2017,10:1441-1449.
[19]Ou Y,Huang J,Yang L.The prognostic significance of pretreatment serumγ-glutamyltranspeptidase in primary liver cancer:a meta-analysis and systematic review[J].Biosci Rep,2018,38(6):pii:BSR20181058.Print 2018 Dec 21.
[20]Luo C,Xu B,Fan Y,et al.Preoperative gamma-glutamyltransferase is associated with cancer-specific survival and recurrence-free survival of nonmetastatic renal cell carcinoma with venous tumor thrombus[J].Biomed Res Int,2017,2017:3142926.
[21]Everhart JE,Wright EC.Association ofγ-glutamyl transferase(GGT)activity with treatment and clinical outcomes in chronic hepatitis C(HCV)[J].Hepatology,2013,57(5):1725-1733.
[22]Pandur S,Pankiv S,Johannessen M,et al.Gammaglutamyltransferase is upregulated after oxidative stress through the Ras signal transduction pathway in rat colon carcinoma cells[J].Free Radic Res,2007,41(12):1376-1384.
[23]Das V,Kalita J,Pal M.Predictive and prognostic biomarkers in colorectal cancer:A systematic review of recent advances and challenges[J].Biomed Pharmacother,2017,87:8-19.
[24]He C,Zhang Y,Song Y,et al.Preoperative CEA levels are supplementary to CA19-9 levels in predicting prognosis in patients with resectable intrahepatic cholangiocarcinoma[J].J Cancer,2018,9(17):3117-3128.
[25]Loosen SH,Roderburg C,Kauertz KL,et al.CEA but not CA19-9 is an independent prognostic factor in patients undergoing resection of cholangiocarcinoma[J].Sci Rep,2017,7(1):16975.
[26]Okubo S,Mitsunaga S,Kato Y,et al.The prognostic impact of differentiation at the invasive front of biliary tract cancer[J].J Surg Oncol,2018,117(6):1278-1287.
[27]Addeo P,Jedidi I,Locicero A,et al.Prognostic impact of tumor multinodularity in intrahepatic cholangiocarcinoma[J].JGastrointest Surg,2018 Nov 26.[Epub ahead of print]