胆囊、胆管和胆管细胞癌中肿瘤标志物的评估及其对预后的影响——一项初步研究

Evaluation of Tumor Markers and Their Impact on Prognosis in Gallbladder, Bile Duct and Cholangiocellular Carcinomas - A Pilot Study.

作者信息

Liska Vaclav, Treska Vladislav, Skalicky Tomas, Fichtl Jakub, Bruha Jan, Vycital Ondrej, Topolcan Ondrej, Palek Richard, Rosendorf Jachym, Polivka Jiri, Holubec Lubos

机构信息

Department of Surgery, Faculty of Medicine in Plzen, Charles University, Plzen, Czech Republic

Biomedical Center, Faculty of Medicine in Plzen, Charles University, Plzen, Czech Republic.

出版信息

Anticancer Res. 2017 Apr;37(4):2003-2009. doi: 10.21873/anticanres.11544.

DOI:10.21873/anticanres.11544

PMID:28373474

Abstract

BACKGROUND/AIM: The behavior of tumor markers in biliary tract malignancies is not well-known and has been scarcely studied. Such markers could play important roles in diagnostic and prognostic schemes as well as in decision-making about the best treatment strategies. This study analyzed the preoperative serum levels of conventional tumor markers (AFP, CEA, CA 19-9, CA 72-4), proliferative marker thymidine kinase (TK) and cytokeratins (TPA, TPS and CYFRA 21.1) in patients with gallbladder carcinoma, bile duct carcinoma (Klatskin) and cholangiocellular carcinoma, in relation to the patient prognosis. The study aimed in finding the role of tumor markers in not properly investigated diseases, where their importance is often marginalized.

MATERIALS AND METHODS

The study included 43 patients, who underwent either radical surgical procedure (n=21) or explorative laparotomy without any surgical treatment (n=22) for gallbladder carcinoma, bile duct carcinoma (Klatskin tumor) and cholangiocellular carcinoma (24, 8 and 11 patients, respectively) between 2003 and 2010 at our Department. The association of serum tumor markers and patients' prognosis were assessed for the entire cohort and for each cancer type and also with regard to treatment (radical surgery versus explorative laparotomy). Overall survival (OS) and disease-free interval (DFI) were estimated by the Kaplan-Meier method and statistically evaluated using the LogRank test. DFI was computed only in the subgroup of patients treated by radical surgery.

RESULTS

The statistical analysis of tumor markers revealed TK as a poor prognostic factor for shorter DFI (HR=3.5, 95%CI=0.6-21.3, p<0.05) and also OS (HR=4.6, 95%CI=1.0-4.7, p<0.05) in patients with gallbladder carcinoma treated with radical surgery. TPS was demonstrated as a poor prognostic factor for OS in patients with gallbladder carcinoma (HR=12.7, 95%CI=1.4-117.7, p<0.05). CEA was proven to be a factor of poor prognosis with shorter OS in patients after explorative laparotomy for all cumulated studied diagnoses (HR=9.8, 95%CI=1.05-92.7, p<0.05).

CONCLUSION

The results of this study suggested the importance of tumor markers for assessment of prognosis (OS or DFI) in patients with gallbladder carcinoma, bile duct carcinoma, and cholangiocellular carcinoma.

摘要

背景/目的：胆道恶性肿瘤中肿瘤标志物的表现尚不为人熟知，且鲜有研究。此类标志物在诊断和预后方案以及最佳治疗策略的决策中可能发挥重要作用。本研究分析了胆囊癌、胆管癌（肝门部胆管癌）和胆管细胞癌患者术前常规肿瘤标志物（甲胎蛋白、癌胚抗原、糖类抗原19-9、糖类抗原72-4）、增殖标志物胸苷激酶（TK）和细胞角蛋白（组织多肽抗原、组织多肽特异性抗原和细胞角蛋白19片段）的血清水平，并探讨其与患者预后的关系。本研究旨在探寻肿瘤标志物在研究尚不充分的疾病中的作用，在这些疾病中其重要性常被忽视。

材料与方法

本研究纳入了43例患者，2003年至2010年间在我院，分别有24例、8例和11例患者因胆囊癌、胆管癌（肝门部胆管癌）和胆管细胞癌接受了根治性手术（n = 21）或未进行任何手术治疗的 exploratory laparotomy（n = 22）。评估了整个队列、每种癌症类型以及治疗方式（根治性手术与 exploratory laparotomy）的血清肿瘤标志物与患者预后的相关性。采用Kaplan-Meier法估计总生存期（OS）和无病生存期（DFI），并使用LogRank检验进行统计学评估。DFI仅在接受根治性手术的患者亚组中计算。

结果

肿瘤标志物的统计分析显示，对于接受根治性手术的胆囊癌患者，TK是DFI缩短（风险比=3.5，95%置信区间=0.6 - 21.3，p<0.05）和OS缩短（风险比=4.6，95%置信区间=1.0 - 4.7，p<0.05）的不良预后因素。TPS被证明是胆囊癌患者OS的不良预后因素（风险比=12.7，95%置信区间=1.4 - 117.7，p<0.05）。对于所有累积研究诊断，在 exploratory laparotomy术后患者中，癌胚抗原被证明是OS缩短的不良预后因素（风险比=9.8，95%置信区间=1.05 - 92.7，p<0.05）。