基于单中心的双原发性肝细胞肝癌和肝内胆管癌术后疗效影响因素分析
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摘要
目的:探讨双原发性肝细胞肝癌与肝内胆管细胞癌(double primary hepatocellular carcinoma and intrahepatic cholangiocarcinoma,dpHCC-ICC)患者手术治疗预后影响因素。方法:回顾性分析26例经手术切除术后病理证实为dpHCCICC患者的临床资料,与同期混合型肝癌(combined hepatocellular carcinoma and cholangiocarcinoma,CHC-CC)患者进行预后比较。结果:26例dpHCC-ICC患者中,男性18例(69%),平均(56.2±14.6)岁,HBsAg阳性17例(65%),Child-Pugh分级A级26例(100%),巴塞罗那分期A、B、C期分别为11、13、2例,肿瘤中位直径为3.3cm(2.0~7.1cm),肿瘤数目:2个19例(73%)、>2个7例(27%)。所有患者均行根治性R0切除。26例患者均有完整随访,术后1、3、5年生存率分别为92%、73%、62%。dpHCC-ICC术前γ-谷氨酰转肽酶(GGT)>60U/L、血清白蛋白(ALB)<35g/L是影响术后无复发生存(recurrencefree survival,RFS)的独立危险因素,微血管侵犯(microvascular invasion,MVI)是影响术后总体生存(overall survival,OS)的独立危险因素。dpHCC-ICC与同期CHC-CC患者术后生存情况无明显差异;巴塞罗那B期患者中,dpHCC-ICC患者RFS优于CHC-CC者(P=0.041)。结论:dpHCC-ICC需经术后组织病理学检查确诊,治疗以外科手术切除为主。术前GGT>60U/L、ALB<35g/L是影响dpHCC-ICC患者术后RFS的独立危险因素;MVI是影响术后OS的独立危险因素。
Objective:To explore the clinicopathological features and prognosis of double primary hepatocellular carcinoma and intrahepatic cholangiocarcinoma(dpHCC-ICC).Methods: We retrospectively analyzed the clinical data of 26 dpHCC-ICC patients who underwent hepatectomy at our center.Data of clinical manifestations,preoperative diagnosis,pathological features,treatments,and prognosis were included.The data of patients with dpHCC-ICC and those with combined hepatocellular carcinoma and cholangiocarcinoma(CHC-CC)at the same time were compared.Results:Eighteen patients(69%)were male,with an average age of(56.2 ± 14.6)years old.Seventeen patients(65%)were HBsAg positive.All patients were Child-Pugh class A grade.There were 11,13,and 2 patients of the Barcelona Clinic Liver Cancer Classification(BCLC)A,B,and C,respectively.The median tumor diameter was 3.3 cm(2.0-7.1 cm).Tumor number:19 cases(73%)with 2 tumor nodules and 7 cases(27%)with more than 2 tumor nodules.All patients underwent R0 resection and were pathologically confirmed as dpHCC-ICC.All patients had complete follow-up after operation,and the 1-,3-,and 5-year survival rates were 92%,73%,and 62%,respectively.For dpHCC-ICC,preoperative GGT > 60 U/L and ALB < 35 g/L were independent risk factors for the recurrence-free survival(RFS)after surgery and microvascular invasion(MVI)was an independent risk factor for the overall survival(OS).There was no significant difference in survival between the dpHCC-ICC and CHC-CC patients during the same period.However,in the BCLC-B subpopulation,the RFS of dpHCC-ICC was superior to the classical CHC-CC(P=0.041).Conclusions:dpHCC-ICC is a clinically rare liver tumor that is difficult to diagnose preoperatively.Definite diagnosis requires postoperative histopathological examination.The main treatment of dpHCC-ICC is surgical resection.For dpHCC-ICC,preoperative GGT >60 U/L and ALB<35 g/L are independent risk factors for the RFS and MVI is an independent risk factor for the OS.
Objective:To explore the clinicopathological features and prognosis of double primary hepatocellular carcinoma and intrahepatic cholangiocarcinoma(dpHCC-ICC).Methods: We retrospectively analyzed the clinical data of 26 dpHCC-ICC patients who underwent hepatectomy at our center.Data of clinical manifestations,preoperative diagnosis,pathological features,treatments,and prognosis were included.The data of patients with dpHCC-ICC and those with combined hepatocellular carcinoma and cholangiocarcinoma(CHC-CC)at the same time were compared.Results:Eighteen patients(69%)were male,with an average age of(56.2 ± 14.6)years old.Seventeen patients(65%)were HBsAg positive.All patients were Child-Pugh class A grade.There were 11,13,and 2 patients of the Barcelona Clinic Liver Cancer Classification(BCLC)A,B,and C,respectively.The median tumor diameter was 3.3 cm(2.0-7.1 cm).Tumor number:19 cases(73%)with 2 tumor nodules and 7 cases(27%)with more than 2 tumor nodules.All patients underwent R0 resection and were pathologically confirmed as dpHCC-ICC.All patients had complete follow-up after operation,and the 1-,3-,and 5-year survival rates were 92%,73%,and 62%,respectively.For dpHCC-ICC,preoperative GGT > 60 U/L and ALB < 35 g/L were independent risk factors for the recurrence-free survival(RFS)after surgery and microvascular invasion(MVI)was an independent risk factor for the overall survival(OS).There was no significant difference in survival between the dpHCC-ICC and CHC-CC patients during the same period.However,in the BCLC-B subpopulation,the RFS of dpHCC-ICC was superior to the classical CHC-CC(P=0.041).Conclusions:dpHCC-ICC is a clinically rare liver tumor that is difficult to diagnose preoperatively.Definite diagnosis requires postoperative histopathological examination.The main treatment of dpHCC-ICC is surgical resection.For dpHCC-ICC,preoperative GGT >60 U/L and ALB<35 g/L are independent risk factors for the RFS and MVI is an independent risk factor for the OS.
引文
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[21]WANG N Y,ZHANG D,ZHAO W,et al.Clinical application of an enzyme-linked immunosorbent assay detecting hepatoma-specific gamma-glutamyltransferase[J].Hepatol Res,2010,39(10):979-987.
[22]YIN X,ZHENG S S,ZHANG B H,et al.Elevation of serum3-glutamyltransferase as a predictor of aggressive tumor behaviors and unfavorable prognosis in patients with intrahepatic cholangiocarcinoma:analysis of a large monocenter study[J].Eur J Gastroenterol Hepatol,2013,25(12):1408-1414.
[23]LI T,QIN L X,ZHOU J,et al.Staging,prognostic factors and adjuvant therapy of intrahepatic cholangiocarcinoma after curative resection[J].Liver Int,2014,34(6):953-960.
[24]JUNG D H,HWANG S,HONG S M,et al.Post-resection prognosis of combined hepatocellular carcinomacholangiocarcinoma according to the 2010 WHO classification[J].World J Surg,2017,41(5):1347-1357.
[2]SUN H C,ZHANG W,QIN L X,et al.Positive serum hepatitis B e antigen associated with higher risk of early recurrence and poorer survival in patients after curative resection of hepatitis B-related hepatocellular carcinoma[J].JHepatol,2007,47(5):684-690.
[3]李桂梅,梅佳,杨志慧,等.混合型原发性肝癌12例临床病理分析[J].诊断病理学杂志,2013,20(8):458-461.
[4]GOODMAN Z D,ISHAK K G,LANGLOSS J M,et al.Combined hepatocellular-cholangiocarcinoma.A histologic and immunohistochemical study[J].Cancer,1985,55(1):124-135.
[5]NAGAFUCHI Y,OKAMOTO K,SHONO M,et al.Separate histogenesis of combined hepatocellular and cholangiocellular carcinoma in two patients[J].Hepatogastroenterology,1998,45(20):523-527.
[6]GARANCINI M,GOFFREDO P,PAGNI F,et al.Combined hepatocellular-cholangiocarcinoma:a populationlevel analysis of an uncommon primary liver tumor[J].Liver Transpl,2014,20(8):952-959.
[7]INABA K,SUZUKI S,SAKAGUCHI T,et al.Double primary liver cancer(intrahepatic cholangiocarcinoma and hepatocellular carcinoma)in a patient with hepatitis C virusrelated cirrhosis[J].J Hepatobiliary Pancreat Surg,2007,14(2):204-209.
[8]JUNG K S,CHUN K H,CHOI G H,et al.Synchronous development of intrahepatic cholangiocarcinoma and hepatocellular carcinoma in different sites of the liver with chronic B-viral hepatitis:two case reports[J].BMC Res Notes,2013,6:520.
[9]YANO Y,YAMAMOTO J,KOSUGE T,et al.Combined hepatocellular and cholangiocarcinoma:a clinicopathologic study of 26resected cases[J].Jpn J Clin Oncol,2003,33(6):283-287.
[10]KOMUTA M,GOVAERE O,VANDECAVEYE V,et al.Histological diversity in cholangiocellular carcinoma reflects the different cholangiocyte phenotypes[J].Hepatology,2012,55(6):1876-1888.
[11]WATANABE T,SAKATA J,ISHIKAWA T,et al.Synchronous development of HCC and CCC in the same subsegment of the liver in a patient with type C liver cirrhosis[J].World J Hepatol,2009,1(1):103-109.
[12]LI A,MA S,PAWLIK T,et al.Surgical treatment of double primary liver cancer:An observational study for a rare type of tumor[J].Medicine(Baltimore),2016,95(32):e4412.
[13]谢胜学,陈江明,余立权,等.46例混合型肝癌临床特点分析[J].肝胆外科杂志,2015,23(2):98-100.
[14]ZHOU Y M,YANG J M,LI B,et al.Clinicopathologic characteristics of intrahepatic cholangiocarcinoma in patients with positive serumα-fetoprotein[J].World J Gastroenterol,2008,14(14):2251-2254.
[15]CAO J,HUANG L,LIU C,et al.Double primary hepatic cancer(hepatocellular carcinoma and intrahepatic cholangiocarcinoma)in a single patient:A clinicopathologic study of 35resected cases[J].J Gastroenterol Hepatol,2013,28(6):1025-1031.
[16]LO G H.Does long-term entecavir treatment really reduce hepatocellular carcinoma incidence in patients with hepatitis Bvirus infection?[J].Hepatology,2014,59(5):2053.
[17]CHO H D,HWANG S,LEE Y J,et al.Changes in the types of liver diseases requiring hepatic resection:a singleinstitution experience of 9016cases over a 10-year period[J].Korean J Hepatobiliary Pancreat Surg,2016,20(2):49-52.
[18]张小峰,汪宇,王文超,等.微血管侵犯在肝癌外科治疗中的临床意义[J].肝胆外科杂志,2017,25(1):7-10.
[19]WITJES C D,WILLEMSSEN F E,VERHEIJ J,et al.Histological differentiation grade and microvascular invasion of hepatocellular carcinoma predicted by dynamic contrastenhanced MRI[J].J Magn Reson Imaging,2012,36(3):641-647.
[20]DU M,CHEN L,ZHAO J,et al.Microvascular invasion(MVI)is a poorer prognostic predictor for small hepatocellular carcinoma[J].BMC Cancer,2014,14:38.
[21]WANG N Y,ZHANG D,ZHAO W,et al.Clinical application of an enzyme-linked immunosorbent assay detecting hepatoma-specific gamma-glutamyltransferase[J].Hepatol Res,2010,39(10):979-987.
[22]YIN X,ZHENG S S,ZHANG B H,et al.Elevation of serum3-glutamyltransferase as a predictor of aggressive tumor behaviors and unfavorable prognosis in patients with intrahepatic cholangiocarcinoma:analysis of a large monocenter study[J].Eur J Gastroenterol Hepatol,2013,25(12):1408-1414.
[23]LI T,QIN L X,ZHOU J,et al.Staging,prognostic factors and adjuvant therapy of intrahepatic cholangiocarcinoma after curative resection[J].Liver Int,2014,34(6):953-960.
[24]JUNG D H,HWANG S,HONG S M,et al.Post-resection prognosis of combined hepatocellular carcinomacholangiocarcinoma according to the 2010 WHO classification[J].World J Surg,2017,41(5):1347-1357.