61例肝门胆管癌的外科治疗及预后分析
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摘要
目的:探讨肝门胆管癌(Hepatic hilar cholangiocarcinoma/Klatskin tumor)的临床特征和治疗方法对患者生存率的影响及其切除术后的预后因素。
方法:对2004年-2009年收治的61例肝门胆管癌患者的临床特点、诊断、手术方式和随访结果进行回顾性分析。选择对肝门胆管癌切除术后预后可能产生影响的临床因素,通过COX比例风险模型进行多因素预后分析。
结果:61例手术治疗的肝门胆管癌,根治性切除30例,根治性切除附加尾状叶及肝叶切除10例,姑息性切除8例,置管引流13例。61例患者总体1、2、3年生存率分别为73.8%、62.3%、36.1%。手术切除组和置管引流组生存率差异有统计学意义(P<0.01),根治性切除组与姑息性切除组生存率差异有统计学意义(P<0.01),根治性切除组与根治性切除附加尾状叶及肝叶切除组生存率有统计学意义(P<0.05)。COX分析结果表明手术方式及肿瘤细胞分化程度是肝门胆管癌的根治切除影响预后的独立因素(P<0.05)。
结论:(1)根治性切除可以提高HCC患者远期生存率。(2)根治性切除特别是附加肝叶切除及肝十二指肠韧带骨骼化清扫,可以延长复发时间,是提高根治切除率及远期疗效的关键。(3)胆管梗阻时间长,肝功能差及残肝功能不足是引起严重并发症的原因。(4)术后三维适型放疗可以提高生存率,但是远期结果尚待进一步总结。
Objective:To explore the impact of clinical features and surgical procedure on survival of hepatic hilar cholangiocarcinoma(HCC)and the prognostic factors in patients with Klatskin tumor after curative resection.
Methods:From 2004 to 2009,61 Klatskin tumor patients undergoing operations were included in this study.The clinical features,diagnosis,surgical procedure and follow up data were retrospectively analyzed.Factors influencing postoperative survival were analyzed using COX multiple stepwise regression mode1.
Results:Of the 61 patients,30 underwent radical resection and 10 underwent radical resection plus liver leaf resection,8 underwent palliative resection,13 underwent drainage or laparotomy.The overall 1-,2-,and 3-year survival rates were 73.8%,62.3%,and 36.1%,respectively.COX analysis showed surgical approach and degree of tumor differentiation were independent prognostic factors after radical resection(P<0.05).
Conclusion: (1)The radical resection is the key factor for increasing the long-term survival rate and improving the life qualities of Klatskin tumor patients(.2)Partial hepatectomy in combination with skeletonization may be helpful for increasing radical resection rate and long term efficacy.(3)Bile duct obstruction for a long time,poor liver function and remnant liver function are causes for serious complications.(4)Three-dimensional conformal radiation therapy after surgery can increase the survival rate type,but long-term results have yet to be further summed.
方法:对2004年-2009年收治的61例肝门胆管癌患者的临床特点、诊断、手术方式和随访结果进行回顾性分析。选择对肝门胆管癌切除术后预后可能产生影响的临床因素,通过COX比例风险模型进行多因素预后分析。
结果:61例手术治疗的肝门胆管癌,根治性切除30例,根治性切除附加尾状叶及肝叶切除10例,姑息性切除8例,置管引流13例。61例患者总体1、2、3年生存率分别为73.8%、62.3%、36.1%。手术切除组和置管引流组生存率差异有统计学意义(P<0.01),根治性切除组与姑息性切除组生存率差异有统计学意义(P<0.01),根治性切除组与根治性切除附加尾状叶及肝叶切除组生存率有统计学意义(P<0.05)。COX分析结果表明手术方式及肿瘤细胞分化程度是肝门胆管癌的根治切除影响预后的独立因素(P<0.05)。
结论:(1)根治性切除可以提高HCC患者远期生存率。(2)根治性切除特别是附加肝叶切除及肝十二指肠韧带骨骼化清扫,可以延长复发时间,是提高根治切除率及远期疗效的关键。(3)胆管梗阻时间长,肝功能差及残肝功能不足是引起严重并发症的原因。(4)术后三维适型放疗可以提高生存率,但是远期结果尚待进一步总结。
Objective:To explore the impact of clinical features and surgical procedure on survival of hepatic hilar cholangiocarcinoma(HCC)and the prognostic factors in patients with Klatskin tumor after curative resection.
Methods:From 2004 to 2009,61 Klatskin tumor patients undergoing operations were included in this study.The clinical features,diagnosis,surgical procedure and follow up data were retrospectively analyzed.Factors influencing postoperative survival were analyzed using COX multiple stepwise regression mode1.
Results:Of the 61 patients,30 underwent radical resection and 10 underwent radical resection plus liver leaf resection,8 underwent palliative resection,13 underwent drainage or laparotomy.The overall 1-,2-,and 3-year survival rates were 73.8%,62.3%,and 36.1%,respectively.COX analysis showed surgical approach and degree of tumor differentiation were independent prognostic factors after radical resection(P<0.05).
Conclusion: (1)The radical resection is the key factor for increasing the long-term survival rate and improving the life qualities of Klatskin tumor patients(.2)Partial hepatectomy in combination with skeletonization may be helpful for increasing radical resection rate and long term efficacy.(3)Bile duct obstruction for a long time,poor liver function and remnant liver function are causes for serious complications.(4)Three-dimensional conformal radiation therapy after surgery can increase the survival rate type,but long-term results have yet to be further summed.
引文
[1] Slattery KD,Cameron JL.Surgery for hilar cholangiocarcinoma:the Johns Hopkins approach[J]. Hepatobiliary pancreat Surg,2000,7(2):115-121
[2] Goldin RD,Patel NK,Thomas HE.Hepatitis C and bile duct loss[J].Clin Pathol,1996,49:836-838
[3]刘小方,邹声泉.肝炎病毒感染与肝门部胆管癌发病关系的探讨.中华外科杂志[J],2002,40(6):420-422
[4] Oh SW,Yoon YS,Shin SA.Effects of excess weight on cancer incidences depending on cancer sites and histologic findings among men:Korea National Health Insurance Corporation Study[J]. Clin Oncol,2005,23:4742-4754
[5] Angelica MI,Jarnagin WR,Blumgart LH.Resectable hilar cholangio- carcinoma: surgical treatment and long-term outcome[J]. Surg Today,2004, 34(11): 885-890
[6] [6] Yi B,Zhang BH,Zhang YJ,et al.Surgical procedure and prognosis of hilar cholangiocarcinoma[J].Hepatobiliary Pancreat Dis Int,2004,3(3):453-457
[7]黄晓强.胆管癌的影像学诊断[J].临床外科杂志,2006,2(14):69-70
[8] Chamberlain RS,Blumgart LH. Hilar cholangiocarcinoma :a review and commentary[J].Ann Surg Oncol,2000,7(1):55-66
[9] Nimura Y,Hayakawi N,Kamiya J,et al.Hepatectomy for hilar bile duct cancer [J].Asian Surg,1996,19:94
[10] Kawasaki S,Imamura H,Kobayashi A,et al.Results ofsurgical resection for patients with hilar bile duct cancer: application of extended hepatectomy after biliary drainage and hemilhepatic portal vein embolization[J].Ann Surg,2003,238:84·92
[11] Yoshida T,Matsumoto T,Sasaki A,et al.Lymphatic spread differs according to rumor location in extra hepatic bile duct cancer[J].Hepato gastroenterology, 2003,50(49):17-20
[12] Sarmiento JM,Nagorney DM.Hepatic resection in the treatment in the treatment of perihilar cholangiocarcinoma[J].Surg Oncol Clin N Am,2002,11(4):893-908
[13]蔡景修,王槐志.肝门部胆管癌手术方式的选择[J].临床外科杂志,2003,11(5):276-277
[14] Su CH,Tsay SH,WuCC,et al.Factors influencing postoperative morbidity mortality and survival after resection for hilar cholangiocarcinoma[J].Ann Surg,1996, 223:384-394
[15] Hemming AW,Reed AI,Fujita S,et al.Surgical management of hilar cholangio- carcinoma[J]. Ann Surg,2005,241(5):693-699
[16] Olivier Farges,Jacques Belghiti,et al.Portal Vein Embolization Before Right Hepatectomy[J].Ann Surg,2003,2237(2):208-217
[17] Masato Nagino,Junichi Kamiya,et al.Two Hundred Forty Consecrtive Portal Vein Embolizations Before Extended Hepatectomy for Biliary Cancer:Surgical Outcome and Long-term Follow-Up[J].Annals of Surgery,2006,243:364-372
[18] Yigitler C,Farges O,Kianmanesh R,et al.The small remnant liver after major liver resection:how common and how relevant Liver Transpl[J].2003,9(suppl):18-25
[19] Chamberlain RS,Blumgart L H.Hilar cholangiocarcinoma: a review and commentary[J].Ann Surg Oncol,2000,7(1):55
[20] Shigeta H,Nagino M,Kamiya J,etal.Bacteremia after hepatectomy:an analysis of single center,10-year experience with 407 patients[J].Langenbecks Arch Surg,2002, 387:117-124
[21]程庆保,张柏和,张永杰等.肝门部胆管癌预后因素分析[J].肿瘤,2005,25:166-169
[22] Yan Meng.Postoperative radiotherapy in locally advanced hepatic hilar cholangiocarcinoma[J].Chinese-German Journal of Clinical Oncology,February 2007,Vol.6,No.1,P18-P21
[1] Tan G.Yilmaz A.De Young BR,et a1.Immunohistochemical analysis of biliary tractlesions[M].Appl Immunohistochem Mol,2004.12:193.197
[2]石运明,王文斌,胡乃东等.p53.nm23.HI蛋白表达与胆管癌生物学特性的研究[J].中华实验外科杂志.2003.20:65
[3] Wang Y,Yamaguchi Y ,Watanabe H,et a1.Usefulness of p53 gene mutations in the supernatant of bile for diagnosis of biliary tract carcinoma:comparison with K-tab mutation[J].J Gastroenterol,2002,37(10) 831-839
[4] Nunez MI,Rosen DG,Ludes-Meyers JH,Abba MC,Kil H Page R Klein-Szanto AJ Godwin AK LiuJ,Mills GB,Aldaz CM.WWOX protein expressionvaries am ong ovarian carcinoma histotypes andcorrelates with less favorable outcome[J].BMC Cancer 2005;5:64
[5]张国梁,迟宝荣,任旭.胆管癌的K-ras和P53基因的研究进展[J].吉林大学学报(医学版).2006.1:32
[6] Palakodeti A Han Yi Jiang Y Le Beau MM. The role of late/slow replication of the FRA16D in common fragile site induction[J].Genes Chromosomes Cancer 2004;39:71-76
[7] ChenHC,Chu RY,HSU Pn,et a1.Loss of E-Cadherin expression correlates with poor diffierentiation and invasion into adiacent organs in gastric adenocareinomas[J]. Cancer lett,2003,201(1):97-106
[8] Yamaguchi K,Nakano K,Nagai E,et al.Ki-ras mutations in codon 12 and p53 mutations (biomarkers) and cytology in bile in patients with hepatobiliarypancreatic carcinoma[J]. Hepatogastroenterology,2005;52:713-718
[9] Yang B, House MG, Guo M, Herman JG, Clark DP. Promoter methylation profiles of tumor suppressor genes in intrahepatic and extrahepatic cholangiocarcinoma[J]. Mod Pathol. 2005;18:412-420
[10]谷化平,尚培中,周翠玲.胆管癌中FI'EN和P16抑癌基因蛋白的表达及其临床意义[J].中国普通外科杂志,2004,13(2):101—103
[11] Sasaki S,Kitagawa Y,Sekido Y,et a1.Molecular processes of chromosome 9p21 delmions in human carcer [J].Oncogene,2003.22(24):3792-3798
[12] Cong W M,Bakker A,Swalsky PA,Raja S,Woods J,Thomas S, Demetris A J,Finkelstein S D.Multiple genetic alterations involved in the tumorigenesis of human cholangiocarcinoma:a molecular genetic and clinicopathological study[J]. Cancer Res Clin Oncol 2001;127:187-92
[13] Ramon Parsons,Human cancer,PTEN and the PT-3 kinase pathway[J].Seminars in cell &Developmental Biology,2004,15(2):171-176
[14] Vickers SM,Jhala NC,Ahn EY,Pan G,Bland KI,McDonald JM. Tamoxifen (TMX)/Fas induced growth inhibition of human cholangiocarcinoma (HCC) by gamma interferon (IFN-gamma)[J].Ann Surg.2002;235:872–878
[15] Ahn EY,Pan G,Vickers SM,McDonald JM.IFN-gamma upregulates apoptosis-related molecules and enhances Fas-mediated apoptosis in human cholangiocarcinoma[J]. Cancer. 2002;100:445-451
[16] Zalcenstein A,Stambolsky P,Weisz L,et al.Mutant p53 gain of function:repression of CD95(Fas/APO-1)gene expression by tumor-associated p53 mutants[J].Oncogene. 2003;22:5667–5676
[17] Kokkonen TS, Augustin MT,Makinen JM,Kokkonen J, Karttunen TJ.High endothelial venules of the lymph nodes express Fas ligand[J]. Histochem Cytochem.2004;52:693–699
[18] Nakazawa K,Dobashi Y,Suzuki S,Fujii H,Takeda Y,Ooi A.Amplification and overexpression of c-erbB-2,epidermal growth factor receptor,and c-met in biliary tract cancers[J].Pathol. 2005;206:356–365
[19] Ueki T,Hsing AW,Gao YT,et al. Alterations of p16 and prognosis in biliary tract cancers from a population-based study in China[J].Clin Cancer Res.2004; 10:1717–1725
[20] Liu XF,Zhu SG,Zhang H,et a1.The methylation status of the I'MS1/ASC gene in cholangiocarcinoma and its clinicalsignificance[J].Hepatobiliary Panereat Dis Int,2006,5:449-453
[21] Koga Y,Kitajima Y,Miyoshi A,et al.Tumor progression through epigenetic gene silencing of O(6)-methylguanine-DNA methyltransferase in human biliary tract cancers[J].Ann Surg Oncol.2005;12:354–363
[22] Olivier M,Eeles R,Hollstein M,Khan MA,Harris C C,Hainaut P. The IARC TP53 database:new online mutation analysis and recommendations to users. Hum Mutat 2002;19:607–14
[2] Goldin RD,Patel NK,Thomas HE.Hepatitis C and bile duct loss[J].Clin Pathol,1996,49:836-838
[3]刘小方,邹声泉.肝炎病毒感染与肝门部胆管癌发病关系的探讨.中华外科杂志[J],2002,40(6):420-422
[4] Oh SW,Yoon YS,Shin SA.Effects of excess weight on cancer incidences depending on cancer sites and histologic findings among men:Korea National Health Insurance Corporation Study[J]. Clin Oncol,2005,23:4742-4754
[5] Angelica MI,Jarnagin WR,Blumgart LH.Resectable hilar cholangio- carcinoma: surgical treatment and long-term outcome[J]. Surg Today,2004, 34(11): 885-890
[6] [6] Yi B,Zhang BH,Zhang YJ,et al.Surgical procedure and prognosis of hilar cholangiocarcinoma[J].Hepatobiliary Pancreat Dis Int,2004,3(3):453-457
[7]黄晓强.胆管癌的影像学诊断[J].临床外科杂志,2006,2(14):69-70
[8] Chamberlain RS,Blumgart LH. Hilar cholangiocarcinoma :a review and commentary[J].Ann Surg Oncol,2000,7(1):55-66
[9] Nimura Y,Hayakawi N,Kamiya J,et al.Hepatectomy for hilar bile duct cancer [J].Asian Surg,1996,19:94
[10] Kawasaki S,Imamura H,Kobayashi A,et al.Results ofsurgical resection for patients with hilar bile duct cancer: application of extended hepatectomy after biliary drainage and hemilhepatic portal vein embolization[J].Ann Surg,2003,238:84·92
[11] Yoshida T,Matsumoto T,Sasaki A,et al.Lymphatic spread differs according to rumor location in extra hepatic bile duct cancer[J].Hepato gastroenterology, 2003,50(49):17-20
[12] Sarmiento JM,Nagorney DM.Hepatic resection in the treatment in the treatment of perihilar cholangiocarcinoma[J].Surg Oncol Clin N Am,2002,11(4):893-908
[13]蔡景修,王槐志.肝门部胆管癌手术方式的选择[J].临床外科杂志,2003,11(5):276-277
[14] Su CH,Tsay SH,WuCC,et al.Factors influencing postoperative morbidity mortality and survival after resection for hilar cholangiocarcinoma[J].Ann Surg,1996, 223:384-394
[15] Hemming AW,Reed AI,Fujita S,et al.Surgical management of hilar cholangio- carcinoma[J]. Ann Surg,2005,241(5):693-699
[16] Olivier Farges,Jacques Belghiti,et al.Portal Vein Embolization Before Right Hepatectomy[J].Ann Surg,2003,2237(2):208-217
[17] Masato Nagino,Junichi Kamiya,et al.Two Hundred Forty Consecrtive Portal Vein Embolizations Before Extended Hepatectomy for Biliary Cancer:Surgical Outcome and Long-term Follow-Up[J].Annals of Surgery,2006,243:364-372
[18] Yigitler C,Farges O,Kianmanesh R,et al.The small remnant liver after major liver resection:how common and how relevant Liver Transpl[J].2003,9(suppl):18-25
[19] Chamberlain RS,Blumgart L H.Hilar cholangiocarcinoma: a review and commentary[J].Ann Surg Oncol,2000,7(1):55
[20] Shigeta H,Nagino M,Kamiya J,etal.Bacteremia after hepatectomy:an analysis of single center,10-year experience with 407 patients[J].Langenbecks Arch Surg,2002, 387:117-124
[21]程庆保,张柏和,张永杰等.肝门部胆管癌预后因素分析[J].肿瘤,2005,25:166-169
[22] Yan Meng.Postoperative radiotherapy in locally advanced hepatic hilar cholangiocarcinoma[J].Chinese-German Journal of Clinical Oncology,February 2007,Vol.6,No.1,P18-P21
[1] Tan G.Yilmaz A.De Young BR,et a1.Immunohistochemical analysis of biliary tractlesions[M].Appl Immunohistochem Mol,2004.12:193.197
[2]石运明,王文斌,胡乃东等.p53.nm23.HI蛋白表达与胆管癌生物学特性的研究[J].中华实验外科杂志.2003.20:65
[3] Wang Y,Yamaguchi Y ,Watanabe H,et a1.Usefulness of p53 gene mutations in the supernatant of bile for diagnosis of biliary tract carcinoma:comparison with K-tab mutation[J].J Gastroenterol,2002,37(10) 831-839
[4] Nunez MI,Rosen DG,Ludes-Meyers JH,Abba MC,Kil H Page R Klein-Szanto AJ Godwin AK LiuJ,Mills GB,Aldaz CM.WWOX protein expressionvaries am ong ovarian carcinoma histotypes andcorrelates with less favorable outcome[J].BMC Cancer 2005;5:64
[5]张国梁,迟宝荣,任旭.胆管癌的K-ras和P53基因的研究进展[J].吉林大学学报(医学版).2006.1:32
[6] Palakodeti A Han Yi Jiang Y Le Beau MM. The role of late/slow replication of the FRA16D in common fragile site induction[J].Genes Chromosomes Cancer 2004;39:71-76
[7] ChenHC,Chu RY,HSU Pn,et a1.Loss of E-Cadherin expression correlates with poor diffierentiation and invasion into adiacent organs in gastric adenocareinomas[J]. Cancer lett,2003,201(1):97-106
[8] Yamaguchi K,Nakano K,Nagai E,et al.Ki-ras mutations in codon 12 and p53 mutations (biomarkers) and cytology in bile in patients with hepatobiliarypancreatic carcinoma[J]. Hepatogastroenterology,2005;52:713-718
[9] Yang B, House MG, Guo M, Herman JG, Clark DP. Promoter methylation profiles of tumor suppressor genes in intrahepatic and extrahepatic cholangiocarcinoma[J]. Mod Pathol. 2005;18:412-420
[10]谷化平,尚培中,周翠玲.胆管癌中FI'EN和P16抑癌基因蛋白的表达及其临床意义[J].中国普通外科杂志,2004,13(2):101—103
[11] Sasaki S,Kitagawa Y,Sekido Y,et a1.Molecular processes of chromosome 9p21 delmions in human carcer [J].Oncogene,2003.22(24):3792-3798
[12] Cong W M,Bakker A,Swalsky PA,Raja S,Woods J,Thomas S, Demetris A J,Finkelstein S D.Multiple genetic alterations involved in the tumorigenesis of human cholangiocarcinoma:a molecular genetic and clinicopathological study[J]. Cancer Res Clin Oncol 2001;127:187-92
[13] Ramon Parsons,Human cancer,PTEN and the PT-3 kinase pathway[J].Seminars in cell &Developmental Biology,2004,15(2):171-176
[14] Vickers SM,Jhala NC,Ahn EY,Pan G,Bland KI,McDonald JM. Tamoxifen (TMX)/Fas induced growth inhibition of human cholangiocarcinoma (HCC) by gamma interferon (IFN-gamma)[J].Ann Surg.2002;235:872–878
[15] Ahn EY,Pan G,Vickers SM,McDonald JM.IFN-gamma upregulates apoptosis-related molecules and enhances Fas-mediated apoptosis in human cholangiocarcinoma[J]. Cancer. 2002;100:445-451
[16] Zalcenstein A,Stambolsky P,Weisz L,et al.Mutant p53 gain of function:repression of CD95(Fas/APO-1)gene expression by tumor-associated p53 mutants[J].Oncogene. 2003;22:5667–5676
[17] Kokkonen TS, Augustin MT,Makinen JM,Kokkonen J, Karttunen TJ.High endothelial venules of the lymph nodes express Fas ligand[J]. Histochem Cytochem.2004;52:693–699
[18] Nakazawa K,Dobashi Y,Suzuki S,Fujii H,Takeda Y,Ooi A.Amplification and overexpression of c-erbB-2,epidermal growth factor receptor,and c-met in biliary tract cancers[J].Pathol. 2005;206:356–365
[19] Ueki T,Hsing AW,Gao YT,et al. Alterations of p16 and prognosis in biliary tract cancers from a population-based study in China[J].Clin Cancer Res.2004; 10:1717–1725
[20] Liu XF,Zhu SG,Zhang H,et a1.The methylation status of the I'MS1/ASC gene in cholangiocarcinoma and its clinicalsignificance[J].Hepatobiliary Panereat Dis Int,2006,5:449-453
[21] Koga Y,Kitajima Y,Miyoshi A,et al.Tumor progression through epigenetic gene silencing of O(6)-methylguanine-DNA methyltransferase in human biliary tract cancers[J].Ann Surg Oncol.2005;12:354–363
[22] Olivier M,Eeles R,Hollstein M,Khan MA,Harris C C,Hainaut P. The IARC TP53 database:new online mutation analysis and recommendations to users. Hum Mutat 2002;19:607–14