肝细胞癌肝切除术中经大网膜静脉注射丝裂霉素对预防术后肿瘤复发的价值
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摘要
目的
探讨肝细胞癌肝切除术中,经大网膜静脉注射丝裂霉素(Mitomycin-C,MMC)对预防术后肿瘤复发的价值。
方法
回顾分析2002年1月至2003年12月我院收治的298例资料完整的肝细胞癌行肝切除患者的临床资料。其中术中经大网膜静脉注射10mg MMC的用药组共计139人,未行任何化疗药物注射的对照组共计159人,随访术后复发情况,并作统计分析。两组在性别、年龄、合并病毒性肝炎、合并肝硬化、术前肿瘤大小、肿瘤是否单发、术前是否接受TACE或PEIT等治疗、肿瘤是否合并门静脉癌栓等临床资料无统计学差别(P＞0.05),仅在术后是否接受TACE治疗上存在差别(P=0.0214)。
结果
两组最长随访时间73个月,中位随访时间12个月,随访到患者257人,其中用药组124人,随访率89.93%,对照组133人,随访率83.65%,总体随访率86.58%。用药组与对照组总体术后复发时间,即无瘤生存期无显著差别,中位无瘤生存期分别为:术后9.5月、6月(P=0.112)。COX回归作多因素分析提示门静脉癌栓、肿瘤多发、肿瘤大小为影响复发的危险因素,危险系数分别为:1.335(x~2=25.5483,P＜.0001),1.637(x~2=18.7575,P＜.0001)及1.661(x~2=10.7741,P=0.0010)。作单因素分析提示:肿瘤单发、最大直径小于5cm、镜下无门脉癌栓者,用药组无瘤生存期显著长于对照组,中位无瘤生存期分别为:13月、8月(P=0.0068);18月、11月(P=0.0404);28月、10月(P=0.0152)。肿瘤多发、最大直径5cm以上、有镜下门脉癌栓或肉眼门脉癌栓、术后是否接受TACE治疗者,用药组与对照组无瘤生存期均无显著差别。
结论
肝细胞癌行肝切除术,术中经大网膜静脉注射丝裂霉素,对于减少术后复发有一定的积极意义,尤其是对于单发、肿瘤直径小于5cm,且无镜下癌栓者,能显著延长无瘤生存期。对于肿瘤较大、多发、合并癌栓者,治疗作用有限,这可能与治疗剂量较小,肿瘤负荷大及肿瘤恶性程度较高有关,前瞻性研究有将着眼于根据肿瘤的大小、数量及合并癌栓等情况调整药物剂量或联合其他化疗药物以提高术中化疗在预防术后肝细胞癌复发的价值。
Objective
To estimate the value of the methed of MMC injected after the resction of tumor during the operation to prevent the recurrence of HCC.
Methods
A retrospective analysis of 298 patients with complete clinical materials was done.All of them received liver resection of HCC from 2002 Jan.to 2003 Dec.Group A include 139 patients who was injected 10mg MMC trans greater omentum vein after the liver tumor was resected.159 patients who was not injected MMC was recruited to group B.The perioed from operation to recurrence of follow-up by telephone was statistical analyzed.There was no significant difference of sex,age,patient number with viral hepatitis,patient number with liver cirrohsis,tumor diameter,tumor number,TACE or PEIT preoperation and patient number with portal vein thrombus between two group(P＞0.05),but there was significant differerance of TACE postoperation between two group(P=0.0214).
Results
257 patients was found and the followup rate was 86.58%.The longest followup time was 73 month after the first operation,median followup time was 12 month.There was no significant difference between two group of the period of disease-free survival(DFS),and median period of DFS of goup A vs.group B was 9.5month vs.6month after the first operation(P=0.112).COX regression analysis showed that PVT,tumor number and tumor diameter are risk factor of the recurrence and the HR was respectively 1.335(x2=25.5483,P＜.0001),1.637(x2= 18.7575,P＜.0001) and 1.661(x2=10.7741,P=0.0010).Single factor analysis showed that the median period of DFS was significant difference between two group with single tumor,tumor diameter＜5cm or tumor without PVTT of micro.The median period of DFS was respectively 13 month vs.8 month(P=P=0.0068),18 month vs.11 month(P=0.0404) and 28 month vs.10 month(P=0.0152).No significant difference was found between two group with other single factors.
Conclusion
Injection of MMC trans greater omentum vein after the liver tumor was resected is a valuable methed to prevent the recurrence of HCC,especially for patient with single tumor,small tumor and without PVTT.There was not great curative effection to the patient with tumor more than one,bigger tumor than 5cm and tumor with PVTT.Perhaps,it was related to the low dosage of MMC.More dosage of MMC or combination with other drugs would get greater result.We need a prospective study to prove it.
探讨肝细胞癌肝切除术中,经大网膜静脉注射丝裂霉素(Mitomycin-C,MMC)对预防术后肿瘤复发的价值。
方法
回顾分析2002年1月至2003年12月我院收治的298例资料完整的肝细胞癌行肝切除患者的临床资料。其中术中经大网膜静脉注射10mg MMC的用药组共计139人,未行任何化疗药物注射的对照组共计159人,随访术后复发情况,并作统计分析。两组在性别、年龄、合并病毒性肝炎、合并肝硬化、术前肿瘤大小、肿瘤是否单发、术前是否接受TACE或PEIT等治疗、肿瘤是否合并门静脉癌栓等临床资料无统计学差别(P＞0.05),仅在术后是否接受TACE治疗上存在差别(P=0.0214)。
结果
两组最长随访时间73个月,中位随访时间12个月,随访到患者257人,其中用药组124人,随访率89.93%,对照组133人,随访率83.65%,总体随访率86.58%。用药组与对照组总体术后复发时间,即无瘤生存期无显著差别,中位无瘤生存期分别为:术后9.5月、6月(P=0.112)。COX回归作多因素分析提示门静脉癌栓、肿瘤多发、肿瘤大小为影响复发的危险因素,危险系数分别为:1.335(x~2=25.5483,P＜.0001),1.637(x~2=18.7575,P＜.0001)及1.661(x~2=10.7741,P=0.0010)。作单因素分析提示:肿瘤单发、最大直径小于5cm、镜下无门脉癌栓者,用药组无瘤生存期显著长于对照组,中位无瘤生存期分别为:13月、8月(P=0.0068);18月、11月(P=0.0404);28月、10月(P=0.0152)。肿瘤多发、最大直径5cm以上、有镜下门脉癌栓或肉眼门脉癌栓、术后是否接受TACE治疗者,用药组与对照组无瘤生存期均无显著差别。
结论
肝细胞癌行肝切除术,术中经大网膜静脉注射丝裂霉素,对于减少术后复发有一定的积极意义,尤其是对于单发、肿瘤直径小于5cm,且无镜下癌栓者,能显著延长无瘤生存期。对于肿瘤较大、多发、合并癌栓者,治疗作用有限,这可能与治疗剂量较小,肿瘤负荷大及肿瘤恶性程度较高有关,前瞻性研究有将着眼于根据肿瘤的大小、数量及合并癌栓等情况调整药物剂量或联合其他化疗药物以提高术中化疗在预防术后肝细胞癌复发的价值。
Objective
To estimate the value of the methed of MMC injected after the resction of tumor during the operation to prevent the recurrence of HCC.
Methods
A retrospective analysis of 298 patients with complete clinical materials was done.All of them received liver resection of HCC from 2002 Jan.to 2003 Dec.Group A include 139 patients who was injected 10mg MMC trans greater omentum vein after the liver tumor was resected.159 patients who was not injected MMC was recruited to group B.The perioed from operation to recurrence of follow-up by telephone was statistical analyzed.There was no significant difference of sex,age,patient number with viral hepatitis,patient number with liver cirrohsis,tumor diameter,tumor number,TACE or PEIT preoperation and patient number with portal vein thrombus between two group(P＞0.05),but there was significant differerance of TACE postoperation between two group(P=0.0214).
Results
257 patients was found and the followup rate was 86.58%.The longest followup time was 73 month after the first operation,median followup time was 12 month.There was no significant difference between two group of the period of disease-free survival(DFS),and median period of DFS of goup A vs.group B was 9.5month vs.6month after the first operation(P=0.112).COX regression analysis showed that PVT,tumor number and tumor diameter are risk factor of the recurrence and the HR was respectively 1.335(x2=25.5483,P＜.0001),1.637(x2= 18.7575,P＜.0001) and 1.661(x2=10.7741,P=0.0010).Single factor analysis showed that the median period of DFS was significant difference between two group with single tumor,tumor diameter＜5cm or tumor without PVTT of micro.The median period of DFS was respectively 13 month vs.8 month(P=P=0.0068),18 month vs.11 month(P=0.0404) and 28 month vs.10 month(P=0.0152).No significant difference was found between two group with other single factors.
Conclusion
Injection of MMC trans greater omentum vein after the liver tumor was resected is a valuable methed to prevent the recurrence of HCC,especially for patient with single tumor,small tumor and without PVTT.There was not great curative effection to the patient with tumor more than one,bigger tumor than 5cm and tumor with PVTT.Perhaps,it was related to the low dosage of MMC.More dosage of MMC or combination with other drugs would get greater result.We need a prospective study to prove it.
引文
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[11]Lin SM,Lin CJ,Hsu CW,et al.Prospective randomized controlled study of interferon-alpha in preventing hepatocellular carcinoma recurrence after medical ablation therapy for primary tumors.Cancer,2004,100:376-82.
[12]Suou T,Mitsuda A,Koda M,et al.Interferon alpha inhibits intrahepatic recurrence in hepatocellular carcinoma with chronic hepatitis C:A pilot study.Hepatol Res,2001,20:301-304.
[13]汤钊猷.原发性肝癌临床研究的新动向.中国肿瘤,1992;2(7):4-7.
[14]杨建青,杨连粤,祝和成.丝裂霉素诱导人肝癌细胞凋亡.世界华人消化杂志,2001,9(3):268-272.
[15]王俊萍,叶红军,杜意平,等.丝裂霉素诱导肝癌细胞Survivin基因表达的研究.临床肝胆病杂志,2005,21(3):145-147.
[1]Yamanaka N,Kmto O,Toyosaka A,et al.Prognostic factors after hepatectomy for hepatocellular carcinomas:a univariate and multivariate analysis.Cancer,1990;65(5):1104-1107.
[2]王学浩,杜竞辉,李相城等。原发性肝癌的现代外科治疗。肝胆外科杂志,1997;5(1):9-11。
[3]Zhou XD.Surgical treatment of recurrent hepatocellular carcinoma.Hepato-Gastroenterol,1993;40:33-35
[4]Yamashita Y,Taketomi A;Itoh S,et al.Longterm favorable results of limited hepatic resections for patients with hepatocellular carcinoma:20years of experience.J-Am-Coll-Surg.2007 Jul;205(1):19-26.
[5]Pooh RT,Fan ST,Ng IO,et al.Different risk factors and prognosis for early and late intrahepatic recurrence after resection of hepatocellular carcinoma.Cancer,2000,89(3):500-507.
[6]Lang H,Sotiropoulos G C,Brokalaki E I,et al.Survival and recurrence rates after resection for hepatocellular carcinoma in noncirrhotic livers.J-Am-Coll-Surg.2007 Jul;205(1):27-36.
[7]Regimbeau JM,Abdalla EK,Vauthek JN,et al.Risk factors for early due to recurrence after liver resection for hepatocarcinoma:results of a multicenter study.J Surg Oncol,2004,85(1):36-41.
[8]杨建青,杨连粤,祝和成。丝裂霉素诱导人肝癌细胞凋亡。世界华人 消化杂志,2001,9(3):268-272。
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[12]王俊萍,叶红军,杜意平,等。丝裂霉素诱导肝癌细胞Survivin基因表达的研究。临床肝胆病杂志,2005,21(3):145-147。
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[2]王学浩等。原发性肝癌的现代外科治疗,肝胆外科杂志,1997;5(1):9-11
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[2]王学浩,杜竞辉,李相城,等.原发性肝癌的现代外科治疗,肝胆外科杂志,1997;5(1):9-11.
[3]Zhou XD.Surgical treatment of recurrent hepatocellular carcinoma.Hepato-Gastroenterol,1993;40:33-35.
[4]Poon RT,Fan ST,Ng IO,et al.Different risk factors and prognosis for early and late intrahepatic recurrence after resection of hepatocellular carcinoma.Cancer,2000,89(3):500-507.
[5]Regimbeau JM,Abdalla EK,Vauthek JN,et al.Risk factors for early due to recurrence after liver resection for hepatocarcinoma:results of a multicenter study.J Surg Oncol,2004,85(1):36-41.
[6]李锦清,张亚奇,张伟章,等.栓塞化疗在肝癌切除后的价值.中华肿瘤杂志,1994;16(5):387-389.
[7]Mathurin P,Raynard B,Dharancy S,et al.Meta analysis:Evaluation of adjuvant therapy after curative liver resection for hepatocellular carcinoma.Aliment Pharmacol Ther,2003,17:1247-1261.
[8]Takayama T,Sekine T,Makuuchi M,et al.Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma:A randomised trial.Lancet,2000,356:802-807.
[9]Kuang M,Peng BG,Lu MD,et al.Phase Ⅱ randomized trial of autologous formalin-fixed tumor vaccine for postsurgical recurrence of hepatocellular carcinoma.Clin Cancer Res,2004,10:1574-1579.
[10]Kubo S,Nishiguchi S,Hirohashi K,et al.Effects of long-term postoperative interferon-alpha therapy on intrahepatic recurrence after resection of hepatitis C virus-related hepatocellular carcinoma:A randomized,controlled trial.Ann Intern Med,2001,134:963-967.
[11]Lin SM,Lin CJ,Hsu CW,et al.Prospective randomized controlled study of interferon-alpha in preventing hepatocellular carcinoma recurrence after medical ablation therapy for primary tumors.Cancer,2004,100:376-82.
[12]Suou T,Mitsuda A,Koda M,et al.Interferon alpha inhibits intrahepatic recurrence in hepatocellular carcinoma with chronic hepatitis C:A pilot study.Hepatol Res,2001,20:301-304.
[13]汤钊猷.原发性肝癌临床研究的新动向.中国肿瘤,1992;2(7):4-7.
[14]杨建青,杨连粤,祝和成.丝裂霉素诱导人肝癌细胞凋亡.世界华人消化杂志,2001,9(3):268-272.
[15]王俊萍,叶红军,杜意平,等.丝裂霉素诱导肝癌细胞Survivin基因表达的研究.临床肝胆病杂志,2005,21(3):145-147.
[1]Yamanaka N,Kmto O,Toyosaka A,et al.Prognostic factors after hepatectomy for hepatocellular carcinomas:a univariate and multivariate analysis.Cancer,1990;65(5):1104-1107.
[2]王学浩,杜竞辉,李相城等。原发性肝癌的现代外科治疗。肝胆外科杂志,1997;5(1):9-11。
[3]Zhou XD.Surgical treatment of recurrent hepatocellular carcinoma.Hepato-Gastroenterol,1993;40:33-35
[4]Yamashita Y,Taketomi A;Itoh S,et al.Longterm favorable results of limited hepatic resections for patients with hepatocellular carcinoma:20years of experience.J-Am-Coll-Surg.2007 Jul;205(1):19-26.
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