临床研究 Open Access
Copyright ©The Author(s) 2004. Published by Baishideng Publishing Group Inc. All rights reserved.
世界华人消化杂志. 2004-03-15; 12(3): 734-737
在线出版日期: 2004-03-15. doi: 10.11569/wcjd.v12.i3.734
胰腺癌扩大切除术后经动脉化疗泵区域灌注化疗30例
吕平, 刘芳, 王春友, 熊炯炘, 陈立波, 万赤丹, 高金波, 润晓勤
吕平, 王春友, 熊炯炘, 陈立波, 万赤丹, 高金波, 润晓勤, 华中科技大学同济医学院附属协和医院胰腺外科中心 湖北省武汉市 430022
刘芳, 华中科技大学同济医学院附属协和医院放射科CT室 湖北省武汉市 430022
吕平, 男, 1968-06-30生, 广西桂平市人, 汉族, 1991年同济医科大学学士, 1999年同济医科大学博士, 主治医师, 主要从事胰腺疾病临床与基础研究.
通讯作者: 吕平, 430022, 湖北省武汉市, 华中科技大学同济医学院附属协和医院胰腺外科中心. luliu@public.wh.hb.cn
电话: 027-85726273 传真: 027-85726830
收稿日期: 2003-09-06
修回日期: 2003-09-20
接受日期: 2003-10-18
在线出版日期: 2004-03-15

目的: 探讨进一步提高胰腺癌扩大切除术患者生存率的方法.

方法: 回顾性分析胰腺癌扩大切除术后患者中未行辅助治疗(对照组, n = 27)或经动脉化疗泵行5-氟尿嘧啶(5-FU)区域灌注(5-FU组, n = 30)两组患者的临床资料并比较其预后.

结果: 5-FU组(中位生存期16 mo)生存率显著高于对照组(中位生存期12 mo)(P<0.05, Kaplan-Meier生存分析, Log rank检验); 5-FU组2年及3年累积生存率分别为37%和26%, 均显著高于对照组(分别为15%和5%)(P<0.05, x2检验); 5-FU组肝转移累积死亡率明显低于对照组(P<0.05, Log rank检验); 5-FU组WHO化疗毒副反应分级多为WHOⅠ, Ⅱ级, 未出现WHO Ⅳ级毒副反应.

结论: 胰腺癌扩大切除术后经动脉化疗泵行5-FU区域灌注化疗能明显减少肝脏转移且毒副反应较轻, 可进一步提高患者生存率.

关键词: N/A
引文著录: 吕平, 刘芳, 王春友, 熊炯炘, 陈立波, 万赤丹, 高金波, 润晓勤. 胰腺癌扩大切除术后经动脉化疗泵区域灌注化疗30例. 世界华人消化杂志 2004; 12(3): 734-737
Regional perfusion chemotherapy via arterial chemotherapy pump after extended resection for pancreatic cancer
Ping Lü, Fang Liu, Chun-You Wang, Jiong-Xing Xiong, Li-Bo Chen, Chi-Dan Wan, Jing-Bo Gao, Xiao-Qing Run
Ping Lü, Chun-You Wang, Jiong-Xing Xiong, Li-Bo Chen, Chi-Dan Wan, Jing-Bo Gao, Xiao-Qing Run, Center for Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
Fang Liu, CT Unit, Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
Correspondence to: Ping Lü, Center for Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China. luliu@public.wh.hb.cn
Received: September 6, 2003
Revised: September 20, 2003
Accepted: October 18, 2003
Published online: March 15, 2004

AIM: To improve the survival rate of pancreatic cancer patients after extended pancreatectomy.

METHODS: The clinical data of pancreatic cancer patients were reviewed after extended pancreatectomy, without adjuvant therapy (control group, n = 27) or with 5-fluorouracil (5-FU) regional perfusion via arterial chemotherapy pump (5-FU group, n = 30), and the prognosis of the two groups were compared.

RESULTS: The survival rate in 5-FU group (median survival time = 16 mo) was significantly better than that in control group (median survival time = 12 mo) (P<0.05, Kaplan-Meier survival analysis, Log rank test); The 2-, 3-year cumulative survival rates in 5-FU group were 37% and 26% respectively, significantly better than those in the control group (15% and 5% respectively) (P < 0.05, x2 test); The cumulative rate of death by hepatic metastasis alone in 5-FU group was significantly lower than that in control group (P < 0.05, Log rank test); The WHO grade toxicities of 5-FU group generally were WHO Ⅰ and Ⅱ, and no WHO Ⅳ toxic events were observed.

CONCLUSION: 5-FU regional perfusion chemotherapy via arterial chemotherapy pump after extended resection for pancreatic cancer can reduce the hepatic metastasis with relatively mild toxicities and increase the survival rate of the patients.

Key Words: N/A
0 引言

近年来胰腺癌发病率国内外都明显增加[1-4], 5年生存率仅为5.0%[4-7]. 局部复发和肝转移仍是胰腺癌术后死亡的常见原因[8-14]. 目前有少数国外研究表明胰腺癌切除术后采用介入方法行腹腔动脉灌注5-FU [15]或经肝动脉和门静脉双途径灌注5-FU [16]能抑制肝脏转移并显著提高患者的生存率. 而国内尚未见报道. 近年我科有关胰腺癌扩大切除术后经动脉化疗泵行区域灌注化疗的结果报道如下.

1 材料和方法
1.1 材料

1995-12/2001-06本中心获扩大切除并存活的胰腺癌患者中有30例术后经动脉化疗泵行5-FU区域灌注化疗(5-FU组), 另27例术后未行辅助治疗的患者作为对照组. 回顾分析至2002-12. 两组无显著性差异(P>0.05), 具有可比性(表1).

表1 两组胰腺癌患者一般资料.
对照组5-FU组t或x2值
n2730
年龄(岁)55.4±13.958.8±11.5-1.000
性别(男/女)16/1115/150.491
胰腺切除方式n(%)0.334
全切2 (7.4)2 (6.7)
胰头切除21 (77.8)25 (83.3)
体尾切除4 (14.8)3 (10.0)
肿瘤大小[cm, n(%)]1.019
0-2.02 (7.4)4 (13.3)
2.1-4.016 (59.3)19 (63.3)
4.1-6.09 (33.3)7 (23.3)
淋巴结受累, n(%)0.929
N03 (11.1)6 (20.0)
N114 (51.9)13 (43.3)
N210 (37.0)11 (36.7)
浸润超过后腹膜n(%)19 (70.4)20 (66.7)0.090
门静脉切除n(%)14 (51.9)12 (40.0)0.805
联合脏器切除n(%)4 (14.8)5 (16.7)0.037
输全血量(mL)607±204587±1960.392
N0 = 无淋巴结受累; N1 = 第1站淋巴结受累; N2 = 第2站淋巴结受累. 年龄、输血量采用t检验, 其余采用x2检验. P>0.05.
1.2 方法

5-FU组关腹前经胃十二指肠动脉断端将化疗泵导管插入腹腔干部位并固定, 化疗泵体固定于切口旁皮下. 5-FU 600 mg/m2经泵缓慢推入, 1次/wk, 并根据患者化疗反应作相应处理. 定期复查血常规, 肝功能, 肾功能, 电解质, 血肿瘤标志物及免疫功能指标等; 肝脏、残留胰腺或胰床B超及CT; 胸部X片等. 观察5-FU组毒副反应、中位生存期及生存率、死因分析.

统计学处理 所有数据应用SPSS10.0统计软件在电脑上进行统计分析. 分别采用t检验和x2检验, 生存分析采用Kaplan-Meier方法.

2 结果
2.1 Kaplan-Meier生存分析

5-FU组中位生存期16 mo, 生存率显著高于对照组中位生存期12 mo (P<0.05, Log rank = 3.98). 5-FU组1, 2, 3及4 a累积生存率分别为63%, 37%, 26%及7%, 而对照组为48%, 15%, 5%及5%; 5-FU组2年及3年累积生存率均显著高于对照组(P<0.05, x2值分别为3.998及4.541), 而1年及4年累积生存率两组间无显著性差异(P>0.05, x2值分别为1.331及0.247, 见图1).

图1
图1 胰腺癌术后生存函数曲线.
2.2 死因分析

将患者死亡原因分为3类: 肝脏转移、局部复发合并肝转移、局部复发. 5-FU组肝转移累积死亡率明显低于对照组(P<0.05, Log rank = 3.87, 图2), 而后两类累积死亡率两组间无显著性差异(P>0.05, Log rank值分别为1.50及0.11).

图2
图2 肝转移死亡函数曲线.
2.3 5-FU组毒副反应

仅1例患者出现化疗泵导管相关并发症, 本组患者的平均化疗次数为10(2-24次), 全组共行化疗299次. 其中出现WHOⅠ, Ⅱ和Ⅲ级毒副反应的化疗次数分别占43%, 23%和6%, 未出现WHO Ⅳ级毒副反应.

3 讨论

胰腺癌预后差的一个重要原因是术后复发转移, 其中局部复发和肝脏转移是造成患者术后死亡的常见原因[8-14]. 病理学证实, 胰腺癌不仅沿区域淋巴结转移, 而且向胰周结缔组织扩散[17]. 胰周神经侵犯的发生率就高达53.5-100%, 且胰周神经有癌细胞残留的患者较无癌细胞残留患者的生存期明显缩短[18]. 由于现代影像学技术的进展, 对胰腺癌可切除性术前判断准确性提高[19-23]. 同时外科手术技术日臻完善(如血管切除吻合技术等), 胰腺癌手术切除率提高, 手术死亡率及术后并发症减少[24-26]. 为减少术后局部复发, 国内外学者均进行了积极的探索. 1973年由Fortner首先报道了胰头癌的区域性切除(regional pancreaticoduodenectomy), 此后日本学者在追求根治切除以希望改善患者生存方面做了大量工作, 开展了胰腺癌扩大切除, 包括广泛清除淋巴结, 腹膜后结缔组织, 受累肠系膜上静脉-门静脉的切除和全胰切除或联合脏器切除[27-29]. Ishikawa et al 采用胰腺癌扩大切除以减少局部复发使患者5a生存率由8%提高到24% [28]. Ohta et al 将哨兵淋巴结(sentinel lymph node)的概念引入胰腺癌, 他们对哨兵淋巴结有转移的患者采用扩大淋巴结清扫的方式, 改善了患者的愈后[30]. 我们的专业小组对常规Whipple胰十二指肠切除方法进行了改进, 在保证安全的前提下提高了切除率[31]. 但肝脏转移使患者的实际生存率得不到显著的提高. 为解决这一问题, Ishikawa et al在胰腺癌术后患者中通过肝动脉与门静脉双途径行肝脏灌注化疗, 通过减少肝脏转移使患者的5 a生存率由24%进一步提高到40%[28]. 德国学者Beger et al在胰腺癌术后患者中采用Seldinger's技术经腹腔干区域化疗, 这一方法使术后肝脏转移率从大于60%降至17%, 中位生存期由10.5 mo延长到23 mo[15]. 我们的小组在胰腺癌患者中开展了术后经动脉化疗泵区域灌注化疗, 患者容易接受. 除1例患者出现化疗泵导管相关并发症外, 其余患者在化疗期间未出现与化疗泵有关的严重并发症. 由于是经动脉区域灌注化疗, 患者的毒副反应较轻, 多为WHOⅠ, Ⅱ级, 一般为胃肠道反应、轻至中度的肝功能受损及骨髓抑制, 经对症处理或暂停化疗均能缓解, 未出现WHO Ⅳ级毒副反应. 该方法方便经济, 术后经动脉化疗泵行区域灌注化疗期间, 多数患者无须住院, 每次化疗时间短, 可在社区医疗机构接受化疗. Kaplan-Meier 生存分析显示, 5-FU组生存率显著高于对照组(P<0.05), 5-FU组2及3 a累积生存率均显著高于对照组(P<0.05). 死因分析显示, 5-FU组肝转移累积死亡率明显低于对照组(P<0.05), Beger et al[15]的研究结果表明胰腺癌切除术后采用介入方法经动脉区域化疗在控制局部复发方面效果并不理想, 但能明显减少肝脏转移的发生率, 这与我们的结果类似.

5-FU是最常用于治疗胰腺癌的化疗药物, 其对增生细胞各期均有杀伤作用. 对进展期胰腺癌患者的药代动力学观察及相关研究发现[32-36], 与全身化疗相比, 经动脉化疗泵灌注5-FU能明显提高胰腺区域的药物浓度, 这有利于化疗药物进入瘤体中心及克服胰腺癌细胞对化疗药物的耐药性. 区域化疗时外周静脉中化疗药物的浓度可保持在较低的水平, 可相对减轻化疗药物的毒性反应. 此外区域化疗时门静脉血中高浓度的化疗药物对于预防胰腺癌的肝转移也有一定的好处. 我们的临床资料从另一侧面印证了上述研究结果. 另外本中心业已开展胰腺癌扩大切除术后经动脉化疗泵行健择或健择联合5-Fu区域灌注化疗的临床研究, 以期进一步提高患者的长期生存率.

编辑: N/A

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