术中动脉灌注化疗于胃癌根治术中的应用研究进展
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摘要
胃癌发病率死亡率均较高,早期胃癌行根治性切除术后复发转移率较低,但进展期胃癌(AGC)即使行R0切除术后复发转移率仍较高,究其原因为外科手术治疗无法根除肿瘤微转移灶。术中动脉灌注化疗(IAIC)能使肿瘤及肿瘤周围组织形成高化疗浓度场所,杀灭外科根治术后残留癌细胞。对AGC行肿瘤R0切除加D2淋巴结清扫配合IAIC能达到宏观及微观上的根治,降低肿瘤的复发转移概率,延长患者生存时间,提高生存质量。IAIC起源于20世纪90年代,经过近30年的发展,其临床效果已得到认可,但缺乏相关大宗随机试验证据支持,其灌注血管选择、用药方案选择等仍未得到规范。本文就IAIC的研究现状做一综述,为相关临床工作提供参考。
Gastric cancer has a high morbidity and mortality. The rate of metastasis and recurrence in early gastric cancer that has undergone radical surgery is low. However, the rate of metastasis and recurrence in advanced gastric cancer(AGC) after curative gastrectomy is high. The reason is that surgical treatment cannot eradicate tumor micro-metastases. Intraoperative arterial infusion chemotherapy(IAIC) can create a high concentration chemotherapy circumstance around the tumor and surrounding tissues, which will kill residual cancer cells following curative gastrectomy. AGC patients after R0 resection with D2 lymph node clearance and IAIC can achieve a radical cure with regard to both macroscopic and microscopic evidence, which will decrease the rate of metastasis and recurrence, prolong patients′ survival time, and improve their quality of survival. IAIC was first developed in the 1990 s, and with nearly 30 years of development, its clinical efficacy has been recognized. However, there is still no large randomized trial evidence to support its efficacy, and it is still not optimized on how to choose blood vessels for perfusion and how to choose a proper chemotherapy regimen. This article summarizes the application of IAIC in AGC patients.
Gastric cancer has a high morbidity and mortality. The rate of metastasis and recurrence in early gastric cancer that has undergone radical surgery is low. However, the rate of metastasis and recurrence in advanced gastric cancer(AGC) after curative gastrectomy is high. The reason is that surgical treatment cannot eradicate tumor micro-metastases. Intraoperative arterial infusion chemotherapy(IAIC) can create a high concentration chemotherapy circumstance around the tumor and surrounding tissues, which will kill residual cancer cells following curative gastrectomy. AGC patients after R0 resection with D2 lymph node clearance and IAIC can achieve a radical cure with regard to both macroscopic and microscopic evidence, which will decrease the rate of metastasis and recurrence, prolong patients′ survival time, and improve their quality of survival. IAIC was first developed in the 1990 s, and with nearly 30 years of development, its clinical efficacy has been recognized. However, there is still no large randomized trial evidence to support its efficacy, and it is still not optimized on how to choose blood vessels for perfusion and how to choose a proper chemotherapy regimen. This article summarizes the application of IAIC in AGC patients.
引文
1 Ferlay J,SoerjomataramⅠ,Dikshit R,et al.Cancer incidence and mortality worldwide:sources,methods and major patterns in GLOBOCAN 2012[J].Int J Cancer,2015,136(5):E359-386.
2 Chen W,Zheng R,Baade PD,et al.Cancer statistics in China,2015[J].CA Cancer J Clin,2016,66(2):115-132.
3 Wanebo HJ,Kennedy BJ,Chmiel J,et al.Cancer of the stomach.Apatient care study by the American College of Surgeons[J].Ann Surg,1993,218(5):583-592.
4 Ajani JA.Evolving chemotherapy for advanced gastric cancer[J].Oncologist,2005,10 Suppl 3:49-58.
5 ThomassenⅠ,van Gestel YR,van Ramshorst B,et al.Peritoneal carcinomatosis of gastric origin:a population-based study on incidence,survival and risk factors[J].Int J Cancer,2014,134(3):622-628.
6 Sasako M,Sano T,Yamamoto S,et al.D2 lymphadenectomy alone or with para-aortic nodal dissection for gastric cancer[J].N Engl J Med,2008,359(5):453-462.
7 Sano T,Yamamoto S,Sasako M.Randomized controlled trial to evaluate splenectomy in total gastrectomy for proximal gastric carcinoma:Japan clinical oncology group study JCOG 0110-MF[J].Jpn J Clin Oncol,2002,32(9):363-364.
8 Hartgrink HH,Bonenkamp HJ,van de Velde CJ.Influence of surgery on outcomes in gastric cancer[J].Surg oncol clin N Am,2000,9(1):97-117,vii-viii.
9王杉,叶颖江.胃癌的综合治疗[J].中华胃肠外科杂志,2011,14(1):8-11.
10 Jain VK,Cunningham D,ChauⅠ.Preoperative and postoperative chemotherapy for gastric cancer[J].Surg Oncol Clin N Am,2012,21(1):99-112.
11 Araki K,Yamamoto H,Kobayashi M,et al.[Experimental and clinical study on intraoperative local infusion chemotherapy(ILIC)for advanced gastric carcinoma][J].Gan To Kagaku Ryoho,1995,22(11):1531-1534.
12 Kobayashi M,Yamamoto H,Sugimoto T,et al.[Intraoperative local infusion chemotherapy(ILIC)for gastric cancer][J].Gan To Kagaku Ryoho,1998,25(9):1281-1283.
13倪家连,刘晓明,郑宝珍,等.活体胃血供的特点及其临床意义[J].中国普通外科杂志,2003,12(4):291-293.
14尤小兰,钱海鑫,秦磊,等.进展期胃癌根治术中腹腔动脉干灌注化疗的应用研究[J].中华胃肠外科杂志,2016,19(9):1044-1048.
15 Ikeda O,Tamura Y,Nakasone Y,et al.Evaluation of extrahepatic perfusion of anticancer drugs in the right gastric arterial region on fused images using combined CT/SPECT:is extrahepatic perfusion predictive of gastric toxicity?[J].Cardiovasc Intervent Radiol,2007,30(3):392-397.
16邰生.术中瘤区动脉灌注化疗胃癌、贲门癌65例体会[J].江苏大学学报(医学版),1999(2):249-250.
17庞君豪,王崇树,魏寿江.胃癌术中区域动脉灌注化疗对癌组织中Survivin及MMP-2表达的影响[J].肿瘤预防与治疗,2010,23(2):119-121,136.
18 Ensminger WD.Intrahepatic arterial infusion of chemotherapy:pharmacologic principles[J].Semin Oncol,2002,29(2):119-125.
19詹晓星,颜小琼.介入放射学中的药代动力学研究[J].国际医学放射学杂志,1989,12(6):327-329.
20邹寿椿,裘华森,陈方宏,等.胃癌血供与供血动脉插管化疗的临床观察[J].中国实用外科杂志,1996,16(11):20-21.
21 Link KH,Aigner KR,Kuehn W,et al.Prospective correlative chemosensitivity testing in high-dose intraarterial chemotherapy for liver metastases[J].Cancer Res,1986,46(9):4837-4840.
22敖劲,张跃伟.原发性肝癌介入治疗的药代动力学研究现状[J].介入放射学杂志,2011,20(9):749-752.
23吴鹏,朱正纲,叶正宝,等.5-氟尿嘧啶-2′-脱氧核苷经胃左动脉介入灌注后的药代动力学实验研究[J].外科理论与实践,2004,9(2):135-139.
24 Maurer CA,Borner M,Buchler MW,et al.Regional chemotherapy of gastrointestinal cancer[J].Dig Surg,1997,14(1):9-22.
25朱志东,蒲永东.氟尿嘧啶经胃左动脉和外周静脉化疗的药代动力学比较[J].中华胃肠外科杂志,2000,3(1):28-30.
26 Shchepotin IB,Chorny V,Hanfelt J,et al.Palliative superselective intra-arterial chemotherapy for advanced nonresectable gastric cancer[J].J Gastrointest Surg,1999,3(4):426-431.
27骆成玉.癌症治疗中血管生成的重要性[J].国际外科学杂志,1999,26(2):67-71.
28蒲永东,朱志东,何建苗,等.超选择靶区动脉置泵综合治疗晚期胃肠道肿瘤[J].肿瘤学杂志,2002,8(5):254-256.
29刘福坤,陈忠豪,李国立,等.胃癌术前介入治疗后血管变化与癌组织坏死的关系[J].世界华人消化杂志,1998,6(8):686-688.
30 Kemeny MM,Adak S,Gray B,et al.Combined-modality treatment for resectable metastatic colorectal carcinoma to the liver:surgical resection of hepatic metastases in combination with continuous infusion of chemotherapy-an intergroup study[J].J Clin Oncol,2002,20(6):1499-1505.
31夏术森,张才全,王崇树,等.胃癌术中区域动脉灌注化疗作用的初步研究[J].重庆医科大学学报,2009,34(3):293-296.
32高登鹏,张霄成,石秀玲,等.胃癌术中术后局部化疗对癌细胞及患者预后的影响[J].现代中西医结合杂志,2005,14(19):2535-2537.
33肖乾虎,彭兵,赖毅,等.胃癌术中动脉区域灌注化疗与全身静脉化疗的临床疗效比较[J].四川大学学报(医学版),2001,32(4):585-586,608.
34吴晓宇,姚学权,李为苏,等.术前区域性动脉灌注联合化疗治疗进展期胃癌的初步报告[J].中国普通外科杂志,2009,18(10):1022-1026.
35 Tao HQ,Zou SC.Effect of preoperative regional artery chemotherapy on proliferation and apoptosis of gastric carcinoma cells[J].World J Gastroenterol,2002,8(3):451-454.
36何运胜,姜淮芜,汪盛贤,等.进展期胃癌术中动脉化疗对p53和ki-67表达及细胞凋亡作用的影响[J].中国现代普通外科进展,2009,12(3):201-205.
37程飞,王天宝,杜宁,等.术中动脉灌注化疗联合腹腔灌注化疗对胃癌患者预后的影响[J].现代肿瘤医学,2011,19(8):1617-1620.
38吴江,陈海军.术中动脉灌注化疗联合术野5-氟尿嘧啶缓释剂植入预防进展期胃癌术后肝脏转移及局部复发的疗效研究[J].中国医药科学,2012,2(20):19-20,23.
39 Cocconi G,Carlini P,Gamboni A,et al.Cisplatin,epirubicin,leucovorin and 5-fluorouracil(PELF)is more active than 5-fluorouracil,doxorubicin and methotrexate(FAMTX)in advanced gastric carcinoma[J].Ann Oncol,2003,14(8):1258-1263.
40 Ohtsu A,Shimada Y,Shirao K,et al.Randomized phaseⅢtrial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable,advanced gastric cancer:The Japan Clinical Oncology Group Study(JCOG9205)[J].J Clin Oncol,2003,21(1):54-59.
41 Al-Batran S E,Hartmann J T,Probst S,et al.3502 ORAL Final results of a randomized phaseⅢtrial in patients with advanced adenocarcinoma of the stomach receiving first-line chemotherapy with fluorouracil,leucovorin and oxaliplatin(FLO)versus fluorouracil,leucovorin and cisplatin(FLP)[J].Ejc Supplements,2006,5(4):259-260.
42徐瑞华,滕开原.晚期胃癌化疗进展[J].癌症,2009,28(10):1108-1113.
43王万河,潘国胜,张家福.进展期胃癌术中化疗治疗体会[J].肿瘤基础与临床,2003,16(5):386.
44张启文,赵伟,王德友,等.进展期胃癌术中化疗加低渗热疗的临床应用[J].中国现代普通外科进展,2004,7(2):72.
45 Tentes AA,Markakidis SK,Karanikiotis C,et al.Intraarterial chemotherapy as an adjuvant treatment in locally advanced gastric cancer[J].Langenbecks Arch Surg,2006,391(2):124-129.
2 Chen W,Zheng R,Baade PD,et al.Cancer statistics in China,2015[J].CA Cancer J Clin,2016,66(2):115-132.
3 Wanebo HJ,Kennedy BJ,Chmiel J,et al.Cancer of the stomach.Apatient care study by the American College of Surgeons[J].Ann Surg,1993,218(5):583-592.
4 Ajani JA.Evolving chemotherapy for advanced gastric cancer[J].Oncologist,2005,10 Suppl 3:49-58.
5 ThomassenⅠ,van Gestel YR,van Ramshorst B,et al.Peritoneal carcinomatosis of gastric origin:a population-based study on incidence,survival and risk factors[J].Int J Cancer,2014,134(3):622-628.
6 Sasako M,Sano T,Yamamoto S,et al.D2 lymphadenectomy alone or with para-aortic nodal dissection for gastric cancer[J].N Engl J Med,2008,359(5):453-462.
7 Sano T,Yamamoto S,Sasako M.Randomized controlled trial to evaluate splenectomy in total gastrectomy for proximal gastric carcinoma:Japan clinical oncology group study JCOG 0110-MF[J].Jpn J Clin Oncol,2002,32(9):363-364.
8 Hartgrink HH,Bonenkamp HJ,van de Velde CJ.Influence of surgery on outcomes in gastric cancer[J].Surg oncol clin N Am,2000,9(1):97-117,vii-viii.
9王杉,叶颖江.胃癌的综合治疗[J].中华胃肠外科杂志,2011,14(1):8-11.
10 Jain VK,Cunningham D,ChauⅠ.Preoperative and postoperative chemotherapy for gastric cancer[J].Surg Oncol Clin N Am,2012,21(1):99-112.
11 Araki K,Yamamoto H,Kobayashi M,et al.[Experimental and clinical study on intraoperative local infusion chemotherapy(ILIC)for advanced gastric carcinoma][J].Gan To Kagaku Ryoho,1995,22(11):1531-1534.
12 Kobayashi M,Yamamoto H,Sugimoto T,et al.[Intraoperative local infusion chemotherapy(ILIC)for gastric cancer][J].Gan To Kagaku Ryoho,1998,25(9):1281-1283.
13倪家连,刘晓明,郑宝珍,等.活体胃血供的特点及其临床意义[J].中国普通外科杂志,2003,12(4):291-293.
14尤小兰,钱海鑫,秦磊,等.进展期胃癌根治术中腹腔动脉干灌注化疗的应用研究[J].中华胃肠外科杂志,2016,19(9):1044-1048.
15 Ikeda O,Tamura Y,Nakasone Y,et al.Evaluation of extrahepatic perfusion of anticancer drugs in the right gastric arterial region on fused images using combined CT/SPECT:is extrahepatic perfusion predictive of gastric toxicity?[J].Cardiovasc Intervent Radiol,2007,30(3):392-397.
16邰生.术中瘤区动脉灌注化疗胃癌、贲门癌65例体会[J].江苏大学学报(医学版),1999(2):249-250.
17庞君豪,王崇树,魏寿江.胃癌术中区域动脉灌注化疗对癌组织中Survivin及MMP-2表达的影响[J].肿瘤预防与治疗,2010,23(2):119-121,136.
18 Ensminger WD.Intrahepatic arterial infusion of chemotherapy:pharmacologic principles[J].Semin Oncol,2002,29(2):119-125.
19詹晓星,颜小琼.介入放射学中的药代动力学研究[J].国际医学放射学杂志,1989,12(6):327-329.
20邹寿椿,裘华森,陈方宏,等.胃癌血供与供血动脉插管化疗的临床观察[J].中国实用外科杂志,1996,16(11):20-21.
21 Link KH,Aigner KR,Kuehn W,et al.Prospective correlative chemosensitivity testing in high-dose intraarterial chemotherapy for liver metastases[J].Cancer Res,1986,46(9):4837-4840.
22敖劲,张跃伟.原发性肝癌介入治疗的药代动力学研究现状[J].介入放射学杂志,2011,20(9):749-752.
23吴鹏,朱正纲,叶正宝,等.5-氟尿嘧啶-2′-脱氧核苷经胃左动脉介入灌注后的药代动力学实验研究[J].外科理论与实践,2004,9(2):135-139.
24 Maurer CA,Borner M,Buchler MW,et al.Regional chemotherapy of gastrointestinal cancer[J].Dig Surg,1997,14(1):9-22.
25朱志东,蒲永东.氟尿嘧啶经胃左动脉和外周静脉化疗的药代动力学比较[J].中华胃肠外科杂志,2000,3(1):28-30.
26 Shchepotin IB,Chorny V,Hanfelt J,et al.Palliative superselective intra-arterial chemotherapy for advanced nonresectable gastric cancer[J].J Gastrointest Surg,1999,3(4):426-431.
27骆成玉.癌症治疗中血管生成的重要性[J].国际外科学杂志,1999,26(2):67-71.
28蒲永东,朱志东,何建苗,等.超选择靶区动脉置泵综合治疗晚期胃肠道肿瘤[J].肿瘤学杂志,2002,8(5):254-256.
29刘福坤,陈忠豪,李国立,等.胃癌术前介入治疗后血管变化与癌组织坏死的关系[J].世界华人消化杂志,1998,6(8):686-688.
30 Kemeny MM,Adak S,Gray B,et al.Combined-modality treatment for resectable metastatic colorectal carcinoma to the liver:surgical resection of hepatic metastases in combination with continuous infusion of chemotherapy-an intergroup study[J].J Clin Oncol,2002,20(6):1499-1505.
31夏术森,张才全,王崇树,等.胃癌术中区域动脉灌注化疗作用的初步研究[J].重庆医科大学学报,2009,34(3):293-296.
32高登鹏,张霄成,石秀玲,等.胃癌术中术后局部化疗对癌细胞及患者预后的影响[J].现代中西医结合杂志,2005,14(19):2535-2537.
33肖乾虎,彭兵,赖毅,等.胃癌术中动脉区域灌注化疗与全身静脉化疗的临床疗效比较[J].四川大学学报(医学版),2001,32(4):585-586,608.
34吴晓宇,姚学权,李为苏,等.术前区域性动脉灌注联合化疗治疗进展期胃癌的初步报告[J].中国普通外科杂志,2009,18(10):1022-1026.
35 Tao HQ,Zou SC.Effect of preoperative regional artery chemotherapy on proliferation and apoptosis of gastric carcinoma cells[J].World J Gastroenterol,2002,8(3):451-454.
36何运胜,姜淮芜,汪盛贤,等.进展期胃癌术中动脉化疗对p53和ki-67表达及细胞凋亡作用的影响[J].中国现代普通外科进展,2009,12(3):201-205.
37程飞,王天宝,杜宁,等.术中动脉灌注化疗联合腹腔灌注化疗对胃癌患者预后的影响[J].现代肿瘤医学,2011,19(8):1617-1620.
38吴江,陈海军.术中动脉灌注化疗联合术野5-氟尿嘧啶缓释剂植入预防进展期胃癌术后肝脏转移及局部复发的疗效研究[J].中国医药科学,2012,2(20):19-20,23.
39 Cocconi G,Carlini P,Gamboni A,et al.Cisplatin,epirubicin,leucovorin and 5-fluorouracil(PELF)is more active than 5-fluorouracil,doxorubicin and methotrexate(FAMTX)in advanced gastric carcinoma[J].Ann Oncol,2003,14(8):1258-1263.
40 Ohtsu A,Shimada Y,Shirao K,et al.Randomized phaseⅢtrial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable,advanced gastric cancer:The Japan Clinical Oncology Group Study(JCOG9205)[J].J Clin Oncol,2003,21(1):54-59.
41 Al-Batran S E,Hartmann J T,Probst S,et al.3502 ORAL Final results of a randomized phaseⅢtrial in patients with advanced adenocarcinoma of the stomach receiving first-line chemotherapy with fluorouracil,leucovorin and oxaliplatin(FLO)versus fluorouracil,leucovorin and cisplatin(FLP)[J].Ejc Supplements,2006,5(4):259-260.
42徐瑞华,滕开原.晚期胃癌化疗进展[J].癌症,2009,28(10):1108-1113.
43王万河,潘国胜,张家福.进展期胃癌术中化疗治疗体会[J].肿瘤基础与临床,2003,16(5):386.
44张启文,赵伟,王德友,等.进展期胃癌术中化疗加低渗热疗的临床应用[J].中国现代普通外科进展,2004,7(2):72.
45 Tentes AA,Markakidis SK,Karanikiotis C,et al.Intraarterial chemotherapy as an adjuvant treatment in locally advanced gastric cancer[J].Langenbecks Arch Surg,2006,391(2):124-129.
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