Detection of 5-FU Concentration and Pathological Effects in Intraoperative Regional Chemotherapy for Colon Cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

DU Jiang ¹ , ZHAO Yuanyu ² , XIA Shusen ¹ , WEI Shoujiang ¹ , KOU Hongyan ¹ , HOU Huafang ¹ , WANG Chongshu ¹

1.Department One of General Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000， Sichuan Province, China;;
2.Department of Histology and Embryology, North Sichuan Medical College, Nanchong 637000， Sichuan Province, China;

Corresponding author：

Keywords：

Colon cancer; Intraoperative regional chemotherapy; 5-FU; Pathology; Ki-67 protein

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ObjectiveTo detect 5-FU concentration and investigate the changes of pathology， and Ki-67 protein expression after intraoperative regional chemotherapy (RC) for colon cancer. MethodsAll the patients were randomized into two groups: RC group (n=20), received intraoperational RC with 100 ml physiological saline contained 5-FU (15 mg/kg) and camptothecine (0.06 mg/kg)； control group (n=20), saline alone. The samples from portal vein blood, peripheral blood, peritoneal fluid， and peri-cancerous tissues in RC group were taken to detect the 5-FU concentration by high performance liquid chromatography (HPLC), respectively at 2, 5, 10, 20, 30, and 60 minutes after treatment. The pathological changes were observed and Ki-67 protein expressions were examined by immunohistochemical staining for all the cancer tissues postoperatively in two groups. ResultsPeak concentration of 5-FU appeared at 2 min after treatment, and decreased gradually. 5-FU concentration in peritoneal fluid was the highest, and the lowest in the peripheral blood (P lt;0.01). In RC group， light karyopyknosis, nuclear swelling, and coagulative necrosis of cancer cells, and light intercellular substance hydropsia, inflammatory cells invasion were observed under light microscopic examination; light vasculitis presented also in five cases. Nuclear swelling, heterochromatin agglutination, perinuclear gap expansion, mitochondrial swelling, endoplasmic reticulum expansion, and Golgi complex expansion were observed with transmission electron microscope. Ki-67 protein expression of colon cance tissues in RC group was lower than that in control group （P lt;0.05）. Conclusions Intraoperative RC for colon cancer may sustain a high concentration of chemotherapy drugs in peritoneal fluid and portal vein blood, and alter histopathological morphology of cancer cells, and suppress Ki-67 protein expression. So, intraoperative RC may play an important role in preventing intraoperative spreading and postoperative recurrence of colon cancer.

Citation： DU Jiang ,ZHAO Yuanyu,XIA Shusen,WEI Shoujiang,KOU Hongyan,HOU Huafang,WANG Chongshu. Detection of 5-FU Concentration and Pathological Effects in Intraoperative Regional Chemotherapy for Colon Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2011, 18(5): 523-527. doi: Copy

1.	Rousselot LM, Cole DR, Grossi CE, et al. Adjuvant chemotherapy with 5fluorouracil in surgery for colorectal cancer: eightyear progress report [J]. Dis Colon Rectum， 1972， 15(3): 169174.
2.	万德森, 李国材, 张亚奇, 等. 肠腔灌注5FU后肠系膜静脉和周围静脉血药浓度测定 [J]. 癌症, 1990， 9(3): 189191.
3.	Muchmore JH, Wanebo HJ. Regional chemotherapy: overview [J]. Surg Oncol Clin N Am, 2008， 17(4): 709730.
4.	杜江, 王崇树, 张才全, 等. 高效液相色谱法测定直肠癌术中区域化疗血液、盆腔液和组织5氟尿嘧啶浓度 [J]. 中国药房, 2006， 17(20): 15641566.
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7.	杨波, 蒲永东, 蒋成来, 等. 胃癌区域动脉置泵化疗及外周静脉化疗前后 T淋巴细胞亚群及免疫球蛋白的变化 [J]. 中国普外基础与临床杂志, 2004， 11(2): 110112.
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9.	Power DG, HealeyBird BR, Kemeny NE. Regional chemotherapy for liverlimited metastatic colorectal cancer [J]. Clin Colorectal Cancer， 2008， 7(4): 247259.
10.	Wieners G, Pech M, Hildebrandt B, et al. PhaseⅡ feasibility study on the combination of two different regional treatment approaches in patients with colorectal “liveronly” metastases: hepatic interstitial brachytherapy plus regional chemotherapy [J]. Cardiovasc Intervent Radiol， 2009， 32(5): 937945.
11.	Pohlen U, Rieger H, KunickPohlen S, et al. PhaseⅡ study of regional chemotherapy using the hypoxic abdominal perfusion technique in advanced abdominal carcinoma. 5FU pharmacokinetics, complications and outcome [J]. Anticancer Res, 2007， 27(1B): 667674.
12.	顾晋, 彭亦凡, 马朝来, 等. 手术前区域动脉灌注化疗治疗结肠直肠癌的远期疗效观察 [J]. 中华外科杂志, 2002， 40(6): 404406.
13.	彭兵, 肖乾虎, 王向东, 等. 胃癌术前介入治疗、术中区域性动脉灌注化疗及全身化疗的疗效评价 [J]. 华西医科大学学报, 2002， 33(2): 314315.
14.	顾晋, 马朝来, 叶颖江. 结肠、直肠癌术前区域动脉灌注化疗的临床病理观察 [J]. 中华外科杂志, 1999， 37(6): 333335.
15.	杜江, 王崇树, 魏寿江, 等. 直肠癌术中区域化疗的临床病理观察 [J]. 中国普外基础与临床杂志, 2008， 15(12): 926928.
16.	朱志东, 蒲永东. 超选择动脉置泵灌注化学药物治疗晚期胃肠道癌 [J]. 中华普通外科杂志, 2001， 16(12): 740741.
17.	Kuniyasu H, Oue N, Shigeishi H, et al. Prospective study of Ki67 labeling index in the mucosa adjacent to cancer as a marker for colorectal cancer metastasis [J]. J Exp Clin Cancer Res, 2001， 20(4): 543548.
18.	顾晋, 马朝来, 王怡, 等. 结直肠癌患者术前区域动脉灌注化疗对癌细胞增殖的影响 [J]. 中国胃肠外科杂志, 2000， 3(4): 213216.
19.	顾晋, 彭亦凡, 李沛, 等. 术前区域动脉灌注化疗对结直肠癌组织中血小板衍生的内皮细胞生长因子表达的影响 [J]. 实用肿瘤杂志, 2001， 16(6): 388390.
20.	徐圣德, 高斌, 文刚, 等. 术前区域动脉热化疗对进展期胃癌病理学的影响 [J]. 医学影像学杂志, 2008， 18(10): 11561159.
21.	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.
22.	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.
23.	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]. 华西医科大学学报, 2001， 32(4): 585586，608.
24.	杜江, 王崇树, 张才全. 直肠癌根治术中区域动脉温热灌注化疗对患者的影响 [J]. 四川医学, 2006， 27(7): 734735.
25.	Hellan M, Pigazzi A. Roboticassisted placement of a hepatic artery infusion catheter for regional chemotherapy [J]. Surg Endosc, 2008， 22(2): 548551.

1. Rousselot LM, Cole DR, Grossi CE, et al. Adjuvant chemotherapy with 5fluorouracil in surgery for colorectal cancer: eightyear progress report [J]. Dis Colon Rectum， 1972， 15(3): 169174.
2. 万德森, 李国材, 张亚奇, 等. 肠腔灌注5FU后肠系膜静脉和周围静脉血药浓度测定 [J]. 癌症, 1990， 9(3): 189191.
3. Muchmore JH, Wanebo HJ. Regional chemotherapy: overview [J]. Surg Oncol Clin N Am, 2008， 17(4): 709730.
4. 杜江, 王崇树, 张才全, 等. 高效液相色谱法测定直肠癌术中区域化疗血液、盆腔液和组织5氟尿嘧啶浓度 [J]. 中国药房, 2006， 17(20): 15641566.
5. 孙世良, 温海燕, 张连阳. 现代大肠癌诊断与治疗 [M]. 重庆: 重庆出版社, 2004: 393.
6. 朱志东, 蒲永东. 胃左动脉区域灌注化疗治疗胃癌的药代动力学研究 [J]. 中国普外基础与临床杂志, 2001， 8(1): 2628.
7. 杨波, 蒲永东, 蒋成来, 等. 胃癌区域动脉置泵化疗及外周静脉化疗前后 T淋巴细胞亚群及免疫球蛋白的变化 [J]. 中国普外基础与临床杂志, 2004， 11(2): 110112.
8. Ragnhammar P, Hafstrm L, Nygren P, et al. A systematic overview of chemotherapy effects in colorectal cancer [J]. Acta Oncol, 2001， 40(23): 282308.
9. Power DG, HealeyBird BR, Kemeny NE. Regional chemotherapy for liverlimited metastatic colorectal cancer [J]. Clin Colorectal Cancer， 2008， 7(4): 247259.
10. Wieners G, Pech M, Hildebrandt B, et al. PhaseⅡ feasibility study on the combination of two different regional treatment approaches in patients with colorectal “liveronly” metastases: hepatic interstitial brachytherapy plus regional chemotherapy [J]. Cardiovasc Intervent Radiol， 2009， 32(5): 937945.
11. Pohlen U, Rieger H, KunickPohlen S, et al. PhaseⅡ study of regional chemotherapy using the hypoxic abdominal perfusion technique in advanced abdominal carcinoma. 5FU pharmacokinetics, complications and outcome [J]. Anticancer Res, 2007， 27(1B): 667674.
12. 顾晋, 彭亦凡, 马朝来, 等. 手术前区域动脉灌注化疗治疗结肠直肠癌的远期疗效观察 [J]. 中华外科杂志, 2002， 40(6): 404406.
13. 彭兵, 肖乾虎, 王向东, 等. 胃癌术前介入治疗、术中区域性动脉灌注化疗及全身化疗的疗效评价 [J]. 华西医科大学学报, 2002， 33(2): 314315.
14. 顾晋, 马朝来, 叶颖江. 结肠、直肠癌术前区域动脉灌注化疗的临床病理观察 [J]. 中华外科杂志, 1999， 37(6): 333335.
15. 杜江, 王崇树, 魏寿江, 等. 直肠癌术中区域化疗的临床病理观察 [J]. 中国普外基础与临床杂志, 2008， 15(12): 926928.
16. 朱志东, 蒲永东. 超选择动脉置泵灌注化学药物治疗晚期胃肠道癌 [J]. 中华普通外科杂志, 2001， 16(12): 740741.
17. Kuniyasu H, Oue N, Shigeishi H, et al. Prospective study of Ki67 labeling index in the mucosa adjacent to cancer as a marker for colorectal cancer metastasis [J]. J Exp Clin Cancer Res, 2001， 20(4): 543548.
18. 顾晋, 马朝来, 王怡, 等. 结直肠癌患者术前区域动脉灌注化疗对癌细胞增殖的影响 [J]. 中国胃肠外科杂志, 2000， 3(4): 213216.
19. 顾晋, 彭亦凡, 李沛, 等. 术前区域动脉灌注化疗对结直肠癌组织中血小板衍生的内皮细胞生长因子表达的影响 [J]. 实用肿瘤杂志, 2001， 16(6): 388390.
20. 徐圣德, 高斌, 文刚, 等. 术前区域动脉热化疗对进展期胃癌病理学的影响 [J]. 医学影像学杂志, 2008， 18(10): 11561159.
21. 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.
22. 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.
23. 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]. 华西医科大学学报, 2001， 32(4): 585586，608.
24. 杜江, 王崇树, 张才全. 直肠癌根治术中区域动脉温热灌注化疗对患者的影响 [J]. 四川医学, 2006， 27(7): 734735.
25. Hellan M, Pigazzi A. Roboticassisted placement of a hepatic artery infusion catheter for regional chemotherapy [J]. Surg Endosc, 2008， 22(2): 548551.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Detection of 5-FU Concentration and Pathological Effects in Intraoperative Regional Chemotherapy for Colon Cancer

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