Favoulet Patrick, Benoit Laurent, Osmak Liliana, Polycarpe Emmanuel, Esquis Philippe, Duvillard Christian, Guiu Boris, Rat Patrick, Favre Jean Pierre, Chauffert Bruno
Unité INSERM 517, Faculty of Medicine, 7 Bd Jeanne d'Arc, 21000 Dijon, France.
World J Surg. 2004 May;28(5):451-6. doi: 10.1007/s00268-004-6927-1. Epub 2004 Apr 19.
Free malignant cells, which are frequently detected in the washing liquid from the peritoneal cavity before and after resection of human colorectal cancer, are suspected to cause recurrent peritoneal cancer. We carried out an experimental study to compare the prophylactic efficacy of washing the peritoneum with several anticancer drugs and the antiseptic povidone-iodine against the development of peritoneal carcinomatosis from colonic origin in rats and nude mice. The in vitro anticancer activity of a short, 15-minute exposure of pirarubicin, doxorubicin, 5-fluorouracil, cisplatin, mitomycin C, and 1% povidone-iodine was first evaluated by an MTT assay on DHD/K12/PROb rat and LS174T human colon cancer cells. For the in vivo experiments, BDIX rats were inoculated intraperitoneally (i.p.) with 1 x 10(6) DHD/K12/PROb cells followed by peritoneal scarring and a colocolic anastomosis. A 15-minute peritoneal washing with the anticancer drugs or povidone-iodine was then performed. Nude mice were i.p.-inoculated with 1 x 10(7) LS174T human cells and treated 2 hours later with i.p. pirarubicin. Only pirarubicin, mitomycin C, and povidone-iodine were fully cytotoxic in vitro against DHD/K12/PROb rat colon cancer cells. In contrast to pirarubicin and povidone-iodine, mitomycin C was not completely active against LS174Tcells. In vivo, pirarubicin cured DHD/K12/PROb-inoculated rats, even at the site of the peritoneal scarring and intestinal anastomosis. i.p. pirarubicin prevented the development of peritoneal carcinomatosis and liver metastasis in LS174T-inoculated mice. i.p. washing with pirarubicin cured 2-day-old, but not 7-day-old, peritoneal carcinomatosis in rats. Short exposure to i.p. pirarubicin is nontoxic and more active than povidone-iodine and other anticancer drugs in preventing the development of peritoneal carcinomatosis from colonic origin in rats and mice. The prophylactic effect of preoperative peritoneal washing with pirarubicin on the development of recurrent peritoneal cancer should be evaluated in a randomized clinical trial.
在人结直肠癌切除前后的腹腔冲洗液中经常检测到的游离恶性细胞，被怀疑会导致复发性腹膜癌。我们进行了一项实验研究，比较用几种抗癌药物和抗菌剂聚维酮碘冲洗腹膜对大鼠和裸鼠结肠源性腹膜癌形成的预防效果。首先通过MTT法在DHD/K12/PROb大鼠和LS174T人结肠癌细胞上评估吡柔比星、多柔比星、5-氟尿嘧啶、顺铂、丝裂霉素C和1%聚维酮碘短时间（15分钟）暴露的体外抗癌活性。对于体内实验，给BDIX大鼠腹腔内接种1×10(6)个DHD/K12/PROb细胞，随后进行腹膜瘢痕形成和结肠结肠吻合术。然后用抗癌药物或聚维酮碘进行15分钟的腹腔冲洗。给裸鼠腹腔内接种1×10(7)个LS174T人细胞，并在2小时后用腹腔内注射吡柔比星进行治疗。只有吡柔比星、丝裂霉素C和聚维酮碘在体外对DHD/K12/PROb大鼠结肠癌细胞具有完全细胞毒性。与吡柔比星和聚维酮碘不同，丝裂霉素C对LS174T细胞没有完全活性。在体内，吡柔比星治愈了接种DHD/K12/PROb的大鼠，即使在腹膜瘢痕形成和肠吻合部位也是如此。腹腔内注射吡柔比星可预防接种LS174T的小鼠发生腹膜癌和肝转移。用吡柔比星进行腹腔冲洗可治愈大鼠2日龄而非7日龄的腹膜癌。短时间腹腔内注射吡柔比星无毒，在预防大鼠和小鼠结肠源性腹膜癌形成方面比聚维酮碘和其他抗癌药物更有效。术前用吡柔比星进行腹腔冲洗对复发性腹膜癌发生的预防作用应在随机临床试验中进行评估。
