Limitations of peritoneal lavage with antiseptics in prevention of recurrent colorectal cancer caused by tumor-cell seeding - Experimental study in rats

Limitations of peritoneal lavage with antiseptics in prevention of recurrent colorectal cancer caused by tumor-cell seeding - Experimental study in rats
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DOI:
10.1007/bf02236856
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发表时间:
2000-12-01
影响因子:
3.9
通讯作者:
Penninckx, F
Penninckx, F
中科院分区:
医学2区
文献类型:
--
作者:
Basha, G;Ghirardi, M;Penninckx, F

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目的:脱落或污染的游离恶性肿瘤细胞对接受胃肠道肿瘤手术的患者有严重的后果。本研究评价了细胞毒性药物在实验模型中预防腹膜腔中细胞接种和肿瘤生长的毒性和有效性。方法:在体外用聚维酮碘或氯己定孵育后,使用台盼蓝排除试验检测Mtln 3腺癌细胞活力。在体内,Fischer大鼠接种10(5)或10(6)个细胞,然后用生理盐水、0.02%氯己定、1%低分子量聚维酮碘或1%和2%高分子量聚维酮碘以不同的量和孵育时间进行腹腔灌洗。研究结果:氯己定0.02%和聚维酮碘低分子量1%或高分子量2%,在体外对10(5)或10(6)个肿瘤细胞的杀伤率超过98%。低分子量1%和高分子量2%的聚维酮碘在腹腔内应用5 ml三次,持续5 min时具有毒性和致死性。在接种105或10(6)个细胞后应用0.02%的氯己定,仅将肿瘤发展减少到70%和80%。接种10(6)个细胞后,应用5 ml聚维酮碘1%低分子量或高分子量,三次,每次1分钟和5分钟,肿瘤摄取没有改变。然而,观察到Mtln3细胞形成转移的抑制。1%低分子量聚维酮碘在10(5)个肿瘤细胞被“污染”后使用3次,每次1分钟,未观察到毒性,肿瘤摄取减少至30%(P < 0.05)。结论:聚维酮碘毒性被证明是体内的主要问题。然而,低分子量1%聚维酮碘在短期使用时是安全的,并且在接种有限数量的肿瘤细胞时非常有效。只有当脱落或污染的癌细胞的“接种量”有限时,使用细胞毒性药物预防患者肿瘤细胞接种引起的复发性疾病才有意义。
PURPOSE: Exfoliated or soiled free malignant cells have serious consequences in patients undergoing gastrointestinal cancer surgery. The present study evaluates the toxicity and efficacy of cytotoxic agents in the prevention of cell seeding and tumor growth in the peritoneal cavity in an experimental model, METHODS: Mtln3 adenocarcinoma cell viability was tested in vitro using the trypan blue exclusion test after incubation with povidone-iodine or chlorhexidine. In vivo, Fischer rats were inoculated with 10(5) or 10(6) cells followed by peritoneal lavage with physiological saline, chlorhexidine 0.02 percent, povidone-iodine low molecular weight 1 percent or povidone-iodine high molecular weight 1 and 2 percent in different quantities and incubation times. RESULTS: Chlorhexidine 0.02 percent and povidone-iodine low molecular weight 1 percent or high molecular weight 2 percent, killed over 98 percent of 10(5) or 10(6) tumor cells in vitro. Povidone-iodine low molecular weight 1 percent and high molecular weight 2 percent were toxic and lethal when 5 mi were applied in the peritoneal cavity three times for five minutes. Chlorhexidine 0.02 percent applied after inoculation of 105 or 10(6) cells, reduced the tumor development only to 70 and 80 percent. Application of 5 mi povidone-iodine 1 percent low molecular weight or high molecular weight, three times for one and five minutes, after inoculation of 10(6) cells did not change the tumor take. However, inhibition of Mtln3 cells to form metastases was observed. When povidone-iodine low molecular weight 1 percent was used three times for one minute after 10(5) tumor cells were "soiled", no toxicity was observed and the tumor take was reduced to 30 percent (P < 0.05). CONCLUSIONS: Povidone-iodine toxicity proved to be a major issue in vivo. However, povidone-iodine low molecular weight 1 percent was safe when used for short periods and very effective when a limited number of tumor cells was inoculated. The use of cytotoxic agents to prevent recurrent disease caused by tumor cell seeding in patients seems to make sense only when the "inoculum size" of exfoliated or soiled cancer cells is limited.