Raa S Ten, Oosterling S J, van der Kaaij N P, van den Tol M P, Beelen R H J, Meijer S, van Eijck C H J, van der Sijp J R M, van Egmond M, Jeekel J
Department of General Surgery, ErasmusMC, Rotterdam, The Netherlands.
J Surg Oncol. 2005 Nov 1;92(2):124-9. doi: 10.1002/jso.20273.
Local recurrence and peritoneal dissemination is common after intentionally curative resection of colorectal carcinoma. It is not yet clear which mechanisms stimulate post-operative intra-abdominal tumor development. Enhanced adhesion or growth of tumor cells and/or post-operative immuno suppression may influence tumor recurrence.
In the present study, we evaluated effects of local and remote surgery on intra-abdominal tumor development.
A standardized intra-abdominal trauma was inflicted by rubbing both uterus horns in laparotomy groups, while a dorsolateral thoracotomy was performed in thoracotomy groups (on day -1, 0, or +3). To induce tumor development rats were injected intra-peritoneally with the coloncarcinoma cell line CC531s on day 0 and evaluated after 21 days.
Rats undergoing laparotomy and injection on day 0 showed significantly higher tumorload than control rats (195 +/- 20 vs. 47 +/- 29, P < 0.001). When a laparotomy was performed, the day before tumor inoculation even higher tumorload was seen (245 +/- 37 vs. 195 +/- 20, P < 0.01). Strikingly, performing a thoracotomy on the day before or on the same day as tumor inoculation resulted in enhanced tumorload compared to controls as well (135 +/- 84 vs. 47 +/- 29; P < 0.001 and 88 +/- 38 vs. 47 +/- 29; P < 0.02, respectively). Either laparotomy or thoracotomy 3 days after tumor cell inoculation did not affect growth of pre-existing tumor cell clusters.
The (post) surgical intra-peritoneal microenvironment enhances successful implantation of spilled tumor cells, whereas growth of adhered tumor cell clusters is not affected. The inflammatory response as a result of remote surgery promotes successful tumor development as well.
在对结直肠癌进行根治性切除术后,局部复发和腹膜播散很常见。目前尚不清楚是哪些机制刺激了术后腹腔内肿瘤的发展。肿瘤细胞黏附或生长增强和/或术后免疫抑制可能会影响肿瘤复发。
在本研究中,我们评估了局部和远程手术对腹腔内肿瘤发展的影响。
在剖腹手术组中,通过摩擦双侧子宫角造成标准化的腹腔内创伤,而在开胸手术组中进行后外侧开胸手术(在第-1、0或+3天)。为诱导肿瘤发展,在第0天给大鼠腹腔注射结肠癌细胞系CC531s,并在21天后进行评估。
在第0天接受剖腹手术并注射的大鼠显示出比对照大鼠显著更高的肿瘤负荷(195±20对47±29,P<0.001)。当在肿瘤接种前一天进行剖腹手术时,观察到更高的肿瘤负荷(245±37对195±20,P<0.01)。令人惊讶的是,在肿瘤接种前一天或当天进行开胸手术与对照相比也导致肿瘤负荷增加(分别为135±84对47±29;P<0.001和88±38对47±29;P<0.02)。在肿瘤细胞接种后3天进行剖腹手术或开胸手术均不影响预先存在的肿瘤细胞簇的生长。
手术(后)腹腔微环境增强了溢出肿瘤细胞的成功植入,而黏附的肿瘤细胞簇的生长不受影响。远程手术引起的炎症反应也促进了肿瘤的成功发展。