Da Costa M L, Redmond H P, Bouchier-Hayes D J
Department of Surgery, Royal College of Surgeons in Ireland, Dublin 9, Ireland.
J Surg Res. 2001 Dec;101(2):111-9. doi: 10.1006/jsre.2001.6250.
Surgical trauma is partly responsible for enhancing tumor growth through a variety of mechanisms that are still not fully elucidated. The use of perioperative immunostimulants may modulate these effects. This study examined the effect of administration of taurolidine after laparotomy or laparoscopy on the growth of solid tumor, the establishment of hepatic and lung metastases, and effects on natural killer (NK) and lymphokine-activated killer (LAK) cell function.
B16 melanoma right flank tumors were established in mice (n = 180). These animals underwent anesthesia only (control) or laparotomy or laparoscopy (n = 60 per group) and were randomized to receive either saline or taurolidine (n = 30 per group) at specific time points. Survival was determined in each group, and in a further 90 mice tumor growth was followed over 10 days postoperatively. The experiment was repeated in 540 mice, which underwent one of the three procedures and were treated with either saline or taurolidine. NK and LAK cell cytotoxicity (NKCC, LAKCC) was determined at several time points postoperatively. In a further experiment, B16 melanoma tumor cells were delivered via tail vein injection (n = 180) and intrasplenic injection (n = 180). The effect of saline or taurolidine administration on survival after the establishment of metastases was determined, and again in a further 180 mice the establishment of metastatic deposits in the liver or lungs was determined after 8 days.
Survival appeared to be significantly decreased in both the solid-tumor model and the metastatic models undergoing laparotomy compared to laparoscopy and controls (P < 0.0001) and to a lesser extent in the laparoscopy group compared to controls (P < 0.001). Flank tumor growth and metastatic tumor formation were more significant in laparotomy groups compared to laparoscopy groups and controls, but also to a lesser extent in laparoscopy groups compared to controls (P </= 0.05). NKCC and LAKCC were significantly decreased in the same patterns (P < or = 0.03). However, treatment with taurolidine abolished these effects, restoring NKCC and LAKCC (P < or = 0.04) and laparoscopy groups (P < or = 0.001).
It appears that changes that occur after the trauma of laparotomy, and to a lesser extent, after laparoscopy, significantly enhance the growth of primary tumors as well as the development of metastases from circulating tumor cells and are associated with a suppression of host antitumor surveillance mechanisms. This not only affected tumor progression in the immediate postoperative period, but also ultimately affected survival. Taurolidine, a known immunostimulant, appears to abrogate the effects of surgical trauma on primary and metastatic tumor growth and also enhances survival. This may have significant value in the management of tumor-bearing patients undergoing resection.
手术创伤通过多种尚未完全阐明的机制在一定程度上促进肿瘤生长。围手术期使用免疫刺激剂可能会调节这些效应。本研究探讨了剖腹术或腹腔镜检查后给予牛磺罗定对实体瘤生长、肝肺转移的形成以及对自然杀伤（NK）细胞和淋巴因子激活的杀伤（LAK）细胞功能的影响。
在小鼠（n = 180）身上建立B16黑色素瘤右腹侧肿瘤。这些动物仅接受麻醉（对照组）或剖腹术或腹腔镜检查（每组n = 60），并随机在特定时间点接受生理盐水或牛磺罗定（每组n = 30）。测定每组的存活率，另外90只小鼠在术后10天内观察肿瘤生长情况。在540只小鼠中重复该实验，这些小鼠接受三种手术之一，并接受生理盐水或牛磺罗定治疗。在术后几个时间点测定NK和LAK细胞的细胞毒性（NKCC、LAKCC）。在另一项实验中，通过尾静脉注射（n = 180）和脾内注射（n = 180）给予B16黑色素瘤肿瘤细胞。测定给予生理盐水或牛磺罗定对转移形成后存活率的影响，同样在另外180只小鼠中，8天后测定肝脏或肺部转移灶的形成情况。
与腹腔镜检查和对照组相比，接受剖腹术的实体瘤模型和转移模型中的存活率似乎显著降低（P < 0.0001），与对照组相比，腹腔镜检查组的存活率降低程度较小（P < 0.001）。与腹腔镜检查组和对照组相比，剖腹术组的腹侧肿瘤生长和转移瘤形成更为显著，但与对照组相比，腹腔镜检查组的程度也较小（P≤0.05）。NKCC和LAKCC以相同模式显著降低（P≤0.03）。然而，牛磺罗定治疗消除了这些影响，恢复了NKCC和LAKCC（P≤0.04）以及腹腔镜检查组（P≤0.001）。
剖腹术创伤后发生的变化，以及在较小程度上腹腔镜检查后发生的变化，似乎显著促进原发性肿瘤的生长以及循环肿瘤细胞转移的发展，并与宿主抗肿瘤监测机制的抑制有关。这不仅影响术后即刻的肿瘤进展，而且最终影响存活率。牛磺罗定是一种已知的免疫刺激剂，似乎可以消除手术创伤对原发性和转移性肿瘤生长的影响，还能提高存活率。这对于接受切除术的肿瘤患者的管理可能具有重要价值。
