Jouvin I, Najah H, Pimpie C, Canet Jourdan C, Kaci R, Mirshahi M, Eveno C, Pocard M
Department of Oncologic & Digestive Surgery, Hospital Lariboisière - AP-HP, 2 rue Ambroise Paré, 75475 Paris Cedex 10, France; Université Paris Diderot, Sorbonne Paris Cité, CART, Carcinomatosis Angiogenesis Translational Research, INSERM U965, F-74575 Paris, France.
Université Paris Diderot, Sorbonne Paris Cité, CART, Carcinomatosis Angiogenesis Translational Research, INSERM U965, F-74575 Paris, France.
Eur J Surg Oncol. 2017 Jun;43(6):1088-1094. doi: 10.1016/j.ejso.2016.12.009. Epub 2017 Jan 9.
There is no standard treatment in patients with high risk metachronous peritoneal carcinomatosis (PC) in colonic cancer, as perforated tumour or synchronous ovarian metastasis. Icodextrin 4% (ICDX), presently used to prevent postoperative abdominal adhesions, could inhibit the coactivation of the tumour cells and the microenvironment cells, associated with the development of PC. The aim of this study was to inhibit the formation of the PC in a murine model mimicking surgical situation using ICDX and intraperitoneal (IP) prophylactic chemotherapy. We created a model of growing PC in mice using cells of murine colonic cancer CT26. Cells and treatments were injected simultaneously. Five groups were created: CT26 (control group), CT26 + ICDX (ICDX group), CT26 + chemotherapy (oxaliplatin and 5FU) (chemo group), CT26 + chemotherapy + ICDX (ICDX chemo group), ICDX (toxicity group). At day 15, PC was evaluated with rodents PCI. In the chemo group, PCI was significantly lower than in the control group (3.2 versus 8.4, p = 0.02). ICDX had a synergetic effect on PC with chemotherapy; indeed PCI in ICDX chemo group was lower than in chemo group (1.4 versus 3.2, p = 0.04). There was no morbidity linked to ICDX in toxicity group. Safety of ICDX needs to be verified, particularly on colonic anastomosis before ICDX associated to IP chemotherapy could be used as a preventive treatment of PC in high risk patients. This prophylactic treatment is easy to use and would be administrated at the end of a curative surgery for a colonic cancer.
对于患有高危异时性腹膜癌转移（PC）的结肠癌患者，如肿瘤穿孔或同时发生卵巢转移，目前尚无标准治疗方法。4%艾考糊精（ICDX）目前用于预防术后腹腔粘连，它可以抑制与PC发生相关的肿瘤细胞和微环境细胞的共激活。本研究的目的是在模拟手术情况的小鼠模型中，使用ICDX和腹腔内（IP）预防性化疗来抑制PC的形成。我们使用小鼠结肠癌CT26细胞建立了小鼠PC生长模型。细胞和治疗同时注射。共分为五组：CT26（对照组）、CT26 + ICDX（ICDX组）、CT26 + 化疗（奥沙利铂和5-氟尿嘧啶）（化疗组）、CT26 + 化疗 + ICDX（ICDX化疗组）、ICDX（毒性组）。在第15天，用啮齿动物腹膜癌指数（PCI）评估PC。在化疗组中，PCI显著低于对照组（3.2对8.4，p = 0.02）。ICDX与化疗对PC有协同作用；实际上，ICDX化疗组的PCI低于化疗组（1.4对3.2，p = 0.04）。毒性组中没有与ICDX相关的发病率。ICDX的安全性需要验证，特别是在将ICDX与IP化疗联合用于高危患者PC的预防性治疗之前，对结肠吻合口的影响。这种预防性治疗易于使用，将在结肠癌根治性手术结束时给药。
