Pelz Joerg O W, Doerfer Joerg, Hohenberger Werner, Meyer Thomas
Department of Surgery, University of Erlangen-Nuremberg, Germany.
BMC Cancer. 2005 May 30;5:56. doi: 10.1186/1471-2407-5-56.
Cytoreduction followed by hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival in patients with peritoneal carcinomatosis of colorectal origin. Animal models are important in the evaluation of new treatment modalities. The purpose of this study was to devise an experimental setting which can be routinely used for the investigation of HIPEC in peritoneal carcinomatosis.
A new peritoneal perfusion system in tumor bearing rats were tested. For this purpose CC531 colon carcinoma cells were implanted intraperitoneally in Wag/Rija rats. After 10 days of tumor growth the animals were randomized into three groups of six animals each: group 1: control (n = 6), group 2: HIPEC with mitomycin C in a concentration of 15 mg/m2 (n = 6), group III: mitomycin C i.p. as monotherapy in a concentration of 10 mg/m2 (n = 6). After 10 days, total tumor weight and the extent of tumor spread, as classified by the modified Peritoneal Cancer Index (PCI), were assessed by autopsy of the animals.
No postoperative deaths were observed. Conjunctivitis, lethargy and loss of appetite were the main side effects in the HIPEC group. No severe locoregional or systemic toxity was observed. All control animals developed massive tumor growth. Tumor load was significantly reduced in the treatment group and was lowest in group II.
The combination of hyperthermia with MMC resulted in an increased tumoricidal effect in the rat model. The presented model provides an opportunity to study the mechanism and effect of hyperthermic intraperitoneal chemotherapy and new drugs for this treatment modality.
细胞减灭术联合热灌注腹腔化疗(HIPEC)可提高结直肠癌腹膜转移患者的生存率。动物模型在评估新的治疗方式中具有重要作用。本研究的目的是设计一种可常规用于研究HIPEC治疗腹膜转移癌的实验环境。
对荷瘤大鼠的一种新的腹腔灌注系统进行测试。为此,将CC531结肠癌细胞腹腔内植入Wag/Rija大鼠。肿瘤生长10天后,将动物随机分为三组,每组6只:第1组:对照组(n = 6);第2组:腹腔内热灌注丝裂霉素C,浓度为15 mg/m²(n = 6);第3组:腹腔内注射丝裂霉素C作为单一疗法,浓度为10 mg/m²(n = 6)。10天后,通过对动物进行尸检评估总肿瘤重量以及根据改良的腹膜癌指数(PCI)分类的肿瘤扩散程度。
未观察到术后死亡。结膜炎、嗜睡和食欲不振是热灌注腹腔化疗组的主要副作用。未观察到严重的局部或全身毒性。所有对照动物均出现大量肿瘤生长。治疗组的肿瘤负荷显著降低,第2组最低。
热疗与丝裂霉素C联合使用在大鼠模型中产生了增强的杀瘤效果。所提出的模型为研究热灌注腹腔化疗的机制和效果以及用于这种治疗方式的新药提供了机会。