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Port site metastasisモデルの作成と成立過程の組織学的検討
医学博士 乙第872号 平成15年4月25日 （埼玉医科大学）
Establishment of a Model of Port Site Metastasis in Rabbit: Histological Examination of the Growth
Hirofumi Yamada(Saitama Medical Center, Saitama Medical School, Kawagoe, Saitama 350-8550, Japan)
The port site metastasis (PSM) is a peculiar phenomenon following laparoscopic tumor surgery. Although the pathomechanisms involved in PSM should be resolved promptly in order to safely expand the indication of laparoscopic tumor surgery, there have been no useful animal models mimicking the PSM that is observed in the clinical setting. Conventionally, small animals such as mice and rats were used as animal experiment model for PSM. This is too far different to represent a model for PSM after laparoscopic surgery in man. The purpose of this study was to establish a model of PSM in rabbits and examine the growth characteristics of this model. In experiment-1, the relationship between the number of tumor cells intraperitoneally inoculated and the frequency of the PSM was examined. Male Japanese rabbits (n＝5, per group) received intraperitoneal inoculation of one of the three different counts of VX2 cancer cells (Group A; 5×103 cells, Group B; 5×104 cells, or Group C; 5×105 cells). Three days after the tumor inoculation, rabbits underwent carbon dioxide pneumoperitoneum at 8 mmHg for 30 minutes with 9 ports inserted into the abdomen. The frequency of port site metastasis detected on day 17 was greater as the number of inoculated VX2 cells suspension increased. The frequency of port site metastasis in group C was 35.6％. Therefore, this model was used in the next experiment. In experiment-2, the same conditions as in the group C rabbits were used to generate port site metastases in 21 rabbits. The rabbits were sacrificed to examine the growth characteristics of PSM on days 3, 5, 7, 9, 13, 17, or 23. The first histological evidence of PSM formation was found on day 13. On day 17, 76 percent of the port sites developed tumors, and 59％ of them invaded into the muscle layer from subperitoneal layer. On day 23, 100％ of the port sites developed tumors, and 96％ of them were found to invade the muscle layer. These results suggest that the initial site of growth of the PSM is subperitoneal tissue and the metastasis grows and invades the muscle layer. Our model is useful because (1) the rabbits, the largest animals with transplantable tumor cell line, are the closest animal model for PSM in man, (2) it is a relatively stable source of PSM that is similar to the form seen in clinical setting, and (3) the developing process of PSM which begins from embedment in the subperitoneal tissue, leading to invasion of muscular layer. In the future, wide range of applications can be expected from this experimental model.
Keywords: port-site metastasis, VX2, pneumoperitoneum, histological examination