腹腔镜检查期间避免腹腔内和腹腔外转移的新治疗策略：大鼠肿瘤模型的结果

New therapeutic strategies to avoid intra- and extraperitoneal metastases during laparoscopy: results of a tumor model in the rat.

作者信息

Jacobi C A, Peter F J, Wenger F A, Ordemann J, Müller J M

机构信息

Department of Surgery, Humboldt University of Berlin, Germany.

出版信息

Dig Surg. 1999;16(5):393-9. doi: 10.1159/000018754.

DOI:10.1159/000018754

PMID:10567800

Abstract

BACKGROUND

Therapeutic strategies to prevent port site recurrences in laparoscopy surgery of malignancies have not been investigated until now.

METHODS

The effects of taurolidine, heparin, and povidone iodine on the growth of rat and human colon adenocarcinoma as well as gallbladder carcinoma were investigated in vitro. Furthermore, cytokine release of growth-stimulating IL-1beta by peritoneal macrophages was measured after incubation with carbon dioxide and additional incubation with the different agents. In the third experiment, prevention of intra- and extraperitoneal metastases by intraperitoneal instillation of the different agents during laparoscopy was investigated in a colon carcinoma model in the rat. Tumor cells were administered intraperitoneally in 100 rats, and pneumoperitoneum (8 mm Hg) was established over 30 min with carbon dioxide. Rats received either tumor cells, cells + heparin, cells + povidone iodine, cells + taurolidine, or cells + taurolidine + heparin.

RESULTS

In vitro, tumor cell growth decreased after incubation with taurolidine, taurolidine/heparin, and povidone iodine. Cytokine release was stimulated by incubation with carbon dioxide and could only be suppressed by incubation with taurolidine in vitro. In vivo, intraperitoneal tumor weight was lower in rats receiving heparin (251 +/- 153 mg) and povidone iodine (134 +/- 117 mg) compared to the control group (541 +/- 291 mg), but even less when taurolidine (79 +/- 82 mg) or taurolidine/heparin (18.3 +/- 30 mg) were instilled.

CONCLUSION

Heparin slightly inhibits intraperitoneal tumor growth in vivo, while povidone iodine and taurolidine cause a significant decrease in tumor cell growth in vitro as well as intraperitoneal tumor growth in vivo. Cytokine release of peritoneal macrophages is only suppressed by taurolidine. Total tumor take and trocar metastases are only suppressed by taurolidine and taurolidine/heparin.

摘要

背景

迄今为止，尚未对腹腔镜恶性肿瘤手术中预防穿刺孔复发的治疗策略进行研究。

方法

在体外研究了牛磺罗定、肝素和聚维酮碘对大鼠及人结肠腺癌以及胆囊癌生长的影响。此外，在与二氧化碳孵育以及与不同药物进一步孵育后，测量腹膜巨噬细胞释放生长刺激因子白细胞介素-1β的情况。在第三个实验中，在大鼠结肠癌模型中研究了腹腔镜检查期间经腹腔注入不同药物对预防腹腔内和腹腔外转移的作用。向100只大鼠腹腔内注射肿瘤细胞，用二氧化碳在30分钟内建立气腹（8毫米汞柱）。大鼠分别接受肿瘤细胞、细胞+肝素、细胞+聚维酮碘、细胞+牛磺罗定或细胞+牛磺罗定+肝素。

结果

在体外，与牛磺罗定、牛磺罗定/肝素和聚维酮碘孵育后，肿瘤细胞生长减少。与二氧化碳孵育可刺激细胞因子释放，且在体外仅牛磺罗定孵育可抑制该释放。在体内，与对照组（541±291毫克）相比，接受肝素（251±153毫克）和聚维酮碘（134±117毫克）的大鼠腹腔内肿瘤重量较低，但注入牛磺罗定（79±82毫克）或牛磺罗定/肝素（18.3±30毫克）时肿瘤重量更低。