Ueno Hideaki, Hihara Jun, Shimizu Katsuhiko, Osaki Akihiko, Yamashita Yoshinori, Yoshida Kazuhiro, Toge Tetsuya
Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Anticancer Res. 2005 Mar-Apr;25(2A):821-5.
Common tracers for sentinel node navigation surgery are blue dye and technetium-99m-labelled colloids. However, in most esophageal or lung cancer patients, it is impossible to detect the sentinel node among mediastinal nodes by blue dye because of the anthracotic pigmentation of mediastinal nodes. The use of technetium-99m-labelled colloids requires a special facility, while a large hot-spot at the injection site prevents detection of the sentinel node around the primary lesion. To overcome these problems, we investigated the use of fluorescent microspheres (0.1-20 microm in diameter) as tracers in animals and detected fluorescence-positive nodes by a simple ultraviolet light irradiation method.
Two milliliters of fluorescent microspheres 0.1-20 microm in diameter diluted to 2.5% weight per volume was injected via the tail vein of 30 rats; systemic side-effects were examined. One milliliter of 1.0 microm-diameter microspheres dilution was injected on the backs of 30 rats; local side-effects were examined. A microsphere dilution (0.2 ml, 1.0 microm-diameter microspheres) was injected into the footpad of 18 rats; the lymphatic pathway and drainage were examined. Five milliliters of 1.0 microm-diameter fluorescent microspheres was injected endoscopically into the submucosa of the esophagus, stomach and small and large bowels of 6 domestic pigs, and 5 ml was injected into the subadventitia of the esophagus or subserosa of the stomach, and small and large bowels. Fluorescence-positive lymph ducts or nodes were carefully observed under ultraviolet light irradiation.
No systemic side-effects were observed in rats. Only mild edema and a mild inflammatory reaction were observed on the backs of rats. Fluorescent microspheres 0.1, 0.5 and 1.0 microm in diameter were detected in lymph ducts or nodes of pigs within 1 hour after injection.
Sentinel node navigation surgery with the use of fluorescent microspheres might be feasible and advantageous for patients with esophageal or lung cancer, especially in the mediastinum.
前哨淋巴结导航手术常用的示踪剂是蓝色染料和锝-99m标记的胶体。然而,在大多数食管癌或肺癌患者中,由于纵隔淋巴结的炭末沉着,使用蓝色染料无法在纵隔淋巴结中检测到前哨淋巴结。使用锝-99m标记的胶体需要特殊设备,而注射部位的大热点会妨碍对原发灶周围前哨淋巴结的检测。为克服这些问题,我们研究了使用荧光微球(直径0.1 - 20微米)作为动物示踪剂,并通过简单的紫外线照射方法检测荧光阳性淋巴结。
将2毫升直径0.1 - 20微米的荧光微球稀释至2.5%重量/体积,经尾静脉注射给30只大鼠;检查全身副作用。将1毫升直径1.0微米微球稀释液注射到30只大鼠的背部;检查局部副作用。将微球稀释液(0.2毫升,直径1.0微米微球)注射到18只大鼠的足垫;检查淋巴途径和引流情况。将5毫升直径1.0微米的荧光微球经内镜注射到6头家猪食管、胃以及小肠和大肠的黏膜下层,5毫升注射到食管外膜下或胃、小肠和大肠的浆膜下。在紫外线照射下仔细观察荧光阳性淋巴管或淋巴结。
在大鼠中未观察到全身副作用。在大鼠背部仅观察到轻度水肿和轻度炎症反应。注射后1小时内在猪的淋巴管或淋巴结中检测到直径0.1、0.5和1.0微米的荧光微球。
使用荧光微球进行前哨淋巴结导航手术对食管癌或肺癌患者可能是可行且有利的,尤其是在纵隔部位。