Intraperitoneal paclitaxel induces regression of peritoneal metastasis partly by destruction of peripheral microvessels.
OBJECTIVE
Intraperitoneal (IP) administration of paclitaxel (PTX) can enable direct infiltrate of high amount of PTX into peritoneal nodules and elicit remarkable clinical responses against peritoneal metastases. In this study, we examined the mechanisms leading to tumor shrinkage after IP PTX.


METHODS
We compared the microscopic features of peritoneal metastases before and after IP PTX in surgically removed human samples, as well as in a murine xenograft model using immunohistochemistry.


RESULTS
We found that many microvessels exist in the peripheral areas of metastatic nodules in human samples before treatment. However, peripheral vessels were greatly reduced in number, and luminal obstructions were observed in lesions showing complete response after chemotherapy including IP PTX. Similar changes were observed in peripheral vessels of peritoneal tumors in MKN45-inoculated nude mice treated with IP-PTX. Moreover, pimonidazole staining revealed that highly hypoxic regions were produced by IP PTX at the tumor periphery.


CONCLUSIONS
These findings strongly suggest that the remarkable efficacy of IP PTX in the treatment of peritoneal metastases is, at least in part, dependent on the destruction of peripheral microvessels by exposure to infiltrated PTX.
Department of Surgical Oncology, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan, kitayama-1SU@h.u-tokyo.ac.jp.
Joji
J
Kitayama
Shigenobu
S
Emoto
Hironori
H
Yamaguchi
Hironori
H
Ishigami
Toshiaki
T
Watanabe
D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D055806:Microvessels / Q000187:drug effects; D017239:Paclitaxel / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010534:Peritoneal Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000556:secondary; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
D017239:Paclitaxel