Limitations of peritoneal lavage with antiseptics in prevention of recurrent colorectal cancer caused by tumor-cell seeding: experimental study in rats.
OBJECTIVE
Exfoliated or soiled free malignant cells have serious consequences in patients undergoing gastrointestinal cancer surgery. The present study evaluates the toxicity and efficacy of cytotoxic agents in the prevention of cell seeding and tumor growth in the peritoneal cavity in an experimental model.


METHODS
Mtln3 adenocarcinoma cell viability was tested in vitro using the trypan blue exclusion test after incubation with povidone-iodine or chlorhexidine. In vivo, Fischer rats were inoculated with 10(5) or 10(6) cells followed by peritoneal lavage with physiological saline, chlorhexidine 0.02 percent, povidone-iodine low molecular weight 1 percent or povidone-iodine high molecular weight 1 and 2 percent in different quantities and incubation times.


RESULTS
Chlorhexidine 0.02 percent and povidone-iodine low molecular weight 1 percent or high molecular weight 2 percent, killed over 98 percent of 10(5) or 10(6) tumor cells in vitro. Povidone-iodine low molecular weight 1 percent and high molecular weight 2 percent were toxic and lethal when 5 ml were applied in the peritoneal cavity three times for five minutes. Chlorhexidine 0.02 percent applied after inoculation of 10(5) or 10(6) cells, reduced the tumor development only to 70 and 80 percent. Application of 5 ml povidone-iodine 1 percent low molecular weight or high molecular weight, three times for one and five minutes, after inoculation of 10(6) cells did not change the tumor take. However, inhibition of Mtln3 cells to form metastases was observed. When povidone-iodine low molecular weight 1 percent was used three times for one minute after 10(5) tumor cells were "soiled", no toxicity was observed and the tumor take was reduced to 30 percent (P < 0.05).


CONCLUSIONS
Povidone-iodine toxicity proved to be a major issue in vivo. However, povidone-iodine low molecular weight 1 percent was safe when used for short periods and very effective when a limited number of tumor cells was inoculated. The use of cytotoxic agents to prevent recurrent disease caused by tumor cell seeding in patients seems to make sense only when the "inoculum size" of exfoliated or soiled cancer cells is limited.
Basha
G
G
Department of Abdominal Surgery, University Hospital Gasthuisberg, Catholic University of Leuven, Belgium.
Ghirardi
M
M
Geboes
K
K
Yap
S H
SH
Penninckx
F
F
D000230:Adenocarcinoma / Q000473:pathology* / Q000628:therapy*; D000818:Animals; D002710:Chlorhexidine / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000517:prevention & control*; D009366:Neoplasm Seeding; D009374:Neoplasms, Experimental; D010533:Peritoneal Lavage / Q000379:methods; D011206:Povidone-Iodine / Q000008:administration & dosage*; D051381:Rats; D011916:Rats, Inbred F344; D012004:Rectal Neoplasms / Q000473:pathology / Q000628:therapy*; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
D011206:Povidone-Iodine; D002710:Chlorhexidine