[An experimental study of local chemotherapy for metastatic lung tumor--isolated lung perfusion and pulmonary artery infusion].
OBJECTIVE
We evaluated the efficacy of local chemotherapy using isolated lung perfusion (ILP) and pulmonary artery infusion (PAI) in vivo to improve prognosis for patients with metastatic lung diseases.


METHODS
Male F344 rats were used. The left lung was isolated and chemotherapeutic agents were administrated to the isolated lung by the ILP or PAI technique. Agents used were cisplatin (CDDP) and fluorouracil (5-FU), and their levels in the perfused lung and serum were measured (renal levels were also measured in CDDP groups). The results were compared with those obtained following intravenous administration (i.v.). In the ILP group, the left pulmonary artery and vein were clamped during perfusion. The agents were infused from the pulmonary artery, and the perfusate was collected from the pulmonary venotomy site following flushing with saline before declamping. In the PAI group, the left pulmonary artery was clamped and perfused with 0.2 ml of the agents, pulmonary arterial flow was occluded for 20 minutes, and perfusate was not collected. Rats were sacrificed 5 minutes after declamping in both groups, and the perfused lung and blood (and also kidneys in the CDDP group) were collected for pharmacokinetic examination. Histological examination of the perfused lung was also performed.


RESULTS
In the ILP group treated with 1 mg of CDDP and PAI group treated with 0.1 mg of CDDP administration, the lung CDDP levels were significantly higher and the serum and renal CDDP levels were significantly lower than those in the IV group. In the ILP group treated with 150 mg of 5-FU and PAI group treated with 10 mg of 5-FU, the lung 5-FU levels were significantly higher than those in all IV groups and the serum 5-FU levels were lower than those in the IV group treated with 10 mg and 15 mg of 5-FU. The bronchopulmonary construction was histologically maintained in the perfused lung in each group.


CONCLUSIONS
We concluded that local chemotherapy using ILP or PAI could be a safe and effective choice of therapy, and this method may be clinically applicable.
Omiya
H
H
Department of Thoracic and Cardiovascular Surgery, Kansai Medical University, Osaka, Japan.
Machida
H
H
Saito
Y
Y
Imamura
H
H
Okamura
A
A
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005472:Fluorouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007261:Infusions, Intra-Arterial / Q000379:methods*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D011651:Pulmonary Artery; D051381:Rats; D011916:Rats, Inbred F344
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D002945:Cisplatin; D005472:Fluorouracil