Single-pass isolated lung perfusion versus recirculating isolated lung perfusion with melphalan in a XXXX model.

@entity5721 @entity242 @entity5 @entity2 @entity35 @entity420
BACKGROUND: Isolated lung perfusion (ILuP) with melphalan (MN) is superior to intravenous infusion for the treatment of @entity2 and @entity242 metastases. However, it is unknown whether a bolus injection of MN into the perfusion circuit or ILuP with a fixed concentration of MN will result in the highest lung levels. METHODS: ILuP with 0.5 mg MN was performed in Wag-Rij @entity35 for 30 minutes either by a single-pass system (SP) (fixed concentration) (n = 10) or by @entity5721 ( @entity5721 ) (bolus injection) (n = 10). In a separate experiment, @entity35 were perfused with blood as the perfusate. In a third experiment, @entity5 levels were compared between SP, @entity5721 , or intravenous therapy with a dose of 0.5 mg. For induction of pulmonary metastases, 0.5 x 10(6) single @entity420 cells were injected intravenously and therapy was given on day 30. For comparison of drug concentrations, unpaired Student's t test was applied. Statistical significance was accepted at p less than 0.05. RESULTS: Lung perfusion studies were succesfully performed without systemic leakage. Temperature of perfusate and @entity35 was 34 degrees C to 37 degrees C. A significantly higher hematocrit (mean 27.9) compared with buffered starch (mean 2.5) did not result in higher MN lung levels or lower wet-to-dry ratio. Tumor levels were significantly higher after ILuP compared with intravenous therapy. However, no difference in @entity5 and lung levels was seen between single-pass and @entity5721 . CONCLUSIONS: Both ILuP techniques resulted in significantly higher MN lung levels than after intravenous therapy. Because no difference was seen between single-pass and recirculating perfusion, MN can be injected as a bolus into the closed perfusion circuit.
