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Ann Thorac Surg 1998;66:1719-1725
© 1998 The Society of Thoracic Surgeons

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Original articles: general thoracic

Isolated lung perfusion with melphalan and tumor necrosis factor for metastatic pulmonary adenocarcinoma

^a Laboratory for Experimental Surgery, University of Antwerp, Antwerp, Belgium

Address reprint requests to Dr Hendriks, Division of Thoracic and Vascular Surgery, Department of Surgery, University Hospital Antwerp (UZA), Wilrijkstraat 10, B-2650 Edegem, Belgium
e-mail: (j.hendriks{at}planetinternet.be)

Presented at the Thirty-fourth Annual Meeting of The Society of Thoracic Surgeons, New Orleans, LA, Jan 26–28, 1998.

Background. Isolated left lung perfusion with melphalan and human tumor necrosis factor- for pulmonary metastatic adenocarcinoma in the WAG/Rij rat was studied.

Methods. Survival was determined for melphalan, human tumor necrosis-. Lung, pulmonary effluent, and serum melphalan were analyzed by chromatography after isolated lung perfusion or intravenous injection. On day 0, rats were injected with 2.0 x 10⁶ CC531S cells intravenously. On day 7, rats underwent sham thoracotomy, received melphalan intravenously, or underwent isolated left lung perfusion with saline, melphalan, tumor necrosis factor, and a combination of the latter two. On day 14, tumor nodules were counted.

Results. For the doses of 400 µg tumor necrosis factor, 1,000 µg tumor necrosis factor, or both melphalan and tumor necrosis factor (2 mg + 200 µg), survival rates after contralateral pneumonectomy were 33%, 17%, and 80%, respectively. Survival in all other groups was 100%. Left lung melphalan level was significantly higher after isolated lung perfusion compared to intravenous administration. Significantly fewer left lung nodules were found for 0.5 mg isolated lung perfusion with melphalan (28 ± 17) compared to isolated administration (200 ± 0) (p = 0.001), and for 1.0 mg intravenous lung perfusion with melphalan (16 ± 10) compared to controls (171 ± 65) (p = 0.00047). Tumor necrosis factor showed no significant effect.

Conclusions. Isolated lung perfusion with melphalan is an effective treatment for pulmonary metastases from adenocarcinoma in the rat.

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