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An experimental study of local chemotherapy for metastatic lung tumor —Isolated lung perfusion and pulmonary artery infusion—

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Abstract

Purpose

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.

Material and 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 (IV). 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. Conclusion: 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.

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References

  1. 1)

    Pastorino U, Buyse M, Friedel G, Ginsberg RJ, Girard P, Goldstraw P, Johnston M, McCormack P, Pass H, Putnam JB Jr: Long-term results of lung metastasectomy. Prognostic analyses based on 5206 cases. J Thorac Cardiovasc Surg 113: 37–49, 1997

  2. 2)

    32: 998–1004, 1984

  3. 3)

    45: 643–650, 1986

  4. 4)

    9: 672–677, 1995

  5. 5)

    Baron O, Amini M, Duveau D, Despins P, Sagan CA, Michaud LJ: Surgical resection of pulmonary metastases from colorectal carcinoma. Five-year survival and main prognostic factors. Eur J Cardio-thorac Surg 10: 347–351, 1996

  6. 6)

    Okumura S, Kondo H, Tsuboi M, Nakayama H, Asamura H, Tsuchiya R, Naruke T: Pulmonary resection for metastatic colorectal cancer. Experiences with 159 patients. J Thorac Cardiovasc Surg 112: 867–874, 1996

  7. 7)

    Huth JF, Holmes EC, Vernon SE, Callery CD, Ramming KP, Morton DL: Pulmonary resection for metastatic sarcoma. Am J Surg 140: 9–16, 1980

  8. 8)

    46: 437–441,1987

  9. 9)

    90: 598–604, 1989

  10. 10)

    Lanza LA, Putnam JB Jr, Benjamin RS, Roth JA: Response to chemotherapy does not predict survival after resection of sarcomatous pulmonary metastases. Ann Thorac Surg 51: 219–224, 1991

  11. 11)

    Casper ES, Gaynor JJ, Hadju SI, Magill GB, Tan C, Ariedrich C, Brennan MF: A prospective randomized trial of adjuvant chemotherapy with bolus versus continuous infusion of doxorubicin in patients with high-grade extremity soft tissue sarcoma and an analysis of prognostic factors. Cancer 68: 1221–1229, 1991

  12. 12)

    Ratto GB, Toma S, Civalleri D, Passerone GC, Esposito M, Zaccheo D, Canepa M, Romano P, Palumbo R, De Cian F, Scarano F, Vannozzi M, Spessa E, Fantino G: Isolated lung perfusion with platinum in the treatment of pulmonary metastases from soft tissue sarcomas. J Thorac Cardiovasc Surg 112: 614–622, 1996

  13. 13)

    Johnston MR, Minchin R, Shull JH, Thenot JP, McManus BM, Terrill R, Boyd MR: Isolated lung perfusion with Adriamycin. A preclinical study. Cancer 52: 404–409, 1983

  14. 14)

    Weksler B, Schneider A, Ng B, Burt M: Isolated single lung perfusion in the rat. An experimental model. J Appl Physiol 74: 2736–2739, 1993

  15. 15)

    Ratto GB, Esposito M, Leprini A, Civalleri D, DeCian F, Vannozzi M, Romano P, Canepa M, Zaccheo D: In situ lung perfusion with cisplatin. An experimental study. Cancer 71: 2962–2970, 1993

  16. 16)

    Miller BJ, Rosenbaum AS: The vascular supply to metastatic tumors of lung. Surg Gynecol Obstet 125: 1009–1012, 1967

  17. 17)

    Milne EC, Noonan CD, Margulis AR, Stoughton JA: Vascular supply of pulmonary metastases. Experimental study in rats. Invest Radiol 4: 215–229, 1969

  18. 18)

    Pierpont H, Blades B: Lung perfusion with chemotherapeutic agents. J Thorac Cardiovasc Surg 39: 159–165, 1960

  19. 19)

    Jacobs JK, Flexner JM, Scott HW Jr: Selective isolated perfusion on the right or left lung. J Thorac Cardiovasc Surg 42: 546–552, 1961

  20. 20)

    Cisplatin (CDDP) /5-fluorouracil (5-FU) 23: 1770–1779, 1996

  21. 21)

    5-fluorouracil Cisplatin. 24: 959–964, 1997

  22. 22)

    Human Cell 6: 88–93, 1993

  23. 23)

    Wang HY, Ng B, Blumberg D, Port JL, Hochwald SN, Burt ME: Pulmonary artery perfusion of doxorubicin with blood flow occlusion. Pharmacokinetics and treatment in a metastatic sarcoma model. Ann Thorac Surg 60: 1390–1394, 1995

  24. 24)

    Smyth NP, Blades B: Selective chemotherapy of the lung during unilateral pulmonary arterial occlusion with a balloon-tipped catheter. J Thorac Cardiovasc Surg 40: 653–666, 1960

  25. 25)

    Karakousis CP, Park HC, Sharama SD, Kanter P: Regional chemotherapy via the pulmonary artery for pulmonary metastases. J Surg Oncol 18: 249–255, 1981

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Omiya, H., Machida, H., Saito, Y. et al. An experimental study of local chemotherapy for metastatic lung tumor —Isolated lung perfusion and pulmonary artery infusion—. Jpn J Thorac Caridovasc Surg 46, 976–982 (1998). https://doi.org/10.1007/BF03217858

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Keywords

  • CDDP
  • Lung Perfusion
  • Left Pulmonary Artery
  • Extremity Soft Tissue Sarcoma
  • Metastatic Lung Tumor