Ann Thorac Surg 2006;82:2030
© 2006 The Society of Thoracic Surgeons
Original Articles: General Thoracic
Invited commentary
Thorsten Walles, MD
Department of Surgery, Robert-Bosch-Krankenhaus, Auerbachstrasse 110, Stuttgart, 70376 Germany
(Email: twalles{at}yahoo.com).
The concept of isolated lung perfusion to increase the effective chemotherapeutic dose in the target tumor tissue by avoiding systemic side effects has been intensively investigated and has already been clinically applied. Retrograde lung perfusion by cannulating the pulmonary veins is a rather new experimental approach. It is hypothesized that a more homogenous drug distribution in the lung tissue can be attained by retrograde perfusion of the pulmonary artery and the bronchial artery vascular tree. In their article, Krueger and colleagues [1] tested the hypothesis of whether retrograde lung perfusion results in an enhanced drug concentration in pulmonary tumors. They used a rodent model generating pulmonary sarcomatous tumors in the left lower lobe of rats. Their results demonstrate a weak tumor penetration by the applied chemotherapeutic agent (doxorubicin), which was confined to the tumor periphery, whereas higher drug levels were found in the healthy lung tissue. No difference was found between isolated antegrade and retrograde lung perfusion. The authors attribute their findings to a low permeability of the endothelial barrier of the tumor vasculature.
The reason for lower drug concentrations in the generated tumor tissues compared with normal lung parenchyma may be missing vascularization of the growing sarcomatous nodules. The results presented by Krueger and colleagues [1] mirror our experience of capillary ingrowth in a rodent transplant model (ie, avascular tissues with a diameter of less than 1 mm are supplied by diffusion for a time period of 2 weeks) [2]. Tissue revascularization starts approximately 2 weeks after transplantation and continues up to the 8th postoperative week [3]. In their applied animal model, Krueger and coworkers [1] treated the growing sarcomatous tumor already 10 days after seeding. It is suspected that no significant vascularization of the tumor tissue exists at time of treatment. This thesis is supported by the identical effect of antegrade and retrograde lung perfusion and the finding that sporadic fluorescence signaling an emerging from the tumors was confined to the tumor periphery (Fig 2A–D). In contrast, in an acute rodent model applying isolated antegrade and retrograde lung perfusion in healthy lung tissue, recently Romijn and coworkers [4] could show that retrograde lung perfusion increased the drug concentration of melphalan in hilar and basal regions of the lung compared with antegrade perfusion [4]. From this perspective the article of Krueger and coworkers [1] raises numerous interesting questions. Does their applied animal model allow the growth of tumor tissue for a period of 4 weeks and longer? If so, does the tumor tissue become revascularized? Finally, does antegrade or retrograde lung perfusion cause different effects in these vascularized tumors?
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References
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- Krueger T, Kuemmerle T, Andrejevic-Blant S, et al. Antegrade versus retrograde isolated lung perfusion: doxorubicin uptake and distribution in a sarcoma model Ann Thorac Surg 2006;82:2024-2030.[Abstract/Free Full Text]
- Walles T, Herden T, Haverich A, Mertsching H. Influence of scaffold thickness and scaffold composition on bioartificial graft survival Biomaterials 2003;24:1233-1239.[Medline]
- Walles T, Puschmann C, Haverich A, Mertsching H. Acellular scaffold implantation—no alternative to tissue engineering Tissue Eng 2003;26(3):225-234.
- Romijn S, Hendriks JM, Van Putte BP, et al. Anterograde versus retrograde isolated lung perfusion with melphalan in the WAG-Rij rat Eur J Cardiothorac Surg 2005;27(6):1083-1085.[Abstract/Free Full Text]
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Antegrade Versus Retrograde Isolated Lung Perfusion: Doxorubicin Uptake and Distribution in a Sarcoma Model
- Thorsten Krueger, Andrea Kuemmerle, Snezana Andrejevic-Blant, Hua Yan, Youmin Pan, Jean-Pierre Ballini, Walter Klepetko, Laurent Arthur Decosterd, Roger Stupp, and Hans-Beat Ris
Ann. Thorac. Surg. 2006 82: 2024-2030.
[Abstract]
[Full Text]
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