Artikel
Assessment of cisplatin concentration and penetration depth in human lung tissue after hyperthermic exposure
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Autoren
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M. Ried
- Abteilung für Thoraxchirurgie, Universitätsklinikum Regensburg, Regensburg
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K. Lehle
- Klinik und Poliklinik für Herz-, Thorax- und herznahe Gefäßchirurgie, Universitätsklinikum Regensburg, Regensburg
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K. Bielenberg
- Klinik und Poliklinik für Herz-, Thorax- und herznahe Gefäßchirurgie, Universitätsklinikum Regensburg, Regensburg
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T. Potzger
- Abteilung für Thoraxchirurgie, Universitätsklinikum Regensburg, Regensburg
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N. Braune
- Abteilung für Thoraxchirurgie, Universitätsklinikum Regensburg, Regensburg
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R. Neu
- Abteilung für Thoraxchirurgie, Universitätsklinikum Regensburg, Regensburg
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P. Bednarski
- Institut für Pharmazie, Universität Greifswald, Greifswald
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H. S. Hofmann
- Abteilung für Thoraxchirurgie, Universitätsklinikum Regensburg, Regensburg; Klinik für Thoraxchirurgie, Krankenhaus Barmherzige Brüder Regensburg, Regensburg
| Veröffentlicht: | 14. Oktober 2013 |
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Gliederung
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Objective: Only limited data are available about the characteristics and impact of cisplatin regarding the lung tissue after radical pleurectomy followed by hyperthermic intrathoracic chemotherapy perfusion. Therefore, purpose of this study was to evaluate the concentration and penetration depth of cisplatin into human lung tissue after hyperthermic exposure under ex-vivo conditions.
Methods: This experimental study was approved by the local ethics committee and a written informed consent was sign by every patient. Twelve patients were enrolled in this study. Pulmonary wedge resections after elective thoracic lobectomy were performed (resected lobe) and lung tissue (about 1–2 cm3) was incubated (in-vitro) with cisplatin (0.05 mg/ml; 60 minutes, 42°C). Subsequent tissue beds (depth, 0.5 mm; median weight, 70–92 mg) were prepared from the outside to the middle and the amount of cisplatin per tissue weight was analysed using atomic absorption spectrometry (AAS). Afterwards the penetration depth of cisplatin was calculated related to the different concentration per tissue.
Results: Cisplatin penetrated into human lung tissue after ex-vivo hyperthermic exposure. The median amount of cisplatin [nmol cisplatin/g lung tissue] decreased significantly (p≤0.05) with a penetration depth of 23 nmol/g (median depth, 1 mm), 12.5 nmol/g (depth, 2 mm) and 6.7 nmol/g (depth, 3 mm). Calculated median concentrations of cisplatin [µg/ml] were 2.0 µg/ml (depth, 1 mm), 1.2 µg/ml (depth, 2 mm) and 0.5 µg/ml (depth, 3 mm), respectively.
Conclusion: Under ex-vivo hyperthermic conditions cisplatin diffused into lung tissue. The median penetration depth of cisplatin is approximately 3 mm. It can only be speculated, that the local concentration of cisplatin is high enough to induce apoptosis of residual tumor cells. Nevertheless, the penetration of cisplatin into lung tissue may impact the local therapy of residual tumor cells on the lung surface by the hyperthermic intrathoracic chemotherapy perfusion in patients with malignant pleural tumors after radical pleurectomy.
