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Assessment of the Cytotoxic and Immunomodulatory Effects of Substances in Human Precision-cut Lung Slices
Published on: May 9, 2018
Assessment of concentration and penetration depth of cisplatin in human lung tissue after decortication and
Christopher Larisch1, Till Markowiak1, Elena Loch1
1Department for Thoracic Surgery, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
Background:
Hyperthermic perfusion of the pleural cavity with cisplatin after pleurectomy/decortication is an additional therapeutic option to reduce local relapse of malignant pleural tumours. Although there are data on the clinical effect, only little is known about the local impact on human lung tissue by cisplatin. The objective of this experimental study is to evaluate both the concentration and the penetration depth of cisplatin in human lung tissue after normothermic and hyperthermic exposure under ex-vivo-in-vitro conditions.
Methods:
This study was approved by the local ethics committee. In total, 46 patients underwent elective lobectomy and wedge resections were taken from the resected lobes. A decortication of the visceral pleura was performed under ex-vivo conditions, and the tissue samples were incubated with cisplatin (c =0.05 mg/mL) at 37, 42 or 45 °C for 60 minutes. Then the mass concentration of platinum was measured with flameless atomic absorption spectroscopy and then converted into cisplatin concentration. In addition, the current data were compared with previous data of our working group (42 °C, without decortication).
Results:
The overall maximum penetration depth was 7.5 mm due to limitations of our methods. The functional maximum penetration depth did not vary with temperature (P=0.243) but by decortication (P<0.001). The cisplatin concentration decreased with increasing penetration depth (P<0.001). An increase of temperature showed no effect on the cisplatin concentration in decorticated tissue samples (P=0.985). However, decortication at 42 °C significantly increased the cisplatin concentration in comparison to not decorticated tissue samples (P=0.005).
Conclusions:
Decortication of the visceral pleura increases the cisplatin concentration in the lung tissue. Therefore, it possibly reduces the likelihood of a local relapse. An increase of temperature did not show any effect.
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