Assessment of cisplatin concentration and depth of penetration in human lung tissue after hyperthermic exposure

Our plain-English summary of Assessment of cisplatin concentration and depth of penetration in human lung tissue after hyperthermic exposure, by M. Ried, K. Lehle, R. Neu, et al (European Journal of Cardio-thoracic Surgery, 2015).

The study

• Authors: M. Ried, K. Lehle, R. Neu, C. Diez, P. Bednarski, Z. Sziklavari, H.S. Hofmann
• Journal: European Journal of Cardio-thoracic Surgery
• Published: 2015;47(3):563-6
• Cited by: 26 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objectives: The effects of cisplatin on the lung parenchyma during hyperthermic intrathoracic chemotherapy perfusion have not been analysed in detail. The objective of this study was to evaluate both the concentration and depth of the penetration of cisplatin in human lung tissue after hyperthermic exposure under ex vivo conditions.

Methods: This experimental study was approved by the local ethics committee. Twelve patients underwent pulmonary wedge resections after elective thoracic lobectomies were performed (resected lobe), and the lung tissue (approximately 1-2 cm(3)) was incubated (in vitro) with cisplatin (0.05 mg/ml; 60 min, 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. Afterwards, the penetration of cisplatin depth was calculated and related to the different concentrations per tissue.

Results: Cisplatin penetrated into the human lung tissue after ex vivo hyperthermic exposure. The median amount of platinum [nmol cisplatin/g lung tissue] decreased significantly (P ≤ 0.05) depending on the penetration depth: 32 nmol/g (1 mm), 20 nmol/g (2 mm) and 6.8 nmol/g (4 mm). The calculated median concentrations of cisplatin (µg/ml) were 2.4 µg/ml (1 mm), 1.4 µg/ml (2 mm) and 0.5 µg/ml (4 mm), respectively.

Conclusions: Under ex vivo hyperthermic conditions, cisplatin diffused into human lung tissue. The median penetration depth of the cisplatin was approximately 3-4 mm. The penetration of cisplatin into lung tissue may affect the local therapy of residual tumour cells on the lung surface using hyperthermic intrathoracic chemotherapy perfusion in patients with malignant pleural tumours.

© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

In plain English

This laboratory experiment did not study asbestos exposure. It examined cisplatin, a chemotherapy drug used in a treatment for malignant pleural tumours, including malignant pleural mesothelioma. In that treatment, called hyperthermic intrathoracic chemotherapy perfusion, heated cisplatin is applied inside the chest after surgery. The authors took small pieces of lung tissue from 12 patients who had an elective lobectomy at the University Medical Center Regensburg, Germany. They soaked the tissue outside the body in cisplatin solution (0.05 mg/ml) for 1 hour at 42°C, then sliced it in thin layers from the outside inwards and measured platinum in each layer. The concentration fell significantly with depth. The median cisplatin concentration was 2.4 µg/ml at 1 mm, 1.4 µg/ml at 2 mm, 0.7 µg/ml at 3 mm and 0.5 µg/ml at 4 mm. In deeper layers the drug could not be measured because of the method's detection limits. The authors concluded that cisplatin diffused into lung tissue to a median depth of about 3 to 4 mm, despite an intact visceral pleura. They noted that living lung behaves substantially differently from tissue tested outside the body, so the effective concentration in patients remains unclear.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (ex vivo, in vitro) experiment on surgically removed human lung tissue
• Who was studied: Lung tissue from 12 patients who had an elective lobectomy at the Department of Thoracic Surgery, University Medical Center, Regensburg, Germany; a wedge of tissue was taken from the edge of each removed lobe. Patients' diagnoses and study dates are not reported.
• Exposure: Cisplatin solution (0.05 mg/ml in 0.9% sodium chloride) applied to lung tissue for 1 hour at 42°C. The study did not involve asbestos or any fiber exposure.
• Main results:
  • Cisplatin concentration decreased significantly (P less than or equal to 0.05) from the surface in contact with the cisplatin solution to deeper tissue layers
  • Median amount of platinum in the lung tissue: 32 nmol/g at 1 mm, 20 nmol/g at 2 mm and 6.8 nmol/g at 4 mm depth
  • Median cisplatin concentration in the lung tissue: 2.4 µg/ml at 1 mm, 1.4 µg/ml at 2 mm, 0.7 µg/ml at 3 mm and 0.5 at 4 mm
  • A regression estimate gave a median cisplatin concentration of 1 µg/ml at a depth of 2 mm
  • Platinum was still detectable at 3 to 4 mm deep, despite the visceral pleura covering the lung tissue
  • In deeper layers, cisplatin could not be measured because of the detection limits of the method
• The authors' conclusion: The authors concluded that, under ex vivo hyperthermic conditions, cisplatin diffused into human lung tissue with a median penetration depth of about 3 to 4 mm, and that this penetration may affect local treatment of residual tumour cells on the lung surface in patients with malignant pleural tumours
• Limitations the authors state:
  • Only lung tissue with intact visceral pleura was used, so cisplatin concentrations in decorticated lung tissue might be higher
  • Drug behaviour in living, blood-perfused lung differs substantially from an ex vivo model
  • The effective cisplatin concentration in lung tissue in living patients remains unclear
  • Clinical evidence and prospective trials to confirm these laboratory results are still lacking

Topics

Medical terms in this study, explained in our Lexicon: Cisplatin, Parenchyma, Intrathoracic, Chemotherapy.

Related studies

• Local and systemic exposure of cisplatin during hyperthermic intrathoracic chemotherapy perfusion after pleurectomy and decortication for treatment of pleural malignancies — M. Ried, T. Potzger, et al. (2013)
• Hyperthermic intraoperative pleural cisplatin chemotherapy extends interval to recurrence and survival among low-risk patients with malignant pleural mesothelioma undergoing surgical macroscopic complete resection — D.J. Sugarbaker, R.R. Gill, et al. (2013)
• Anesthetic management and renal function in pediatric patients undergoing cytoreductive surgery with continuous hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin — P. Owusu-Agyemang, R. Arunkumar, et al. (2012)
• Toxicity of hyperthermic intraperitoneal chemotherapy (HIPEC) in pediatric patients with sarcomatosis/carcinomatosis: early experience and phase 1 results — A. Hayes-Jordan, H. Green, et al. (2012)
• Acute kidney injury after cytoreductive surgery and hyperthermic intraoperative cisplatin chemotherapy for malignant pleural mesothelioma — T. Hod, K.J. Freedberg, et al. (2021)
• Interim results of pleurectomy/decortication and intraoperative intrapleural hyperthermic cisplatin perfusion for patients with malignant pleural mesothelioma intolerable to extrapleural pneumonectomy — H. Ishibashi, M. Kobayashi, et al. (2015)

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