title: Assessment of cisplatin concentration and depth of penetration in human lung tissue after hyperthermic exposure.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Thoracic Surgery, University Medical Center Regensburg, Regensburg, Germany micha.ried@t-online.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Ried
authors.affiliation: Department of Cardiothoracic Surgery, University Medical Center Regensburg, Regensburg, Germany.
authors.forename: Karla
authors.initials: K
authors.lastname: Lehle
authors.affiliation: Department of Thoracic Surgery, University Medical Center Regensburg, Regensburg, Germany.
authors.forename: Reiner
authors.initials: R
authors.lastname: Neu
authors.affiliation: Department of Thoracic Surgery, University Medical Center Regensburg, Regensburg, Germany.
authors.forename: Claudius
authors.initials: C
authors.lastname: Diez
authors.affiliation: Institute of Pharmacy, University of Greifswald, Greifswald, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Bednarski
authors.affiliation: Department of Thoracic Surgery, Krankenhaus Barmherzige Brüder Regensburg, Regensburg, Germany.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Sziklavari
authors.affiliation: Department of Thoracic Surgery, University Medical Center Regensburg, Regensburg, Germany Department of Thoracic Surgery, Krankenhaus Barmherzige Brüder Regensburg, Regensburg, Germany.
authors.forename: Hans-Stefan
authors.initials: HS
authors.lastname: Hofmann
mesh_terms: D000970:Antineoplastic Agents / Q000032:analysis / Q000493:pharmacokinetics*; D010478:Chemotherapy, Cancer, Regional Perfusion; D002945:Cisplatin / Q000032:analysis / Q000493:pharmacokinetics*; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D008168:Lung / Q000737:chemistry / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism / Q000601:surgery; D008654:Mesothelioma / Q000378:metabolism / Q000601:surgery; D008954:Models, Biological; D010997:Pleural Neoplasms / Q000378:metabolism / Q000601:surgery; D011013:Pneumonectomy
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin
keywords: Chemotherapy perfusion; Cisplatin; Hyperthermic perfusion; Penetration depth