Evaluation of isolated lung perfusion as neoadjuvant therapy of lung metastases using a novel in vivo pig model: II. High-dose cisplatin is well tolerated by the native lung tissue*1

Franke, Ulrich F.W.; Wittwer, Thorsten; Kaluza, Mirko; Albert, Marc; Becker, Valentin; Roskos, Martin; Lessel, Marlene; Wahlers, T

doi:10.1016/j.ejcts.2004.04.046

Cited by 12 publications

(6 citation statements)

References 23 publications

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“…In another study, pigs submitted to IVLP with and without chemotherapy demonstrated higher histologic injury scores and impairment of functional parameters compared with a sham group. 16 Histologic signs of hemorrhagic edema were found in both the control and melphalan-treated groups, 17 raising the question of the potential role that the perfusion circuit may have in causing injury. More recently, Pages and colleagues 18 performed IVLP for 30 minutes in 50-kg pigs, with a perfusion flow that ranged from 500 to 600 mL/min (adjusted to a PA pressure of around 25 mm Hg) and found that the control group had even greater histologic injury compared with lungs perfused with gemcitabine.…”

Section: Discussionmentioning

confidence: 99%

Modified in vivo lung perfusion allows for prolonged perfusion without acute lung injury

Santos

Machuca

Hwang

et al. 2014

The Journal of Thoracic and Cardiovascular Surgery

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Section: Discussionmentioning

confidence: 99%

Modified in vivo lung perfusion allows for prolonged perfusion without acute lung injury

Santos

Machuca

Hwang

et al. 2014

The Journal of Thoracic and Cardiovascular Surgery

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“…Regarding isolated organ perfusion, the classical dose escalation design is useless if extracorporeal circuit lead to a stable state exposing the organ parenchyma to active concentrations associated with normal tissue saturation [36]. In our study, GEM concentrations used during ILP were eighteen to forty-fold higher than in vitro IC50, leading to stable GEM concentrations in the circuit throughout the perfusion, with minimal systemic leaks.…”

Section: Commentsmentioning

confidence: 69%

Isolated Lung Perfusion as an Adjuvant Treatment of Colorectal Cancer Lung Metastases: A Preclinical Study in a Pig Model

et al. 2013

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BackgroundThe lung is a frequent site of colorectal cancer (CRC) metastases. After surgical resection, lung metastases recurrences have been related to the presence of micrometastases, potentially accessible to a high dose chemotherapy administered via adjuvant isolated lung perfusion (ILP). We sought to determine in vitro the most efficient drug when administered to CRC cell lines during a short exposure and in vivo its immediate and delayed tolerance when administered via ILP.MethodsFirst, efficacy of various cytotoxic molecules against a panel of human CRC cell lines was tested in vitro using cytotoxic assay after a 30-minute exposure. Then, early (operative) and delayed (1 month) tolerance of two concentrations of the molecule administered via ILP was tested on 19 adult pigs using hemodynamic, biological and histological criteria.Results In vitro, gemcitabine (GEM) was the most efficient drug against selected CRC cell lines. In vivo, GEM was administered via ILP at regular (20 µg/ml) or high (100 µg/ml) concentrations. GEM administration was associated with transient and dose-dependant pulmonary vasoconstriction, leading to a voluntary decrease in pump inflow in order to maintain a stable pulmonary artery pressure. After this modulation, ILP using GEM was not associated with any systemic leak, systemic damage, and acute or delayed histological pulmonary toxicity. Pharmacokinetics studies revealed dose-dependant uptake associated with heterogenous distribution of the molecule into the lung parenchyma, and persistent cytotoxicity of venous effluent.ConclusionsGEM is effective against CRC cells even after a short exposure. ILP with GEM is a safe and reproducible technique.

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“…It might be of relevant clinical interest if chronic pulmonary conditions require imaging during the pulmonary perfusion cycle to successfully detect changes in lung perfusion patterns not seen on pulmonary CT imaging. In chronic, nonembolic pulmonary diseases of neoplastic origin, information on parenchymal perfusion might help to develop and understand new techniques for application of chemotherapeutic drugs [15][16][17]. Congenital pulmonary diseases, on the other hand, possess a high propensity to cardiac decompensation due to associated cardiac anomalies [18].…”

Section: Discussionmentioning

confidence: 99%

Perfusion abnormalities in congenital and neoplastic pulmonary disease: comparison of MR perfusion and multislice CT imaging

et al. 2005

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The aim of this work was to assess magnetic resonance (MR) perfusion patterns of chronic, non-embolic pulmonary diseases of congenital and neoplastic origin and to compare the findings with results obtained with pulmonary, contrast-enhanced multislice computed tomography (CT) imaging to prove that congenital and neoplastic pulmonary conditions require MR imaging over the pulmonary perfusion cycle to successfully and directly detect changes in lung perfusion patterns. Twenty-five patients underwent concurrent CT and MR evaluation of chronic pulmonary diseases of congenital (n=15) or neoplastic (n=10) origin. Analysis of MR perfusion and contrast-enhanced CT datasets was realized by defining pulmonary and vascular regions of interest in corresponding positions. MR perfusion calculated time-to-peak enhancement, maximal enhancement and the area under the perfusion curve. CT datasets provided pulmonary signal-to-noise ratio measurements. Vessel center-lines of bronchial arteries were determined. Underlying perfusion type, such as pulmonary arterial or systemic arterial supply, as well as regions with significant variations in perfusion were determined statistically. Analysis of the pulmonary perfusion pattern detected pulmonary arterial supply in 19 patients; six patients showed systemic arterial supply. In pulmonary arterial perfusion, MR and multislice CT imaging consistently detected the perfusion type and regions with altered perfusion patterns. In bronchial arterial supply, MR perfusion and CT imaging showed significant perfusion differences. Patients with bronchial arterial supply had bronchial arteries ranging from 2.0 to 3.6 mm compared with submillimeter diameters in pulmonary arterial perfusion. Dynamic MR imaging of congenital and neoplastic pulmonary conditions allowed characterization of the pulmonary perfusion type. CT imaging suggested the presence of systemic arterial perfusion by visualizing hypertrophied bronchial arteries.

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Evaluation of isolated lung perfusion as neoadjuvant therapy of lung metastases using a novel in vivo pig model: II. High-dose cisplatin is well tolerated by the native lung tissue*1

Cited by 12 publications

References 23 publications

Modified in vivo lung perfusion allows for prolonged perfusion without acute lung injury

Modified in vivo lung perfusion allows for prolonged perfusion without acute lung injury

Isolated Lung Perfusion as an Adjuvant Treatment of Colorectal Cancer Lung Metastases: A Preclinical Study in a Pig Model

Perfusion abnormalities in congenital and neoplastic pulmonary disease: comparison of MR perfusion and multislice CT imaging

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