Isolated lung perfusion and related techniques for the treatment of pulmonary metastases☆

Schil, Paul E. Van; Hendriks, Jeroen; Putte, Bart P. van; Stockman, Bernard; Lauwers, Patrick; Broecke, Pieter W. ten; Grootenboers, Marco J.J.H.; Schramel, Franz M.N.H.

doi:10.1016/j.ejcts.2007.12.009

Cited by 37 publications

(20 citation statements)

References 58 publications

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“…This concept was further exploited by the idea of isolated lung perfusion with cytostatic drugs. During pulmonary metastasectomy the pulmonary artery and both pulmonary veins are cannulated, connected to an extracorporeal circuit and high doses of chemotherapy agents are administered [42]. This strategy resulted in higher levels of chemotherapeutic drugs in the lung and the tumor while minimizing systemic responses in phase I trials.…”

Section: Interdisciplinaritymentioning

confidence: 99%

Pulmonary metastasectomy

et al. 2011

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Background: The major obstacle in curing cancer is the limited ability to prevent and treat metastatic disease. Pulmonary metastasectomy is now a standard treatment option in carefully selected cases. With the lung being frequently the only site of metastasis, a complete resection of all tumor masses poses a potentially curative treatment option.Methods: This review article gives an outline of the basics of pulmonary metastasectomy and reviews the latest research in this field.Results and conclusions: Technical advances in thoracic surgery during the past decades made pulmonary metastasectomy a safe procedure with a low morbidity. However, surgical resection must be embedded in an individualized oncological concept.The beginnings of pulmonary metastasectomy can be traced back to the 19th century. The first case of a resection of pulmonary metastases was reported in 1882. Josef Weinlechner, a Viennese pediatric surgeon, accidentally discovered and resected two metastatic nodules in the lung when removing a large sarcoma of the thoracic wall [1]. Unfortunately, this first patient died the day after surgery from shock. Throughout the following decades, single case reports of pulmonary metastasectomy have been described in the literature. In most cases, the resection of pulmonary nodules led to long-term survival. As open chest surgery in those times was itself a life-threatening intervention, beneficial effects of metastasectomy were often restrained by the high mortality and morbidity of the surgical procedure. Since these early days of pulmonary metastasectomy, many advances have been made in surgical techniques and perioperative patient care. Consequently, pulmonary metastasectomy has developed into one of the major surgical procedures in thoracic surgery [2].

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Section: Interdisciplinaritymentioning

confidence: 99%

Pulmonary metastasectomy

et al. 2011

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“…In order to decrease the recurrence of CRC lung metastases, some authors have developed the technique of isolated lung perfusion (ILP) [12], which permits to increase the dose of cytotoxic agent delivered to the lung tissue without systemic exposure. This technique has been proven to be safe and effective against CRC lung metastases in rodent model [13]–[17].…”

Section: Introductionmentioning

confidence: 99%

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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“…In different clinical studies, isolated organ perfusion procedures are generally well tolerated and reproducible offering a valid clinical model for further investigation of combined chemotherapy and surgery in patients with pulmonary metastases [51,52]. …”

Section: Ex Vivo Medical Treatmentmentioning

confidence: 99%

Ex vivo Approach to Treat Failing Organs: Expanding the Limits

Ciubotaru

Haverich

2014

Eur Surg Res

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Background: Advanced organ failure is often classified as an end-stage disease where the treatment options are limited only to transplantation. As an alternative, different attempts have been undertaken to improve the outcome of the treatment of failing organs by using targeted ex vivo approaches. This may solve the issue of organ shortage by treating the donor organs before transplantation and the number of patients requiring transplantation may also be reduced by applying extensive ex vivo treatment followed by autotransplantation. Methods: We performed a literature review of PubMed and included articles published between 1962 and 2013. The following keywords were used (and; or): ex vivo, therapy, surgery, organ perfusion and autotransplantation. This review includes specific methods and attempts related to ex vivo organ perfusion and preservation, temporary life support systems, surgical and other therapeutic approaches, and diagnostic methods applied ex vivo to an isolated organ. Results: For the practical clinical use of ex vivo therapies, we could identify three major directions: (1) ex vivo pretransplant organ reconditioning, (2) ex vivo surgery and (3) ex vivo medical treatment. Different attempts have been made worldwide in the above-mentioned areas focusing on ex vivo organ preservation and treatment. We summarize in the present review the developments in the field of ex vivo organ recovery and evaluate the possibilities of combining and applying different technologies such as organ perfusion and storage, ex vivo exact topographical diagnosis, ex vivo locoregional medical treatment and ex vivo surgical correction. Conclusion: Ex vivo therapies open new horizons in the treatment of end-stage organ pathologies.

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Isolated lung perfusion and related techniques for the treatment of pulmonary metastases☆

Cited by 37 publications

References 58 publications

Pulmonary metastasectomy

Pulmonary metastasectomy

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

Ex vivo Approach to Treat Failing Organs: Expanding the Limits

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