
Unquestionable indications are for Surgical Resection   For  non-resectable lung metastases other treatments must be explored [RFA,  conventional  chemotherapy, and so on.]. Where conventional systemic chemotherapy is chosen, but is ineffective, there are alternative methods of delivering the chemotherapy agent that maximizes tumor exposure. 

Chemoembolisation can provide the tumor with high drug concentrations without provoking systemic side effects. These procedures do not prevent the appearance of extra-regional recurrence or metastases. 

Isolated lung perfusion is a regional treatment technique that delivers high dose chemotherapy, biologic agents, and hyperthermia via a completely isolated vascular recirculating perfusion circuit as a means of regionally treating tumors. . The chemotherapy and other agent[s] are injected into the lung circulation, but do NOT get into the rest of the body's circulation. The lung's blood circulation is ISOLATED from the rest of the body. After perfusing the lung for an hour with the high concentration chemotherapy agent[s], the lung is given a 'washout' and then reconnected to the systemic circulation. This allows higher concentration of toxic chemicals to be given to the lung, and spares the rest of the body the side effects.
 
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<b>Pulmonary Metastases & Isolated Lung Perfusion
Selected Medical Journal Annotated References </b>


Anticancer Res 1998 Sep-Oct;18(5D):3899-905 
<b>TNF alpha in isolated perfusion systems: success in the limb, developments for the liver credits, debits and future perspectives. </b>
Eggermont AM. 
University Hospital Rotterdam, Daniel den Hoed Cancer Center, The Netherlands. eggermont@chih.azr.nl 

The clinical applicability of Tumor Necrosis Factor-a pi (TNF) is under renewed investigation because of its successful use in the isolated limb perfusion in patients with irresectable soft tissue extremity sarcomas. The high response rate of > 80% with a similarly successful limb salvage rate in this patient population has led to the submission of TNF for registration for this indication in Europe. Similarly, the agent has been shown to be successful in the isolated limb perfusion setting for tumors other than sarcomas, e.g. melanoma, carcinomas. This has caused renewed interest in TNF alpha and in its application in isolated organ perfusions, such as isolated hepatic perfusion. <b>At the Rotterdam Cancer Center a preclinical-clinical interactive development program has been established dedicated to isolated limb, kidney, liver and lung perfusions and the application of new drugs such as TNF and TNF-mutants in these systems. Moreover a program dedicated to reduce the magnitude of surgical procedures by using occlusion balloon catheters is investigating the techniques and pharmacokinetics of procedures such as balloon catheter mediated hypoxic pelvic perfusions (HPP) and isolated hypoxic hepatic perfusions (IHHP).</b> Here we present an overview of these developments. Publication Types: Review Review, tutorial 
&&url PMID: 9854502 


J Thorac Cardiovasc Surg 1995 Aug;110(2):368-73 
<b>Lung perfusion with chemotherapy in patients with unresectable metastatic sarcoma to the lung or diffuse bronchioloalveolar carcinoma. </b>
Johnston MR, Minchen RF, Dawson CA. 
Division of Thoracic Surgery, Mt. Sinai Hospital, Toronto, Canada. 

<b>Eight patients with metastatic sarcoma to the lung (n = 4) or diffuse bronchioloalveolar carcinoma of the lung (n = 4) underwent isolated lung perfusion with chemotherapy in a pilot study.</b> Ages ranged from 18 to 60 years and half were female. The left lung was perfused in three patients (single lung perfusion) and both lungs in five patients (total lung perfusion). Perfusions ranged from 45 to 60 minutes at ambient or normothermic temperatures. One patient received perfusion at moderate hyperthermia (40 degrees C). Escalating doses of doxorubicin (1 to 10 micrograms/ml perfusate) was used in six patients, whereas two received cisplatin (14 and 20 micrograms/ml perfusate). <b>There were two major complications and no objective responses. </b>The isolated perfusion systems gave excellent separation between systemic and pulmonary circulations with zero to 15% of the measured peak drug concentration of the pulmonary perfusate detected in the systemic circulation. `Drug concentrations in normal lung and tumor generally increased with higher drug dosages and drug was detectable in mediastinal lymph nodes of three out of four patients in whom sampling was done. Isolated lung perfusion with chemotherapy can be done safely in patients with lung malignancies and evidence suggests that higher drug dosages should be well tolerated. Publication Types: Clinical trial 
&&url PMID: 7637354 


Verh K Acad Geneeskd Belg 1999;61(4):517-50 
<b>Isolated lung perfusion for the treatment of pulmonary metastases an experimental study in the rat. </b>
Van Schil P, Hendriks J. Department of Surgery, University Hospital of Antwerp, Edegem. 

The lung is a common site of metastatic involvement and 5-year survival rates after complete surgical resection of lung metastases vary between 16 and 42%. As isolated limb or liver perfusion, isolated lung perfusion offers a new therapeutic option to deliver high-dose chemotherapy with minimal systemic side-effects ..... Clinical studies are necessary to determine its effect on pulmonary metastases in man, especially in case of unresectable disease or possibly as adjuvant therapy after surgical resection. 
&&url PMID: 10500475 


Cancer 1993 May 15;71(10):2962-70 
<b>In situ lung perfusion with cisplatin. An experimental study. [ed. in PIGS.] </b>
Ratto GB, Esposito M, Leprini A, Civalleri D, De Cian F, Vannozzi MO, Romano P, Canepa M, Zaccheo D. Department of Patologia Chirurgica, University of Genoa, Italy. 

....This study provides the pharmacokinetic rationale for the application of lung perfusion to patients with pulmonary metastases. 
&&url PMID: 8490824 


J Surg Res 1991 Feb;50(2):124-8 
<b>Pharmacokinetics and toxicity of isolated perfusion of lung with doxorubicin. </b>
Baciewicz FA Jr, Arredondo M, Chaudhuri B, Crist KA, Basilius D, Bandyopadhyah S, Thomford NR, Chaudhuri PK. 
Department of Surgery, Medical College of Ohio, Toledo 43699-0008. 

The treatment of pulmonary metastases from soft tissue sarcomas with chemotherapy has an overall response rate of less than 30%, and the majority of these responses are short lived. It is postulated that increased drug delivery to the pulmonary metastases may improve the outcome of these patients. An isolated perfusion system would have the ability of delivering increased levels of drug to target tissue without the systemic toxic effect of the drug. The purpose of this study was to establish the pharmacokinetics of doxorubicin delivery, lung toxicity, and the ideal dose for clinical application in an in vivo isolated perfusion model. Our results suggest that normothermic isolated perfusion of the lung with doxorubicin using a dose level up to 6 micrograms/ml in the perfusate can be accomplished without histologic lung injury, systemic toxicity, or adverse clinical outcome. Perfusate concentration of greater than 7 micrograms/ml caused significant histologic injury and adverse clinical outcome without systemic toxicity. The technique may be utilized in selective settings to improve treatment in mesenchymal tumors metastatic to the lung. 
&&url PMID: 1990216 

