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Isolated lung perfusion is an innovative medical technique primarily utilized for the treatment of lung cancer and other thoracic diseases by delivering high doses of chemotherapeutic agents directly into the pulmonary circulation while minimizing systemic exposure. This method, often performed as part of a surgical procedure, involves the temporary isolation of the lung or portion of the lung from the rest of the circulatory system. The isolation is achieved by clamping the pulmonary arteries and veins, allowing for the perfusion of selected drugs directly into the lung tissue. Following isolation, a selected chemotherapeutic agent is infused through the pulmonary artery, ensuring a high local concentration of the drug in the targeted area while significantly reducing the impact on other organs and overcoming common issues associated with systemic chemotherapy, such as toxicity and resistance. This localized delivery system also capitalizes on the unique anatomy of the pulmonary circulation, where the blood flow is predominantly low-pressure, enabling a controlled infusion of therapeutic agents that can be tailored based on the specific pathology of the lung. The lung is subsequently perfused for a predetermined period, usually ranging from 30 minutes to 2 hours, depending on the agent used and the clinical protocol, after which the perfusate is drained and systemic circulation is restored. Importantly, because the technique allows for the use of higher doses of chemotherapy, it can effectively target tumors that are otherwise difficult to treat with traditional systemic methods due to dose-limiting toxicities. Isolated lung perfusion is particularly beneficial for cases of unilateral lung cancer, where there is a need to avoid systemic exposure due to various potential side effects, such as nausea, fatigue, and immunosuppression. Additionally, this modality offers an avenue for exploring novel therapeutic agents and combinations that could lead to improved responses in resistant lung cancers. The procedure requires a multidisciplinary approach involving surgical oncologists, thoracic surgeons, and perfusionists to ensure optimal outcomes. Nevertheless, the use of isolated lung perfusion is not without challenges; it necessitates careful patient selection, thorough understanding of pulmonary vascular anatomy, and comprehensive monitoring during the procedure to manage potential complications such as pulmonary embolism or respiratory distress. Despite these hurdles, isolated lung perfusion stands as a promising option for localized cancer treatment, allowing for innovative therapeutic strategies that enhance the efficacy of cancer therapy while preserving the patient's quality of life. Ongoing research and clinical trials continue to evaluate the safety and effectiveness of this technique, aiming to standardize protocols and expand its applicability in clinical settings. This approach exemplifies a significant advancement in the field of oncology, merging surgical and interventional techniques to provide targeted therapy with potentially improved outcomes for patients facing challenging diagnoses within the pulmonary system.