Abstract
Sarcomas are characterized by a high metastatic potential and aggressive growth. Despite surgery, chemotherapy plays an important role in the treatment of these tumors. Optimal anti-cancer therapy with maximized local efficacy and minimized systemic side effects has been the object of many studies for a long time. To improve the local efficacy of anti-tumor therapy, isolated limb perfusion with high-dose cytostatic agents has been introduced in surgical oncology. In order to control the local distribution of substances, radiolabeled cytostatic drugs or perfusion solutions have been applied but often require the presence of specialized personnel and result in a certain exposure to radiation. In this study, we present a novel strategy using indocyanine green to track tumor perfusion with high-dose cytostatic therapy. In a rat cadaver model, the femoral vessels were cannulated and connected to a peristaltic pump to provide circulation within the selected limb. The perfusion solution contained indocyanine green and high-dose doxorubicin. An infrared camera enabled the visualization of indocyanine green during limb perfusion, and subsequent leakage control was successfully performed. Histologic analysis of sections derived proximally from the injection site excluded systemic drug dispersion. In this study, the application of indocyanine green was proven to be a safe and cost- and time-efficient method for precise leakage control in isolated limb perfusion with a high-dose cytostatic agent.
Highlights
Sarcomas are tumors that are characterized by an aggressive growth pattern, early metastasis, and poor prognosis [1,2,3]
indocyanine green (ICG)-fluorescence imaging showed locally restricted distribution of the perfusion fluid containing the cytostatic drug by causing the cannulated limb to emit a glowing signal (Figure 1A,B)
In contrast to isolated limb perfusion (ILP), ICG-fluorescence imaging of whole-body perfusion after inverting the cannulation direction of the femoral vessels showed a glowing signal over the entire body (Figure 1C,D)
Summary
Sarcomas are tumors that are characterized by an aggressive growth pattern, early metastasis, and poor prognosis [1,2,3]. Oncologic surgery comprises many medical disciplines and therapeutic approaches. Surgical resection is an important aspect in cancer treatment and often involves additional lymphadenectomy of sentinel lymph nodes and downstream lymph node stations [4]. Radiotherapy is performed for local disease control and to increase functional outcomes [5]. Despite lymph node resection, radiation increases the risk of lymphatic vessel damage and lymphatic complications [6,7]. An exclusively surgical approach often results in the loss of the entire limb. In the last few decades, neoadjuvant chemotherapy and adjuvant chemotherapy have been added to the treatment protocols of sarcomas. A combination of doxorubicin, cisplatin, and methotrexate with leucovorin and ifosfamide represents the most commonly used combination of chemotherapeutic agents for the treatment of sarcomas [8].
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