The diagnostic value of modified systemic ınflammation score in predicting post-operative outcomes of cutaneous melanoma patients who underwent ısolated limb perfusion

Background In-transit metastasis is considered a locoregional disease in cutaneous melanoma (CM) patients. Isolated limb perfusion (ILP) is among the treatment options in selected cases. The aim of this study was to determine the success of pre- and post-perfusion mSIS values in predicting the potential complications and the prognosis of the disease by investigating the early and long-term results of mSIS values calculated before and after ILP in CM cases with in-transit metastases. Materials and methods Patients who underwent ILP within the period from 2014 to 2020 in our department were retrospectively scanned. A total of 20 patients were found to undergo ILP. The scores obtained from modified inflammation score (mSIS) were formulated according to albumin (Alb) and lymphocyte to monocyte ratio (LMR) scores. Results The mean follow-up time was 20.47 months. Complications requiring surgical intervention developed in three patients. According to the Wieberdink local toxicity classification, the majority (70%) of the patients were found to be grade II. Based on pre-perfusion mSIS values, 8 patients were classified as mSIS 0 while six patients were classified as mSIS 1 and 2. Based on post-perfusion mSIS values, 14 patients and one patient were classified as mSIS 2 (70%) and mSIS 0, respectively. Accordingly, univariate analysis showed that mSIS 1 and mSIS 2 were negative prognostic factors for mean survival in the pre-perfusion period (HR 0.162, 95% CI 0.036–0.729; p = 0.018 and HR: 0.223, 95% CI 0.049–1.019; p = 0.053) whereas albumin (Alb) and lymphocyte to monocyte ratio (LMR) were not independent prognostic factors for mean survival. Conclusion The mSIS values calculated in the pre-perfusion period can give an opinion about the OS of the patients whereas post-perfusion mSIS values may predict potential surgical complications and local toxicities.

Indocyanine Green for Leakage Control in Isolated Limb Perfusion

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.

Role of Isolated Limb Perfusion in the Era of Targeted Therapies and Immunotherapy in Melanoma. A Systematic Review of The Literature

Background. Isolated limb perfusion (ILP) is a locoregional procedure indicated by the unresectable melanoma of the limbs. Its complexity and highly demanding multidisciplinary approach means that it is a technique only implemented in a few referral centers around the globe. This report aims to examine its potential role in the era of targeted therapies and immunotherapy by conducting a systematic review of the literature on ILP. Methods. PubMed, Embase and Cochrane Library were searched. The eligibility criteria included publications from 2000–2020 providing valid data o effectiveness, survival or toxicity. Studies in which the perfusion methodology was not clearly described, letters to the editor, non-systematic reviews and studies that applied outdated clinical guidelines were excluded. To rule out studies of a low methodological quality and assess the risk of bias, the following aspects were also required: a detailed description of the applied ILP regimen, the clinical context, follow-up periods, analyzed clinical endpoints, and the number of analyzed ILPs. The disagreements were resolved by consensus. The results are presented in tables and figures. Results. Twenty-seven studies including 2637 ILPs were selected. The median overall response rate was 85%, with a median complete response rate of 58.5%. The median overall survival was 38 months, with a 5-year overall survival of 35%. The toxicity was generally mild according to Wieberdink toxicity criteria. Discussion. ILP still offer a high efficacy in selected patients. The main limitation of our review is the heterogeneity and age of most of the articles, as well as the absence of clinical trials comparing ILP with other procedures, making it difficult to transfer its results to the current era. Conclusions. ILP is still an effective and safe procedure for selected patients with unresectable melanoma of the limbs. In the era of targeted therapies and immunotherapy, ILP remains an acceptable and reasonable palliative treatment alternative, especially to avoid limb amputations. The ongoing clinical trials combining systemic therapies and ILP will provide more valuable information in the future to clarify the potential synergism of both strategies.

Isolated Limb Perfusion for the Treatment of Unresectable In- Transit Metastases of Cutaneous Squamous Cell Carcinoma

Squamous cell carcinoma (SCC) is the second most common non-melanoma skin cancer and its incidence has been increasing over the past decades. SCC in-transit metastases are rare and predict a poor prognosis. We present the case of a 69-year-old patient with a right lower leg SCC, surgically excised with free margins. One month later, erythematous to violaceous, firm papules begin to erupt on the right lower leg, evolving to ulcerated nodules over a period of weeks. Homolateral inguinal and iliac nodal metastases were documented by percutaneous biopsy of an inguinal palpable lymph node and later documented by positron emission tomography – computed tomography (PET-CT). Given the unresectability of the disease, regional chemotherapy involving isolated limb perfusion (ILP) with melphalan and tumor necrosis factor-alpha (TNFα) was performed in order to avoid amputation. Macroscopic regression ensued, with complete resolution of all visible in-transit metastases 12 weeks after perfusion. However, a fatal outcome was observed 4 months later, due to systemic metastases. ILP is an effective and well-established technique in the treatment of advanced tumors of the extremities. Its main indications are in-transit metastases of malignant melanoma and advanced soft tissue sarcomas. However, studies have shown its effectiveness in other tumors such as locally advanced SCC. Despite the unfortunate outcome, it was possible to avoid amputation of the limb, with complete local disease remission.

Effectiveness criteria for application of the isolated limb perfusion in soft tissue sarcoma

It perdormed the literature data analysis on the criteria and methods for assessing the clinical efficacy of the isolated limb perfusion method in the treatment of soft tissue sarcoma. It is noted that the use of isolated limb perfusion is a rather effective method providing local control of the tumor process in locally advanced forms of soft tissue sarcoma. It has been demonstrated that the use of such a neoadjuvant treatment regimen allows administration of the drug with the achievement of high local concentrations of chemotherapeutic drugs with a relatively low incidence of systemic side effects. Criteria for tumor response to therapy, in particular RECIST (Response Evaluation Criteria In Solid Tumors), Choi criteria, adapted for magnetic resonance imaging, are presented. It is noted that a number of studies have studied the possibility of using positron emission tomography with fluorodeoxyglucose labeled with 18F (18F-FDG) to assess the response to treatment in sarcomas. At the same time, it was shown that the results of studying the metabolic response are superior in accuracy to the method of assessment using the RECIST criteria and the assessment performed by the dynamics of the tumor tissue volume has significant potential in assessing the response to isolated limb perfusion in patients with soft tissue sarcoma. The importance of a one-time assessment of positron emission tomography with 18F-FDG parameters and Magnetic Resonance Imaging for soft tissue sarcoma is confirmed by the results of a combined analysis that takes into account both morphological characteristics and quantitative metabolic parameters of the tumor. The high potential of the combined assessment of metabolic and volume-morphological parameters obtained using these methods was demonstrated; it was noted that the combination of positron emission tomography data with 18F-FDG and Magnetic Resonance Imaging enhances the reliability and efficiency of planning and monitoring of soft tissue sarcoma treatment using the isolated limb perfusion method.