Purpose: to study the changes in the temperature outside and inside the long tubular bones of animals under the influence of different temperature regimes for a given time.Material and Methods. The experiments were conducted using fresh frozen pig long bones. The heating was carried out using surface heaters, the temperature of which was determined by the selected mode for 1 hour; fixation of temperature values was carried out every minute. Four heating modes were used: 3 modes of constant heating (60, 70, 80 °C) and the maximum heating mode, in which no special temperature limit was set, so heating was carried out up to 120 °C.Results. During the first 10 min of heating, a rapid rise in temperature occurred. The temperature increase rate on the outer surface outstripped the temperature increase rate on the inner surface of the bone, thus leading to a significant temperature difference. Further, there was a slowdown in the rate of temperature increase, which led to a gradual convergence of the temperature values inside and outside the bone, followed by temperature stabilization at a stable level (plateau), which was different for the studied areas. During this period, the temperature difference was 3.5–6 °C and it remained at this level until the end of the study. At a constant heating mode (60/70/80 °C), temperature stabilization occurred at the level of 55/61/70 °C in the center of the medullary canal and at the level of 58/67/75 °C under the heater, respectively. The period before reaching the stabilization temperature was 30–40 min. The stable temperature levels both inside and outside the bone were below the temperature stabilization level of the heater. Therefore, to achieve the planned temperature in the center of the bone to its outer surface, it is necessary to apply a high temperature, i.e., a downward temperature gradient is formed: the heater stabilization temperature – the temperature on the outer surface – the temperature inside the medullary canal. Increasing the exposure temperature can shorten the heating period, but increase the temperature difference during the heating period (up to 25 °C in the fifth minute of heating when using the maximum heating mode).Conclusion. To ensure reaching the required temperature (60°C) within a short time (15–20 min) while maintaining optimal temperature parameters, it was proposed to develop variable temperature modes that would combine the initial use of the maximum heating mode until reaching the desired temperature in medullary cavity, followed by switching to a constant temperature mode, which allowed maintaining the achieved temperature level during therapeutic exposure.
15 September 2023 in Bone and soft tissue sarcomas, tumors of the skin
Introduction. Difficult diagnosis, aggressive progression, and absence of an increase in treatment effectiveness (especially in patients with osteosarcoma and Ewing sarcoma) make malignant tumors of the bones a significant medical problem. Use of traditional therapy methods is often associated with development of drug resistance and frequent recurrences. Therefore, there is a need for new treatment strategies and overcoming of the limitations of traditional methods through their improvement, combination or substitution to achieve higher survival, lower recurrence rate, and wider availability for patients with bone tumors.Aim. To present a clinical observation of the use of a new method of radical intraoperative thermal ablation for bone tumors, assess exposure tolerance, long-term oncological and functional results.Clinical observation. This article presents a clinical case of the use of a new radical treatment method for a patient with tibial osteosarcoma who underwent intraoperative thermal ablation using a new domestic complex of local hyperthermia “Phoenix-2”.Results. A session of intraoperative thermal ablation was performed in the operating room under anesthesia directly in the wound for 48 minutes. Access to the tumor-affected bone was performed with the standard oncological approach (en-block), the bone was not transected or removed. A constant heating mode of 90 °С was used, assuming a gradual increase in temperature. Thus, 60 °С reached 20 minutes, and the temperature at the end of high-temperature exposure was 78 °С (inside the medullary canal). The operation time was 2 hours 30 minutes. The postoperative period proceeded without complications. After 38 months of follow-up, examinations did not reveal any recurrence or progression in the patient.Conclusion. The technique of radical intraoperative thermal ablation using a local hyperthermia complex Phoenix-2 is effective and allows to widen the toolkit of treatment methods for patients with bone tumors. It can serve as an alternative or addition to organ-preserving surgical treatment without costly reconstruction stages.
BACKGROUND: Thermal ablation is a promising method for the treatment of bone tumors. However, to maximize the potential of this method, it is important to select the optimal dose/time ratio of high temperature exposure. AIM: The aim of the study was to evaluate in vivo the response of rabbit bone tissue during early recovery (days 3 and 7) after local intraoperative hyperthermic ablation at 55–60°C in the medullary canal. MATERIALS AND METHODS: The study used 6 outbred rabbits aged 15 weeks and weighing 3–4 kg. Animals were removed from the experiment on days 3 and 7 after local thermal ablation of the femoral diaphysis. Microscopic visual examination of bone tissue sections was performed after standard hematoxylin and eosin staining. In addition, the morphometric measurements were performed to determine area of non-mineralized bone matrix (Mallory staining); absorbance and area of osteoblast cytoplasm; absorbance and area of osteocyte nuclei (Einarson staining for nucleic acid detection). The results obtained were compared with those of the femur of the contralateral limb, which was not subjected to direct hyperthermia and served as a control. R-Studio, a free development environment for R programming language, was used to statistically process the data. RESULTS: After high temperature exposure, histological sections of bone tissue stained with hematoxylin and eosin showed evidence of cellular abnormalities such as denucleated osteocytes and empty bone lacunae. Mallory staining showed no evidence of a negative effect of local thermal ablation on the intercellular bone matrix. Morphometry of Einarson stained sections showed an increase in osteoblast area on day 7 after exposure, with a decrease in their synthetic activity, signs of which were observed as early as day 3 of the experiment. There was also a decrease in the area and absorbance of osteocyte nuclei in the diaphysis of thermally ablated bones by day 3 after exposure. However, on day 7 after exposure, the area of nuclei in mature bone cells did not differ from the corresponding value in the contralateral limb. Considering the decrease in nuclei absorbance, the described changes may indicate colliquative necrosis of osteocytes. CONCLUSIONS: Local intraoperative thermal ablation of the femoral diaphysis in rabbits at a marrow canal temperature of 55–60℃ reduces the absorbance of osteoblast cytoplasm and osteocyte nuclei in the early recovery period, reflecting damage to the organelles of bone cells and disruption of metabolic processes in these cells. However, there was evidence of remodeling of the damaged area, presumably caused by migration of endosteal and periosteal cells from the metaphysis, which had not been exposed to direct hyperthermia. The results obtained may be useful for choosing the optimal regime (dose and duration) of high temperature exposure to bone tissue tumors, given the higher sensitivity of malignant cells to heating.
7 July 2022 in Bone and soft tissue sarcomas, tumors of the skin
Introduction. An additional or the only way to treat tumors of the chest wall is often a surgical method, which inevitably results in a post-resection defect. Reconstruction of extensive chest wall defects remains an unsolved problem for surgeons around the world.The study objective – to present the long-term oncological and functional results of treatment of a patient with multiple locally recurrent leiomyosarcoma after reconstruction of an extensive post-resection chest wall defect using superelastic 3D frame modules made of titanium nickelide. Reconstruction of the chest wall with 3D modules after extensive block resection showed the possibility of not only restoring the anatomy in the area of the post-resection defect, but also maintaining the biomechanics of breathing in the postoperative period.Clinical observation. This study presents a clinical case of extensive resection and successful one-stage reconstruction of the chest wall skeleton with 3D superelastic titanium nickelide modules in a patient with recurrent leiomyoma with locally recurrent leiomyosarcoma.Results. The superelastic modules did not limit the width of the resection during the operation and ensured long-term stability of the position of the reinforcing elements of the artificial framework. Control examinations showed no tumor recurrence after 12 months and maintaining patient performance.Conclusion. The effectiveness of the proposed reconstruction expands the possibilities of treating patients with tumors of the chest wall.
Introduction. Bone tumors are heterogeneous group of skeletal neoplasms characterized by frequent recurrences, aggressive clinical course and low survival rates. The development of new treatment methods continues to pose pressing challenges. Radical intraoperative thermal ablation (RIT) using high-temperature exposure is emerging as a new and promising strategy for organ-preserving treatment. This study focuses on the effect of thermal ablation (TA) on tumors.Objective of the Study to assess the impact of TA (using the RIT method) on the viability of tumor cells.Material and Methods. The study included 8 patients with bone tumors. Tumors underwent TA at a temperature of 60 °C for 30 minutes ex vivo. Apoptosis was studied in tumor tissue samples before and after TA. Apoptosis was assessed using two methods: flow cytometry and the TUNEL assay.Results. The TA procedure developed by our scientific group represents a promising organ-preserving approach for treating malignant bone tumors. A temperature regime of 60 °C for 30 minutes was effective in initiating tumor cells death. This was confirmed by two independent methods – flow cytometry and TUNEL assay – which demonstrated a significant increase in the number of apoptotic cells immediately following the procedure and a notable rise in the number of cells exhibiting signs of late apoptosis one hour post thermal ablation. Therefore, the collected data confirm a pronounced antitumor effect immediately after implementing RIT.Conclusion. The findings confirm that RIT is a viable organ-preserving method for treating bone tumors, meriting further investigation to expand its application in clinical practice.
Aim. To evaluate the response of mesenchymal stromal/stem cells (MSCs) in vitro and the status of bone cells (osteoblasts, osteocytes) during regeneration of the femoral bone after local thermoablation at 55–60 °C. Materials and methods. Morphology and viability (MTT assay) of human adipose tissue-derived MSCs were analyzed after incubation at 37 °C or 56 °C for 0–60 minutes. In vivo , a heating cuff was applied to the femur of anesthetized rabbits, and intraoperative thermoablation was performed for 30 minutes (bone marrow canal temperature: 55–60 °C). Bone tissue was histologically examined (hematoxylin – eosin and Einarson staining) immediately and 14 days post-treatment. Quantitative morphometry was implemented in ImageJ, with subsequent statistical analysis performed in R. Results.In vitro , signs of massive MSC death were observed after 15 minutes of heating; at 30 minutes, viable fibroblast-like cells were nearly absent. In vivo , local thermoablation caused direct death of osteoblasts and osteocytes, evidenced by morphological signs of apoptosis and necrosis, as well as impaired DNA/RNA synthesis. Morphological and molecular markers of cellular damage significantly increased by day 14 post-treatment. Conclusion. Moderate thermoablation (55–60 °C) exerts significant direct and delayed damaging effects on osteogenic cells, from stem to mature forms. These findings are relevant for combined treatment of tumor and metastatic bone lesions.