Cryoimmunology for malignant bone and soft-tissue tumors

Several new methods have recently been developed for the treatment of malignant bone and soft-tissue tumors, and many of these targeted therapies have yielded promising initial results in clinical settings. As more sarcomas become amenable to effective molecular-targeting therapy, the need to evaluate the synergistic effects of combination therapies with anticancer drugs will grow. Other immunologic therapies have also been reported, such as exogenous cytokines, dendritic cell (DC) therapy and peptide vaccines. Cryoimmunology has shown promising results in some malignant tumors after cryosurgery and is expected to influence the next generation of tumor immunotherapy. In this report, we describe the induction of a systemic antitumor immune response following liquid nitrogen cryotreatment of a destructive murine osteosarcoma. Combining tumor cryotreatment with DCs to promote tumor-specific immune responses enhanced systemic immune responses and inhibited metastatic tumor growth. We also describe the induction of a systemic antitumor immune response following reconstruction for malignant bone tumors using frozen autografts treated with liquid nitrogen. © Japan Society of Clinical Oncology 2011

Histological examination of frozen autograft treated by liquid nitrogen removed after implantation

金沢大学医薬保健研究域医学系Background: Several oncological sterilization methods involving autoclaving, irradiation, or pasteurization have been developed for limb reconstruction of large bone defects following tumor excision. Studies involving histological examinations of these autografts have all found that osteogenesis occurs slowly. We have used frozen autografts treated by liquid nitrogen for limb reconstruction and have achieved excellent results for bone union. To determine if frozen autografts exhibit early bone remodeling, we investigated the repair processes of the frozen bones. Methods: We analyzed frozen autografts treated by liquid nitrogen, retrieved at a mean of 19.1 months (2-75 months) after implantation because of complications or local tumor recurrence. The specimens were obtained from six patients with a mean age of 36.2 years (8-68 years). The six grafts comprised three osteoarticular grafts, two intercalary grafts, and one joint graft. We histologically reviewed the autograft-containing sections for tumor cell necrosis, evidence of cortical repair, the cortical junction, and joint cartilage. Results: Tumor cells were completely eradicated from the frozen bone in all cases. In a specimen retrieved 5 months after implantation, a small area of the bone showed active osteocytes and osteoblasts. In three cases retrieved more than 1 year after implantation, osteocytes and osteoblasts were observed in broad portions of the frozen bones, indicating the onset of osteogenesis in the frozen bone at an early stage. The cortical host-graft junction showed incorporation along with continuity of bone trabeculae. In addition, we were able to fi nd normal chondrocytes on the articular surface. Conclusions: The frozen bone specimens in this study thus showed evidence of newly formed bone and earlier osteogenesis than has been previously reported. Our results suggest that frozen autografts may be considered one of the most useful recycled materials for biological reconstruction. © 2009 The Japanese Orthopaedic Association

Histological examination of frozen autograft treated by liquid nitrogen removed 6 years after implantation

金沢大学附属病

Treatment strategies for well-differentiated liposarcomas and therapeutic outcomes

This study examined 45 patients with welldifferentiated liposarcoma who were surgically treated at our hospital (initial surgery in 41 patients and reoperation in 4). Only one patient had recurrence among patients who underwent initial surgery, and the recurrence was localised in the retroperitoneal space. For patients who underwent reoperation, the mean time between the initial surgery and the recurrence was 16.5 years. None of the 45 patients developed distant metastasis. It is important to preserve not only neurovascular bundles but also lower limb muscles in order to maintain ambulatory ability in the elderly patients. For well-differentiated liposarcomas of the limbs, it is important to establish a surgical margin beyond the marginal resection border and to perform muscle resection to the extent that would not greatly reduce the muscle strength

Инновационный потенциал и инновационная активность вузов УрФО

<p>Characteristics of the study patients.</p

Activity of bone morphogenetic protein-7 after treatment at various temperatures: Freezing vs. pasteurization vs. allograft

Insufficient bone union is the occasional complication of biomechanical reconstruction after malignant bone tumor resection using temperature treated tumor bearing bone; freezing, pasteurization, and autoclaving. Since bone morphogenetic protein (BMP) plays an important role in bone formation, we assessed the amount and activity of BMP preserved after several temperature treatments, including -196 and -73 °C for 20 min, 60 and 100 °C for 30 min, 60 °C for 10 h following -80 °C for 12 h as an allograft model, and 4 °C as the control. The material extracted from the human femoral bone was treated, and the amount of BMP-7 was analyzed using an enzyme-linked immunosorbent assay. Then, the activity of recombinant human BMP-7 after the treatment was assessed using a bioassay with NIH3T3 cells and immunoblotting analysis to measure the amount of phospho-Smad, one of the signaling substrates that reflect the intracellular reaction of BMPs. Both experiments revealed that BMP-7 was significantly better preserved in the hypothermia groups. The percentages of the amount of BMP-7 in which the control group was set at 100% were 114%, 108%, 70%, 49%, and 53% in the -196, -73, 60, 100 °C, and the allograft-model group, respectively. The percentages of the amount of phospho-Smad were 89%, 87%, 24%, 4.9%, and 14% in the -196, -73, 60, 100 °C, and the allograft-model group, respectively. These results suggested that freezing possibly preserves osteoinductive ability than hyperthermia treatment. © 2011 Elsevier Inc. All rights reserved

Pedicle versus free frozen autograft for reconstruction in malignant bone and soft tissue tumors of the lower extremities

Background: Of the biological reconstruction methods for malignant bone and soft tissue tumors, reconstruction with liquid nitrogen has the advantage of maintaining continuity on the distal side of the tumor bone site (pedicle freezing procedure; PFP). This method is expected to result in early blood flow recovery, with early union and low complication rate. The purpose of this study was to compare the outcomes of the PFP and free freezing procedure (FFP) in the lower extremities. Methods: The study included 20 patients (12 men and 8 women) with frozen autografts (FFP, 13 cases; PFP, 7 cases). The mean age of the subjects was 36.3 years (range 11-79 years), and the mean follow-up period was 56.4 months (range 12-142 months). Results: Final bone union occurred in 11 patients in the FFP group (84.6 %) and in 7 patients in the PFP group (100 %). The mean union period in patients who did not need additional surgery was 9.8 months (range 4-21 months) in the FFP group and 4.8 months (range 2-7 months) in the PFP group. Postoperative complications occurred in 8 cases: infection in 3 cases, fracture in 3 cases, and joint destruction in 2 cases. Six FFP patients, and 2 PFP patients (two cases of fracture), developed postoperative complications. Conclusions: The union period was shorter and the rate of postoperative complications was lower with the PFP than with the FFP. We considered that early blood flow recovery might have led to the above results in the PFP. © 2013 The Japanese Orthopaedic Association