Cryoimmunology for malignant bone and soft-tissue tumors

Nishida, Hiroyuki; Yamamoto, Norio; Tanzawa, Yoshikazu; Tsuchiya, Hiroyuki

doi:10.1007/s10147-011-0218-2

Cited by 44 publications

(23 citation statements)

References 52 publications

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“…In particular, a novel method of reconstruction with liquid nitrogen (frozen autograft) was developed and has been implemented in patients since 1999 [7]. The advantages of using frozen autografts are as follows: simplicity, osteoinduction, osteoconduction, short treatment time, preservation of the cartilage matrix, perfect fit, sufficient biochemical strength, no contagion, no need for bone banking, easy attachment of tendons and ligaments, desirable bone stock, and cryo immunological activity [7][8][9][10]. The developers also modified this technique to produce a pedicle frozen autograft to maintain anatomical continuity on one side (Fig.…”

Section: Introductionmentioning

confidence: 99%

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

Shimozaki¹,

Yamamoto²,

Shirai³

et al. 2014

Journal of Orthopaedic Science

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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.

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Section: Introductionmentioning

confidence: 99%

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

Shimozaki¹,

Yamamoto²,

Shirai³

et al. 2014

Journal of Orthopaedic Science

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“…Previous reports have suggested immune system activation brought about by cryosurgery [4], [5], [8], [9]. Nishida et al reported that re-implantation of tumor tissue frozen using liquid nitrogen induces antitumor activity against murine osteosarcoma [10] and the serum levels of INF-γ and IL-12 increased after treatment [11]. Moreover, they reported on a patient with metastases from renal cell carcinoma involving the lungs and bone (femur).…”

Section: Discussionmentioning

confidence: 98%

Increase of IL-12 following Reconstruction for Total En Bloc Spondylectomy Using Frozen Autografts Treated with Liquid Nitrogen

et al. 2013

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BackgroundTotal en bloc spondylectomy (TES) is a surgery designed to achieve complete resection of a malignant spinal tumor such as spinal metastasis. Although this procedure decreases the rate of local recurrence, it is questionable whether local control prolongs patient’s survival. We developed a “second-generation TES” that brings about TES enhancing antitumor immunity to prolong patient’s survival. Our purpose is to present a second-generation TES applied tumor-induced cryoimmunology and assess the immunity-enhancing effect after implementing this surgery.MethodsWe performed a retrospective review of prospectively collected data in second-generation TES as carried out in 56 cases. In second-generation TES, instead of harvesting autograft from the ilium or fibula, the resected lamina and vertebral body from TES are frozen using liquid nitrogen and used as grafted bone for spinal reconstruction. In recent 26 of the 56 cases, in addition to the TES procedure, a small amount of the tumor tissue from the resected tumor-bearing vertebra was also placed into liquid nitrogen. This small amount of tumor tissue was then implanted subcutaneously on one side of the axilla. In 52 of 56 cases, measurement of interleukin 12 (IL-12) was performed before surgery and at both 1 and 3 months after surgery.ResultsIL-12 increased after TES surgery in 38 of 52 cases (73.1%). The mean IL-12 relative concentrations at both 1 and 3 months after surgery, as compared to before surgery, were significantly higher (121±89 and 149±111%: P<0.05 and P<0.01).ConclusionsOur results show that second-generation TES may provide not only a local radical cure but also a systemic immunological enhancement. Further prolonged survival in patients with a malignant spinal tumor is promising by second-generation TES.

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“…e potential advantage of tumor immunogenicity to help improve survival has not been tested as a hypothesis in human study cohorts. Nishida et al demonstrated the induction of systemic antitumor response in malignant bone 2 Sarcoma tumors following reconstruction with frozen autografts using liquid nitrogen in a murine osteosarcoma model and in a few select human cohorts with unresectable metastatic osteosarcoma combined with dendritic cell therapy [4,5]. Various other studies have also shown immunological effects of cryosurgery [6,8].…”

Section: Discussionmentioning

confidence: 99%

“…It is widely used in diaphyseal sarcomas where saving the adjacent joints is oncologically safe. Reconstruction is usually performed using allografts with or without a live vascularised fibula, diaphyseal endoprosthesis, or reimplantation of the excised bone after sterilizing it using either external radiation [1,2], pasteurization [3], autoclaving, or liquid nitrogen [4]. Reimplantation offers the advantage of an easier fit to the host bone compared to allografts and obviates the need of a tissue bank.…”

Section: Introductionmentioning

confidence: 99%

Does Reconstruction with Reimplantation of Sterilized Tumor Bone Provide Survival Benefit in Diaphyseal Osteosarcoma?

Nayak

Gulia

Puri

2020

Sarcoma

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Does reimplantation of sterilized tumor bone for reconstruction provide outcome benefits in intercalary osteosarcoma based on the potential immunogenic effect of reimplanted sterilized tumor tissue? Of 720 cases of surgically treated high-grade osteosarcoma patients treated at our institute from 2006 to 2013, 61 had predominantly diaphyseal disease. All patients were nonmetastatic at presentation. Patient and tumor characteristics, treatment details, and local recurrence-free, metastasis-free, and overall survival were compared for 24 patients who had reconstruction with sterilized tumor bone reimplantation vs 37 who did not. Both the groups were well matched in terms of baseline characteristics. Means were compared with the t-test, proportions with the chi-square test, and survival with the log-rank test. The Kaplan‐Meier method was used to construct time to event curves. Cox proportional hazard regression modeling was employed for multivariate time to event analysis. Twenty-two had extracorporeal radiation and reimplantation (ECRT) with or without the vascularised fibula. Fifty-gray single dose was used in all cases. Two had pasteurization and reimplantation. Thirty seven had non-reimplantation reconstructions (including intercalary or osteoarticular endoprosthesis, pedicled bone grafts, rotation-plasty, and amputations). Five-year local recurrence-free survival was 85% for reimplantation and 97% for non-reimplantation groups (p=0.17). Five-year metastasis-free survival was 63% and 54%, respectively (p=0.44). Five-year overall survival was 70% and 58%, respectively (p=0.39). The data from this study did not demonstrate significantly better local recurrence-free, distant relapse-free, or overall survival benefit in the tumor bone reimplantation group.

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Cryoimmunology for malignant bone and soft-tissue tumors

Cited by 44 publications

References 52 publications

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

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

Increase of IL-12 following Reconstruction for Total En Bloc Spondylectomy Using Frozen Autografts Treated with Liquid Nitrogen

Does Reconstruction with Reimplantation of Sterilized Tumor Bone Provide Survival Benefit in Diaphyseal Osteosarcoma?

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