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 Table of Contents  
EDITORIAL
Year : 2018  |  Volume : 4  |  Issue : 1  |  Page : 3-5

Biological reconstruction after tumor resection


Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa City, Ishikawa 920-8641, Japan

Date of Web Publication3-May-2018

Correspondence Address:
Dr. Hiroyuki Tsuchiya
Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-Machi, Kanazawa City, Ishikawa 920-8641
Japan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jllr.jllr_9_18

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How to cite this article:
Tsuchiya H. Biological reconstruction after tumor resection. J Limb Lengthen Reconstr 2018;4:3-5

How to cite this URL:
Tsuchiya H. Biological reconstruction after tumor resection. J Limb Lengthen Reconstr [serial online] 2018 [cited 2018 Oct 16];4:3-5. Available from: http://www.jlimblengthrecon.org/text.asp?2018/4/1/3/231792



Various methods have been attempted to reconstruct bone defects after bone tumor resection. Biological reconstruction is a technique using materials that are biologically modified for the use in living body. As a result, employing this technique can enhance revitalization of the bone, help achieve union and subsequent remodeling. In addition, soft tissue attachment to bones can be anatomically restored, resulting in better and more efficient limb function.

Materials used for biological reconstruction are largely divided into two categories: living bioactive bone and devitalized modified bone. Living bone includes vascularized bone and that resulting from distraction osteogenesis, while devitalized bone includes allograft and bone that is heat treated, irradiated, or frozen. Tumor-bearing bone can be reimplanted following treatment by pasteurization, autoclaving, irradiation, or freezing with liquid nitrogen and thus is referred to as “recycled bone.” Living bone restores bone structure and blood supply, providing osteogenic cells and proteins to the incorporation site or graft interface. Vascularized bone may be inadequate in size and moreover is commonly retrieved by sacrificing healthy tissues. Distraction osteogenesis regenerates living bone in the human body, with a biomechanical strength approaching that of native bone over time. Bone structure and osteogenic proteins are preserved with the use of allograft, pasteurized, or frozen bone. Only bone structure is preserved in autoclaved bone, albeit with some heat-induced degeneration. Artificial bone substitutes, predominantly used to fill defects following curettage of benign bone tumors, provide only scaffolding.

In theory, it is desirable to perform reconstruction using living bone due to its inherent osteoinductive and osteoconductive properties. Living bone regenerated by distraction osteogenesis appears to have the best qualities. The bone transport or shortening-distraction surgical procedures can be utilized for reconstructing bone defects following tumor excision. However, it requires a long period of external fixation. Whenever feasible, intramedullary nailing is combined with external fixation to shorten the time period the external fixator is applied.[1],[2]

For recycled bone, treatment with liquid nitrogen is considered advantageous because the strength of frozen bone is preserved, with minimal reduction in protein activity.[3] Moreover, the procedure is simple. Either the tumor-bearing segment is removed, or the tumor-bearing portion is exposed while maintaining bony continuityin vivo and freezing treatment with liquid nitrogen are performed. The former is called the “free freezing method,” and the latter, the “pedicle freezing method.” After destroying tumor cells by freezing (−196°C) and subsequent thawing, the frozen bone is used to reconstruct the defect and stabilized by intramedullary nailing and/or plate fixation.[4],[5] Secure anatomic reconstruction is therefore achieved.

In cases requiring upper extremity biological reconstruction in children, reconstruction by vascularized fibular transfer is a viable option. In contrast to adults, good bone remodeling can be expected. Soft-tissue coverage may be done simultaneously with the bony reconstruction, when necessary. However, when this method is used in the lower extremities, fracture is a common complication, even with the use of orthotics.

When the epiphysis of long bones can be preserved, the defect should be restored by biological reconstruction to maintain normal joint function. When the epiphysis can no longer be preserved, arthrodesis by either bone lengthening or vascularized fibular transfer is an option. Moreover, liquid nitrogen-treated bones combined with surface-type artificial joints can be utilized as a composite graft for tumors involving almost entire epiphysis. Tumor endoprosthesis can be applied especially following resection of large osteolytic tumors with severe bony destruction.[6]


  Why Are Biological Reconstruction Methods Selected Top


With any limb surgery, there is always the desire and goal to preserve or restore the normal living anatomy and function of that limb. Patients, and their treating physicians alike, prefer to avoid artificial materials as much as possible and instead opt for ways to keep the affected limb appearing and functioning as intended. Although satisfactory limb function can be achieved using tumor prosthetic replacement, tumor endoprostheses do not allow for full-athletic activities. Therefore, our goal must be the restoration of active life through a multidisciplinary treatment approach, normalizing both function and appearance of affected limbs. Through advances in orthopedic surgery and regenerative medicine, this goal is now being realized with the utilization of biological reconstruction methods. Furthermore, using tumor reduction surgery, it is now possible to preserve normal tissues − neurovascular bundle, muscle, ligament, tendon, and epiphysis − especially in those patients who respond optimally to preoperative chemotherapy. In these patients, normalization of both function and appearance of the affected limb using biological reconstruction is very reliable.[7] Therefore, the preservation of normal tissue through reduction surgery and effective preoperative chemotherapy is extremely important. With recent and upcoming innovations in bioengineering, sarcoma treatment is likely to improve dramatically.


  Advantages and Disadvantages of Treatment Top


An ideal reconstruction must be biocompatible, be resistant to infection, have durability, and provide good function and stable results over the long term. With this being considered, there is no reconstruction material better than living bone. It is unlikely that living bone will cause problems from complications following completion of treatment. Furthermore, with reduction surgery, getting back to full-strength athletics, such as full-speed running, skiing, or soccer, is possible even when devitalized modified bone is used for biological reconstruction. However, when a vascularized fibula is utilized, a brace may be necessary for added support to prevent fractures and deformity until sufficient strength is attained. With distraction osteogenesis, there is the burden of an external fixator for a long duration and throughout the administration of postoperative chemotherapy. When reconstructing defects with materials having no blood circulation − allograft, irradiated bone, heat-treated bone, and liquid nitrogen-treated bone − additional surgeries may be required to address complications. Compared to reconstructions using tumor prostheses, the frequency of infections occurring in the early postoperative period may be similar to that where a biological method is used. However, delayed infection, loosening or breakage, and bone resorption occur more frequently following endoprosthetic reconstructions over time. The 10−15-year survival rate of a tumor prosthesis in the distal femur, which arguably has the best treatment outcome, is reported to be 50%−70%.[8],[9] In addition, with biological reconstructions, return to daily activities is often delayed for a longer period of time. In addition, thermal treatment of tumor-bearing autograft is often complicated by a long processing time as special equipment is required for irradiating bone. Since allogeneic bone is difficult to obtain in Japan, we initially used autoclaved bone for reconstruction; this resulted in weak bone in terms of strength. There is little revitalization of the autoclaved bone following implantation and the frequency of complications exceeded 50% in our series. We therefore developed a new method using liquid nitrogen-treated autograft for bony defects following sarcoma resection. We examined nitrogen-treated bone implant specimens taken at the time of repeat surgeries for complications (3 months to 6 years postoperatively). Histologic examination confirmed revitalization of the liquid nitrogen-treated bone, with the presence of normal osteoblasts, bone marrow formation, and good bone remodeling.[10] However, when joint transplantation is performed using liquid nitrogen-treated autograft, cartilage degeneration occurs over time and is unpreventable resulting in the necessity of requiring a surface-type artificial joint replacement procedure.


  Future Prospects Top


Despite recent developments in bioengineering and regenerative medicine, there remain numerous opportunities for innovation in biological reconstruction. During bone lengthening, it usually takes a month to regenerate 1 cm of new living bone. Therefore, an external fixator must be worn for 10−15 months to reconstruct 10−15 cm of bone defect. By combining external fixation with intramedullary nail fixation, this interval for lengthening can now be shortened, at most, to half the usual time. To accelerate maturation of distracted callus, applying ultrasonic stimulation during bone lengthening is also currently being considered.[11] If these attempts to shorten periods of callus maturation and fracture healing prove to be practical and efficient, additional effective reconstruction methods can be offered. For example, with liquid nitrogen treatment of tumor-bearing autograft, attention is being focused on promoting revitalization using angiogenic factors (i.e., vascular endothelial growth factor, hepatocyte growth factor), as well as developing protective agents for chondrocytes.[12],[13] If these developments do come into practical use, both revitalization and durability of the autograft will be further enhanced. Interestingly, there is an accompanying phenomenon called “induction of cryoimmunology.” It is known that the host immune response can be induced by dead tumor tissue returned in the living body following frozen autograft reconstruction.[14] Liquid nitrogen-treated autograft can therefore be widely and actively used even in metastatic bone diseases, not only for reconstruction of bony defects but also for its immunotherapeutic effect. This development is currently under clinical trial in combination with dendritic cell therapy.[15]



 
  References Top

1.
Tsuchiya H, Tomita K, Minematsu K, Mori Y, Asada N, Kitano S, et al. Limb salvage using distraction osteogenesis. A classification of the technique. J Bone Joint Surg Br 1997;79:403-11.  Back to cited text no. 1
    
2.
Tsuchiya H, Abdel-Wanis ME, Sakurakichi K, Yamashiro T, Tomita K. Osteosarcoma around the knee. Intraepiphyseal excision and biological reconstruction with distraction osteogenesis. J Bone Joint Surg Br 2002;84:1162-6.  Back to cited text no. 2
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3.
Takata M, Sugimoto N, Yamamoto N, Shirai T, Hayashi K, Nishida H, et al. Activity of bone morphogenetic protein-7 after treatment at various temperatures: Freezing vs. Pasteurization vs. Allograft. Cryobiology 2011;63:235-9.  Back to cited text no. 3
    
4.
Tsuchiya H, Wan SL, Sakayama K, Yamamoto N, Nishida H, Tomita K, et al. Reconstruction using an autograft containing tumour treated by liquid nitrogen. J Bone Joint Surg Br 2005;87:218-25.  Back to cited text no. 4
    
5.
Tsuchiya H, Nishida H, Srisawat P, Shirai T, Hayashi K, Takeuchi A, et al. Pedicle frozen autograft reconstruction in malignant bone tumors. J Orthop Sci 2010;15:340-9.  Back to cited text no. 5
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6.
Subhadrabandhu S, Takeuchi A, Yamamoto N, Shirai T, Nishida H, Hayashi K, et al. Frozen autograft-prosthesis composite reconstruction in malignant bone tumors. Orthopedics 2015;38:e911-8.  Back to cited text no. 6
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7.
Tsuchiya H, Tomita K, Mori Y, Asada N, Yamamoto N. Marginal excision for osteosarcoma with caffeine assisted chemotherapy. Clin Orthop Relat Res 1999;358:27-35.  Back to cited text no. 7
    
8.
Jeys LM, Kulkarni A, Grimer RJ, Carter SR, Tillman RM, Abudu A, et al. Endoprosthetic reconstruction for the treatment of musculoskeletal tumors of the appendicular skeleton and pelvis. J Bone Joint Surg Am 2008;90:1265-71.  Back to cited text no. 8
    
9.
Houdek MT, Wagner ER, Wilke BK, Wyles CC, Taunton MJ, Sim FH, et al. Long term outcomes of cemented endoprosthetic reconstruction for periarticular tumors of the distal femur. Knee 2016;23:167-72.  Back to cited text no. 9
    
10.
Tanzawa Y, Tsuchiya H, Yamamoto N, Sakayama K, Minato H, Tomita K, et al. Histological examination of frozen autograft treated by liquid nitrogen removed 6 years after implantation. J Orthop Sci 2008;13:259-64.  Back to cited text no. 10
    
11.
Sakurakichi K, Tsuchiya H, Uehara K, Yamashiro T, Tomita K, Azuma Y, et al. Effects of timing of low-intensity pulsed ultrasound on distraction osteogenesis. J Orthop Res 2004;22:395-403.  Back to cited text no. 11
    
12.
Matsubara H, Tsuchiya H, Watanabe K, Takeuchi A, Tomita K. Percutaneous nonviral delivery of hepatocyte growth factor in an osteotomy gap promotes bone repair in rabbits: A preliminary study. Clin Orthop Relat Res 2008;466:2962-72.  Back to cited text no. 12
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13.
Hayashi M, Tsuchiya H, Otoi T, Agung B, Yamamoto N, Tomita K, et al. Influence of freezing with liquid nitrogen on whole-knee joint grafts and protection of cartilage from cryoinjury in rabbits. Cryobiology 2009;59:28-35.  Back to cited text no. 13
    
14.
Nishida H, Tsuchiya H, Tomita K. Re-implantation of tumour tissue treated by cryotreatment with liquid nitrogen induces anti-tumour activity against murine osteosarcoma. J Bone Joint Surg Br 2008;90:1249-55.  Back to cited text no. 14
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15.
Miwa S, Nishida H, Tanzawa Y, Takeuchi A, Hayashi K, Yamamoto N, et al. Phase 1/2 study of immunotherapy with dendritic cells pulsed with autologous tumor lysate in patients with refractory bone and soft tissue sarcoma. Cancer 2017;123:1576-84.  Back to cited text no. 15
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