En bloc resection, inactivation and replantation combined with chemotherapy for tibial metastasis: a case report and literature review

En bloc resection, inactivation and replantation combined with chemotherapy for tibial metastasis: a case report and literature review | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report En bloc resection, inactivation and replantation combined with chemotherapy for tibial metastasis: a case report and literature review Dawei Chu, Rui Huang, Jianping Zheng, Zongqiang Yang, Ningkui Niu, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5309327/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background The extremities are the most common sites of bone metastasis of malignant tumors. Bone defect reconstruction after bone tumor resection has always been a great challenge in clinical treatment. At present, the most widely used method is individualized artificial prosthesis replacement, but it is expensive and difficult for patients with poor economic ability to bear. Therefore, choosing which reconstruction method can achieve good curative effect and economical affordability has become a problem of clinical thinking. Case presentation: We present here the case of a 43-year-old man who had been suffering from pain in his left calf for the past 2 years that had aggravated 6 months before the presentation. His tibia had osteolytic destruction on both X-ray and CT, while MRI showed malignant neoplastic lesions. Preoperative incision biopsy of the lesion revealed metastatic poorly differentiated adenocarcinoma, which required artificial prosthesis replacement. The patient came to our hospital considering that he could not afford the high cost of surgery. Based on the patient's medical history, physical manifestations, physical and auxiliary examinations, and disease characteristics, we diagnosed him as metastatic poorly differentiated adenocarcinoma of the left tibia and reconstructed with liquid nitrogen-inactivated autologous bone. The postoperative pathological results showed that the histopathology of the patient was a metastatic tumor of the left tibia from breast cancer. After multidisciplinary discussion, chemotherapy was followed. At present, the patient has been followed up for more than 26 months, and there is no tumor recurrence. Conclusions There are many methods for reconstruction of large bone defects after resection of bone tumors, but the choice of reconstruction method needs to be based on the different conditions of each patient. For patients in economically underdeveloped areas, liquid nitrogen-inactivated autologous bone replantation for bone metastasis may be an economical and safe choice. liquid nitrogen inactivation bone metastasis reconstruction tibial en bloc resection replantation Figures Figure 1 Figure 2 Figure 3 1. Introduction The extremities are the most common sites of bone metastasis of malignant tumors, which seriously affect the quality of life of patients. With the updating of bone defect reconstruction techniques, limb salvage surgery has become a safe and effective method for the treatment of secondary bone tumors. A variety of reconstruction methods have been reported in clinical practice, but the most widely applied surgical treatment is artificial prosthesis replacement. However, the high price is its deficiency, and it is difficult for patients with poor economic ability to bear. Choosing which reconstruction method can not only achieve good curative effect, but also be affordable has become a clinical problem. In February 2022, our department admitted a patient with bone metastasis in the upper middle tibia with poor economic status. After comprehensive consideration, liquid nitrogen-inactivated autologous bone cement filling combined with bilateral titanium plate fixation was selected for reconstruction. Now surviving disease free for 3 years and achieving permanent biological reconstruction. It is proved that liquid nitrogen-inactivated autologous bone replantation for bone metastasis is an economical and safe reconstruction method, which provides a choice for patients with poor economic conditions. 2. Case presentation 2.1 General information The patient, a 43-year-old male, was admitted to hospital in February 2022 due to "pain and swelling of the left calf with limited movement for more than 2 years". Two years ago, the patient had pain and swelling in the left calf without any obvious cause, and did not pay attention to it. In recent 6 months, the above symptoms were aggravated with limited activity and increased local skin temperature. X-ray from the local hospital showed that mixed density destruction was seen in the upper middle of the left tibia, with high density as the main focus, irregular shape and uneven density, obvious swelling of the lesion, clear boundary, no obvious periosteum reaction, and malignant lesions were considered (Fig. 1 A-B). For further diagnosis and treatment, an open biopsy was performed in a tertiary hospital in Beijing. For further diagnosis and treatment, an incisional biopsy was performed in a tertiary hospital in Beijing. The postoperative pathology showed that the tumor was metastatic poorly differentiated adenocarcinoma required surgical treatment. Because the patient could not afford the cost of artificial prosthesis replacement, he was admitted to our hospital. Admission physical examination: the local skin of the left calf was red and swollen, the skin temperature was high, there was no ulceration and pus, and the left calf tenderness was positive. It can reach about 5*4*3cm subcutaneous mass, hard quality, unclear boundary, and no limitation of limb movement. 2.2 Preoperative examination and diagnosis Laboratory examination: Routine blood tests, biochemistry, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and procalcitonin (PCT) results were normal. Tumor markers including prostate specific antigen (PSA), CA19-9, CA12-5, and AFP results were normal. Imaging examination: CT and MRI showed osteolytic bone destruction in the upper middle of the left tibia. The lesion was obviously dilated, and the bone cortex became thinner and thickened and hardened in some areas. Irregular clusters of high density and ground glass shadows were seen in the lesion, and the intraosseous ground glass lesion was significantly enhanced after enhancement, which considered the possibility of malignancy (Fig. 1 c-f). PET-CT indicated: (1) High metabolic space in the left upper middle of tibia, consistent with malignant tumor, several high metabolic lymph nodes in the left external iliac vessel and the left groin, reactive hyperplasia and metastatic tumor waiting to be removed. (2) Full prostate, diffuse metabolic activity slightly increased, malignancy is not completely excluded. (3) No tumor-like lesions were found in other parts. The PET-CT results do not exclude the possibility of prostate cancer metastasis. Therefore, the prostate biopsy was performed, and the pathology showed benign prostate tissue. Preoperative diagnosis: Metastatic poorly differentiated adenocarcinoma of the left tibia. Mirels has a rating of 9. On February 28, 2022, under general anesthesia, "left tibial upper middle en bloc bone tumor resection and liquid nitrogen-inactivated autologous bone replantation, bone cement filling and bilateral titanium plate fixation reconstruction" were performed. 2.3 Intraoperative operations En bloc resection: The anterolateral approach was taken to expose the tibial tumor in normal tissue under the principle of no tumor. The tibia was cut with a swinging saw 2cm away from the tumor boundary, and the tibia of the tumor segment was about 17cm. The tumor was extensively resected 1-2cm outside the envelope ( Fig. 2 A-C). Liquid nitrogen inactivation of tumor bone: The fleshy tumor tissue, cancellous bone and all soft tissues of the tibial tumor were removed by aseptic operation on the operating cart. The tumor segments were frozen in a -196°C liquid nitrogen tank for 20 min, removed and rewarmed at room temperature (26°C) for 15 min, and rewarmed in distilled water for 15 min (Fig. 2 D-E). Bone cement filling and replantation: Fill the tibial bone defect and medullary cavity of the tumor segment with bone cement and replant the tumor segment to the tibial bone defect (Fig. 2 F). Screw fixation with bilateral titanium plate: Titanium plates of appropriate length were selected for fixation inside and outside the tibia respectively, and the lacuna of the osteotomy site was filled with BMP bone graft material to promote bone healing (Fig. 2 G). 2.4 Postoperative chemotherapy and follow-up On the first day after surgery, reexamination X-ray showed that the tumor lesion was completely removed, internal fixation and lower limb force line were good (Fig. 3 A). The wound healed well and the patient was discharged from hospital successfully. FISH/DISH indicated that it was a poorly differentiated adenocarcinoma originating from breast cancer. Stitches were removed 2 weeks after surgery. After multidisciplinary discussion, chemotherapy with T (docetaxel, 120mg) + C (cyclophosphamide, 1.1g) regimen was received 1 month after surgery, with 6 cycles, each lasting 21 days. Reexamination of X-ray, CT and MRI one year after surgery showed that there was no tumor recurrence (Fig. 3 B, 3 D- 3 F). At present, 26 months after surgery, the patient was reviewed by X-ray (Fig. 3 C), and both ends of the tumor segment had osseous healing. The patient's left lower limb function was normal, and there was no local swelling and pain. Regular review of the operative area (X-ray, CT and MRI) and the tumor status of the whole body (chest CT and SPECT whole body bone scanning) showed no signs of local recurrence and metastasis, which is still under continuous follow-up. 3. Discussion and literature review 3.1 Bone defect reconstruction The reconstruction of bone defects after bone tumor resection has always been a great challenge in clinical treatment. At present, there are a variety of reconstruction methods for long bone diaphyseal defects, which can be divided into two categories: biological reconstruction and mechanical prosthesis implantation [ 1 ] , both of which can achieve good therapeutic effects. Among them, biological reconstruction includes inactivated autologous bone replantation technology, Ilizarov bone transport surgery, Masquelet membrane induced technique, massive allograft reconstruction, fibula transplantation and novel biomaterials reconstruction technology [ 2 ] . The prosthesis construction is mainly for customized artificial prosthesis replacement. As for Ilizarov bone transport surgery and Masquelet membrane induced technique, the two reconstruction methods have long treatment cycle, more complications, and high requirements for patients' dependence and psychological quality [ 3 ] . Fibula transplantation has risk of fracture, especially in the lower limb bone located in the weight-bearing area [ 4 ] . Large segments of allogeneic bone have good morphological matching, but they are based on bone banks, and there are complications of fracture and bone nonunion [ 5 ] . The reconstruction technology of novel biological materials is expensive and the reconstruction effect is not exact, and it is rarely used in clinical practice [ 6 ] . At present, the most widely used method is artificial prosthesis replacement [ 7 8 ] . After prosthesis replacement, patients can carry weight in a short time and perform functional exercise earlier, which is favored by patients and surgeons. The fly in the ointment is that inorganic metal are not part of the human body after all and cannot be physiologically fused with their own bones, and revision is often inevitable due to loosening or abrasion after long-term use [ 9 ] . 3.2 Liquid nitrogen-inactivated autologous bone replantation Autologous bone inactivation is done via several methods, such as high temperature and pressure inactivation [ 10 ] , pasteurization [ 11 ] , external radiation [ 12 ] , etc. However, the above inactivation methods have high requirements for equipment or temperature, and some inactivation is incomplete or weakens bone strength and osteogenic activity. In recent years, the application of liquid nitrogen inactivation of autologous bone to reconstruct bone defect is increasing. It has complete inactivation, bone conduction and inductivity, and the healing rate of bone end after treatment is as high as 88%. There is no need for complex equipment and more clinical evidence. As early as 1969, Marcove et al [ 13 ] used liquid nitrogen to inactivate the tumor cavity after curettage of bone tumors to reduce the local recurrence rate. Until 2005, Tsuchiya et al [ 14 ] reported the surgical method of using liquid nitrogen inactivated autogenous bone replantation and reconstruction. The specific method was to freeze the autogenous bone in liquid nitrogen at -196 ℃ for 20 min, monitor the temperature of the autogenous bone surface and pulp cavity to -60 ℃, and then re-warm in room temperature and distilled water successively. The autogenous bone was re-fixed with intramedullary nailing or titanium plate. During the follow-up period, the recurrence rate was low and osteotomy ends healed well, and good therapeutic effect were obtained. The principle is that after the autologous bone is inactivated by liquid nitrogen, the tumor cells in the tumor bone undergo dehydration and protein degeneration and necrosis. In addition, deep hypothermia also has the effect of inhibiting tumor immune response, which can inhibit tumor growth factors [ 15 – 17 ] . In addition, part of the activity of BMP in the frozen autografts is retained [ 18 ] , which makes the autografts and host bone have strong healing ability. This reconstruction method also has some shortcomings, such as a certain recurrence rate (7.1%-13.6%), but most of them are located in the surrounding soft tissue rather than in the frozen autografts [ 19 – 21 ] . At the same time, there is the incidence of postoperative complications, common complications include bone nonunion, bone fracture, etc. After inactivation, bone strength is reduced, which will lead to fracture risk. However, after appropriate surgical improvement, good reconstruction results can also be obtained. Li Y et al [ 22 ] used frozen autografts combined with bone cement to make up for the deficiency of bone strength, and the long-term follow-up results were satisfactory. In the case of patients with poor financial ability, the use of liquid nitrogen-inactivated autologous bone replantation to reconstruct bone defect is also a treatment option. 3.3 Clinical characteristics and diagnosis and treatment tactics of this case In this case, the main symptoms of the patient were left calf pain with limited movement. Preoperative open biopsy revealed metastatic tumor, but there was no primary tumor lesion and no history of malignant tumor. It is possible that the primary lesion is too subtle to be detected by current examination and only presents as an isolated metastatic lesion in the upper middle tibia. If the bone strength is further weakened, pathological fracture will occur. Studies have shown that the survival of extensive resection of single metastasis is four times longer than that of palliative surgery [ 23 ] . Considering the patient's history, age, imaging and pathological findings, extensive resection and inactivation of autologous bone were performed. Postoperative pathology results were discussed by MDT, it was considered that the possibility of breast cancer metastasis was high, and chemotherapy was supplemented. After 26 months of follow-up, there was no recurrence of local tumor, and good results were achieved. According to the postoperative follow-up results, the operation was successful, and the patient's cost was greatly saved. The case is still undergoing regular review (every 3 months). Such patients are not rare in outpatients. Patients from remote areas have poor economic status and cannot afford the high cost of artificial prosthesis replacement. The treatment process of this patient has inspired us to adopt the relatively low-cost reconstruction method of tumor en bloc resection and liquid nitrogen inactivation, which can also achieve good surgical results. However, our study is only a case study, and we need to further expand the sample size if we want to further confirm its clinical efficacy. 4. Conclusion In summary, we believe that for patients with long segmental bone defect after bone tumor resection, liquid nitrogen-inactivated autologous bone replantation for bone metastasis is an economic and safe choice, especially for economically underdeveloped areas. However, due to the limited clinical data and literatures available for reference, large-scale prospective controlled studies need to be conducted through multi-center cooperation to further verify the safety and reliability of this technology. Abbreviations CT= Computed tomography, MRI= Magnetic resonance imaging, PET-CT= Positron emission tomography-computed tyomography, MDT= Multi-disciplinary treatment. Declarations Funding This research was funded by the Key Program of Ningxia Hui Autonomous Region Natural 353 Science Foundation of China, grant number (No. 2024AAC02069). Availability of data and materials All basic data can be found in articles and supplementary documents. Ethics approval and consent to participate The collection of patient’s clinical data was approved by the Ethics Committee of the General Hospital of Ningxia Medical University and performed in accordance with the Declaration of Helsinki. Authors' contributions Dawei Chu and Rui Huang prepared the report and drafted the manuscript. Jiandang Shi provided funds and revised the article. Ningkui Niu provided technical guidance and revised figures. Jianping Zheng and Zongqiang Yang collected clinical data. All 6 authors have approved the submitted manuscript. Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Consent for publication Not Applicable. Informed consent for release of information and images was obtained from all individual participants in the study. And the patient has signed a written informed consent for publication of the personal and clinical details along with all the identifying images. Clinical Trial Number Not applicable. Acknowledgments Not applicable. References Lehner B, Omlor GW, Geisbüsch A, Bollmann J. [Specific intraoperative and secondary complications of biological reconstructions following extralesional tumour resections of malignant bone tumours]. Orthopade 2020; 49 (2):149-56. Nishida J. Biological reconstruction for massive bone defect following resection of tumor in Japan. J Orthop Sci 2023; 28 (3):507-08. Klein C, Monet M, Barbier V, et al. The Masquelet technique: Current concepts, animal models, and perspectives. J Tissue Eng Regen Med 2020; 14 (9):1349-59. Ghoneimy AME, Sherbiny ME, Kamal N. Use of Vascularized Fibular Free Flap in the Reconstruction of the Femur in Pediatric and Adolescent Bone Sarcomas: Complications and Functional Outcome. J Reconstr Microsurg 2019; 35 (2):156-62. Aponte-Tinao LA, Ayerza MA, Albergo JI, Farfalli GL. Do Massive Allograft Reconstructions for Tumors of the Femur and Tibia Survive 10 or More Years after Implantation? Clin Orthop Relat Res 2020; 478 (3):517-24. Zhang M, Matinlinna JP, Tsoi JKH, et al. Recent developments in biomaterials for long-bone segmental defect reconstruction: A narrative overview. J Orthop Translat 2020; 22 :26-33. Vitiello R, Matrangolo MR, El Motassime A, et al. Three-Dimension-Printed Custom-Made Prosthetic Reconstructions in Bone Tumors: A Single Center Experience. Curr Oncol 2022; 29 (7):4566-77. Angelini A, Trovarelli G, Berizzi A, Pala E, Breda A, Ruggieri P. Three-dimension-printed custom-made prosthetic reconstructions: from revision surgery to oncologic reconstructions. Int Orthop 2019; 43 (1):123-32. Yamamoto N, Hayashi K, Tsuchiya H. Progress in biological reconstruction and enhanced bone revitalization for bone defects. J Orthop Sci 2019; 24 (3):387-92. Asada N, Tsuchiya H, Kitaoka K, Mori Y, Tomita K. Massive autoclaved allografts and autografts for limb salvage surgery. A 1-8 year follow-up of 23 patients. Acta Orthop Scand 1997; 68 (4):392-5. Lee SY, Jeon DG, Cho WH, Song WS, Kim BS. Are Pasteurized Autografts Durable for Reconstructions After Bone Tumor Resections? Clin Orthop Relat Res 2018; 476 (9):1728-37. Salunke AA, Shah J, Chauhan TS, et al. Reconstruction with biological methods following intercalary excision of femoral diaphyseal tumors. J Orthop Surg (Hong Kong) 2019; 27 (1):2309499018822242. Marcove RC, Miller TR. Treatment of primary and metastatic bone tumors by cryosurgery. Jama 1969; 207 (10):1890-4. Tsuchiya H, Wan SL, Sakayama K, Yamamoto N, Nishida H, Tomita K. Reconstruction using an autograft containing tumour treated by liquid nitrogen. J Bone Joint Surg Br 2005; 87 (2):218-25. Yonezawa N, Murakami H, Demura S, et al. Abscopal Effect of Frozen Autograft Reconstruction Combined with an Immune Checkpoint Inhibitor Analyzed Using a Metastatic Bone Tumor Model. Int J Mol Sci 2021; 22 (4). Kawano M, Nishida H, Nakamoto Y, Tsumura H, Tsuchiya H. Cryoimmunologic antitumor effects enhanced by dendritic cells in osteosarcoma. Clin Orthop Relat Res 2010; 468 (5):1373-83. Nishida H, Yamamoto N, Tanzawa Y, Tsuchiya H. Cryoimmunology for malignant bone and soft-tissue tumors. Int J Clin Oncol 2011; 16 (2):109-17. Chen CM, Chen CF, Wang JY, et al. Bone morphogenetic protein activity preservation with extracorporeal irradiation- and liquid nitrogen freezing-treated recycled autografts for biological reconstruction in malignant bone tumor. Cryobiology 2019; 89 :82-89. Li D, Li P, Ma H, et al. Extraperiosteal segmental excision for osteofibrous dysplasia of tibia with reconstruction by liquid nitrogen-treated recycled autograft. J Orthop Sci 2019; 24 (2):342-46. Garg SK, Aggarwal P, Virk J, Punia RPS, Dimri K, Jindal R. Limb Salvage Using Liquid Nitrogen-Treated Tumour-Bearing Autograft: A Single Institutional Experience of 10 Patients. Indian J Orthop 2020; 54 (2):200-07. Kimura H, Yamamoto N, Shirai T, et al. Clinical Outcome of Reconstruction Using Frozen Autograft for a Humeral Bone Tumor. Anticancer Res 2016; 36 (12):6631-35. Li Y, Yang Y, Huang Z, Shan H, Xu H, Niu X. Bone defect reconstruction with autologous bone inactivated with liquid nitrogen after resection of primary limb malignant tumors: An observational study. Medicine (Baltimore) 2020; 99 (24):e20442. Ratasvuori M, Wedin R, Hansen BH, et al. Prognostic role of en-bloc resection and late onset of bone metastasis in patients with bone-seeking carcinomas of the kidney, breast, lung, and prostate: SSG study on 672 operated skeletal metastases. J Surg Oncol 2014; 110 (4):360-5. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5309327","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":370476180,"identity":"c5a51b18-e12f-4f0d-925c-764fa5d4af72","order_by":0,"name":"Dawei Chu","email":"","orcid":"","institution":"Ningxia Medical University, Ningxia Hui Autonomous Region","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Dawei","middleName":"","lastName":"Chu","suffix":""},{"id":370476181,"identity":"ce9805a6-2bb8-4cd0-992d-8efa67c9a2cb","order_by":1,"name":"Rui Huang","email":"","orcid":"","institution":"Ningxia Medical University, Ningxia Hui Autonomous Region","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Rui","middleName":"","lastName":"Huang","suffix":""},{"id":370476182,"identity":"a8a6f66e-e4d6-45ed-8de7-c9716f49dd4b","order_by":2,"name":"Jianping Zheng","email":"","orcid":"","institution":"General Hospital of Ningxia Medical University, Hui Autonomous Region","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jianping","middleName":"","lastName":"Zheng","suffix":""},{"id":370476183,"identity":"b0fe02e6-c739-4dd5-8a2a-fe7c4d27642a","order_by":3,"name":"Zongqiang Yang","email":"","orcid":"","institution":"General Hospital of Ningxia Medical University, Hui Autonomous Region","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zongqiang","middleName":"","lastName":"Yang","suffix":""},{"id":370476184,"identity":"978126bf-9af2-4cd1-a00c-850917ddb90e","order_by":4,"name":"Ningkui Niu","email":"","orcid":"","institution":"General Hospital of Ningxia Medical University, Hui Autonomous Region","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ningkui","middleName":"","lastName":"Niu","suffix":""},{"id":370476185,"identity":"2525f75f-c3a2-452a-9339-e94616b232fd","order_by":5,"name":"Jiandang Shi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/UlEQVRIiWNgGAWjYDACCcYGBgkDIOMAEH+ACRKthXEGcVpgDKAWZh5itMjPbm5gsCiwy+M7fvbwa9sdh6MNDjAfvM3DYJeHS4vBnYMghyUXS57JS7POPZOWu+EAW7I1D0NyMU4tEokgLcyJGw7kmBnnttkAtfCYSfMwHACK43DYDLCW+sQN59+YGVu2SQC18H/Dq4XhBljL4cQNN3KMHzNCbGHDq8UAouV44swbb8wYe9vScmceZjO2nGOQjMdh6Q+YJf5UJ/adzzH+8LPtcG7f8eaHN95U2OF2GAMD+29oNLBBaGaw7bjVgwAjNJ0wf8CvbhSMglEwCkYqAACfMVmlLEbplAAAAABJRU5ErkJggg==","orcid":"","institution":"Ningxia Medical University, Ningxia Hui Autonomous Region","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Jiandang","middleName":"","lastName":"Shi","suffix":""}],"badges":[],"createdAt":"2024-10-22 07:23:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5309327/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5309327/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":67634831,"identity":"73052da3-2eac-43b4-b065-78978a67d9ea","added_by":"auto","created_at":"2024-10-28 09:21:23","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":139680,"visible":true,"origin":"","legend":"\u003cp\u003eA 43-year-old male with left proximal tibial metastases involving the diaphysis. Preoperative imaging of the left tibia and fibula. A-B. Preoperative anterior-to-lateral radiographs showed tumor involving the diaphysis of the proximal tibia. C-F. Preoperative CT and MRI showed expansive bone destruction, cortical thinning and soft tissue infiltration.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-5309327/v1/cacff61ad1abd137c02c37f7.png"},{"id":67634832,"identity":"78262c64-6c5a-4f0f-a412-ff3f56ed7051","added_by":"auto","created_at":"2024-10-28 09:21:23","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":308437,"visible":true,"origin":"","legend":"\u003cp\u003eSurgical procedure. A-B. Fully exposed and free tumor tissue outside the envelope. C. The tumor segment was completely removed. D. The fleshy tumor tissue, cancellous bone and all soft tissues of the tibial tumor were removed. E. Tumor after liquid nitrogen inactivation. F. Bone cement fills the bone defect. G. Tumor bone and tibia were joined with two titanium plates. H Intraoperative freeze pathology.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-5309327/v1/4c831d83261aee0acaf4d756.png"},{"id":67634853,"identity":"12b40bfc-e72d-4bbf-b27c-26a43abde50a","added_by":"auto","created_at":"2024-10-28 09:21:23","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":312843,"visible":true,"origin":"","legend":"\u003cp\u003ePost-operative follow-up imaging. A. X-ray on the first day after surgery showed that the tumor was completely removed and the inactivated autologous bone was well fixed. B. 1 year after surgery, the plates could be seen in place without loosening or fracture. C. X-ray reexamination 26 months after the operation showed that the position of the plates and screw was good, and no loosening or fracture was found. D. 1 year after surgery, CT indicated that the inactivated autologous bone had healed with the host bone. E-F. MRI showed no recurrence of the tumor 1 year after surgery.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-5309327/v1/93129dae61e84c6c57ef1612.png"},{"id":71498873,"identity":"c4f6743d-905d-41f4-9794-a35397ab4035","added_by":"auto","created_at":"2024-12-16 08:47:27","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1202235,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5309327/v1/280af030-b3a4-4e19-a333-bd9ad793977c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"En bloc resection, inactivation and replantation combined with chemotherapy for tibial metastasis: a case report and literature review","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eThe extremities are the most common sites of bone metastasis of malignant tumors, which seriously affect the quality of life of patients. With the updating of bone defect reconstruction techniques, limb salvage surgery has become a safe and effective method for the treatment of secondary bone tumors. A variety of reconstruction methods have been reported in clinical practice, but the most widely applied surgical treatment is artificial prosthesis replacement. However, the high price is its deficiency, and it is difficult for patients with poor economic ability to bear. Choosing which reconstruction method can not only achieve good curative effect, but also be affordable has become a clinical problem. In February 2022, our department admitted a patient with bone metastasis in the upper middle tibia with poor economic status. After comprehensive consideration, liquid nitrogen-inactivated autologous bone cement filling combined with bilateral titanium plate fixation was selected for reconstruction. Now surviving disease free for 3 years and achieving permanent biological reconstruction. It is proved that liquid nitrogen-inactivated autologous bone replantation for bone metastasis is an economical and safe reconstruction method, which provides a choice for patients with poor economic conditions.\u003c/p\u003e"},{"header":"2. Case presentation","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n \u003ch2\u003e2.1 General information\u003c/h2\u003e\n \u003cp\u003eThe patient, a 43-year-old male, was admitted to hospital in February 2022 due to \u0026quot;pain and swelling of the left calf with limited movement for more than 2 years\u0026quot;. Two years ago, the patient had pain and swelling in the left calf without any obvious cause, and did not pay attention to it. In recent 6 months, the above symptoms were aggravated with limited activity and increased local skin temperature. X-ray from the local hospital showed that mixed density destruction was seen in the upper middle of the left tibia, with high density as the main focus, irregular shape and uneven density, obvious swelling of the lesion, clear boundary, no obvious periosteum reaction, and malignant lesions were considered (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eA-B). For further diagnosis and treatment, an open biopsy was performed in a tertiary hospital in Beijing. For further diagnosis and treatment, an incisional biopsy was performed in a tertiary hospital in Beijing. The postoperative pathology showed that the tumor was metastatic poorly differentiated adenocarcinoma required surgical treatment. Because the patient could not afford the cost of artificial prosthesis replacement, he was admitted to our hospital. Admission physical examination: the local skin of the left calf was red and swollen, the skin temperature was high, there was no ulceration and pus, and the left calf tenderness was positive. It can reach about 5*4*3cm subcutaneous mass, hard quality, unclear boundary, and no limitation of limb movement.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n \u003ch2\u003e2.2 Preoperative examination and diagnosis\u003c/h2\u003e\n \u003cp\u003eLaboratory examination: Routine blood tests, biochemistry, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and procalcitonin (PCT) results were normal. Tumor markers including prostate specific antigen (PSA), CA19-9, CA12-5, and AFP results were normal. Imaging examination: CT and MRI showed osteolytic bone destruction in the upper middle of the left tibia. The lesion was obviously dilated, and the bone cortex became thinner and thickened and hardened in some areas. Irregular clusters of high density and ground glass shadows were seen in the lesion, and the intraosseous ground glass lesion was significantly enhanced after enhancement, which considered the possibility of malignancy (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003ec-f). PET-CT indicated: (1) High metabolic space in the left upper middle of tibia, consistent with malignant tumor, several high metabolic lymph nodes in the left external iliac vessel and the left groin, reactive hyperplasia and metastatic tumor waiting to be removed. (2) Full prostate, diffuse metabolic activity slightly increased, malignancy is not completely excluded. (3) No tumor-like lesions were found in other parts. The PET-CT results do not exclude the possibility of prostate cancer metastasis. Therefore, the prostate biopsy was performed, and the pathology showed benign prostate tissue.\u003c/p\u003e\n \u003cp\u003ePreoperative diagnosis: Metastatic poorly differentiated adenocarcinoma of the left tibia. Mirels has a rating of 9. On February 28, 2022, under general anesthesia, \u0026quot;left tibial upper middle en bloc bone tumor resection and liquid nitrogen-inactivated autologous bone replantation, bone cement filling and bilateral titanium plate fixation reconstruction\u0026quot; were performed.\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n \u003ch2\u003e2.3 Intraoperative operations\u003c/h2\u003e\n \u003cp\u003eEn bloc resection: The anterolateral approach was taken to expose the tibial tumor in normal tissue under the principle of no tumor. The tibia was cut with a swinging saw 2cm away from the tumor boundary, and the tibia of the tumor segment was about 17cm. The tumor was extensively resected 1-2cm outside the envelope ( Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eA-C).\u003c/p\u003e\n \u003cp\u003eLiquid nitrogen inactivation of tumor bone: The fleshy tumor tissue, cancellous bone and all soft tissues of the tibial tumor were removed by aseptic operation on the operating cart. The tumor segments were frozen in a -196\u0026deg;C liquid nitrogen tank for 20 min, removed and rewarmed at room temperature (26\u0026deg;C) for 15 min, and rewarmed in distilled water for 15 min (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eD-E).\u003c/p\u003e\n \u003cp\u003eBone cement filling and replantation: Fill the tibial bone defect and medullary cavity of the tumor segment with bone cement and replant the tumor segment to the tibial bone defect (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eF).\u003c/p\u003e\n \u003cp\u003eScrew fixation with bilateral titanium plate: Titanium plates of appropriate length were selected for fixation inside and outside the tibia respectively, and the lacuna of the osteotomy site was filled with BMP bone graft material to promote bone healing (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eG).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\n \u003ch2\u003e2.4 Postoperative chemotherapy and follow-up\u003c/h2\u003e\n \u003cp\u003eOn the first day after surgery, reexamination X-ray showed that the tumor lesion was completely removed, internal fixation and lower limb force line were good (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eA). The wound healed well and the patient was discharged from hospital successfully. FISH/DISH indicated that it was a poorly differentiated adenocarcinoma originating from breast cancer.\u003c/p\u003e\n \u003cp\u003eStitches were removed 2 weeks after surgery. After multidisciplinary discussion, chemotherapy with T (docetaxel, 120mg)\u0026thinsp;+\u0026thinsp;C (cyclophosphamide, 1.1g) regimen was received 1 month after surgery, with 6 cycles, each lasting 21 days. Reexamination of X-ray, CT and MRI one year after surgery showed that there was no tumor recurrence (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eB, \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eD-\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eF). At present, 26 months after surgery, the patient was reviewed by X-ray (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eC), and both ends of the tumor segment had osseous healing. The patient\u0026apos;s left lower limb function was normal, and there was no local swelling and pain. Regular review of the operative area (X-ray, CT and MRI) and the tumor status of the whole body (chest CT and SPECT whole body bone scanning) showed no signs of local recurrence and metastasis, which is still under continuous follow-up.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"3. Discussion and literature review","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Bone defect reconstruction\u003c/h2\u003e \u003cp\u003eThe reconstruction of bone defects after bone tumor resection has always been a great challenge in clinical treatment. At present, there are a variety of reconstruction methods for long bone diaphyseal defects, which can be divided into two categories: biological reconstruction and mechanical prosthesis implantation\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e, both of which can achieve good therapeutic effects. Among them, biological reconstruction includes inactivated autologous bone replantation technology, Ilizarov bone transport surgery, Masquelet membrane induced technique, massive allograft reconstruction, fibula transplantation and novel biomaterials reconstruction technology\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. The prosthesis construction is mainly for customized artificial prosthesis replacement.\u003c/p\u003e \u003cp\u003eAs for Ilizarov bone transport surgery and Masquelet membrane induced technique, the two reconstruction methods have long treatment cycle, more complications, and high requirements for patients' dependence and psychological quality\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. Fibula transplantation has risk of fracture, especially in the lower limb bone located in the weight-bearing area\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. Large segments of allogeneic bone have good morphological matching, but they are based on bone banks, and there are complications of fracture and bone nonunion\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. The reconstruction technology of novel biological materials is expensive and the reconstruction effect is not exact, and it is rarely used in clinical practice\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. At present, the most widely used method is artificial prosthesis replacement\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. After prosthesis replacement, patients can carry weight in a short time and perform functional exercise earlier, which is favored by patients and surgeons. The fly in the ointment is that inorganic metal are not part of the human body after all and cannot be physiologically fused with their own bones, and revision is often inevitable due to loosening or abrasion after long-term use\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Liquid nitrogen-inactivated autologous bone replantation\u003c/h2\u003e \u003cp\u003eAutologous bone inactivation is done via several methods, such as high temperature and pressure inactivation\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e, pasteurization\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e, external radiation\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e, etc. However, the above inactivation methods have high requirements for equipment or temperature, and some inactivation is incomplete or weakens bone strength and osteogenic activity. In recent years, the application of liquid nitrogen inactivation of autologous bone to reconstruct bone defect is increasing. It has complete inactivation, bone conduction and inductivity, and the healing rate of bone end after treatment is as high as 88%. There is no need for complex equipment and more clinical evidence. As early as 1969, Marcove et al\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e used liquid nitrogen to inactivate the tumor cavity after curettage of bone tumors to reduce the local recurrence rate. Until 2005, Tsuchiya et al\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e reported the surgical method of using liquid nitrogen inactivated autogenous bone replantation and reconstruction. The specific method was to freeze the autogenous bone in liquid nitrogen at -196 ℃ for 20 min, monitor the temperature of the autogenous bone surface and pulp cavity to -60 ℃, and then re-warm in room temperature and distilled water successively. The autogenous bone was re-fixed with intramedullary nailing or titanium plate. During the follow-up period, the recurrence rate was low and osteotomy ends healed well, and good therapeutic effect were obtained.\u003c/p\u003e \u003cp\u003eThe principle is that after the autologous bone is inactivated by liquid nitrogen, the tumor cells in the tumor bone undergo dehydration and protein degeneration and necrosis. In addition, deep hypothermia also has the effect of inhibiting tumor immune response, which can inhibit tumor growth factors\u003csup\u003e[\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e. In addition, part of the activity of BMP in the frozen autografts is retained\u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e, which makes the autografts and host bone have strong healing ability. This reconstruction method also has some shortcomings, such as a certain recurrence rate (7.1%-13.6%), but most of them are located in the surrounding soft tissue rather than in the frozen autografts\u003csup\u003e[\u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e. At the same time, there is the incidence of postoperative complications, common complications include bone nonunion, bone fracture, etc. After inactivation, bone strength is reduced, which will lead to fracture risk. However, after appropriate surgical improvement, good reconstruction results can also be obtained. Li Y et al\u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e used frozen autografts combined with bone cement to make up for the deficiency of bone strength, and the long-term follow-up results were satisfactory. In the case of patients with poor financial ability, the use of liquid nitrogen-inactivated autologous bone replantation to reconstruct bone defect is also a treatment option.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Clinical characteristics and diagnosis and treatment tactics of this case\u003c/h2\u003e \u003cp\u003eIn this case, the main symptoms of the patient were left calf pain with limited movement. Preoperative open biopsy revealed metastatic tumor, but there was no primary tumor lesion and no history of malignant tumor. It is possible that the primary lesion is too subtle to be detected by current examination and only presents as an isolated metastatic lesion in the upper middle tibia. If the bone strength is further weakened, pathological fracture will occur. Studies have shown that the survival of extensive resection of single metastasis is four times longer than that of palliative surgery\u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e. Considering the patient's history, age, imaging and pathological findings, extensive resection and inactivation of autologous bone were performed. Postoperative pathology results were discussed by MDT, it was considered that the possibility of breast cancer metastasis was high, and chemotherapy was supplemented. After 26 months of follow-up, there was no recurrence of local tumor, and good results were achieved. According to the postoperative follow-up results, the operation was successful, and the patient's cost was greatly saved. The case is still undergoing regular review (every 3 months).\u003c/p\u003e \u003cp\u003eSuch patients are not rare in outpatients. Patients from remote areas have poor economic status and cannot afford the high cost of artificial prosthesis replacement. The treatment process of this patient has inspired us to adopt the relatively low-cost reconstruction method of tumor en bloc resection and liquid nitrogen inactivation, which can also achieve good surgical results. However, our study is only a case study, and we need to further expand the sample size if we want to further confirm its clinical efficacy.\u003c/p\u003e \u003c/div\u003e"},{"header":"4. Conclusion","content":"\u003cp\u003eIn summary, we believe that for patients with long segmental bone defect after bone tumor resection, liquid nitrogen-inactivated autologous bone replantation for bone metastasis is an economic and safe choice, especially for economically underdeveloped areas. However, due to the limited clinical data and literatures available for reference, large-scale prospective controlled studies need to be conducted through multi-center cooperation to further verify the safety and reliability of this technology.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCT= Computed tomography, MRI= Magnetic resonance imaging, PET-CT= Positron emission tomography-computed tyomography, MDT= Multi-disciplinary treatment.\u003c/p\u003e\n"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was funded by the Key Program of Ningxia Hui Autonomous Region Natural 353 Science Foundation of China, grant number (No. 2024AAC02069).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll basic data can be found in articles\u0026nbsp;and\u0026nbsp;supplementary documents.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe collection of patient\u0026rsquo;s clinical data was approved by the Ethics Committee of the General Hospital of Ningxia Medical University and performed in accordance with the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDawei Chu and Rui Huang prepared the report and drafted the manuscript. Jiandang Shi provided funds and revised the article. Ningkui Niu provided technical guidance and revised figures. Jianping Zheng and Zongqiang Yang collected clinical data. All 6 authors have approved the submitted manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclaration of competing interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot Applicable. Informed consent for release of information and images was obtained from all individual participants in the study. And the patient has signed a written informed consent for publication of the personal and clinical details along with all the identifying images.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Trial Number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLehner B, Omlor GW, Geisb\u0026uuml;sch A, Bollmann J. [Specific intraoperative and secondary complications of biological reconstructions following extralesional tumour resections of malignant bone tumours]. Orthopade 2020;\u003cstrong\u003e49\u003c/strong\u003e(2):149-56.\u003c/li\u003e\n\u003cli\u003eNishida J. Biological reconstruction for massive bone defect following resection of tumor in Japan. J Orthop Sci 2023;\u003cstrong\u003e28\u003c/strong\u003e(3):507-08.\u003c/li\u003e\n\u003cli\u003eKlein C, Monet M, Barbier V, et al. The Masquelet technique: Current concepts, animal models, and perspectives. J Tissue Eng Regen Med 2020;\u003cstrong\u003e14\u003c/strong\u003e(9):1349-59.\u003c/li\u003e\n\u003cli\u003eGhoneimy AME, Sherbiny ME, Kamal N. Use of Vascularized Fibular Free Flap in the Reconstruction of the Femur in Pediatric and Adolescent Bone Sarcomas: Complications and Functional Outcome. J Reconstr Microsurg 2019;\u003cstrong\u003e35\u003c/strong\u003e(2):156-62.\u003c/li\u003e\n\u003cli\u003eAponte-Tinao LA, Ayerza MA, Albergo JI, Farfalli GL. Do Massive Allograft Reconstructions for Tumors of the Femur and Tibia Survive 10 or More Years after Implantation? Clin Orthop Relat Res 2020;\u003cstrong\u003e478\u003c/strong\u003e(3):517-24.\u003c/li\u003e\n\u003cli\u003eZhang M, Matinlinna JP, Tsoi JKH, et al. Recent developments in biomaterials for long-bone segmental defect reconstruction: A narrative overview. J Orthop Translat 2020;\u003cstrong\u003e22\u003c/strong\u003e:26-33.\u003c/li\u003e\n\u003cli\u003eVitiello R, Matrangolo MR, El Motassime A, et al. Three-Dimension-Printed Custom-Made Prosthetic Reconstructions in Bone Tumors: A Single Center Experience. Curr Oncol 2022;\u003cstrong\u003e29\u003c/strong\u003e(7):4566-77.\u003c/li\u003e\n\u003cli\u003eAngelini A, Trovarelli G, Berizzi A, Pala E, Breda A, Ruggieri P. Three-dimension-printed custom-made prosthetic reconstructions: from revision surgery to oncologic reconstructions. Int Orthop 2019;\u003cstrong\u003e43\u003c/strong\u003e(1):123-32.\u003c/li\u003e\n\u003cli\u003eYamamoto N, Hayashi K, Tsuchiya H. Progress in biological reconstruction and enhanced bone revitalization for bone defects. J Orthop Sci 2019;\u003cstrong\u003e24\u003c/strong\u003e(3):387-92.\u003c/li\u003e\n\u003cli\u003eAsada N, Tsuchiya H, Kitaoka K, Mori Y, Tomita K. Massive autoclaved allografts and autografts for limb salvage surgery. A 1-8 year follow-up of 23 patients. Acta Orthop Scand 1997;\u003cstrong\u003e68\u003c/strong\u003e(4):392-5.\u003c/li\u003e\n\u003cli\u003eLee SY, Jeon DG, Cho WH, Song WS, Kim BS. Are Pasteurized Autografts Durable for Reconstructions After Bone Tumor Resections? Clin Orthop Relat Res 2018;\u003cstrong\u003e476\u003c/strong\u003e(9):1728-37.\u003c/li\u003e\n\u003cli\u003eSalunke AA, Shah J, Chauhan TS, et al. Reconstruction with biological methods following intercalary excision of femoral diaphyseal tumors. J Orthop Surg (Hong Kong) 2019;\u003cstrong\u003e27\u003c/strong\u003e(1):2309499018822242.\u003c/li\u003e\n\u003cli\u003eMarcove RC, Miller TR. Treatment of primary and metastatic bone tumors by cryosurgery. 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Indian J Orthop 2020;\u003cstrong\u003e54\u003c/strong\u003e(2):200-07.\u003c/li\u003e\n\u003cli\u003eKimura H, Yamamoto N, Shirai T, et al. Clinical Outcome of Reconstruction Using Frozen Autograft for a Humeral Bone Tumor. Anticancer Res 2016;\u003cstrong\u003e36\u003c/strong\u003e(12):6631-35.\u003c/li\u003e\n\u003cli\u003eLi Y, Yang Y, Huang Z, Shan H, Xu H, Niu X. Bone defect reconstruction with autologous bone inactivated with liquid nitrogen after resection of primary limb malignant tumors: An observational study. Medicine (Baltimore) 2020;\u003cstrong\u003e99\u003c/strong\u003e(24):e20442.\u003c/li\u003e\n\u003cli\u003eRatasvuori M, Wedin R, Hansen BH, et al. Prognostic role of en-bloc resection and late onset of bone metastasis in patients with bone-seeking carcinomas of the kidney, breast, lung, and prostate: SSG study on 672 operated skeletal metastases. J Surg Oncol 2014;\u003cstrong\u003e110\u003c/strong\u003e(4):360-5.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"liquid nitrogen inactivation, bone metastasis, reconstruction, tibial, en bloc resection, replantation","lastPublishedDoi":"10.21203/rs.3.rs-5309327/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5309327/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe extremities are the most common sites of bone metastasis of malignant tumors. Bone defect reconstruction after bone tumor resection has always been a great challenge in clinical treatment. At present, the most widely used method is individualized artificial prosthesis replacement, but it is expensive and difficult for patients with poor economic ability to bear. Therefore, choosing which reconstruction method can achieve good curative effect and economical affordability has become a problem of clinical thinking.\u003c/p\u003e\u003ch2\u003eCase presentation:\u003c/h2\u003e \u003cp\u003eWe present here the case of a 43-year-old man who had been suffering from pain in his left calf for the past 2 years that had aggravated 6 months before the presentation. His tibia had osteolytic destruction on both X-ray and CT, while MRI showed malignant neoplastic lesions. Preoperative incision biopsy of the lesion revealed metastatic poorly differentiated adenocarcinoma, which required artificial prosthesis replacement. The patient came to our hospital considering that he could not afford the high cost of surgery. Based on the patient's medical history, physical manifestations, physical and auxiliary examinations, and disease characteristics, we diagnosed him as metastatic poorly differentiated adenocarcinoma of the left tibia and reconstructed with liquid nitrogen-inactivated autologous bone. The postoperative pathological results showed that the histopathology of the patient was a metastatic tumor of the left tibia from breast cancer. After multidisciplinary discussion, chemotherapy was followed. At present, the patient has been followed up for more than 26 months, and there is no tumor recurrence.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThere are many methods for reconstruction of large bone defects after resection of bone tumors, but the choice of reconstruction method needs to be based on the different conditions of each patient. For patients in economically underdeveloped areas, liquid nitrogen-inactivated autologous bone replantation for bone metastasis may be an economical and safe choice.\u003c/p\u003e","manuscriptTitle":"En bloc resection, inactivation and replantation combined with chemotherapy for tibial metastasis: a case report and literature review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-28 09:21:18","doi":"10.21203/rs.3.rs-5309327/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d918bacf-e7d0-4356-a22b-7c719281a34d","owner":[],"postedDate":"October 28th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-12-16T08:39:15+00:00","versionOfRecord":[],"versionCreatedAt":"2024-10-28 09:21:18","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5309327","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5309327","identity":"rs-5309327","version":["v1"]},"buildId":"zQwnuV7TCBrMSSSToR1PI","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}