title: Systemic antitumor immune response following reconstruction using frozen autografts for total en bloc spondylectomy.
abstract: BACKGROUND
  Total 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 a patient's survival. In cryosurgery, antitumor immunity is activated after percutaneous cryoablation of tumors. We applied this tumor-induced cryoimmunology to TES surgery and developed a "second-generation TES" that brings about TES enhancing antitumor immunity to prolong a patient's survival.
  
  
  OBJECTIVE
  To present a second-generation TES applied tumor-induced cryoimmunology and assess the immunity-enhancing effect after implementing this surgery.
  
  
  METHODS
  This is a retrospective review of prospectively collected data.
  
  
  METHODS
  The sample consisted of 65 consecutive patients who underwent second-generation TES.
  
  
  METHODS
  Interferon gamma (IFN-γ) and interleukin-12 (IL-12) before surgery and at both 1 and 3 months after surgery was used to assess the immunity-enhancing effect.
  
  
  METHODS
  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 the most recent 33 of the 65 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 at the end of the TES surgery. In 60 of 65 cases, measurement of IFN-γ and IL-12 was performed.
  
  
  RESULTS
  IFN-γ increased after surgery in 45 (75%) of 60 cases. The mean IFN-γ relative concentrations at both 1 and 3 months after surgery, as compared with before surgery, were significantly higher (284%±596% and 275%±354%: p<.05). IL-12 increased after surgery in 44 (73.3%) of 60 cases. The mean IL-12 relative concentrations at both 1 and 3 months after surgery, as compared with before surgery, were significantly higher (277%±385% and 486%±1032%: p>.05 and p<.01) at 3 months. At final follow-up, 13 of the 65 patients died due to progression of metastases (mean 12.6 months after TES), 15 remained free from disease, and 36 patients were alive with disease.
  
  
  CONCLUSIONS
  The second-generation TES using frozen tumor-bearing autograft inside a cage affords three benefits: (1) no pain at the bone harvest site, (2) shortening of operation time, and (3) decrease of blood loss. Moreover, our results show that second-generation TES provides not only a local radical cure but also a systemic immunological enhancement.
authors: Department of Orthopaedic Surgery, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan. Electronic address: hmuraka@med.kanazawa-u.ac.jp.
authors: Hideki
authors: H
authors: Murakami
authors: Department of Orthopaedic Surgery, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
authors: Satoru
authors: S
authors: Demura
authors: Department of Orthopaedic Surgery, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
authors: Satoshi
authors: S
authors: Kato
authors: Department of Orthopaedic Surgery, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
authors: Katsuhito
authors: K
authors: Yoshioka
authors: Department of Orthopaedic Surgery, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
authors: Hiroyuki
authors: H
authors: Hayashi
authors: Department of Orthopaedic Surgery, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
authors: Kei
authors: K
authors: Inoue
authors: Department of Orthopaedic Surgery, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
authors: Takashi
authors: T
authors: Ota
authors: Department of Orthopaedic Surgery, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
authors: Kazuya
authors: K
authors: Shinmura
authors: Department of Orthopaedic Surgery, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
authors: Noriaki
authors: N
authors: Yokogawa
authors: Department of Orthopaedic Surgery, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
authors: Xiang
authors: X
authors: Fang
authors: Department of Orthopaedic Surgery, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
authors: Hiroyuki
authors: H
authors: Tsuchiya
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D064592:Autografts; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D018664:Interleukin-12 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D019736:Prostheses and Implants; D019651:Plastic Surgery Procedures / Q000379:methods*; D012189:Retrospective Studies; D013125:Spinal Neoplasms / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000601:surgery*; D013131:Spine / Q000473:pathology / Q000601:surgery*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018664:Interleukin-12; D007371:Interferon-gamma
keywords: Antitumor immune response; Frozen autograft; Spinal tumor; Total en bloc spondylectomy