Elsevier

The Spine Journal

Volume 14, Issue 8, 1 August 2014, Pages 1567-1571
The Spine Journal

Clinical Study
Systemic antitumor immune response following reconstruction using frozen autografts for total en bloc spondylectomy

https://doi.org/10.1016/j.spinee.2013.09.030Get rights and content

Abstract

Background context

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.

Purpose

To present a second-generation TES applied tumor-induced cryoimmunology and assess the immunity-enhancing effect after implementing this surgery.

Study design

This is a retrospective review of prospectively collected data.

Patient sample

The sample consisted of 65 consecutive patients who underwent second-generation TES.

Outcome measures

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.

Introduction

Total en bloc spondylectomy (TES) is a radical surgery designed to achieve complete resection of an aggressive benign spinal tumor or a malignant spinal tumor, including spinal metastasis, in addition to providing an adequate tumor margin [1]. This procedure has been reported to decrease the rate of local recurrence because local radical cure is achieved [2], [3]. However, it is questionable whether local control prolongs a patient's survival.

In cryosurgery, antitumor immunity is activated after percutaneous cryoablation of the tumor, such as in breast cancer, prostate cancer, renal cell carcinoma, and hepatocellular carcinoma [4], [5]. It has been reported that the metastatic lesions decreased in size or the metastases disappeared because of the cryoimmunological effect after cryosurgery [6]. We applied this tumor-induced cryoimmunology to TES surgery. We have developed a “second-generation TES” that brings about TES enhancing antitumor immunity; this provides promise of improving the patient's life prognosis. Our purpose was to evaluate the immunity-enhancing effect after implementing second-generation TES.

Section snippets

Study patients

We performed 65 cases of second-generation TES applied tumor-induced cryoimmunology from May 2010 to January 2013. We performed a retrospective review of prospectively collected data in the 65 patients (33 males and 32 females). The average follow-up period for the 65 patients was 22 months (range 5–37 months). The mean age at surgery for these patients was 53.3 years (range 16–75 years).

Of the 65 cases, 57 involved metastatic tumors and 8 involved primary tumors. Of the 57 patients with a

Results

IFN-γ increased after surgery in 45 (75%) of 60 patients. Evaluating all 60 patients, 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) (Fig. 2). In the series of 27 patients without subcutaneous implantation of the tumor tissue, the mean IFN-γ relative concentrations at both 1 and 3 months after surgery, as compared with before surgery, were higher (409%±852% and 336%±450%:

Discussion

In second-generation TES, instead of harvesting autograft from the iliac crest or fibula, the resected lamina and vertebral body from TES are frozen using liquid nitrogen and used as grafted bone for spinal anterior reconstruction. Although we use tumor-bearing vertebra as grafted bone, the tumor cells are completely killed by being placed into liquid nitrogen for 20 minutes. Tsuchiya et al. [7] already reported on bone reconstruction for malignant tumors in the extremities and pelvis being

Acknowledgments

The authors thank William C. Hutton, DSc, for his kind criticism and advice.

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FDA device/drug status: Not applicable.

Author disclosures: HM: Grant: Medical Research Encouragement Prize given by the Japan Medical Association (C); Japanese Foundation for Multidisciplinary Treatment of Cancer (C); Princess Takamatsu Cancer Research Fund (11-24316) (C); Astellas Foundation for Research on Metabolic Disorders (C). SD: Nothing to disclose. SK: Nothing to disclose. KY: Nothing to disclose. HH: Nothing to disclose. KI: Nothing to disclose. TO: Nothing to disclose. KS: Nothing to disclose. NY: Nothing to disclose. XF: Nothing to disclose. HT: Nothing to disclose.

The disclosure key can be found on the Table of Contents and at www.TheSpineJournalOnline.com.

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