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整块全脊椎切除术采用冷冻自体骨移植重建后的全身抗肿瘤免疫反应。

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

作者信息

Murakami Hideki, Demura Satoru, Kato Satoshi, Yoshioka Katsuhito, Hayashi Hiroyuki, Inoue Kei, Ota Takashi, Shinmura Kazuya, Yokogawa Noriaki, Fang Xiang, Tsuchiya Hiroyuki

机构信息

Department of Orthopaedic Surgery, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan.

Department of Orthopaedic Surgery, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan.

出版信息

Spine J. 2014 Aug 1;14(8):1567-71. doi: 10.1016/j.spinee.2013.09.030. Epub 2013 Oct 17.

DOI:10.1016/j.spinee.2013.09.030
PMID:24314768
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.

摘要

背景

整块全脊椎切除术(TES)是一种旨在实现恶性脊柱肿瘤(如脊柱转移瘤)完全切除的手术。尽管该手术降低了局部复发率,但局部控制是否能延长患者生存期仍存在疑问。在冷冻手术中,经皮冷冻消融肿瘤后可激活抗肿瘤免疫。我们将这种肿瘤诱导的冷冻免疫应用于TES手术,并开发了一种“第二代TES”,其可增强TES的抗肿瘤免疫以延长患者生存期。

目的

介绍应用肿瘤诱导冷冻免疫的第二代TES,并评估该手术后的免疫增强效果。

研究设计

这是一项对前瞻性收集数据的回顾性研究。

患者样本

样本包括65例连续接受第二代TES的患者。

观察指标

术前、术后1个月和3个月的干扰素γ(IFN-γ)和白细胞介素-12(IL-12)用于评估免疫增强效果。

方法

在第二代TES中,不再从髂骨或腓骨获取自体移植物,而是将TES切除的椎板和椎体用液氮冷冻,并用作脊柱重建的移植骨。在65例患者中的最近33例中,除了TES手术外,还将切除的含肿瘤椎体的少量肿瘤组织放入液氮中。然后在TES手术结束时将这少量肿瘤组织皮下植入腋窝一侧。65例患者中的60例进行了IFN-γ和IL-12的检测。

结果

60例患者中有45例(75%)术后IFN-γ升高。与术前相比,术后1个月和3个月的平均IFN-γ相对浓度显著更高(分别为284%±596%和275%±354%:p<0.05)。60例患者中有44例(73.3%)术后IL-12升高。与术前相比,术后1个月和3个月的平均IL-12相对浓度在3个月时显著更高(分别为277%±385%和486%±1032%:p>0.05和p<0.01)。在最后随访时,65例患者中有13例因转移进展死亡(TES术后平均12.6个月),15例无疾病复发,36例带瘤生存。

结论

在椎间融合器内使用冷冻的含肿瘤自体移植物的第二代TES有三个优点:(1)取骨部位无疼痛,(2)缩短手术时间,(3)减少失血。此外,我们的结果表明第二代TES不仅能实现局部根治,还能实现全身免疫增强。

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