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[恶性肿瘤的冷冻疗法:动物实验中的MRI研究及与形态学变化的比较]

[Cryotherapy of malignant tumors: studies with MRI in an animal experiment and comparison with morphological changes].

作者信息

Romaneehsen B, Anders M, Röhrl B, Hast H J, Hengstler J G, Schiffer I, Neugebauer B, Teichmann E, Schreiber W G, Thelen M

机构信息

Klinik und Poliklinik für Radiologie, Johannes Gutenberg-Universität Mainz.

出版信息

Rofo. 2001 Jul;173(7):632-8. doi: 10.1055/s-2001-15832.

DOI:10.1055/s-2001-15832
PMID:11512236
Abstract

PURPOSE

Aim of our study was to investigate the efficacy of 7 F cryoprobes for percutaneous use morpho- and histologically, to examine the role of apoptosis after cryotherapy, and to compare contrast-enhanced MRI with histopathological findings at different time intervals in a tumor-mouse model.

METHODS

Percutaneous cryotherapy was performed in 15 immunocompromised nude mice with subcutaneously implanted tumors using the non-small-cell lung cancer cell line Lu 1. In group a) 7 mice were sacrificed after definite time intervals and histological examinations were done for evaluation of necrosis and apoptosis (HE; TUNEL assay); 2 mice are in long-term follow-up. In group b) in 6 mice tumor destruction and perfusion before and after freezing were investigated with native and contrast-enhanced MR imaging (T1- and T2-weighted spin-echo) and compared with histopathological findings. Histological control were done in 2 untreated mice.

RESULTS

We observed fast tumor-reduction within two weeks (ca. 50%). On long-term follow-up (> 6 months) no recurrence has been noticed so far. Tumors were well vascularized prior to treatment and did not-show contrast enhancement an any time after cryotherapy. A narrow contrast-enhanced zone was seen on the tumor border subcutaneously as a sign of peripheral hyperemia and central vascular stasis after cryotherapy. On histology there was evidence of both apoptosis and necrosis.

CONCLUSION

We have established a tumor-mouse model for further investigations. Two minutes freezing of a 2-cm tumor in the mouse model is sufficient for tumor ablation with scarred healing. Apoptosis may play a role in cryotherapy of experimental tumors. Contrast-enhanced MRI is suitable for the estimation of the cryolasion.

摘要

目的

本研究旨在从形态学和组织学方面探讨7F冷冻探头经皮使用的疗效,研究冷冻治疗后细胞凋亡的作用,并在肿瘤小鼠模型中比较不同时间间隔的对比增强磁共振成像(MRI)与组织病理学结果。

方法

使用非小细胞肺癌细胞系Lu 1,对15只皮下植入肿瘤的免疫缺陷裸鼠进行经皮冷冻治疗。在a组中,7只小鼠在特定时间间隔后处死,进行组织学检查以评估坏死和凋亡(苏木精-伊红染色;TUNEL检测);2只小鼠进行长期随访。在b组中,对6只小鼠在冷冻前后进行常规和对比增强磁共振成像(T1加权和T2加权自旋回波)以研究肿瘤破坏和灌注情况,并与组织病理学结果进行比较。对2只未治疗的小鼠进行组织学对照。

结果

我们观察到两周内肿瘤快速缩小(约50%)。到目前为止,长期随访(>6个月)未发现复发。治疗前肿瘤血管丰富,冷冻治疗后任何时候均未显示对比增强。冷冻治疗后,在肿瘤皮下边界可见狭窄的对比增强区,提示外周充血和中央血管淤滞。组织学检查显示有凋亡和坏死的证据。

结论

我们建立了一个用于进一步研究的肿瘤小鼠模型。在小鼠模型中,对2 cm肿瘤冷冻2分钟足以实现肿瘤消融并瘢痕愈合。细胞凋亡可能在实验性肿瘤的冷冻治疗中起作用。对比增强MRI适用于评估冷冻消融效果。

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