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非荷瘤猪的临床前大脑冷冻消融。

Preclinical cerebral cryoablation in non-tumor bearing pigs.

机构信息

Department of Neurosurgery, Odense University Hospital, J. B. Winsløws Vej 4, 5000, Odense C, Denmark.

Department of Clinical Research and BRIDGE (Brain Research-Inter Disciplinary Guided Excellence), University of Southern Denmark, Odense, Denmark.

出版信息

Sci Rep. 2022 Feb 7;12(1):1977. doi: 10.1038/s41598-022-05889-2.

DOI:10.1038/s41598-022-05889-2
PMID:35132097
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8821607/
Abstract

Patients with brain metastases, the most common intracranial tumor, have an average survival ranging from a few months to 40 months, and new treatment initiatives are needed. Cryoablation is a minimally invasive, well-tolerated, and effective procedure commonly applied for treatment of renal tumors and certain other malignancies. We aimed to examine the clinical usefulness of this procedure in a step-by-step program starting with cerebral cryoablation in healthy pigs. In four terminal and four non-terminal non-tumor bearing pigs, we studied immediate and delayed effects of cerebral cryoablation. Safety was assessed by computed tomography (CT), and clinical observation of behavior, neurological deficits, and wellbeing. Effects were assessed by histological and immuno-histochemical analyses addressing structural and metabolic changes supported by additional magnetic resonance imaging (MRI) and positron emission tomography (PET) in the non-terminal animals. Using CT-guidance, cryoablation probes were successfully inserted without complications, and ice formation could be monitored real-time with CT. No animal developed neurological deficits or signs of discomfort. Histological and immunohistochemical analyses, MRI, and PET revealed profound structural and biological damage within the lesion. MRI and PET revealed no long-term damage to healthy tissue outside the cryoablation zone. Cerebral cryoablation appears to be a feasible, safe, and controllable procedure that can be monitored successfully with CT. The net effect is a dead brain lesion without damage of either nearby or remote healthy structures. Immediate changes are local hemorrhage and edema; delayed effects are perfusion defects, immune system activation, and astrogliosis.

摘要

脑转移瘤是最常见的颅内肿瘤,患者的平均生存时间为数月至 40 个月,因此需要新的治疗方法。冷冻消融是一种微创、耐受性好且有效的治疗方法,常用于治疗肾肿瘤和某些其他恶性肿瘤。我们旨在通过在健康猪中逐步开展脑冷冻消融来检验该方法的临床应用价值。在 4 只终末期和 4 只非终末期无肿瘤猪中,我们研究了脑冷冻消融的即刻和延迟效应。通过计算机断层扫描(CT)评估安全性,并通过行为、神经功能缺损和健康状况的临床观察评估安全性。通过组织学和免疫组织化学分析评估效果,这些分析涉及结构和代谢变化,并通过非终末期动物的额外磁共振成像(MRI)和正电子发射断层扫描(PET)进行支持。使用 CT 引导,冷冻消融探针成功插入,无并发症,并且可以实时用 CT 监测冰形成。没有动物出现神经功能缺损或不适迹象。组织学和免疫组织化学分析、MRI 和 PET 显示病变内存在严重的结构和生物学损伤。MRI 和 PET 显示冷冻消融区外的健康组织无长期损伤。脑冷冻消融似乎是一种可行、安全且可控制的方法,可以用 CT 成功监测。其净效应是无活力的脑损伤,不会损伤附近或远处的健康结构。即刻变化是局部出血和水肿;延迟效应是灌注缺陷、免疫系统激活和星形胶质增生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/951e/8821607/2686d937d8b7/41598_2022_5889_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/951e/8821607/9dfab41e3eaf/41598_2022_5889_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/951e/8821607/bdeb59b40b44/41598_2022_5889_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/951e/8821607/23ebff7d0b2b/41598_2022_5889_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/951e/8821607/2686d937d8b7/41598_2022_5889_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/951e/8821607/9dfab41e3eaf/41598_2022_5889_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/951e/8821607/5ceced4ee30e/41598_2022_5889_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/951e/8821607/bdeb59b40b44/41598_2022_5889_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/951e/8821607/23ebff7d0b2b/41598_2022_5889_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/951e/8821607/2686d937d8b7/41598_2022_5889_Fig5_HTML.jpg

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J Clin Oncol. 2020 Nov 10;38(32):3773-3784. doi: 10.1200/JCO.20.01255. Epub 2020 Sep 15.
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Validation of a low-cost, carbon dioxide-based cryoablation system for percutaneous tumor ablation.验证一种基于二氧化碳的低成本冷冻消融系统用于经皮肿瘤消融。
PLoS One. 2019 Jul 3;14(7):e0207107. doi: 10.1371/journal.pone.0207107. eCollection 2019.
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A Comparison of Cryoablation with Heat-Based Thermal Ablation for Treatment of Clinical T1a Renal Cell Carcinoma: A National Cancer Database Study.
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J Vasc Interv Radiol. 2019 Jul;30(7):1027-1033.e3. doi: 10.1016/j.jvir.2019.01.029. Epub 2019 Jun 5.
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Stereotactic Cryodestruction of Gliomas.
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