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钇-90 门静脉放射性栓塞在 Sprague-Dawley 大鼠中的应用:正常肝脏的剂量依赖性成像和病理变化。

Yttrium-90 Portal Vein Radioembolization in Sprague-Dawley Rats: Dose-Dependent Imaging and Pathological Changes in Normal Liver.

机构信息

Department of Radiology, Northwestern University Feinberg School of Medicine, 676 N. St. Clair, Suite 800, Chicago, IL, 60611, USA.

Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA.

出版信息

Cardiovasc Intervent Radiol. 2020 Dec;43(12):1925-1935. doi: 10.1007/s00270-020-02614-2. Epub 2020 Aug 16.

DOI:10.1007/s00270-020-02614-2
PMID:32803285
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7655630/
Abstract

PURPOSE

Portal vein embolization (PVE) is an established neoadjuvant method to induce future liver remnant hypertrophy prior to surgical resection of hepatic tumors. The purpose of our study was to examine the feasibility of PVE with glass Y microspheres (Y90 PVE) in Sprague-Dawley rats. We tested the hypothesis that increased doses of Y90 PVE would increase target lobe fibrosis and atrophy.

METHODS

Twenty-two rats were assigned to four groups for Y90 PVE to the right median lobe: very high- (273.8 MBq; n = 2), high- (99.9 MBq; n = 10), medium- (48.1 MBq; n = 5), and low-dose (14.8 MBq; n = 5). An untreated control group included seven rats. Y PET/CT of Y distributions confirmed lobar targeting. MRI volumes were measured at baseline, 2-, 4-, 8- and 12-weeks. Explanted hepatic lobes were weighed, sectioned, and stained for H&E and immunohistochemistry. Digitized slides allowed quantitative measurements of fibrosis (20 foci/slide).

RESULTS

Ex vivo measurements confirmed 91-97% activity was localized to the target lobe (n = 4). The percent growth of the target lobe relative to baseline was - 5.0% (95% CI - 17.0-6.9%) for high-, medium dose rats compared to + 18.6% (95% CI + 7.6-29.7%) in the low-dose group at 12-weeks (p = 0.0043). Radiation fibrosis increased in a dose-dependent fashion. Fibrotic area/microsphere was 22,893.5, 14,946.2 ± 2253.3, 15,304.5 ± 4716.6, and 5268.8 ± 2297.2 μm for very high- (n = 1), high- (n = 4), medium- (n = 3), and low-dose groups (n = 5), respectively.

CONCLUSION

Y90 PVE was feasible in the rat model, resulted in target lobe atrophy, and dose-dependent increases in hepatic fibrosis at 12 weeks. The onset of imaging-based volumetric changes was 8-12 weeks.

摘要

目的

门静脉栓塞术(PVE)是一种成熟的新辅助方法,可在肝肿瘤手术切除前诱导未来肝残块的肥大。我们研究的目的是检查使用玻璃 Y 微球(Y90PVE)对 Sprague-Dawley 大鼠进行 PVE 的可行性。我们验证了这样一个假设,即增加 Y90PVE 的剂量会增加靶叶纤维化和萎缩。

方法

22 只大鼠被分为四组进行右中叶 Y90PVE:极高剂量(273.8MBq;n=2)、高剂量(99.9MBq;n=10)、中剂量(48.1MBq;n=5)和低剂量(14.8MBq;n=5)。未治疗的对照组包括 7 只大鼠。Y 正电子发射断层扫描/计算机断层扫描(PET/CT)确认了叶定位。在基线、2 周、4 周、8 周和 12 周时测量 MRI 体积。取出的肝叶称重、切片、用 H&E 和免疫组化染色。数字化切片允许对纤维化(20 个焦点/幻灯片)进行定量测量。

结果

离体测量证实 91-97%的活性定位于靶叶(n=4)。与低剂量组 12 周时+18.6%(95%置信区间+7.6-29.7%)相比,高剂量和中剂量组靶叶相对于基线的生长百分比分别为-5.0%(95%置信区间-17.0-6.9%)(p=0.0043)。辐射纤维化呈剂量依赖性增加。非常高剂量组(n=1)、高剂量组(n=4)、中剂量组(n=3)和低剂量组(n=5)的纤维性区域/微球分别为 22893.5、14946.2±2253.3、15304.5±4716.6 和 5268.8±2297.2μm。

结论

Y90PVE 在大鼠模型中是可行的,可导致靶叶萎缩,并在 12 周时导致肝纤维化的剂量依赖性增加。基于成像的体积变化的发生时间为 8-12 周。

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Extended liver venous deprivation before major hepatectomy induces marked and very rapid increase in future liver remnant function.在进行大范围肝切除术之前进行延长的肝静脉阻断可导致未来肝残余功能显著且非常迅速地增强。
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(90) Y radiation lobectomy: Outcomes following surgical resection in patients with hepatic tumors and small future liver remnant volumes.(90) Y 射线肝叶切除术:肝肿瘤患者手术切除后及未来肝残余体积较小时的预后情况。
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