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热疗法对人良性前列腺增生疗效的体外评估

In vitro assessment of the efficacy of thermal therapy in human benign prostatic hyperplasia.

作者信息

Bhowmick P, Coad J E, Bhowmick S, Pryor J L, Larson T, De La Rosette J, Bischof J C

机构信息

Department of Public Health, University of Minnesota, Minneapolis, Minnesota 55455, USA.

出版信息

Int J Hyperthermia. 2004 Jun;20(4):421-39. doi: 10.1080/02656730310001637343.

Abstract

The successful management of BPH with minimally invasive thermal therapies requires a firm understanding of the temperature-time relationship for tissue destruction. In order to accomplish this objective, the present in vitro study assesses the cellular viability of human BPH tissue subjected to an experimental matrix of different temperature-time combinations. Hyperplastic prostate tissue was obtained from 10 radical prostatectomy specimens resected for adenocarcinoma. A portion of hyperplastic tissue from the lateral lobe of each prostate was sectioned into multiple 1 mm thick tissue strips, placed on a coverslip and thermally treated on a controlled temperature copper block with various temperatures (45-70 degrees C) for various times (1-60 min). After heat treatment, the tissue slices were cultured for 72 h and viability was assessed using two independent assays: histology and dye uptake for stromal tissue and using histology alone for the glandular tissue. The hyperplastic human prostate tissue showed a progressive histological increase in irreversible injury with increasing temperature-time severity. The dye uptake and histology results for stromal viability were similar for all temperature-time combinations. In vitro thermal injury showed 85-90% stromal destruction (raw data) of human BPH for temperature-time combinations of 45 degrees C for 60 min, 50 degrees C for 30 min, 55 degrees C for 5 min, 60 degrees C for 2 min and 70 degrees C for 1 min. Apoptosis was also identified in the control and milder treated tissues with the degree of glandular apoptosis (about 20%) more than that seen in the stromal regions (< 5%). The Arrhenius model of injury was fitted to the data for conditions leading to a 90% drop in viability (normalized to control) obtained for stromal tissue. The activation energies (E) were 40.1 and 38.4 kcal/mole for the dye uptake study and histology, respectively, and the corresponding frequency factors (A) were 1.1 x 10(24) and 7.78 x 10(22)/s. This study presents the first temperature-time versus tissue destruction relation for human BPH tissue. Moreover, it supports the concept that higher temperatures can be used for shorter durations to induce tissue injury comparable with the current clinically recommended lower temperature-longer time treatments (i.e. 45 degrees C for 60 min) for transurethral microwave thermotherapy of the prostate.

摘要

采用微创热疗法成功治疗良性前列腺增生(BPH)需要深入理解组织破坏的温度 - 时间关系。为实现这一目标,本体外研究评估了人BPH组织在不同温度 - 时间组合实验条件下的细胞活力。增生性前列腺组织取自10例因腺癌而切除的根治性前列腺切除术标本。将每个前列腺侧叶的一部分增生组织切成多个1毫米厚的组织条,置于盖玻片上,并在可控温度的铜块上用不同温度(45 - 70摄氏度)处理不同时间(1 - 60分钟)。热处理后,将组织切片培养72小时,并使用两种独立的检测方法评估活力:对基质组织采用组织学和染料摄取检测,对腺组织仅采用组织学检测。随着温度 - 时间严重程度的增加,增生性人前列腺组织的不可逆损伤在组织学上呈渐进性增加。对于所有温度 - 时间组合,基质活力的染料摄取和组织学结果相似。体外热损伤显示,对于45摄氏度60分钟、50摄氏度30分钟、55摄氏度5分钟、60摄氏度2分钟和70摄氏度1分钟的温度 - 时间组合,人BPH的基质破坏率为85 - 90%(原始数据)。在对照组织和轻度处理的组织中也发现了凋亡,腺细胞凋亡程度(约20%)高于基质区域(<5%)。将损伤的阿伦尼乌斯模型拟合到基质组织活力下降90%(相对于对照进行归一化)的条件下的数据。染料摄取研究和组织学的活化能(E)分别为40.1和38.4千卡/摩尔,相应的频率因子(A)分别为1.1×10²⁴和7.78×10²²/秒。本研究首次呈现了人BPH组织的温度 - 时间与组织破坏关系。此外,它支持了这样一种概念,即较高温度可用于较短时间以诱导与当前临床推荐的较低温度 - 较长时间治疗(即45摄氏度60分钟)相当的组织损伤,用于前列腺经尿道微波热疗。

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