In vitroassessment of the efficacy of thermal therapy in human benign prostatic hyperplasia

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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 (45-70degreesC) 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 45degreesC for 60 min, 50degreesC for 30 min, 55degreesC for 5 min, 60degreesC for 2 min and 70degreesC 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&DEG;C for 60 min) for transurethral microwave thermotherapy of the prostat