Evaluation of prostate volume by transrectal ultrasonography for use in a brachytherapy program.

OBJECTIVES: To evaluate two methods of measuring the prostate volume using transrectal ultrasonography. The measurements were performed in vivo at preplanning and again preoperatively in connection with brachytherapy. The accurate measurement of the prostate volume is important in a brachytherapy program for treatment planning. METHODS: A total of 43 patients with biopsy-proven prostate cancer underwent prospective determination of the prostate volume, by one physician, using transrectal ultrasonography. Volume calculations were made at the preplanning and preoperative settings, both by a hand-held rectal probe using the prolate ellipsoid formula and by a mounted probe in a stepping device using the planimetric method. RESULTS: The coefficient of variation between the preplanning and preoperative prostate volumes with the probe holder was less than 3% compared with the hand-held probe, which was greater than 10%. The difference between the median values at the preplanning and preoperative settings by serial planimetry was 2.5 cm(3) (range 0.2 to 9.4). The difference in the median volumes between the preplanning and preoperative ellipsoid calculations was 6.7 cm(3) (range 0.3 to 38.7). The difference between the median values with the ellipsoid volume was significant (P <0.001). The Pearson correlation coefficient for all values using the planimetric method was 0.92 versus 0.58 for the ellipsoid method. The correlation coefficient was significantly greater for the planimetric method (P <0.001). CONCLUSIONS: On the basis of these data, planimetric prostate volume determination, by a single ultrasonographer, is an accurate and reproducible method with applicability to a brachytherapy program.

Mitoxantrone in patients with prostate specific antigen progression after local therapy for prostate carcinoma.

BACKGROUND: Molecular mechanisms of chemotherapy resistance are present in prostate carcinoma, some of which increase after androgen ablation (AA) therapy. Therefore, the authors hypothesized that chemotherapy in patients with prostate specific antigen (PSA) progression after local therapy, before androgen ablation therapy, will have greater antitumor activity. METHODS: Twenty-three hormone-naive patients with PSA progression after prostatectomy or radiation therapy were registered in this study. Twenty-two were treated with 10 mg/m(2) of mitoxantrone initially, followed by 12 mg/m(2) every 3 weeks for a maximum of 8 cycles. Prostatectomy specimens were assessed, when possible, for topoisomerase II alpha, multidrug resistance protein MRP, and bcl-2 by immunohistochemistry. RESULTS: Twenty-two patients received a total of 131 cycles of therapy. Three patients had transient Grade 3 or 4 neutropenia without fever. During treatment, 10 of 22 patients showed a decrease in PSA, without an associated decrease in testosterone. In this group of 10 patients, the mean PSA decrease was 29% at 3 months and 43% at 6 months. Overall, 4 of 22 patients had a decrease in PSA of greater than or equal to 50%. The PSA decreased in three of seven patients whose cancer overexpressed MRP and in three of seven patients who overexpressed bcl-2. No patient with overexpression of topoisomerase II alpha (n = 4) had a decrease in PSA during the study. CONCLUSIONS: To the authors' knowledge, this is the first reported study of mitoxantrone in patients with hormone-naive prostate carcinoma and PSA progression after local therapy; mitoxantrone was safe and biochemically active, similar to prior studies in hormone refractory prostate carcinoma, suggesting that critical molecular mechanisms of chemotherapy resistance are present independent of AA. Further studies are warranted to determine whether pharmacogenomic assessment of topoisomerase II, MRP, or bcl-2 may predict for response to mitoxantrone.

Diminished neurogenic but not pharmacological erections in the 2- to 3-month experimentally diabetic F-344 rat.

The rapid spread of locally restricted neural and hormonal signals among the vast array of largely inexcitable corporal smooth muscle cells is an absolute prerequisite to normal erectile function. And yet the mechanism(s) responsible for this phenomenon is not well understood. As a first step toward a more integrative understanding of erectile physiology and/or dysfunction, an 8- to 12-wk period of experimental diabetes was induced in 2-mo-old male Fischer 344 rats by either intraperitoneal streptozotocin (STZ) injection (35 mg/kg; n = 22) or subtotal pancreatectomy (n = 11). Fourteen age-matched control animals received injection of vehicle only while nine others served as sham-operated control animals. Eight STZ-diabetic animals received insulin replacement. Erectile function was assessed by evaluation of penile reflexes and monitoring of intracavernous pressure responses to both electrical stimulation of the cavernous nerve and intracorporal papaverine or nitroglycerin injection. Intracavernous pressure responses to neurostimulation were significantly attenuated in both STZ-diabetic and subtotal pancreatectomy animals compared with age-matched control animals (P < 0.05). Penile reflexes were also significantly diminished (P < 0.05). Regression analysis revealed that diabetes-related decreases in neurostimulated intracavernous pressure responses were strongly correlated with diminished synaptophysin immunoreactivity in the corpora (P < 0.001; r = 0.88). However, there were no detectable diabetes-related differences in pharmacological erections induced by intracavernous papaverine or nitroglycerin injection. Northern analysis revealed a marked diabetes-related increase in the amount of connexin 43 mRNA measured in frozen corporal tissue. Insulin replacement partially restored (attenuated the loss of) synaptophysin immunoreactivity and maintained neurostimulated intracavernous pressure responses to control levels while having no effect on penile reflexes. These observations may have important implications to the understanding of erectile physiology as well as the etiology of diabetes-related erectile dysfunction.