Rikiya Taoka

Effect of the Phytotherapeutic Agent Eviprostat on Inflammatory Changes and Cytokine Production in a Rat Model of Nonbacterial Prostatitis

OBJECTIVES To examine the effect of the phytotherapeutic agent Eviprostat on the stromal-to-epithelial (S/E) ratio, level of macrophage infiltration, expression of the macrophage inhibitory cytokine-1 (Mic1) gene, and tumor necrosis factor-alpha (TNF-α) and interleukin-8 (IL-8) concentrations in prostate tissues in a rat model of nonbacterial prostatitis (NBP). MATERIALS AND METHODS Ten-month old Wistar rats were divided into 4 groups of 10: (1) NBP non-mixed feed (prostatitis control group); (2) NBP Eviprostat (0.1%) mixed feed (prostatitis Eviprostat group); (3) non-NBP non-mixed feed (nonprostatitis control group); and (4) non-NBP Eviprostat mixed-feed (nonprostatitis Eviprostat group). NBP was induced by castration followed by daily subcutaneous injection of 17β-estradiol for 30 days. Ventral prostate lobes were histopathologically examined with Massons trichrome staining or immunostaining with antimacrophage antibody. Mic1 mRNA levels were quantified by real-time reverse transcriptase polymerase chain reaction. Tissue concentrations of TNF-α and IL-8 were determined by enzyme-linked immunosorbent assay. RESULTS Stroma was the most abundant in prostatitis control rats. The mean S/E ratio in prostatitis Eviprostat rats was significantly lower than in prostatitis control rats (P < .0001). The high levels of macrophage infiltration found in prostatitis control rats were significantly reduced in prostatitis Eviprostat rats (P < .0001). The up-regulation of the Mic1 gene observed in prostatitis control rat prostates was significantly suppressed in prostatitis Eviprostat rats (P < .0001). A marked suppression of TNF-α and IL-8 secretion was also observed in prostatitis Eviprostat rats (P < .05). CONCLUSIONS Eviprostat significantly suppressed the S/E ratio, level of macrophage infiltration, Mic1 gene expression, and proinflammatory cytokines/chemokines in the prostate in a rat NBP model.

Influence of Inflammation and Aging on Macrophage Inhibitory Cytokine-1 Gene Expression in Rat Ventral Prostate

OBJECTIVES We have previously reported that the macrophage inhibitory cytokine-1 (MIC-1) gene is downregulated in human symptomatic benign prostatic hyperplasia. The aim of this study was to investigate the histologic changes and MIC-1 gene expression in the prostate of young nonbacterial prostatitis model (Y-NBP) and aging rats. METHODS A total of 35 Wistar male rats, 13 weeks old, were castrated and subjected to (a) castration alone for 14 days, (b) Y-NBP-14d (0.25 mg/2 mL/kg beta-estradiol injection for 14 days), or (c) Y-NBP-30d (beta-estradiol injection for 30 days). A total of 5 male rats, 10 months old, were also analyzed. We used 21 male rats, 13 weeks old, who had undergone sham surgery as the controls. The ventral lobes of the prostate were histologically examined with Massons trichrome staining or immunostaining using an anti-macrophage antibody. The MIC-1 mRNA levels were quantitatively assessed using real-time reverse transcriptase-polymerase chain reaction. RESULTS The MIC-1 gene mRNA levels in the castration alone, Y-NBP-14d, and Y-NBP-30d rat prostates were greater than those in the control rats (P < .005). In contrast, those of the 10-month-old rats were lower than those of the controls (P = .0093). The mean stroma-to-epithelium ratio in the Y-NBP-30d rats, 10-month-old rats, and 13-week-old controls was 1.28, 0.26, and 0.10, respectively (Y-NBP-30d vs 10-month-old rats, P = .0008; 10-month-old vs 13-week-old rats, P = .001). The number of infiltrating macrophages in the Y-NBP-14d, Y-NBP-30d, and 10-month-old rats was greater than that of the 13-week-old controls (P < .001). CONCLUSIONS Castration causes induction of MIC-1 gene expression. Estradiol treatment has little effect on MIC-1 gene expression but causes a significant increase in the stroma-to-epithelium ratio. The aging rat prostate is more similar to human benign prostatic hyperplasia than is the Y-NBP model in light of MIC-1 gene expression and histologic changes.

The influence of asymptomatic inflammatory prostatitis on the onset and progression of lower urinary tract symptoms in men with histologic benign prostatic hyperplasia

Benign prostatic hyperplasia (BPH) is a condition that greatly affects the quality of life of middle-aged and elderly men. Histopathologically, hyperplastic changes frequently occur in the prostate tissue of elderly men, the incidence of which has been reported to reach approximately 80% in men in their 70s. In clinical practice, approximately 25% of men with histologic BPH are assumed to experience lower urinary tract symptoms (LUTS) and receive some kind of treatment. In other words, there are some men with histologic BPH who do not exhibit LUTS. For that reason, many factors, such as the change in hormonal environment, the immune or autoimmune response, the alteration of gene expression, and so on, are thought to affect the onset and progression of LUTS in men with histologic BPH. One such factor that has long drawn attention is the presence of asymptomatic histological inflammation, which very often accompanies symptomatic BPH. Recent studies have suggested that asymptomatic histological inflammation causes repeated destruction, healing, and regeneration of the prostate tissue, leading to the enlargement of prostatic nodules, while at the same time causing stromal tissue-predominant remodeling of the prostate tissue, which can increase urination resistance and result in the condition changing from asymptomatic BPH to symptomatic BPH. In future, the biomolecular clarification of the significance of asymptomatic histological inflammation in the prostate tissue could help develop new treatment strategies for BPH accompanied by LUTS.

Evidenced‐based clinical practice guideline for prostate cancer (summary: Japanese Urological Association, 2016 edition)

These guidelines cover a wide range of topics from prostate cancer epidemiology to palliative care. Questions arising in daily clinical practice have been extracted and formulated as clinical questions. In the 4 years since the previous edition, there have been major changes – for example, robot‐assisted prostatectomy has rapidly come into widespread use, and new hormones and anticancer drugs have been developed for castration‐resistant prostate cancer. In response to these developments, the number of fields included in this guideline was increased from 11 in the 2012 edition to 16, and the number of clinical questions was increased from 63 to 70. The number of papers identified in searches of the existing literature increased from 4662 in the first edition, published in 2006, to 10 490 in the 2012 edition. The number of references has reached 29 448 just during this review period, indicating the exponential increase in research on the topic of prostate cancer. Clinical answers have been prepared based on the latest evidence. Recommendation grades for the clinical answers were determined by radiologists, pathologists, and other specialists in addition to urologists in order to reflect the recent advances and diversity of prostate cancer treatment. Here, we present a short English version of the original guideline, and overview its key clinical issues.

The Effect of Steep Trendelenburg Positioning on Retinal Structure and Function during Robotic-Assisted Laparoscopic Procedures

Purpose Robotic-assisted laparoscopic radical prostatectomy (RALP) has become a standard treatment choice for localized prostate cancer. RALP requires a steep Trendelenburg position, which leads to a significant increase in intraocular pressure (IOP). This study evaluated the effect on the retinal structure and function in patients undergoing RALP. Methods Standard automated perimetry (SAP) and optical coherence tomography (OCT) were performed in 20 males scheduled for RALP at 1 month and 1 day before the operation and at 1 and 3 months after the operation. IOP measurements were made in the supine position at 5 min after intubation under general anesthesia (T1), at 6 discrete time points (5, 30, 60, 120, 180, and 240 min; T2-7), and at 5 min after returning to a horizontal supine position (T8). Serial retinal nerve fiber layer (RNFL) thicknesses and visual field progression were assessed using the guided progression analysis software program. RNFL thickness progression and visual field progression were evaluated by event analysis. Results Average IOP (mmHg) for each time point was as follows: T1 = 12.3 ± 2.6, T2 = 20.4 ± 4.2, T3 = 23.3 ± 3.8, T4 = 24.0 ± 3.2, T5 = 24.3 ± 3.4, T6 = 27.1 ± 7.2, T7 = 29.8 ± 8.7, and T8 = 20.1 ± 4.4. During RALP, IOP significantly increased. There was no progression of the visual field and RNFL thickness after surgery or any other ocular complications found. Conclusions Although IOP significantly increased during RALP, there were no significant changes in the retinal structure and function between the pre- and postoperation observations.