Effects of inflammatory prostatitis on the development and progression of benign prostatic hyperplasia: A literature review.

Benign prostatic hyperplasia is a major disease that affects the quality of life of middle-aged and older men. Although >70% of men aged >70 years have pathological benign prostatic hyperplasia, its pathogenesis and progression remain unclear. In this article, we reviewed the scientific literature on this condition and examined the development of lower urinary tract symptoms. Clinically, the weight of the prostate is not always proportional to the severity of the symptoms, and many factors can influence the progression of benign prostatic hyperplasia. Other than androgens, chronic inflammation can play an essential role in its development and the induction of symptoms, especially in symptomatic hyperplasia, because inflammatory cell infiltration is frequently observed in the prostate. Inflammation-induced changes in the prostate environment lead to changes in gene expression and subsequent chronicity of inflammation. It has been suggested that chronic asymptomatic prostatitis might be associated with changes in prostate structure and subsequent symptoms. In animal studies, the administration of anti-inflammatory drugs in rats with chronic prostatitis prevented the infiltration of inflammatory cells and increased the gland-to-stroma ratio. It is hoped that future research on the molecular biology of asymptomatic prostatitis might help to develop new therapeutic strategies for lower urinary tract symptoms associated with symptomatic prostatitis. Our conclusions provide a comprehensive insight into the prevalence and development of benign prostate hyperplasia and the treatment methods that can be used to treat it.

CLINICAL OUTCOMES OF EXTERNAL-BEAM RADIOTHERAPY COMBINED WITH NEOADJUVANT ANDROGEN DEPRIVATION THERAPY FOR HIGH-RISK PROSTATE CANCER.

(Purpose) We investigated the outcome of external-beam radiotherapy (EBRT) with neoadjuvant androgen deprivation therapy (NeoADT) for high-risk prostate cancer defined by National Comprehensive Cancer Network (NCCN) guideline. (Patients and method) From 2002 to 2013, 70 patients with high-risk prostate cancer (PSA ≥20 ng/ml or clinical T stage ≥T3a, Gleason score ≥8) were treated with NeoADT and EBRT. EBRT consisted of three-dimensional conformal or intensity modulated radiotherapy with or without whole-pelvic radiation. Biochemical failure was defined according to the Phoenix definition. Biochemical progression-free survival (bPFS) and overall survival (OS) were calculated by Kaplan-Meier method, and prognostic factors for bPFS were analyzed by using the Cox proportional hazard model. (Result) The median age and initial prostate-specific antigen (PSA) level were 72 years old and 25.2 ng/ml, respectively. 43 patients had PSA level ≥20 ng/ml, 51 patients had clinical stage ≥T3a, 27 patients had Gleason score ≥8. The number of risk factors patients possessed was 1 (RiskN-1) in 31 patients, 2 (RiskN-2) in 27 patients and 3 (RiskN-3) in 12 patients. Median EBRT dose and duration of Neo ADT were 74 Gy and13.0 months, respectively. Whole-pelvic radiation was administered in 7 patients. After median follow-up of 4.8 years, biochemical and clinical failure occurred in 23 and 2 patients, respectively. No patients died of cancer. Five-year/8-year bPFS and OS were 63%/54% and 100%/91%, respectively. In multivariate analysis, three high-risk factor of NCCN guideline (PSA, clinical stage, Gleason score) did not predict outcome after EBRT independently, but RiskN (-1 vs -2, 3, HR 35.35, 95%CI 2.51-498.05, p<0.01) and pre-EBRT PSA (continuous, hazard ratio 1.31, 95%CI 1.01-1.71, p<0.05) were the significant predictors of bPFS. Five-year/8-year bPFS in RiskN-1 group and RiskN-2 or -3 group were 89%/79% and 47%/39%, respectively. Grade 3/4 adverse events (CTCAE ver4.0-JCOG) occurred in 2 patients. (Conclusion) Median dose of 74 Gy EBRT with intermediate-term NeoADT was safe and beneficial for high-risk prostate cancer. The number of risk factors and pre-EBRT PSA level were the independent prognostic factors for biochemical progression-free survival.

Case of vascular air embolism during holmium laser enucleation of the prostate.

Vascular air embolism is a rare complication during transurethral surgery. A case of air embolism during holmium laser enucleation of the prostate in a 76-year-old man is presented. During the step of morcellation, the patient's blood pressure suddenly oscillated up and down, and end-tidal CO2 and arterial saturation decreased. Transesophageal and transthoracic echocardiography showed air collection in the right atrium. It was also discovered that incorrect assembly of the tube from the morcellator caused rapid entrainment of air into the vein. Computed tomography and abdominal X-ray showed niveau formation in the femoral vein and air collection in the pelvic retroperitoneal space. The patient recovered with careful observation and was discharged 7 days after the operation with no sequelae. This report is presented to remind urologists of this unusual complication that can occur during holmium laser enucleation of the prostate procedures.

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 17ß-estradiol for 30 days. Ventral prostate lobes were histopathologically examined with Masson's 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.

Effect of a phytotherapeutic agent, Eviprostat®, on prostatic and urinary cytokines/chemokines in a rat model of nonbacterial prostatitis.

BACKGROUND: Chronic inflammation in the prostate has recently been recognized as an important component of the symptom progression of benign prostatic hyperplasia. The objective of this study was to evaluate a range of cytokines/chemokines in prostate tissue and urine to identify markers of prostate inflammation in a prostatitis model and to investigate the effect of a phytotherapeutic agent, Eviprostat®, on these markers. METHODS: Ten-month-old male Wistar rats were divided into four groups. Nonbacterial prostatitis (NBP) was experimentally induced in groups 2-4 by castration followed by daily subcutaneous injection of 17ß-estradiol for 30 days. Control rats were fed a standard diet, while animals in the Eviprostat groups were fed a diet containing 0.05 or 0.1% Eviprostat for 30 days. The levels of cytokines/chemokines in prostate tissue on the 31st day and in urine collected the day before castration and the day before removal of the prostate were determined. RESULTS: Experimentally induced NBP increased the prostatic levels of the cytokines interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α). The levels of the chemokines CCL2/monocyte chemoattractant protein-1 (MCP-1), CCL3/macrophage inflammatory protein-1α (MIP-1α), CXCL1/CINC-1, CXCL3/CINC-2, and CXCL5/LIX were elevated in both prostate and urine. Eviprostat significantly suppressed the increases in prostate IL-1ß, TNF-α and CCL3/MIP-1α and prostatic and urinary CCL2/MCP-1 and CXCL1/CINC-1. CONCLUSIONS: Chemokines, including CCL2/MCP-1 and CXCL1/CINC-1, were elevated in the prostate and urine of NBP rats, and Eviprostat potently suppressed the increases in CCL2/MCP-1 and CXCL1/CINC-1. These chemokines are therefore candidate diagnostic biomarkers for nonbacterial chronic prostatic inflammation.