Fumimasa Fukuta

A Randomized Controlled Study of the Efficacy of Tamsulosin Monotherapy and its Combination with Mirabegron for Overactive Bladder Induced by Benign Prostatic Obstruction

PURPOSE We evaluated the efficacy and safety of add-on treatment with a β3-adrenoceptor agonist (mirabegron) for overactive bladder symptoms remaining after α1-blocker (tamsulosin) treatment in men with benign prostatic obstruction. MATERIALS AND METHODS Patients with benign prostatic obstruction with urinary urgency at least once per week and a total OABSS of 3 or more points after 8 or more weeks of treatment with tamsulosin were enrolled in the study. They were randomly allocated to receive 0.2 mg tamsulosin daily or 0.2 mg tamsulosin and 50 mg mirabegron daily for 8 weeks. The primary end point was change in total OABSS. Safety assessments included change in post-void residual urine volume and adverse events. RESULTS From January 2012 through September 2013 a total of 94 patients were randomized. Of these patients 76 completed the protocol treatment. In the full analysis set the change in total OABSS during the treatment period was significantly greater in the combination group than in the monotherapy group (-2.21 vs -0.87, p=0.012). The changes in scores for urinary urgency, daytime frequency, International Prostate Symptom Score storage symptom subscore and quality of life index at 8 weeks were significantly greater in the combination group. The change in post-void residual urine volume was significantly greater in the combination group. Although 6 patients experienced adverse events in the combination group, urinary retention was observed in only 1 patient. CONCLUSIONS Combined tamsulosin and mirabegron treatment is effective and safe for patients with benign prostatic obstruction who have overactive bladder symptoms after tamsulosin monotherapy.

Influence of isoflavone intake and equol-producing intestinal flora on prostate cancer risk.

BACKGROUND The age-adjusted incidence rate of prostate cancer (PCa) has been reported to be lower among Asians than Western populations. A traditional Japanese meal, high in soybean products or isoflavones, may be associated with a decreased risk of PCa. Equol, which is converted from daidzein by human intestinal flora, is biologically more active than any other isoflavone aglycone. MATERIALS AND METHODS We reviewed not only recent epidemiological studies on association of isoflavones with PCa risk, but also recent research on human intestinal bacteria responsible for converting daidzein into equol. Studies were systematically searched from the database published within the last 5 years of from 2008-2012. RESULTS Five out of 6 articles showed significant association of isoflavones with a decreased risk of PCa, and two of them consistently showed that equol-producers carry a significantly reduced risk of PCa. Furthermore, 5 human intestinal bacteria that can convert daidzein into equol were identified in the last 5 years. CONCLUSIONS If equol can reduce risk of PCa, a possible strategy for reducing the risk of PCa may be to increase the proportion of equol-producers by changing the intestinal flora to carrying an equol-producing bacterium with dietary alteration or probiotic technology.

Prognostic impact of the expression of ALDH1 and SOX2 in urothelial cancer of the upper urinary tract

Aldehyde dehydrogenase 1 (ALDH1) and sex determining region-Y-related high mobility group box 2 (SOX2) have been identified as putative cancer stem-like cell/tumor-initiating cell markers in various cancer tissues. The aim of this study was to elucidate the prognostic impact of these putative cancer stem-like cell/tumor-initiating cell markers in upper urinary tract urothelial cell carcinoma. Immunohistochemical staining for ALDH1 and SOX2 was carried out on archival specimens from 125 patients with upper urinary tract urothelial cell carcinoma who underwent radical nephroureterectomy. The prognostic value of ALDH1 and SOX2 expression and other clinicopathological features was evaluated. On univariate analysis, tumor grade, pathological T stage, pathological N stage, lymphovascular invasion, ALDH1 expression and SOX2 expression were associated with a poor prognosis. On multivariate analysis, the independent factors of prognosis were tumor grade (P=0.014), pathological N stage (P=0.005) and ALDH1 expression (P=0.002). In subgroup analysis, those subgroups with no positive, one positive or two positive results in immunohistochemistry for ALDH1 and SOX2 expression had estimated 5-year cancer-specific survival rates of 80%, 49% and 22%, respectively (P<0.001). Neither ALDH1 nor SOX2 expression correlated with intravesical recurrence after radical nephroureterectomy. These findings suggest that cancer stem-like cells/tumor-initiating cells are linked to more aggressive behavior of upper urinary tract urothelial cell carcinoma, supporting the current cancer stem cell hypothesis. Thus, therapeutic targeting of cancer stem-like cells/tumor-initiating cells in upper urinary tract urothelial cell carcinoma is a future possibility.

Paclitaxel, ifosfamide, and nedaplatin as second-line treatment for patients with metastatic urothelial carcinoma: A phase II study of the SUOC group

There is no standard second‐line chemotherapy treatment for recurrent or metastatic urothelial cancer (MUC). The purpose of this phase II study was to evaluate the efficacy and toxicity of the three‐drug combination of paclitaxel, ifosfamide, and nedaplatin (TIN). Patients with MUC were eligible after treatment failure with methotrexate, vinblastine, doxorubicin, and cisplatin, or gemcitabine and cisplatin. Doses for TIN therapy were paclitaxel 175 mg/m2 on day 1, ifosfamide 1500 mg/m2 on days 1–3, and nedaplatin 70 mg/m2 on day 1, every 4 weeks. Tumor response, the primary efficacy parameter, was assessed according to unidimensional measurements (Response Evaluation Criteria in Solid Tumors criteria, version 1.0). Secondary efficacy parameters were overall survival (OS) and progression‐free survival (PFS). Toxicity was assessed according to the National Cancer Institute Common Toxicity Criteria, version 3.0. A total of 45 patients (13 females and 32 males) with MUC were evaluable for response and toxicity. The overall response rate was 40.0%. Median PFS time was 4.0 months (95% confidence interval [CI], 4.6–11.6). Median OS time was 8.9 months (95% CI, 10.5–18.9). Grade 3 or 4 hematologic adverse events were neutropenia (95.6%), anemia (15.6%), and thrombocytopenia (17.8%). The most common grade 3 or 4 non‐hematologic adverse events were anorexia (4.4%) and elevated aspartate transaminase/alanine transaminase (2.2%). No toxic death was observed. The main limitation of this study is that only 10 patients (22.2%) who were previously treated with gemcitabine and cisplatin were included. In conclusion, TIN as second‐line treatment for MUC is an active regimen with a manageable toxicity profile. (Cancer Sci 2011; 102: 1171–1175)

Natural history of lower urinary tract symptoms in Japanese men from a 15-year longitudinal community-based study.

Study Type – Symptom prevalence (cohort)

Traditional Japanese diet and prostate cancer.

The traditional Japanese diet has been suggested by some researchers to be associated with a decreased risk of prostate cancer (PCa). In this paper, we assumed the following three characteristics of the traditional Japanese diet high in soybean products, high in fish, and low in red meat. Isoflavones, polyunsaturated long chain (n - 3) fatty acids, and saturated fatty acids were thought to be micronutrients in biological etiology relevant to soybean products, fish, and red meat, respectively. Analytical epidemiological studies on the risk of PCa were identified using the MEDLINE database from 1998 to 2007. Some published studies showed a negative association of soybean products and isoflavones to PCa risk, an inverse association for fish or polyunsaturated long chain (n - 3) fatty acids such as eicosapentaenic acid (EPA) and docosahexaenoic acid (DHA) with PCa risk, and a positive association of red meat or saturated fatty acids with PCa risk, respectively. In conclusion, although it is possible that the traditional Japanese diet may reduce the risk of PCa through a combination of characteristics such as being high in soybean products, high in fish, and low in red meat, further well-designed epidemiological studies such as nested case-control studies with nutritional analyses of blood samples are needed to confirm this association.

Prognostic Value of Surgical Margin Status for Biochemical Recurrence Following Radical Prostatectomy

OBJECTIVE We evaluated the preoperative parameters to predict a positive surgical margin (SM) at radical prostatectomy for patients with prostate cancer. In addition, the prognostic factors for biochemical recurrence were determined in patients with positive SMs. METHODS We retrospectively analysed 238 patients with prostate cancer who underwent retropubic radical prostatectomy and bilateral pelvic lymph node dissection from May 1985 to July 2005 in our hospital. Biochemical recurrence was defined as an increase of undetectable prostate-specific antigen (PSA) to 0.2 ng/ml or greater. RESULTS Of the 238, 82 patients (34.4%) had positive SMs. On multivariate analysis, preoperative PSA (>/=10 ng/ml), clinical T stage (>/=T2a) and the positive core rate (>/=35%) were parameters that could predict a positive SM. During the median follow-up of 31.2 months, 48 patients (20.2%) developed biochemical recurrence. The 5-year biochemical progression-free survival rates were 81.7% and 62.6% in patients with negative and positive SMs, respectively (P < 0.001). In the Cox proportional hazards model, preoperative PSA of >/=20 ng/ml and a pathological T stage of pT3a/pT3b were significant risk factors for biochemical recurrence in patients with positive SMs. CONCLUSIONS SM status at radical prostatectomy depends on preoperative PSA, clinical stage and the positive core rate. Patients with a positive SM had a higher risk for biochemical recurrence than those with a negative one. Patients with a positive margin had a higher risk for biochemical recurrence if they exhibited preoperative PSA of >/=20 ng/ml and/or pathological T stage of pT3a/pT3b.

Internal prostatic architecture on transrectal ultrasonography predicts future prostatic growth: Natural history of prostatic hyperplasia in a 15-year longitudinal community-based study

From 1992 to 1993, we conducted a cross‐sectional community‐based study to clarify the prevalence of benign prostatic hyperplasia in Japanese men aged 40–79. Based on the results, we hypothesized that the internal prostatic architecture (IPA) on transrectal ultrasonography (TRUS) would predict future prostatic growth. We investigated the changes in prostate volume (PV) over time and validated our hypothesis on predictors for future prostatic growth.

FEMALE URETHRAL HEMANGIOMA

A 59-year-old woman presented elsewhere with genital bleeding, pollakiuria and urgency. The gynecologist noted a raised tumor next to the external meatus and the patient was referred to us. On physical examination the tumor was erythematous, protrusive, inflamed and surrounding the urethral meatus. The lesion was 2.5 cm. in diameter, solid and partly rubbery in consistency. It did not appear to be a urethral caruncle, which is typically a benign, red, raspberrylike, friable tumor involving the posterior lip of the external meatus. There were no lesions on the body surface. The uterus and adnexa were unremarkable. Laboratory values were normal except for urinalysis, which revealed numerous red blood cells. Urinary cytology demonstrated no malignancy. Cystourethroscopy revealed reddish mucosa at the distal urethra but not in the bladder. The lesion was not obstructive. Pelvic magnetic resonance imaging (MRI) in the sagittal plane showed a protrusive mass with low intensity on T1-weighted images, which was clear with high intensity on T2-weighted images (fig. 1). There was clinical suspicion for a malignant tumor. After obtaining informed consent, we performed a biopsy with the patient under lumbar anesthesia. Microscopically, the specimens consisted of clusters of dilated venous-like vessels with thrombi, which were composed of thin endothelial lined spaces. Blood containing spaces were large sinusoids lined by flattened endothelial cells (fig. 2). The specimen was pathologically diagnosed as cavernous hemangioma of the urethra. The tumor was resected completely. The patient was symptom-free at 6-month followup with no evidence of tumor recurrence.

Long‐term outcome of small, organ‐confined renal cell carcinoma (RCC) is not always favourable

Small, organ‐confined renal cell carcinoma (RCC) generally has favourable pathological characteristics and a good prognosis. However, late recurrence is a known characteristic of the biological behaviour of RCC and no consensus has been established for surveillance protocols from 5 years after radical or partial nephrectomy. In the present study with long‐term follow‐up of patients with small RCCs, 18 of 172 patients (10.5%) with pT1a RCC developed recurrence and eight of these (4.7%) died from cancer. Patients with microvascular invasion had a higher risk for cancer death than those without (P < 0.001, Log‐rank test). Therefore long‐term follow‐up is required after surgery, particularly when the disease has microvascular invasion.