Satoru Muto

Focal Therapy with High-intensity-focused Ultrasound in the Treatment of Localized Prostate Cancer

BACKGROUND We evaluated the efficacy and feasibility of high-intensity-focused ultrasound (HIFU) for localized prostate cancer. METHODS Seventy patients received HIFU using Sonablate((R)) 500 (Focus Surgery, IN, USA). In patients whose cancer was confined to only one lobe by multi-regional biopsies, total peripheral zone and a half portion of transitional zone were ablated (focal therapy). Otherwise, patients received whole organ ablation (whole therapy). Scheduled biopsies were performed at 6 and 12 months after treatment. Pre- and post-HIFU serum testosterone levels were measured. Result The 2-year biochemical disease-free survival (DFS) rates in patients at low, intermediate and high risk were 85.9, 50.9 and 0%, respectively, (P = 0.0028). After 12 months, 81.6% (40/49) of patients were biopsy negative; 84.4% in patients who received whole therapy, whereas 76.5% in those with focal therapy. The 2-year biochemical DFS rates for the patients at low and intermediate risk was 90.9 and 49.9%, respectively, in patients with whole therapy, whereas 83.3 and 53.6% in patients with focal therapy. In patients without neoadjuvant androgen deprivation, serum testosterone levels continuously decreased after whole therapy, whereas no changes were seen in those with focal therapy. The patients whose follow-up biopsies were positive tended to have significantly higher changes in prostate-specific antigen levels than biopsy-negative patients. CONCLUSIONS In patients with low-risk prostate cancer, HIFU monotherapy resulted in comparable immediate cancer control with other modalities. Particularly, focal therapy might offer a feasible minimally invasive therapeutic option, which maintained serum testosterone level. To our knowledge, this is the first report that whole, but not focal, therapy affects the serum testosterone level.

Combined inhibitory effects of soy isoflavones and curcumin on the production of prostate-specific antigen.

Sustained chronic inflammation in the prostate promotes prostate carcinogenesis. Since an elevated level of prostate‐specific antigen (PSA) per se reflects the presence of inflammation in the prostate, intervention to improve the PSA value might potentially have beneficial effects for the prevention of the development of prostate cancer. Isoflavones and curcumin have anti‐inflammatory and anti‐oxidant properties. We examined the biological effects of soy isoflavones and curcumin on LNCaP cells. After that, we conducted a clinical trial for men who received prostate biopsies, but were not found to have prostate cancer, to evaluate the effects of soy isoflavones and curcumin on serum PSA levels.

Molecular Biomarkers in Bladder Cancer: Novel Potential Indicators of Prognosis and Treatment Outcomes.

Although many clinical and molecular markers for predicting outcomes in bladder cancer (BC) have been reported, their application in clinical practice remains unclear. Bladder carcinogenesis has two distinct molecular pathways that direct the development of BC. FGFR3 mutations are common in low-grade BC, while TP53 mutation or loss of RB1 is associated with muscle-invasive BC. However, no tissue-based gene markers confirmed by prospective large-scale trials in BC have been used in clinical practice. Micro-RNA analyses of BC tissue revealed that miR-145 and miR-29c⁎ function as tumor suppressors, whereas miR-183 and miR-17-5p function as oncogenic miRNAs. In liquid biopsy, circulating tumor cells (CTC), exosomes, or cell-free RNA is extracted from the peripheral blood samples of cancer patients to analyze cancer prognosis. It was reported that detection of CTC was associated with poor prognostic factors. However, application of liquid biopsy in BC treatment is yet to be explored. Although several cell-free RNAs, such as miR-497 in plasma or miR-214 in urine, could be promising novel circulating biomarkers, they are used only for diagnosing BC as the case that now stands. Here, we discuss the application of novel biomarkers in evaluating and measuring BC outcomes.

The effect of eicosapentaenoic acid on renal function and volume in patients with ADPKD

BACKGROUND Soy protein ameliorates rat polycystic kidney disease with concomitant renal enrichment of omega3-polyunsaturated fatty acids. A study was conducted to examine the effects of eicosapentaenoic acids (EPA) on renal volume and function in patients with autosomal dominant polycystic kidney disease (ADPKD). METHODS Non-azotemic patients were randomized to either a control group (n = 20) or an EPA group (n = 21). EPA capsules (2.4 g/day) were administered in the EPA group for 2 years. Twenty-four hours of urine was collected for the creatinine clearance (Ccr) measurement every year. At baseline and 24 months, fatty acid compositions in erythrocytes were measured and computerized tomographies were obtained for calculation of renal volume by the modified ellipsoid and volumetric methods. RESULTS In the EPA group, the EPA concentration (1.80 +/- 0.99 versus 4.40 +/- 1.79 area%, P < 0.001) and the omega3/omega6 ratio in the erythrocyte increased, but docosahexaenoic acid (DHA) (6.76 +/- 1.19 versus 5.64 +/- 1.45 area%, P < 0.010) concentration decreased. Ccr decreased by 8.5 +/- 9.5 and 9.0 +/- 13.0 ml/min/1.73 m(2)/2 years in the control and EPA groups, respectively (NS). The increases in renal volume calculated by either method were not significantly different between the two groups. CONCLUSIONS A beneficial effect of EPA on renal function and kidney volume in ADPKD patients could not be confirmed in the present study. Administration of EPA with DHA supplementation and/or longer intervention might be necessary to demonstrate preventive effects of omega3-polyunsaturated fatty acids on progression of ADPKD.

Incidentally discovered adrenal myelolipoma associated with hyperthyroidism

Adrenal myelolipomas are uncommon, nonfunctioning tumors that tend to be discovered incidentally on imaging. Such tumors are composed of mature adipose tissue and hematopoietic elements, but their etiology is still unknown. Thyroid hormones have important effects on development, growth, and metabolism, as well as tumorigenesis. We report a case of adrenal myelolipoma in a patient with hyperthyroidism; this benign tumor expressed both thyroid hormone receptor α and β.

Impact of aging and comorbidity on the efficacy of low-intensity shock wave therapy for erectile dysfunction

To evaluate the efficacy of low‐intensity shock wave therapy and to identify the predictive factors of its efficacy in Japanese patients with erectile dysfunction.

Feasibility and accuracy of computational robot-assisted partial nephrectomy planning by virtual partial nephrectomy analysis

To evaluate the feasibility and accuracy of virtual partial nephrectomy analysis, including a color‐coded three‐dimensional virtual surgical planning and a quantitative functional analysis, in predicting the surgical outcomes of robot‐assisted partial nephrectomy.

Testosterone augments polyphenol-induced DNA damage response in prostate cancer cell line, LNCaP

Recently, we reported that combined ingestion of soy isoflavones and curcumin significantly decreased the serum level of prostate‐specific antigen based on a randomized placebo‐controlled double‐blind clinical study. We investigated whether these polyphenols inhibited the proliferation of prostate cancer cells by activating a DNA damage response. The effects of isoflavones and curcumin on the expression and phosphorylation of ataxia‐telangiectasia‐mutated kinase (ATM), histone H2AX variant (H2AX) and checkpoint kinase2 (Chk2) were examined in LNCaP cells. The induction of apoptosis in LNCaP cells was evaluated by poly(ADP‐ribose) polymerase (PARP) cleavage. Furthermore, the effects of a testosterone supplement on modulation of the DNA damage response were examined. Combined treatment of isoflavones and curcumin additively suppressed cellular proliferation and induced phosphorylation of ATM, histone H2AX, Chk2 and p53. Testosterone augmented the activation of the DNA damage response and PARP cleavage induced by curcumin. Our results indicate that activation of the DNA damage response by polyphenols might suppress the malignant transformation of prostate cancer. In addition, testosterone, when combined with curcumin, may have suppressive effects on the progression of prostate cancer. (Cancer Sci 2011; 102: 468–471)

Inhibitory effects of nicorandil, a KATP channel opener and a nitric oxide donor, on overactive bladder in animal models

To investigate the effects of nicorandil, an ATP‐sensitive potassium (KATP) channel opener with a nitric oxide (NO) donor property, on overactive bladder (OAB) in animal models. Nicorandil is currently used clinically to treat ischaemic heart disease.

Enumeration of Bacterial Cell Numbers and Detection of Significant Bacteriuria by Use of a New Flow Cytometry-Based Device

ABSTRACT A new, automated flow cytometry-based urine bacterium analyzer (UBA) was developed. We assessed the UBA for linearity of measurement, reproducibility of results, carryover rate, and correlation of measured results with those determined by urine culture. We also evaluated its ability to screen urine samples for significant bacteriuria. The UBA showed excellent linearity and a minor carryover rate. Results from the UBA were highly reproducible, and in between-run precision assays, the coefficients of variation for the UBA results were smaller than those for the urine culture results. Two hundred seventy-three urine specimens from patients attending the outpatient clinics of two university-based hospitals were examined. The results for the UBA were compared with those for urine culture. The UBA detected significant bacteriuria with a sensitivity of 96.6%, a specificity of 79.9%, a positive predictive value of 57.0%, a negative predictive value of 98.8%, a false-positive rate of 15.8%, a false-negative rate of 0.7%, and an accuracy of 83.5%. These results were comparable to or better than those obtained with previously reported screening procedures. The UBA can perform accurate enumeration of bacterial cells automatically in 90 seconds and can be used for the screening of significant bacteriuria.