Yoshiji Miwa

Prognostic value of 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography imaging for patients with prostate cancer.

PURPOSE The purpose of this study was to investigate the prognostic value of measuring glucose metabolism of primary prostate cancer lesions, using 2-Deoxy-2-[F-18]Fluoro-D-Glucose positron emission tomography (FDG-PET). PROCEDURES Forty-two patients with prostate cancer were investigated with FDG-PET, and standardized uptake value (SUV) of the prostate was calculated. After PET study, radical prostatectomy was performed in 17 patients (RPT group), and endocrine therapy in 25 patients (ET group). Relapse-free survival curves were created by the Kaplan-Meier method. RESULTS In the RPT group, the patients with high SUV had a poorer prognosis compared to those with low SUV (P = 0.033). In the ET group, the patients with high SUV were likely to have a poorer prognosis with low significance at a level of P = 0.087. CONCLUSIONS FDG-PET appeared to have a defined prognostic value for patients with prostate cancer undergoing radical prostatectomy, and more patients need to be studied for patients undergoing endocrine therapy.

Association Between Lower Urinary Tract Symptoms and Serum Levels of Sex Hormones in Men

OBJECTIVES Despite the well-known association between lower urinary tract symptoms (LUTS) and male sexual dysfunction, few data are available that describe the relationship between LUTS and sex hormones. The aim of this study was to investigate a possible association between the severity of LUTS and the serum levels of sex hormones in men. METHODS A total of 182 randomly selected men attending our general urology clinic were recruited. All participants completed the International Prostate Symptom Score (IPSS), and their sera were evaluated for serum levels of prostate-specific antigen, total and free testosterone, dehydroepiandrosterone sulfate (DHEA-S), luteinizing hormone, follicle-stimulating hormone, prolactin, and estradiol. Storage symptoms were evaluated by the sum of IPSS questions 2, 4, and 7. Voiding symptoms were evaluated by the sum of IPSS questions 3, 5, and 6. The relationship between the IPSSs and serum hormone levels was determined. RESULTS On univariate analysis, the total IPSS was significantly associated with age, DHEA-S, and free testosterone. Storage symptoms were significantly associated with age, DHEA-S, free testosterone, and prostate-specific antigen. Voiding symptoms were significantly associated with age and DHEA-S. On multivariate linear regression analysis, only age was significantly associated with LUTS. However, within the subgroup of men 65-82 years old, DHEA-S was significantly associated with the total IPSS and storage symptoms. CONCLUSIONS In our study, the severity of LUTS was not associated with serum levels of sex hormones in men. However, in older men, storage symptoms could be affected by the serum DHEA-S level.

Long-lasting breaches in the bladder epithelium lead to storage dysfunction with increase in bladder PGE2 levels in the rat

Increase in bladder mucosal permeability can be reproduced by intravesical administration of protamine sulfate (PS); however, the influence of PS once administered into the bladder disappears within several days. We developed a chronic animal model of urothelial injury using PS. Insertion of a polyethylene catheter through the bladder dome was performed in female Wistar rats. The other end of the catheter was connected to an osmotic pump for continuous delivery of PS or vehicle for 2 wk. Urinary frequency (UF) and voided volume (VV) were measured in the metabolic cage. The fifth group of rats received a high dose of PS (10 mg/ml) for 2 wk and were followed for a further 2 wk without PS. The sixth group received a high dose of PS for 2 wk and loxoprofen (0.1 mg.kg(-1).day(-1)) for 4 wk. UF was increased, and VV was reduced in rats treated with a high dose of PS but not changed in rats treated with a vehicle or a low dose of PS (1 mg/ml). UF was further increased in the fifth group, while unchanged in the sixth group. Histological sections in rats treated with a high dose of PS demonstrated a loss of the upper layer of urothelial cells and an increased number of mast cells. PGE2 level in the bladder was significantly elevated in the fifth group. These results indicate that chronic urotherial injury leads to an increase in UF and a decrease in VV. Increased PGE2 level in the bladder is likely to be associated with long-lasting storage dysfunction.

Prognostic value of nuclear morphometry on needle biopsy from patients with prostate cancer: is volume-Weighted mean nuclear volume superior to other morphometric parameters?

OBJECTIVES To compare the prognostic value of stereologically estimated volume-weighted mean nuclear volume (MNV) with other nuclear morphometric parameters using pretreatment needle-biopsy specimens of prostate cancer. METHODS The MNV, mean nuclear area, form factor, and coefficients of variation for nuclear area (VNA) and form factor were measured on pretreatment needle biopsy specimens from 66 patients with prostate cancer (clinical Stage B, n = 9; Stage C, n = 14; and Stage D, n = 43), all of whom underwent androgen deprivation therapy. The prognostic value of those morphometric parameters, as well as Gleason score and clinical stage, was examined in terms of cause-specific patient survival using univariate and multivariate analysis (Cox proportional hazard model). RESULTS Univariate analysis of the nuclear morphometric parameters revealed that MNV, mean nuclear area, VNA, coefficient of variation for form factor, and clinical stage were significant prognostic factors for cause-specific patient survival. However, when the patients with Stage D disease were selectively analyzed for survival, only the VNA was a significant prognostic parameter. Furthermore, the multivariate analysis, including the morphometric parameters, clinical stage, and Gleason score revealed that only VNA and clinical stage were independent variables. CONCLUSIONS The present comparative study could not demonstrate any prognostic superiority of MNV over other nuclear morphometric parameters in patients with prostate cancer.

Immunohistochemical expression of p53 and bcl-2 proteins is not associated with sarcomatoid change in renal cell carcinoma

Abstract An immunhistochemical study was conducted to examine the expression of p53 and bcl-2 proteins in RCC (renal cell carcinoma) with sarcomatoid change in order to determine whether abnormalities in those proteins are associated with an enhanced malignant potential of RCC. Paraffin-embedded tissues from 11 patients with RCC, in which sarcomatoid change was prominent, were stained using anti-p53, bcl-2 and Ki-67 antibodies. Immunoreactivities for these antibodies were compared between the sarcomatoid components and corresponding basic histologic (clear or papillary) components in individual cases. Measurement of the mean nuclear areas of each component was also performed using an image analyzer system. There was no substantial increase in immunoreactivity for p53 or bcl-2 proteins in sarcomatoid components as compared with basic components. In contrast, the percentage of Ki-67-positive cells and the mean nuclear area were signficantly larger in sarcomatous components than in basic components. The expression of p53 and bcl-2 proteins was not likely to play a major role in the sarcomatoid change of RCC.

Ultrasound-Estimated Bladder Weight Predicts Risk of Surgery for Benign Prostatic Hyperplasia in Men Using α-Adrenoceptor Blocker for LUTS

OBJECTIVES Although invasive and expensive, the pressure-flow study is known as the reference standard for the diagnosis of bladder outlet obstruction. We investigated the usefulness of ultrasound-estimated bladder weight (UEBW) as a predictor of the need for surgery for benign prostatic hyperplasia (BPH). METHODS A total of 97 consecutive male patients >50 years old with lower urinary tract symptoms (LUTS) were prospectively enrolled in this study. The surgery rate was correlated with the UEBW, the results of uroflowmetry, the postvoid residual urine volume, prostate volume, and International Prostate Symptom Score. RESULTS Surgery for BPH was performed in 37 of the 97 patients studied. The surgery rate was associated with a high UEBW (>or=35 g), severe LUTS (International Prostate Symptom Score of >or=20), a voided volume of <100 mL at free uroflowmetry, and poor uroflow (maximal flow rate of <10 mL/s). Multivariate analysis revealed that severe LUTS and a high UEBW were the risk factors for surgery for BPH. CONCLUSIONS The results of our study have shown that the UEBW can be regarded as a useful parameter to identify patients with LUTS who are at risk of needing surgery for BPH.

Antimuscarinics Suppress Adenosine Triphosphate and Prostaglandin E2 Release From Urothelium With Potential Improvement in Detrusor Overactivity in Rats With Cerebral Infarction

PURPOSE Antimuscarinics improve detrusor overactivity. We evaluated the effects and action mechanisms of imidafenacin (Kyorin Pharmaceutical, Tokyo, Japan), a novel therapeutic agent for overactive bladder with antimuscarinic activity, on mediator release from urothelium and detrusor overactivity induced by cerebral infarction. MATERIALS AND METHODS Bladder hydrodistention was achieved by intravesical infusion of Krebs solution. Bladder adenosine triphosphate and prostaglandin E(2) were measured in the presence and absence of anticholinergics using luciferin-luciferase assay and enzyme-linked immunoassay, respectively. Cerebral infarction was induced in rats by occluding the left middle cerebral artery. The effects of intravenous imidafenacin on bladder function were examined using cystometry in rats with cerebral infarction and in those pretreated with resiniferatoxin. RESULTS Increased intravesical adenosine triphosphate and prostaglandin E(2) were shown by induced distention of isolated rat bladders. Imidafenacin and darifenacin (Kemprotec, Middlesbrough, United Kingdom) significantly suppressed the increases in adenosine triphosphate and prostaglandin E(2). Decreased bladder capacity was observed in rats with cerebral infarction. Detrusor overactivity was suppressed with a minimum intravenous dose of 0.001 mg/kg imidafenacin. The effects of imidafenacin were not noted in rats pretreated with resiniferatoxin. CONCLUSIONS Results support the hypothesis or suggest that imidafenacin improves cerebral infarction induced detrusor overactivity by suppressing peripheral C-fibers. This effect is thought to be associated with suppression of the release of adenosine triphosphate and prostaglandin E(2) from the urothelium.

Acetylcholinesterase inhibitor acting on the brain improves detrusor overactivity caused by cerebral infarction in rats

PURPOSE The functional contribution of the cholinergic pathway in the frontal cortex to micturition was evaluated following cerebral ischemia. Furthermore, it was examined whether reactivation of this regulatory system using acetylcholinesterase inhibitor could improve detrusor overactivity. METHODS Left middle cerebral artery occlusion (MCAO) was performed in female Sprague-Dawley rats. Choline acetyltransferase (ChAT) activities after MCAO were assayed to assess the damage to cholinergic neurons. ChAT activities in the bilateral cortex, hippocampus, and pons were calculated by measuring the conversion of 1-[14C] acetyl-coenzyme A to [14C] acetylcholine. Effects on cystometrography of i.v. or i.c.v. donepezil hydrochloride (DON), a centrally acting acetylcholinesterase inhibitor, were investigated in conscious sham-operated (SO) and cerebral infarcted (CI) rats. To investigate whether DON in the forebrain was affected, we decerebrated rats after CI or SO, and investigated the effects on cystometrography of i.v. DON. RESULTS Bladder capacity was markedly decreased after MCAO, and remained below half of the pre-occlusion capacity. The greatest increase in bladder capacity was attained at 1.2 x 10(-2) nM/kg of DON given i.v., with a change of 52.8% (P < 0.05). In cases of i.c.v. DON, the greatest increase in bladder capacity was at the dose of 6 x 10(-2) pmol with the change of 95.8% (P < 0.01). The activity of ChAT was decreased in the left cortex and hippocampus 24 h after MCAO (P < 0.05). In decerebrated rats, low dose of DON did not change micturition parameters. CONCLUSIONS These results suggest that by upregulation of the forebrain muscarinic inhibitory mechanism, acetylcholinesterase inhibitor improves detrusor overactivity by cerebral infarction.

Comparison of nuclear morphometric results between needle biopsy and surgical specimens from patients with prostate cancer

OBJECTIVES To compare nuclear morphometric values and Gleason scores between biopsy and radical prostatectomy specimens in patients with clinically localized prostate cancer. METHODS The mean nuclear area (MNA), volume-weighted mean nuclear volume (MNV), and form factor (FF) were measured on the 18-gauge needle biopsy and radical prostatectomy specimens of 25 patients with clinically localized prostate cancer. The correlation between biopsy and surgical specimens was investigated for MNA, MNV, FF, and Gleason scores. RESULTS The average values for the MNA, MNV, and FF of the biopsy specimens (36.2 microm2, 366 microm3, and 0.86, respectively) were significantly smaller than those of the prostatectomy specimens (51.4 microm2, 646 microm3, and 0.91) by Students paired t test. The Pearson correlation of morphometric parameters between the biopsy and surgical specimens was significant only for FF. A comparison of histologic grading between the biopsy and surgical specimens revealed identical Gleason scores in 32% and identical grades (on a three-grade system) in 68% of all the cases. CONCLUSIONS Discrepant nuclear morphometric results were observed between biopsy and surgical specimens of localized prostate cancer. The reason for such differing results is unclear but may be caused by artifacts associated with tissue sampling and processing. It is recommended that data obtained by biopsy should be considered separately from that obtained from surgical specimens.

Diagnosis of complex renal cystic masses and solid renal lesions using PET imaging: comparison of 11C-acetate and 18F-FDG PET imaging.

Purpose The study aims to assess the usefulness of PET with 11C-acetate and 18F-FDG to differentiate renal cell carcinoma (RCC) from complicated renal cysts. Methods Thirty-one patients were enrolled, 14 patients with complicated renal cysts (12 with Bosniak III and 2 with Bosniak IV) and 17 patients with 19 solid renal tumors. The patients underwent both 11C-acetate PET and FDG PET. Nephrectomy or partial nephrectomy was performed after the PET scans. Results In 29 patients, 32 renal lesions were diagnosed as RCC. Twenty-three of the 32 RCCs (72%) had positive 11C-acetate PET findings, whereas only 7 FDG PET studies were positive (22%). Considering the relationship between tumor size measured by macroscopic appearance of resected tumors and PET results, 22 of 25 (88%) tumors more than 1.5 cm showed positive 11C-acetate PET findings. In 12 patients with Bosniak III renal cysts, 10 renal lesions were diagnosed as RCC. In this subgroup, 5 of the 10 RCCs (50%) had positive 11C-acetate PET findings, whereas 2 RCCs (20%) had positive FDG PET findings. None of the cases with benign findings had positive 11C-acetate PET or FDG PET scans. Conclusions 11C-acetate PET demonstrates a pronounced increase in tracer uptake in RCC, especially in renal tumors more than 1.5 cm, and displays a higher sensitivity than FDG PET. These preliminary data show that 11C-acetate may be a useful PET tracer to exclude RCC in complex renal cysts.