Usefulness of diffusion-weighted imaging and dynamic contrast-enhanced magnetic resonance imaging in the diagnosis of prostate transition-zone cancer.

BACKGROUND: Conventional T2-weighted (T2-WI) magnetic resonance imaging (MRI) has poor sensitivity for prostate transition-zone (TZ) cancer detection. PURPOSE: To retrospectively evaluate the clinical value of diffusion-weighted MRI (DW-MRI) and dynamic contrast-enhanced MRI (DCE-MRI) in combination with T2-WI for the diagnosis of TZ cancer. MATERIAL AND METHODS: Twenty-six TZ cancers in 23 patients with at least one tumor (tumor size >10 mm) located predominantly in the TZ were included in the study. Sixteen peripheral-zone (PZ) cancers in 12 patients with PZ cancer but without TZ cancer (control group) were selected by step-section pathologic maps. All patients underwent MRI and radical prostatectomy. MRI was obtained by a 1.5T superconducting system with a phased-array coil. Imaging sequences were T2-WI with fat saturation (FST2-WI), DW-MRI (single-shot echoplanar image, b=0 and 1000 s/mm(2), apparent diffusion coefficient [ADC] map findings), and DCE-MRI (3D fast spoiled gradient recalled [SPGR], contrast medium [0.2 mmol/kg], total injection time 5 s, image acquisition 30, 60, and 90 s). Sensitivity, specificity, accuracy, and positive predictive value (PPV) for the diagnosis of TZ cancer were evaluated in four protocols: A) FST2-WI alone, B) FST2-WI plus DW-MRI, C) FST2-WI plus DCE-MRI, D) FST2-WI plus DW-MRI plus DCE-MRI. RESULTS: Sensitivity, specificity, accuracy, and PPV in protocol A (FST2-WI alone) were 61.5%, 68.8%, 64.3%, and 76.2%, respectively. FST2-WI plus DW-MRI (protocol B) improved the sensitivity, specificity, accuracy, and PPV. In FST2-WI plus DW-MRI plus DCE-MRI (protocol D), the number of true-negative lesions increased and false-positive lesions decreased, and the sensitivity, specificity, accuracy, and PPV were 69.2%, 93.8%, 78.6%, and 94.7%, respectively. There was a significant difference between protocols A and D (P<0.05). CONCLUSION: Adding DW-MRI to FST2-WI in the diagnosis of prostate TZ cancer increased the diagnostic accuracy. The addition of DCE-MRI may be an option to improve the specificity and PPV of diagnosing TZ cancer with FST2-WI and DW-MRI.

Knockdown of astrocyte-elevated gene-1 inhibits prostate cancer progression through upregulation of FOXO3a activity.

Astrocyte-elevated gene-1 (AEG-1) has been reported to be upregulated in several malignancies and play a critical role in Ha-ras-mediated oncogenesis through the phosphatidylinositol 3-kinase/AKT signaling pathway. However, the role of AEG-1 in prostate cancer (PC) has never been reported. We now show that AEG-1 is overexpressed in clinical PC tissue samples and cultured PC cells compared to benign prostatic hyperplasia tissue samples and normal prostate epithelial cells. Interestingly, AEG-1 knockdown induced cell apoptosis through upregulation of forkhead box (FOXO) 3a activity. This alteration of FOXO3a activity was dependent on reduction of AKT activity in LNCaP and PC-3 cells with high constitutive AKT activity, but not in DU145 cells with low constitutive AKT activity, although AEG-1 knockdown had no impact on phosphatase and tensin homolog expression in these cells. AEG-1 knockdown also attenuated the constitutive activity of the nuclear factor kappaB (NF-kappaB) and the activator protein 1 (AP-1) with a corresponding depletion in the expression of NF-kappaB and AP-1-regulated genes (interleukin (IL)-6, IL-8 and matrix metalloproteinase-9) and significantly decreased cell invasion properties of PC-3 and DU145 cells. Overall, our findings suggest that aberrant AEG-1 expression plays a dominant role as a positive auto-feedback activator of AKT and as a suppressor of FOXO3a in PC cells. AEG-1 may therefore represent a novel genetic biomarker to serve as an attractive molecular target for new anticancer agents to prevent PC cell progression and metastasis.

Downregulation of androgen, estrogen and progesterone receptor genes and protein is involved in aging-related erectile dysfunction.

We hypothesize that downregulation of sex hormone receptors (androgen, estrogen and progesterone receptors) is involved in aging-related erectile dysfunction. To test this hypothesis, we investigated the expression of sex hormone receptors in penile crura of aging rats. A total of 40 rats were divided into four groups based on age (6, 12, 18 and 24 months), and the erectile function was analyzed by the measurement of intracavernous pressure. Gene and protein expressions of sex hormone receptors were analyzed by RT-PCR and immunostaining, respectively. The mean intracavernous pressures of 6-, 12-, 18- and 24-month-old rats were 110.1, 89.6, 73.5 and 42.7 cm H(2)O, respectively. Gene and protein expressions for androgen receptor, estrogen receptor-beta and progesterone receptor were present in similar levels in 6-, 12- and 18-month-old rat crura, but significantly lower or absent in 24-month-old crura. This is the first study to demonstrate that downregulation of sex hormone receptors in aging rat crura is associated with erectile dysfunction.

Transrectal colour Doppler ultrasonography for quantifying angiogenesis in prostate cancer.

OBJECTIVE: To assess the correlation between angiogenesis and Doppler signal intensity using transrectal colour Doppler ultrasonography (CDUS) in patients with prostate cancer. PATIENTS AND METHODS: The study comprised 56 patients who underwent radical prostatectomy and had untreated tumours with a volume of> 0.1 mL in the peripheral zone. CDUS images were recorded on videotape before surgery. The Doppler signal intensity in tumours was evaluated using the colour pixel intensity (PI). Microvessel density (MVD) and vascular endothelial growth factor (VEGF) immunoreactivity were determined in the prostatectomy specimens. Microvessels were identified by immunohistochemical staining of endothelial cells for CD31. RESULTS: The PI in the tumour correlated with MVD (P < 0.001) and increased with higher levels of VEGF immunoreactivity (P = 0.004). There was no correlation between Gleason score and MVD or PI in the tumour. CONCLUSION: Blood flow assessed by CDUS may reflect the state of angiogenesis in prostate cancer. CDUS may be a useful technique for predicting tumour progression or prognosis, and may be useful for monitoring the effects of anti-angiogenic agents in the future.

Modulation of heat-induced cell death in PC-3 prostate cancer cells by the antioxidant inhibitor diethyldithiocarbamate.

OBJECTIVE: To examine the relationships between the form of cell death (apoptosis or necrosis), reactive oxygen species (ROS) generation, superoxide dismutase (SOD) activity and the level of heat-shock protein 70 (hsp 70) expression after thermotherapy of PC-3 prostate cancer cells; also assessed were the tumoricidal effects of combined treatment with both heat and the antioxidant inhibitor diethyldithiocarbamate (DDC). MATERIALS AND METHODS: PC-3 cells were treated with thermotherapy at 42, 43 or 44 degrees C for 30, 60, 90 or 120 min. Cell proliferation, ROS generation, SOD activity and cellular hsp 70 level were determined using tetrazolium-based cytotoxicity, fluorescent dichlorofluorescein (DCF) and nitroblue tetrazolium assays, Western blot analysis and flow cytometry, respectively. The apoptotic and necrotic cells were determined by staining with propidium iodide and fluorescein isothiocyanate-labelled annexin V. These variable were also measured after combined treatment of PC-3 cells with 1 mmol/L DDC and thermotherapy at 43 or 44 degrees C for 60 min. RESULTS: Cell survival was significantly lower after heating cells at 43 degrees C for 60, 90 and 120 min and at 44 degrees C for all periods tested (P<0.05). At 43 degrees C apoptosis increased with the duration of heating and was similarly enhanced after heating at 44 degrees C for 30 min. Necrosis was not increased by heating at 42 or 43 degrees C, but was markedly enhanced after heating at 44 degrees C with both the duration of heating and with time after heating. Significant increases in DCF production were induced by heating at 43 degrees C for 60, 90 and 120 min (P<0.05) and at 44 degrees C at all times (P<0.010-0.005). There was a significant correlation between the level of ROS generation and necrosis (P<0.001) but no correlation between the ROS level and apoptosis. SOD activity increased in cells after heating at 43 degrees C, with significant differences among cells heated for 60, 90 and 120 min (P<0.05). After heating at 44 degrees C, SOD activity was maximal in cells heated for 30 min (P<0.005), by 30 min and then decreased with time after heating. There were significant increases in hsp 70 level in cells heated at 43 degrees C for 90 and 120 min (P<0.05) and at 44 degrees C for 30 and 60 min (P<0.05 and <0.025, respectively). Hsp 70 levels decreased after heating at 44 degrees C for 90 and 120 min. The combination of DDC and heating significantly increased ROS generation and the percentage of cell death, and decreased SOD activity (P<0.05). CONCLUSION: These findings show a qualitative change in the form of cell death induced by thermotherapy of PC-3 cells, which changed from apoptosis to necrosis according to the degree and duration of heating. Mild thermotherapy induced marginally low occurrence of apoptosis of PC-3 cells and DDC may represent a useful future strategy for the treatment of prostate carcinoma.

Alterations of beta- and gamma-catenin in N-butyl-N-(-4-hydroxybutyl)nitrosamine-induced murine bladder cancer.

Abnormal degradation of beta-catenin caused by alteration of the glycogen synthase kinase-3beta (GSK-3beta) consensus motif is an important step for carcinogenesis. We hypothesize that beta- and gamma-catenin may play an important role in the pathogenesis of bladder cancer. We tested this hypothesis through analysis of beta- and gamma-catenin in both murine and human bladder cancers. A murine bladder cancer model was prepared by use of N-butyl-N-(-4-hydroxybutyl)nitrosamine (BBN) in 6-week-old male B6D2F1 mice. After 4, 8, 12, 16, 20, 24, and 28 weeks of BBN treatment, bladder specimens were harvested and analyzed for both protein and gene expression for beta- and gamma-catenin. Mutational analysis of the NH(2)-terminal regulatory domains of beta- and gamma-catenin was performed in each specimen by PCR-single-strand conformational polymorphism (SSCP) analysis. Mutations were further confirmed by direct DNA sequencing with a dye terminator method. Human bladder cancer specimens with normal tissues, dysplasia, carcinoma in situ, and carcinoma of grades, 1, 2, and 3 were also analyzed for beta- and gamma-catenin expression. beta- and gamma-catenin were analyzed for mutations by SSCP and direct DNA sequencing. Intracellular accumulation of beta- and gamma-catenin was observed in 6 of 20 invasive carcinoma specimens. There was no intracellular accumulation of beta- and gamma-catenin in mucosal dysplasia, papillary or nodular dysplasia, and carcinoma in situ specimens. On an SSCP analysis for beta-catenin, abnormal bandshifts were detected in two invasive carcinomas with intracellular beta-catenin accumulation. Further sequencing revealed two mutations [AGT(S) to ATT(I) and TCT(S) to CCT(P)] within the consensus motif for GSK-3beta phosphorylation. On the other hand, SSCP analysis for gamma-catenin followed by sequencing revealed three mutations in two invasive carcinomas with intracellular accumulation of gamma-catenin. These three alterations affected the 3' downstream region outside the GSK-3beta phosphorylation site [ACC(T) to GCC(A), CTC(L) to ATC(I), and CTC(L) to ATG(M)]. In human bladder cancer, beta- and gamma-catenin expression was significantly weaker than in normal bladder. On SSCP analysis one abnormal bandshift was observed in high-grade human bladder cancer with intracellular beta-catenin accumulation. DNA sequencing revealed mutation TCT(S) to TGT(C). In summary, alterations in beta- and gamma-catenin are late events favoring tumor progression in mouse BBN-induced bladder cancer. Changes affecting the GSK-3beta phosphorylation site appear to be associated with activation of beta-catenin, but not with activation of gamma-catenin. In human blabber cancer, beta- and gamma-catenin expression is similar to the expression in the mouse model. The present study demonstrates that beta- and gamma-catenin may play an important role in bladder cancer progression.

Multilocular spermatocele: a case report.

We describe a case of a multilocular spermatocele. Ultrasound examination revealed several cystic spaces at the head of the left epididymis. Epididymal tumor could not be excluded, and therefore surgical exploration was performed. Histopathological examination of the specimen revealed a multilocular spermatocele arising from the rete testis. Most spermatoceles remain small and rarely present marked clinical problems. but they are occasionally large, and may simulate a solid tumor.

Activation of visual cortex in REM sleep measured by 24-channel NIRS imaging.

To visualize dreaming brain functions we studied hemodynamic changes in the visual cortex during the transition from non-rapid eye movement (NREM) to rapid eye movement (REM) sleep, using a 24-channel Near-Infrared Spectroscopy (NIRS) imaging method. Results were compared to the activation in visual cortex by visual stimulation during wakefulness. Subjects were four healthy males between 25 and 49 years of age. Five all-night polysomnographic and NIRS recordings were made. Increases in the oxygenated hemoglobin concentration in visual cortex were observed from nine of 14 REM periods. The activated areas were broader during REM sleep than during visual stimulation. These findings suggest that activation of visual cortex in REM sleep might represent dream-related brain activity.

Concomitant presence of bladder cancer and neurogenic bladder in a patient with HTLV-1 carrier: a case report.

We describe a case of an HTLV-1 carrier who developed bladder cancer and neurogenic bladder. HTLV-1 is thought to alter host immune function and to contribute to the development of other malignancies. It is also sometimes reported that urinary symptoms precede pyramidal symptoms in patients with HAM. To our knowledge, concomitant presence of bladder cancer and neurogenic bladder in an HTLV-1 carrier has not been previously reported.

Pilsicainide for conversion and maintenance of sinus rhythm in chronic atrial fibrillation: a placebo-controlled, multicenter study.

BACKGROUND: Pilsicainide is a newly synthesized antiarrhythmic agent with class Ic properties. Various antiarrhythmic agents have been used to convert atrial fibrillation (AF) to sinus rhythm or decrease the rate of relapse of AF. METHODS: We randomly assigned 62 patients with chronic AF to oral treatment of either a placebo (10 patients) or 150 mg/day of pilsicainide (52 patients) for 4 weeks before electrical cardioversion. Before oral administration of pilsicainide, 41 patients underwent transesophageal echocardiography to investigate whether there was thrombus formation in the heart chambers. Patients without pharmacologic defibrillation underwent direct current cardioversion to restore sinus rhythm. After successful cardioversion, all patients continued to receive pilsicainide and were monitored for up to 2 years. RESULTS: Before cardioversion, 11 patients in the pilsicainide group (21%) reverted to sinus rhythm. No patients in the placebo group reverted to sinus rhythm. Direct current cardioversion was performed in 51 patients; however, 8 patients were not converted to sinus rhythm (5 patients receiving pilsicainide, 3 patients receiving placebo), and 3 patients needed intracardiac cardioversion to convert to sinus rhythm. Asymptomatic bradyarrhythmias were observed in 5 patients in the pilsicainide group. During the follow-up period, 33 patients (71%) in the pilsicainide group remained in sinus rhythm at 1 month; this number decreased to 23 patients (49%) at 3 months, 20 (43%) at 6 months, 16 (34%) at 12 months, 16 (34%) at 18 months, and 16 (34%) at 24 months. All patients receiving placebo continued to receive placebo after the cardioversion, and AF recurred a few days after cardioversion in all cases. No independent discriminant variables were identified in the groups between maintenance and nonmaintenance of sinus rhythm. Although no serious side effects regarding pilsicainide have been documented, one patient died of acute myocardial infarction, most likely not related to pilsicainide administration. CONCLUSIONS: Pilsicainide is effective in restoring or maintaining sinus rhythm in patients with chronic AF lasting longer than an average duration of 22 months. No major adverse effects were observed.

The role of colour Doppler ultrasonography in detecting prostate cancer.

OBJECTIVE: To determine the usefulness of colour Doppler ultrasonography (CDUS) in detecting prostate cancer, by comparing CDUS with grey-scale transrectal ultrasonography (TRUS) and magnetic resonance imaging (MRI). PATIENTS AND METHODS: In all, 278 patients who underwent prostate biopsies because of an abnormal digital rectal examination, elevated prostate specific antigen levels, and/or abnormal TRUS between May 1998 and November 1999 were evaluated. The diagnostic accuracies of TRUS, CDUS, MRI and combinations of these imaging techniques in detecting prostate cancer were compared, based on the biopsy results. RESULTS: Carcinoma was detected in 233 of 1696 specimens, and 87 patients were diagnosed with prostate cancer. For each detected cancer site, the sensitivity of CDUS was lower than those of other imaging techniques, but CDUS had high a specificity and positive predictive value. The combination of grey-scale TRUS and CDUS or MRI improved the sensitivity and negative predictive value. The specificity and positive predictive value of the combination of grey-scale TRUS and MRI were less than those for grey-scale TRUS alone, while those for the combination of grey-scale TRUS and CDUS were higher than those for grey-scale TRUS alone. Five tumours were isoechoic but seen as hypervascular lesions with CDUS. CONCLUSION: CDUS provides information useful for detecting prostate cancer when used in combination with grey-scale TRUS, and should be included in the routine examination for prostate cancer.

Activation of the visual cortex imaged by 24-channel near-infrared spectroscopy.

Near-infrared spectroscopy (NIRS) is a noninvasive technique for continuous monitoring of the amounts of total hemoglobin (total-Hb), oxygenated hemoglobin, (oxy-Hb) and deoxygenated hemoglobin (deoxy-Hb). The purpose of the present study was to demonstrate the utility of NIRS in functional imaging of the human visual cortex. A new NIRS imaging system enabled measurements from 24 scalp locations covering a 9 cm sq area. Topographic images were obtained from interpolations of the concentration changes between measurement points. Five healthy subjects between 25 and 49 years of age were investigated. After a resting baseline period of 50 s, the subjects were exposed to a visual stimulus for 20 s, followed by a 50 s resting period in a dimly lit, sound attenuating room. The visual stimulus was a circular, black and white, alternating checkerboard. In four of five subjects the visual cortex was the most activated area during visual stimulation. This is the first reported use of a NIRS-imaging system for assessing hemodynamic changes in the human visual cortex. The typical hemodynamic changes expected were observed; the total-Hb and oxy-Hb increased just after the start of stimulation and plateaued after 10 s of the stimulation period.

Heat-induced cellular damage and tolerance in combination with adriamycin for the PC-3 prostate cancer cell line: relationships with cytotoxicity, reactive oxygen species and heat shock protein 70 expression.

OBJECTIVE: To analyze the relationships among the antitumor effect of chemothermotherapy, generation of reactive oxygen species (ROS), and expression of heat shock protein 70 (HSP-70) in the PC-3 prostate cancer cell line. MATERIALS AND METHODS: Changes in cell proliferation, cell cycle fractions, intracellular ROS accumulation and HSP-70 expression were examined after thermotherapy of PC-3 cells at 41, 42, 43 and 44 degrees C and/or simultaneous treatment with Adriamycin for 1 h, using the trypan blue dye exclusion method, flow cytometry, fluorescent 2', 7'-dichlorofluorescein (DCF) assay, and Western blot analysis. RESULTS: A significant decrease in the number of viable cells was observed with chemothermotherapy compared with thermotherapy at 42, 43, or 44 degrees C (p<0.05). DNA distribution histograms revealed cell accumulation in the S-G(2)/M phase after thermotherapy at 43 degrees C and after chemothermotherapy at 37, 41, 42 and 43 degrees C. After thermotherapy and chemothermotherapy at 44 degrees C, DNA histograms revealed no accumulation of cells with S-G(2)/M DNA content and cells exhibited a marked loss of viability. A significant increase in DCF production was observed with chemothermotherapy compared with thermotherapy at 42, 43 or 44 degrees C (p<0.05, p<0.01 and p<0.01, respectively). HSP-70 levels increased linearly with increasing temperature. HSP-70 levels after thermotherapy and chemothermotherapy increased with time and reached plateaus at 30 min, whereas the level after thermotherapy at 44 degrees C decreased at 60 min. CONCLUSIONS: In conclusion, one possible synergism in cytotoxic effects of chemothermotherapy and Adriamycin could be evaluated by the relationship between ROS accumulation and HSP-70 expression in the PC-3 prostate cancer cell line.

Comparison of MR imaging and urodynamic findings in benign prostatic hyperplasia.

OBJECTIVE: In benign prostatic hyperplasia (BPH), it is uncertain whether the size of the prostate is related to the degree of urodynamically demonstrated bladder outlet obstruction. We compared MR imaging findings and urodynamic data in patients with surgically confirmed BPH. MATERIALS AND METHODS: We prospectively studied 43 benign prostatic hyperplasia (BPH) patients in whom transurethral resection of the prostate (TURP) was planned. We obtained T1- and T2-weighted images in the transverse and sagittal planes with a 1.5 Tesla superconducting unit. The predicted volume of the inner gland and the peripheral zone were obtained on T2-weighted transverse images. Prostatic protrusion into the urinary bladder (IB protrusion) and the inner gland ratio (IG ratio: inner gland volume/total prostatic volume) were determined. RESULTS: IB protrusion and inner IG ratio were significantly greater in patients with severe stenosis than in those without. A surgical capsule (SC) was seen in 20 of 25 patients (80%) with severe stenosis and 8 of 18 (44%) of those without it. The accuracy of IB protrusion + IG ratio, IB protrusion + surgical capsule, and IB protrusion + IG ratio + surgical capsule was 89%, and that of IG ratio + surgical capsule was 86%. CONCLUSION: The inner gland ratio, protrusion into the bladder, and presence of surgical capsule were the most important factors in bladder outlet obstruction. The probability of outlet stenosis increases in patients with more than two of these criteria.

Successful radiofrequency catheter ablation from the supravalvular region of the aortic valve in a patient with outflow tract ventricular tachycardia.

Outflow tract ventricular tachycardia (OT-VT) was successfully ablated from the right coronary cusp of the aortic valve. The 12-lead ECG was totally different from the typical right ventricular OT-VT because the R/S ratio in precordial lead V1 was equal to 1 and tall R waves in precordial leads V2-6 were seen. Radiofrequency energy application from the right coronary cusp of the aortic valve successfully ablated this VT without complications. Radiofrequency catheter ablation from the right coronary cusp of the aortic valve can be done safely and effectively.

Electrocardiographic characteristics of left ventricular outflow tract tachycardia.

Catheter ablation of idiopathic left ventricular outflow tract tachycardia (LVOT-VT) is rare because a safe ablation technique at this site has not been described, and serious complications may occur. This study compared the QRS morphology of LVOT-VT with that of idiopathic right ventricular outflow tract tachycardia. A comparison was made between the electrocardiographic characteristics of LVOT-VT originating from the supravalvular region of a coronary cusp (Supra-Ao group) with those of LVOT-VT originating from the infravalvular endocardial region of a coronary cusp of the aortic valve within the LV (Infra-Ao group). After precise mapping of the right ventricle, left ventricle, pulmonary artery, coronary cusps, and proximal portion of the anterior interventricular vein, there were 17 patients in whom VT was thought to be located at the LVOT by both activation and pace mapping. They were divided between a Supra-Ao group (n = 8), and an Infra-Ao group (n = 9). Analysis of the 12-lead electrocardiogram (ECG) revealed an S wave in lead I in all 17 patients. A precordial R wave transition was also observed at V1 or V2 in 16 patients (94%). In 7 of 8 patients (88%) with Supra-Ao LVOT-VT, no S wave was observed in either V5 or V6. In contrast, an Rs pattern was observed in both V5 and V6, or in V6 only, in 100% of the patients with Infra-Ao LVOT-VT. A LVOT-VT should be suspected when the ECG shows an S wave in lead I and an R/S ratio greater than 1 in lead V1 or V2, versus a coronary cusp location if there is no S wave in either lead V5 or V6.