Impact of NADiA ProsVue PSA slope on secondary treatment decisions after radical prostatectomy.

BACKGROUND: Selecting appropriate candidates for postprostatectomy radiotherapy is challenging, because adverse pathological features cannot accurately predict clinical recurrence. Biomarkers that identify residual disease activity may assist clinicians when counseling patients on the risks, benefits and costs of secondary treatment. NADiA ProsVue PSA slope results ≤2.0 pg ml(-1) month(-1) are predictive of a reduced risk of clinical recurrence; however, its clinical utility has not yet been studied. METHODS: We prospectively enrolled men treated by radical prostatectomy in a multicenter, institutional review board-approved clinical trial. At postsurgical follow-up, investigators (N=17) stratified men into low-, intermediate- or high-risk groups for prostate cancer recurrence based on clinicopathological findings and other factors. Investigators documented their initial treatment plan for each subject and serially collected three serum samples for ProsVue testing. After the ProsVue result was reported, investigators recorded whether or not the initial treatment plan was changed. The proportion of cases referred for secondary treatment before and after ProsVue was reported, and the significance of the difference determined. RESULTS: Complete assessments were reported for 225 men, 128 (56.9%) of whom were stratified into intermediate- and high-risk groups. Investigators reported that they would have referred 41/128 (32.0%) at-risk men for secondary treatment. However, after results were known, they referred only 15/128 (11.7%) men. The difference in proportions (-20.3%, 95% confidence interval (CI) -29.9 to -10.3%) is significant (P<0.0001). Odds of a referral was significantly reduced after results were reported (odds ratio 0.28, 95% CI 0.15-0.54, P<0.0001). CONCLUSIONS: Knowledge of a ProsVue result had significant impact on the final treatment plan. A ProsVue result ⩽2.0 pg ml(-1) month(-1) significantly reduced the proportion of men at risk of recurrence who otherwise would have been referred for secondary treatment.

Observation of a complex multistage transition in the JT-60U H-mode edge.

A complex multistage transition of the edge radial electric field is observed in JT-60U H-mode phase without edge localized mode. An interesting feature is that the poloidal rotation velocity of the carbon impurity ions changes in the later H-phase without a comparable change in the main ion pressure gradient, indicating a change in the parallel momentum (and particle) balance channel.

Observation of an energetic-particle-driven instability in the wall-stabilized high-beta plasmas in the JT-60U tokamak.

We have observed a bursting mode in the high-beta plasmas above the ideal beta limit without a conducting wall. The mode frequency is chirping down as the mode amplitude increases, and its initial value is close to the precession frequency of the trapped energetic particle from the perpendicular neutral beams. The mode structure is radially extended with a peak around the q = 2 surface. This mode can finally trigger the resistive wall mode (RWM) despite enough plasma rotation for RWM stabilization. It is concluded that the mode is driven by trapped energetic particles. The mode is attributed to the interaction between the trapped energetic particles and a marginally stable mode in the wall-stabilized high-beta_{N} region.

Magnetic fluctuation profile measurement using optics of motional Stark effect diagnostics in JT-60U.

Motional Stark effect (MSE) diagnostics in JT-60U works as polarimeter to measure the pitch angle of magnetic field as well as beam-emission-spectroscopy (BES) monochromator simultaneously at 30 spatial channels. Fluctuation in the BES signal using MSE optics (MSE/BES) contains fluctuations in not only the density but also the pitch angle (or the magnetic field). Correlation analysis of the magnetic fluctuation between two spatial channels is applied to high-beta plasma with a magnetohydrodynamic activity at frequency of about 0.9 kHz. It has been found that the magnetic fluctuation measured by the MSE/BES is spatially localized near the magnetic flux surface having safety factor and that the phase of the fluctuation is inverted at about the surface, suggesting magnetic island structure by tearing mode. The phase of the magnetic fluctuation measured by the MSE/BES at outside of the q=2 surface is consistent with that by the pickup coil placed outside the plasma.

Transition between internal transport barriers with different temperature-profile curvatures in JT-60U Tokamak plasmas.

A spontaneous transition phenomena between two states of a plasma with an internal transport barrier (ITB) is observed in the steady-state phase of the magnetic shear in the negative magnetic shear plasma in the JT-60U tokamak. These two ITB states are characterized by different profiles of the second radial derivative of the ion temperature inside the ITB region (one has a weak concave shape and the other has a strong convex shape) and by different degrees of sharpness of the interfaces between the L mode and the ITB region, which is determined by the turbulence penetration into the ITB region.

Measurement of derivative of ion temperature using high spatial resolution charge exchange spectroscopy with space modulation optics.

A new technique to measure the first and second derivatives of the ion temperature profile has been developed by using a charge exchange spectroscopy system with space modulation optics. The space observed is scanned up to +/-3 cm with a cosine wave modulation frequency up to 30 Hz by shifting the object lens in front of the optical fiber bundle by 0.5 mm with a piezoelement. The first and second derivatives of ion temperature are derived from the modulation component of the ion temperature measured by using Fourier series expansion.

Role of pressure gradient on intrinsic toroidal rotation in tokamak plasmas.

The toroidal plasma rotation generated by the external momentum input and by the plasma itself (intrinsic rotation) has been separated through a novel momentum transport analysis in the JT-60U tokamak device. The toroidal rotation, which is not determined by the momentum transport coefficients and the external momentum input, has been observed. It is found that this intrinsic rotation is locally determined by the local pressure gradient and increases with increasing pressure gradient. This trend is almost the same for various plasmas: low and high confinement mode, co and counterrotating plasmas.

Identification of a low plasma-rotation threshold for stabilization of the resistive-wall mode.

The plasma rotation necessary for stabilization of resistive-wall modes (RWMs) is investigated by controlling the toroidal plasma rotation with external momentum input by injection of tangential neutral beams. The observed threshold is 0.3% of the Alfvén velocity and much smaller than the previous experimental results obtained with magnetic braking. This low critical rotation has a very weak beta dependence as the ideal wall limit is approached. These results indicate that for large plasmas such as in future fusion reactors with low rotation, the requirement of the additional feedback control system for stabilizing RWM is much reduced.

Forced magnetic reconnection and field penetration of an externally applied rotating helical magnetic field in the TEXTOR tokamak.

The magnetic field penetration process into a magnetized plasma is of basic interest both for plasma physics and astrophysics. In this context special measurements on the field penetration and field amplification are performed by a Hall probe on the dynamic ergodic divertor (DED) on the TEXTOR tokamak and the data are interpreted by a two-fluid plasma model. It is observed that the growth of the forced magnetic reconnection by the rotating DED field is accompanied by a change of the plasma fluid rotation. The differential rotation frequency between the DED field and the plasma plays an important role in the process of the excitation of tearing modes. The momentum input from the rotating DED field to the plasma is interpreted by both a ponderomotive force at the rational surface and a radial electric field modified by an edge ergodization.

Excitation of toroidicity-induced Alfvén eigenmodes by the electrodes inserted in a heliotron/torsatron plasma.

A novel method of exciting shear Alfvén waves using electrodes inserted in a plasma was developed for basic study of Alfvén eigenmodes in a heliotron/torsatron plasma. The electrodes can induce excitation current along the confinement field line, and generate magnetic perturbations perpendicular to the confinement field. By sweeping the frequency of the current in a cold plasma, the toroidicity-induced Alfvén eigenmode was resonantly excited at the predicted frequency and radial location. Plasma response to the applied magnetic perturbations indicates a fairly large damping rate caused by continuum damping.

Toroidal plasma rotation induced by the dynamic ergodic divertor in the TEXTOR tokamak.

The first results of the Dynamic Ergodic Divertor in TEXTOR, when operating in the m/n=3/1 mode configuration, are presented. The deeply penetrating external magnetic field perturbation of this configuration increases the toroidal plasma rotation. Staying below the excitation threshold for the m/n=2/1 tearing mode, this toroidal rotation is always in the direction of the plasma current, even if the toroidal projection of the rotating magnetic field perturbation is in the opposite direction. The observed toroidal rotation direction is consistent with a radial electric field, generated by an enhanced electron transport in the ergodic layers near the resonances of the perturbation. This is an effect different from theoretical predictions, which assume a direct coupling between rotating perturbation and plasma to be the dominant effect of momentum transfer.

Inward turbulent transport produced by positively sheared radial electric field in stellarators.

Inward turbulent particle transport observed in the rf heated plasma of the H-1 toroidal heliac is reproduced in the CHS heliotron/torsatron by generating a region of positive radial electric field shear (E'(r)>0) using electron cyclotron resonance heating of the plasma edge. Empirical condition of the radial reversal of the turbulent flux derived from two experiments indicates that the shear electric field might be universally responsible for the recorrelation of the density and plasma potential fluctuations leading to the inward transport.

Mass screening for cancer of the endometrium in Miyagi Prefecture, Japan.

OBJECTIVE: To survey the results of mass screening for cancer of the endometrium performed over a six-year period in Miyagi Prefecture, Japan. STUDY DESIGN: Materials were cytodiagnostic samples of the endometrium examined by the Miyagi Cancer Society. The samples were classified into two groups: The mass screening group, from whom samples were collected according to the Health and Medical Service Law for the Aged, and the outpatient group, consisting of samples from other patients. The rates of subjects judged to require close examination and the detection rate of cancer of the endometrium in the two groups were compared. RESULTS: In the mass screening group, the rate of subjects judged to require close examination and the detection rate of cancer of the endometrium were 2.3% and 0.11%, respectively, while they were 5.9% and 0.39%, respectively, in the outpatient group; the differences between the two groups were significant. CONCLUSION: To improve the detection rate in mass screening for endometrial cancer according to the Health and Medical Service Law for the Aged, it is necessary to establish a new criterion for selecting subjects.

Mass screening for cancer of the uterine cervix in Miyagi Prefecture, Japan. Effects and problems.

OBJECTIVE: To evaluate the effects of and problems with mass screening and in Miyagi Prefecture, Japan. STUDY DESIGN: About 3,570,000 females who underwent mass screening for cervical cancer between 1962 and 1994. RESULTS: The screening rate in the female population aged 30 years or older was 9.5% in 1970, gradually increased and exceeded that rate in 1991 but showed only slight changes thereafter. The standardized death rate due to malignant neoplasm of the cervix fell from 12.1 per 100,000 in 1961 to 4.0 in 1994. CONCLUSION: There still remain various problems, such as lack of a further increase in the screening rate, the fixation of examinees and an increase in the incidence of cervical cancer in young females.

Immunolocalization of cyclins D and E and cyclin dependent kinase (cdk) 2 and 4 in human breast carcinoma.

We studied the immunolocalization of cyclins D1 and E and their corresponding partner cyclin dependent kinases (cdk), cdk4 and cdk2 in 41 cases of human breast malignancy (21 invasive ductal carcinomas and 19 invasive lobular carcinomas) and examined the correlation of the labeling indexes among these cyclins, cdks, Ki67, estrogen receptor (ER) and progesterone receptor (PR). Cyclin D1 immunoreactivity was observed exclusively in the nuclei of tumor cells in 27/41 (65%) of the cases examined. Immunoreactivity for cyclin E and cdk2 was detected in all the cases and observed in the nuclei of both carcinoma and non-carcinoma cells. cdk4 immunoreactivity was detected in 39/41 (95%) cases and found in carcinoma and non-carcinoma cells. In all carcinomas examined, a significant correlation was observed only between Ki67 and cyclin D1 (p = 0.0037). However, when examining only invasive ductal carcinomas, a significant correlation was detected between Ki67 and cyclin D1 (p = 0.0069), Ki67 and cdk2 (p = 0.0043) and cyclin D1 and cdk4 (P = 0.0024). Only cyclin D1 correlated with the pathologic stages of the disease and histological grades of invasive ductal carcinoma. Among these cyclins and cdk, overexpression of cyclin D1 is considered to play an important role in the development of human breast malignancy through abnormal proliferation. No significant correlation was observed between steroid receptor status and any of cyclins and cdks examined. Cyclin D1 and cdk2 expression correlated with cell proliferation (Ki67) and cyclin D1 expression with expression of cdk4 in invasive ductal carcinoma but not invasive lobular carcinoma. Cyclin E expression did not correlate with cell proliferation, cyclin D1 or cdks possibly due to deregulation of its expression. These results also indicate different patterns of cyclin D1, cyclin E, cdk2 and cdk4 expression between invasive ductal and lobular carcinoma of human breast.

Cost-effective analysis of mass screening for cervical cancer in Japan.

Cost-effectiveness analysis for cervical cancer screening in Japan was performed to estimate the cost per life-year saved by the screening; cost-effectiveness ratio (CER). The analysis was made using a simulation model to estimate long-term cost and effectiveness of the screening programs. CER of cervical cancer screening was estimated to be US$ 40,604 which was 2.4 times more expensive than that for gastric cancer screening but was about the same as that for colorectal cancer screening. It was within the range of cost-effectiveness of other cancer screening programs financed under the Health and Medical Services Law for the Aged in Japan. We performed sensitivity analysis on the following seven estimates, the screening charge, the sensitivity and the specificity of the screening test, the frequency of carcinoma in situ (CIS) among cases detected in the screening program, the initial cost and the terminal cost for patients with invasive cancer, and the incidence rate of cervical cancer. The sensitivity analysis demonstrated that the screening charge was the most influential factor on CER. CER was fairly stable under various assumptions on the accuracy of the screening test, the frequency of carcinoma in situ (CIS), the treatment cost for patient, and the incidence of cervical cancer. CER was less sensitive to the changes in incidence, even to as low as a 50% decrease of the current figure. Then if the incidence rate becomes 85% of the current figure in 2015, CER would be US$ 48,176 and it was suggested that the cervical cancer screening would remain reasonably cost-effective until the year 2015.

Aromatase in human bone tissue.

Peripheral aromatization of androgens exert estrogenic actions in many tissues. Recently in situ production of estrogens by aromatase was detected in human bone and cultured osteoblasts and has been proposed to participate in the maintenance of bone mass. We examined aromatase expression by immunohistochemistry and mRNA in situ hybridization in 16 cases of tibia (female 2 male, 14 female, 62 +/- 5.2 years old) and quantified the level of aromatase mRNA in 28 cases of rib, femur, and lumbar vertebrae (16 male, 12 female, 58.0 +/- 11.3 years old) by reverse transcriptase-polymerase chain reaction (RT-PCR) in order to study whether or not and in which cell types aromatase was expressed in human bone tissues. We also studied alternative use of multiple exons 1 of its gene and immunolocalization of type I 17 beta-hydroxysteroid dehydrogenase (HSD), which converts estrone produced by aromatase to estradiol. Strong aromatase immunoreactivity and mRNA hybridization as well as type I 17 beta-HSD immunoreactivity were detected in lining cells, osteoblasts, chondrocytes of articular cartilage, and adipocytes adjacent to bone trabeculae in all the cases examined. Amounts of aromatase mRNA varied greatly among the subjects (11.25 +/- 9.77, 0.61-42.84 attomol/ng of total RNA). The amount of aromatase expression was not correlated with age or gender of the subjects but positively correlated with the degree of osteroporotic changes evaluated by radiological findings of lumbar vertebrae. Analysis of multiple exons 1 revealed that 1b or fibroblast type was predominantly (23/26) utilized as a promoter of aromatase gene expression. These results demonstrated that aromatase is expressed widely in human bone tissue and may play important roles in maintenance of human bone tissue.

Localization of mineralocorticoid receptor and 11 beta-hydroxysteroid dehydrogenase type II in human breast and its disorders.

Mineralocorticoid receptors have been detected in the normal human breast and breast cancers. The expression of mineralocorticoid receptor (MR) and 11 beta-hydroxysteroid dehydrogenase type II (11sHSD2), which confers specificity on MR for aldosterone, was examined by immunohistochemistry in 114 samples from normal human breast and benign and malignant breast lesions in order to study its possible biological significance. MR and 11sHSD2 were immunolocalized in the ductal epithelium in 39/40 (98%) and 36/40 cases (90%) of normal breast, 21/22 (95%) and 15/22 cases (68%) of fibrocystic changes, and 11/11 (100%) and 8/11 (73%) cases of fibroadenoma, respectively. Cases positive for 11 sHSD2 also expressed MR but the patterns of expression varied greatly among examples of normal breast and benign breast diseases. There was a significant correlation between labeling indices of MR and 11sHSD2 in normal breast (p < 0.01) and in benign breast disease (fibrocystic change (p < 0.05) and fibroadenoma (p < 0.05)). In invasive carcinomas, immunoreactivity for MR and 11sHSD2 was detected in malignant cells in 32/41(78%) and 16/41(39%) cases. Both MR and 11sHSD2 labeling indices were significantly higher in invasive ductal carcinoma (22 cases) than invasive lobular carcinoma (19 cases) (p < 0.01). There was a significant correlation between labeling indices of MR and 11sHSD2 when analyzing all infiltrating carcinomas (p < 0.01), but not when assessing invasive lobular or invasive ductal carcinomas separately. These results indicate that the 11 sHSD2 enzyme generally colocalizes with the MR in the ductal epithelial cells of human breast, which may allow aldosterone to occupy its physiological receptor, and the expression of MR and 11sHSD2 appears to be related to ductal differentiation of breast carcinomas.