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The switching fields and thermal stability of CoPt/Ru dot arrays with various dot thickness [delta] (5-20 nm) were experimentally investigated as a function of the dot diameter, D, (130-300 nm). All dot arrays showed a single domain state, even after removal of an applied field equal to the remanence coercivity [H.sub.r]. The angular dependence of [H.sub.r] for the dot arrays indicated coherent rotation of the magnetization during nucleation. We estimated the values of the 'intrinsic' remanence coercivity Ho obtained by subtracting the effect of thermal agitation on the magnetization and the stabilizing energy barrier to nucleation [E.sub.o]/([k.sub.B] T). The variation in [H.sub.o] as a function of [delta] and D was qualitatively in good agreement with that of the effective anisotropy field at the dot center [H.sup.eff.sub.k] (r = 0), calculated taking account of the demagnetizing field in the dots. The ratio of [H.sub.o] to [H.sup.eff.sub.k] (r = 0) for the dot arrays with [delta] = 10 nm increased from 0.53 to 0.70 as D decreased from 300 to 140 nm, and no significant difference in the [H.sub.o] to [H.sup.eff.sub.k] (r = 0) ratio due to the difference in 6 was observed. On the other hand, [E.sub.o]/([k.sub.B] T) decreased as [delta] decreased. [E.sub.o]/([k.sub.B] T) increased slightly as D decreased, but, was not so sensitive to D over the present D range. Index Terms--CoPt perpendicular films, dot arrays, remanence coercivity, single domain, thermal stability, patterned media.

The switching field distributions (SFD) of CoPtCr-Si[O.sub.2] perpendicular media as a function of Pt content were characterized by subtracting the effect of thermal agitation, and discussed in relation to the microstructure. DC demagnetizing (DCD) magnetization curves and minor dc demagnetizing (M-DCD) magnetization curves were measured at applied field sweep rates of ~10 Oe/s and ~[10.sup.8] Oe/s. We estimated the width of SFD, [DELTA] SFD, from the difference between the DCD and M-DCD curves, and defined them as [DELTA] [H.sub.r]/[H.sub.r] (at 10 Oe/s) and [DELTA] [H.sup.P.sub.r]/[DELTA] [H.sup.P.sub.r] (at ~108 Oe/s). The values of [DELTA] SFD characterized by subtracting the effect of thermal agitation, [DELTA] [H.sub.o]/[H.sub.o], were nearly half those of [DELTA][H.sub.r]/[H.sub.r] for 10-nm-thick media. [DELTA][H.sub.o]/[H.sub.o] was about 0.10 at 10 at % Pt content, and increased as the Pt content increased, reaching 0.17 at 30 at % Pt content. The increase in [DELTA][H.sub.o]/Ho was probably caused by an increase in the stacking fault density and the formation of fcc layers in the hcp CoPtCr lattice. A simple calculation based on the coherent switching of magnetization revealed that the c-axis distribution results in [DELTA][H.sub.o]/[H.sub.o] of about 0.08, independent of Pt content. These results suggest that the [DELTA] SFD due to the grain-to-grain anisotropy field variation was small, only 0.02-0.03. Index Terms--CoPtCr-Si[O.sub.2] perpendicular recording media, film composition, pulse field, switching field distribution, thermal agitation of magnetization.

The magnetic properties of dot arrays made of CoPt/Ru perpendicular films (20 nm thickness) were examined as a function of Pt content. The CoPt dot arrays with a dot size D of 140 nm showed a single domain state, after removal of the applied field equal to [H.sub.r]. [H.sub.r] decreased from 5.2 kOe to 3.0 kOe as the Pt content decreased from 20 at% to 14 at%. The angular dependence of [H.sub.r] for these dot arrays indicated coherent rotation of the magnetization during nucleation. The effective magnetic anisotropy, including the demagnetizing energy due to the dot shape, [K.sup.eff.sub.u], decreased as the Pt content decreased, resulting in the [H.sub.r] reduction. The values of the switching volume for nucleation, [V.sub.sw], evaluated from the stabilizing energy barrier [E.sub.0], were a few percent of the dot volume. The switching diameter for nucleation, [D.sub.sw], increased slightly as the Pt content decreased, which was qualitatively in good agreement with the increase in the exchange length of magnetization. The value of [E.sub.0]/[k.sub.B]T ([k.sub.B] is the Boltzmann constant and T is the absolute temperature) reduced as the Pt content decreased; however, [E.sub.0]/[k.sub.B]T still had a high of 440 even at 14 at% Pt content. We successfully demonstrated the reduction of [H.sub.r] for CoPt/Ru patterned films on reducing the Pt content, while simultaneously maintaining a high thermal stability. A calculation based on the experimental results suggested the potential recording density of CoPt/Ru dot arrays used for patterned media to be over 1 Tb/[in.sup.2]. Index Terms--CoPt/Ru perpendicular films, dot arrays, patterned media, remanence coercivity, single domain, thermal stability.

The effect of thermal agitations on the switching field distribution (SFD) of CoPtCr-Si[O.sub.2] perpendicular media was investigated, and the 'intrinsic' SFD caused by variations in the grain-to-grain switching field was determined. DC demagnetizing (DCD) magnetization curves and minor DCD (M-DCD) magnetization curves were measured at applied field-sweep rates of ~ 10 Oe/s and ~ [10.sup.8] Oe/s. We estimated the SFD from the difference between the DCD and M-DCD curves, and defined them as [DELTA][H.sub.r]/[H.sub.r] (at ~ 10 Oe/s) and [DELTA] [H.sup.P.sub.r]/[H.sup.P.sub.r] (at ~ [10.sup.8] Oe/s). The values of [DELTA] [H.sub.r]/[H.sub.r] were much larger than those of [DELTA] [H.sup.P.sub.r]/[H.sup.Psub.r]. Moreover [DELTA] [H.sub.r]/[H.sub.r] increased faster than [DELTA] [H.sup.P.sub.r]/[H.sup.P.sub.r] as the thickness decreased, suggesting that the SFD measured at vibrating sample magnetometer (VSM) time scales is significantly influenced by thermal agitation. The intrinsic SFD estimated using a series of media with various film thicknesses was about 0.14, which was 55%-75% of [DELTA] [H.sub.r]/[H.sub.r] for 8-16-nm-thick media. An analysis of the temperature dependence of [DELTA] [H.sub.r]/[H.sub.r] supported this conclusion. It is concluded that the SFD measured at VSM time scales is significantly influenced by thermal agitation of the magnetization, and the intrinsic SFD is likely to be nearly half that measured at VSM time scales. Index Terms--Film thickness, perpendicular recording media, pulse field, switching field distribution (SFD), temperature, thermal agitation of magnetization.

Dot arrays with diameter ranging from 80 to 245 nm are made of [Co.sub.80] [Pt.sub.20] films with large perpendicular anisotropy. Magnetic properties are investigated by detecting the anomalous Hall effect. The all arrays show angular dependence of remanent coercivity similar to coherent rotation. The result shows that reversal process is independent of dot diameter. The energy barrier height of magnetization reversal is estimated as 1.0 x [10.sup.-10] erg for the array consists of 140-nm-diameter dots. From the energy value, the switching volume is estimated as equivalent to the volume of a physical grain in the film. The results indicate that the reversal process starts from a nucleation of a 'reversed grain' followed by propagation process. Index Terms--Magnetic dot array, magnetic hysteresis, magnetization reversal.

The first and second order energy terms of uniaxial magnetic anisotropy, [K.sub.u1] and [K.sub.u2], of CoPtCr-Si[O.sub.2] perpendicular recording media were studied as a function of film composition and film structure. Moreover, the fabrication of CoPtCr-Si[O.sub.2] media having adequate values of [K.sub.u1] and [K.sub.u2] for high recording density was preliminarily studied. An analysis of CoPtCr films with various kinds of seed layer materials revealed that the values of [K.sub.u1] and [K.sub.u2] varied significantly with the seed layer material used, probably due to epitaxial growth of CoPtCr on the seed layers. [K.sub.u2] increased, accompanied by a reduction in [K.sub.u1] as the c/a ratio of the hcp-CoPtCr lattice increased. Moreover, experimental results suggest that a high stacking-fault density enhances the [K.sub.u2] values, especially in the high Pt content region. The addition of Si[O.sub.2] reduces the total anisotropy, [K.sub.u1] + [K.sub.u2], but no significant change in the ratio of [K.sub.u2]/[K.sub.u1] was observed. The fabrication of CoPtCr-Si[O.sub.2] media with adequate values of [K.sub.u1] and [K.sub.u2] was successfully demonstrated, although more intensive efforts to enhance grain isolation are required to confirm the advantages conferred by the [K.sub.u2] term. Index Terms--CoPtCr-Si[O.sub.2] high order energy term, lattice deformation, magnetic anisotropy, perpendicular recording media, thermal stability.

The switching field distributions (SFD) of CoPtCr-SiO2 perpendicular media as a function of Pt content were characterized by subtracting the effect of thermal agitation, and discussed in relation to the microstructure. DC demagnetizing (DCD) magnetization curves and minor dc demagnetizing (M-DCD) magnetization curves were measured at applied field sweep rates of ~10 Oe/s and ~108 Oe/s. We estimated the width of SFD, ΔSFD, from the difference between the DCD and M-DCD curves, and defined them as ΔHr/Hr (at ~ 10 Oe/s) and ΔHrP/HrP (at ~108 OeIs). The values of ΔSFD characterized by subtracting the effect of thermal agitation, ΔH0/H0, were nearly half those of ΔHr/Hr for 10-nm-thick media. ΔH0/H0 was about 0.10 at 10 at%Pt content, and increased as the Pt content increased, reaching 0.17 at 30 at %Pt content. The increase in ΔH0/H0 was probably caused by an increase in the stacking fault density and the formation of fcc layers in the hcp CoPtCr lattice. A simple calculation based on the coherent switching of magnetization revealed that the c-axis distribution results in ΔH0/H0 of about 0.08, independent of Pt content. These results suggest that the ΔSFD due to the grain-to-grain anisotropy field variation was small, only 0.02-0.03. [ABSTRACT FROM AUTHOR]

The effect of thermal agitations on the switching field distribution (SFD) of CoPtCr-SiO2 perpendicular media was investigated, and the ‘intrinsic’ SFD caused by variations in the grain-to-grain switching field was determined. DC demagnetizing (DCD) magnetization curves and minor DCD (M-DCD) magnetization curves were measured at applied field-sweep rates of ∼ 10 Oe/s and ∼ 108 Oe/s. We estimated the SFD from the difference between the DCD and M-DCD curves, and defined them as ΔHr/Hr (at ∼ 108 Oe/s) and ΔHrP/HrP (at ∼ 108 Oe/s). The values of ΔHr/Hr were much larger than those of ΔHrP/HrP. Moreover, ΔHr/Hr increased faster than ΔHrP/HrP as the thickness decreased, suggesting that the SFD measured at vibrating sample magnetometer (VSM) time scales is significantly influenced by thermal agitation. The intrinsic SFD estimated using a series of media with various film thicknesses was about 0.14, which was 55%–75% of ΔHr/Hr- for 8–16-nm-thick media. An analysis of the temperature dependence of ΔHr/Hr supported this conclusion. It is concluded that the SFD measured at VSM time scales is significantly influenced by thermal agitation of the magnetization, and the intrinsic SFD is likely to be nearly half that measured at VSM time scales. [ABSTRACT FROM AUTHOR]

The first and second order energy terms of uniaxial magnetic anisotropy, Ku1 and Ku2, of CoPtCr-SiO2 perpendicular recording media were studied as a function of film composition and film structure. Moreover, the fabrication of CoPtCr-SiO2 media having ade- quate values of Ku1u1 and Ku2 for high recording density was preliminarily studied. An analysis of CoPtCr films with various kinds of seed layer materials revealed that the values of Ku1 and Ku2 varied significantly with the seed layer material used, probably due to epitaxial growth of CoPtCr on the seed layers. Ku3 increased, accompanied by a reduction in Ku1 as the c/a ratio of the hcp-CoPtCr lattice increased. Moreover, experimental results suggest that a high stacking-fault density enhances the Ku2 values, especially in the high Pt content region. The addition of SiO2 reduces the total anisotropy, Ku1 + Ku2, but no significant change in the ratio of Ku2/Ku1 was observed. The fabrication of CoPtCr-SiO2 media with adequate values of Ku1 and Ku2 was successfully demonstrated, although more intensive efforts to enhance grain isolation are required to confirm the advantages conferred by the Ku2 term. [ABSTRACT FROM AUTHOR]

Background: In men undergoing upfront active surveillance, predictors of adverse pathology in radical prostatectomy specimens, including intraductal carcinoma of the prostate and cribriform patterns, remain unknown. Therefore, we aimed to examine whether adverse pathology in radical prostatectomy specimens could be predicted using preoperative patient characteristics., Methods: We re-reviewed available radical prostatectomy specimens from 1035 men prospectively enrolled in the PRIAS-JAPAN cohort between January 2010 and September 2020. We defined adverse pathology on radical prostatectomy specimens as Gleason grade group ≥3, pT stage ≥3, pN positivity or the presence of intraductal carcinoma of the prostate or cribriform patterns. We also examined the predictive factors associated with adverse pathology., Results: All men analyzed had Gleason grade group 1 specimens at active surveillance enrolment. The incidence of adverse pathologies was 48.9% (with intraductal carcinoma of the prostate or cribriform patterns, 33.6%; without them, 15.3%). The addition of intraductal carcinoma of the prostate or cribriform patterns to the definition of adverse pathology increased the incidence by 10.9%. Patients showing adverse pathology with intraductal carcinoma of the prostate or cribriform patterns had lower biochemical recurrence-free survival (log-rank P = 0.0166). Increasing age at active surveillance enrolment and before radical prostatectomy was the only predictive factor for adverse pathology (odds ratio: 1.1, 95% confidence interval: 1.02-1.19, P = 0.0178; odds ratio: 1.12, 95% confidence interval: 1.02-1.22, P = 0.0126)., Conclusions: Increasing age could be a predictive factor for adverse pathology. Our findings suggest that older men could potentially derive advantages from adhering to the examination schedule in active surveillance., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Poor prognostic cardiac function is known among some patients with primary aldosteronism (PA). However, studies with echocardiograms on whether the normalization of aldosterone after laparoscopic adrenalectomy (LADX) improves myocardial hypertrophy and diastolic cardiac dysfunction have been inadequate. Between August 2009 and December 2021, 147 patients with unilateral PA who underwent pre- and post-LADX echocardiography at a single center were enrolled in this retrospective study. We evaluated the cardiac impact of LADX by comparing patients who demonstrated complete clinical success (CS) with those who demonstrated partial or absent CS. Adjusted odds ratios (ORs) for not obtaining complete CS were calculated using binomial logistic regression analysis for clinically significant items among the pre- and postoperative clinical and echocardiographic markers. Overall, 47 (29%) and 104 (71%) patients had complete and partial or absent CS, respectively. Compared to patients with complete CS, patients with partial CS or without CS tended to have preoperative low early to late diastolic transmitral flow velocity (E/A) (< 0.8 cm/s) (41% vs. 21%, P < 0.05) and postoperative supranormal left ventricular ejection fraction (LVEF) (> 70%) (37% vs. 21%, P < 0.05). Furthermore, laparoscopic adrenalectomy improved the low and high echocardiographic values of E/A and LVEF, respectively, in both groups. The risk factors for not reaching complete CS were male sex (OR 3.42), low preoperative E/A (OR 3.11), and postoperative supranormal LVEF (OR 3.17). Although low preoperative E/A and postoperative supranormal LVEF are associated with poor clinical outcomes, LADX can improve diastolic cardiac function in patients with PA.

Objectives: This study aimed to evaluate whether oncological outcomes of radical prostatectomy differ depending on adherence to the criteria in patients who opt for active surveillance., Materials and Methods: We retrospectively reviewed the data of 1035 patients enrolled in a prospective cohort of the PRIAS-JAPAN study. After applying the exclusion criteria, 136 of 162 patients were analyzed. Triggers for radical prostatectomy due to pathological reclassification on repeat biopsy were defined as on-criteria. Off-criteria triggers were defined as those other than on-criteria triggers. Unfavorable pathology on radical prostatectomy was defined as pathological ≥T3, ≥GS 4 + 3 and pathological N positivity. We compared the pathological findings on radical prostatectomy and prostate-specific antigen recurrence-free survival between the two groups. The off-criteria group included 35 patients (25.7%), half of whom received radical prostatectomy within 35 months., Results: There were significant differences in median prostate-specific antigen before radical prostatectomy between the on-criteria and off-criteria groups (6.1 vs. 8.3 ng/ml, P = 0.007). The percentage of unfavorable pathologies on radical prostatectomy was lower in the off-criteria group than that in the on-criteria group (40.6 vs. 31.4%); however, the differences were not statistically significant (P = 0.421). No significant difference in prostate-specific antigen recurrence-free survival was observed between the groups during the postoperative follow-up period (median: 36 months) (log-rank P = 0.828)., Conclusions: Half of the off-criteria patients underwent radical prostatectomy within 3 years of beginning active surveillance, and their pathological findings were not worse than those of the on-criteria patients., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The present case study was conducted on a 74-year-old man who visited our department due to a left renal and retroperitoneal tumor on computed tomography (CT). The patient was diagnosed with left renal cancer lymph node metastasis and was hospitalized a few weeks prior to surgery due to fever, malaise, and severe appetite loss. Biochemical laboratory findings at admission showed markedly high levels of inflammation. The cause of high inflammatory response was paraneoplastic syndrome. Tumor resection was considered necessary, and left nephrectomy and lymphadenectomy were performed; however, it did not improve the inflammatory response. After operation, positron emission tomography-CT revealed hyperaccumulation of 18F-fluorodeoxyglucose in the bone marrow throughout the body. Pathological examination of the resected specimen and bone marrow aspiration revealed the coexistence of idiopathic multicentric Castleman disease (CD) and renal cancer. Prednisolone and tocilizumab were administered for idiopathic multicentric CD and a tyrosine kinase inhibitor for renal cancer; however, they had poor therapeutic effect, and the patient died. CD is characterized by systemic symptoms due to the overproduction of interleukin-6. Treatment for idiopathic multicentric CD involves steroid and anti-interleukin-6 therapy. The diagnostic criteria for CD require the exclusion of malignant tumors although there are some cases in which CD and malignant tumors coexist. The prognosis for CD is relatively good; however, as in this case, the prognosis of CD coexisting with uncontrollable renal cancer is insufficient due to poor improvement in the inflammatory response.

During an angioscopy operation, a transparent liquid called dextran is sprayed out from a catheter to flush the blood away from the space between the camera and target. Medical doctors usually inject dextran at a constant flow rate. However, they often cannot obtain clear angioscopy visibility because the flushing out of the blood is insufficient. Good flushing conditions producing clear angioscopy visibility will increase the rate of success of angioscopy operations. This study aimed to determine a way to improve the clarity for angioscopy under different values for the parameters of the injection waveform, endoscope position, and catheter angle. We also determined the effect of a stepwise waveform for injecting the dextran only during systole while synchronizing the waveform to the cardiac cycle. To evaluate the visibility of the blood-vessel walls, we performed a computational fluid dynamics (CFD) simulation and calculated the visible area ratio ( VAR ), representing the ratio of the visible wall area to the total area of the wall at each point in time. Additionally, the normalized integration of the VAR called the area ratio ( AR VAR ) represents the ratio of the visible wall area as a function of the dextran injection period. The results demonstrate that the AR VAR with a stepped waveform, bottom endoscope, and three-degree-angle catheter results in the highest visibility, around 25 times larger than that under the control conditions: a constant waveform, a center endoscope, and 0 degrees. This set of conditions can improve angioscopy visibility.

To improve treatment outcomes in real practice, useful biomarkers are desired when predicting postoperative recurrence for renal cell carcinoma (RCC). We collected data from patients who underwent definitive surgery for RCC and for benign urological tumor at our department between November 2016 and December 2019. We evaluated the differences in pre- and postoperative urinary metabolites with our precise quantitative method and identified predictive factors for RCC recurrence. Additionally, to clarify the significance of metabolites, we measured the intracellular metabolite concentration of three RCC cell lines. Among the 56 patients with RCC, nine had a recurrence (16.0%). When comparing 27 patients with T1a RCC and 10 with benign tumor, a significant difference was observed between pre- and postoperative concentrations among 10 urinary metabolites. In these 10 metabolites, multiple logistic regression analysis identified five metabolites (lactic acid, glycine, 2-hydroxyglutarate, succinic acid, and kynurenic acid) as factors to build our recurrence prediction model. The values of area under the receiver operating characteristic curve, sensitivity, and specificity in this predictive model were 0.894%, 88.9%, and 88.0%, respectively. When stratified into low and high risk groups of recurrence based on this model, we found a significant drop of recurrence-free survival rates among the high risk group. In in vitro studies, intracellular metabolite concentrations of metastatic tumor cell lines were much higher than those of primary tumor cell lines. By using our quantitative evaluation of urinary metabolites, we could predict postoperative recurrence with high sensitivity and specificity. Urinary metabolites could be noninvasive biomarkers to improve patient outcome., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: Whilst intravascular endoscopy can be used to identify lesions and assess the deployment of endovascular devices, it requires temporary blockage of the local blood flow during observation, posing a serious risk of ischaemia. Objective: To aid the design of a novel flow-blockage-free intravascular endoscope, we explored changes in the haemodynamic behaviour of the flush flow with respect to the flow injection speed and the system design. Methods: We first constructed the computational models for three candidate endoscope designs ( i.e. , Model A, B, and C). Using each of the three endoscopes, flow patterns in the target vessels (straight, bent, and twisted) under three different sets of boundary conditions ( i.e. , injection speed of the flush flow and the background blood flowrate) were then resolved through use of computational fluid dynamics and in vitro flow experiments. The design of endoscope and its optimal operating condition were evaluated in terms of the volume fraction within the vascular segment of interest, as well as the percentage of high-volume-fraction area (PHVFA) corresponding to three cross-sectional planes distal to the microcatheter tip. Results: With a mild narrowing at the endoscope neck, Model B exhibited the highest PHVFA, irrespective of location of the cross-sectional plane, compared with Models A and C which, respectively, had no narrowing and a moderate narrowing. The greatest difference in the PHVFA between the three models was observed on the cross-sectional plane 2 mm distal to the tip of the microcatheter (Model B: 33% vs. Model A: 18%). The background blood flowrate was found to have a strong impact on the resulting volume fraction of the flush flow close to the vascular wall, with the greatest difference being 44% (Model A). Conclusion: We found that the haemodynamic performance of endoscope Model B outperformed that of Models A and C, as it generated a flush flow that occupied the largest volume within the vascular segment of interest, suggesting that the endoscope design with a diameter narrowing of 30% at the endoscope neck might yield images of a better quality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past co-authorship with several of the authors MZ, ST, HA, and MO., (Copyright © 2021 Li, Zhang, Tupin, Mitsuzuka, Nakayama, Anzai and Ohta.)

The metastatic burden is a critical factor for decision-making in the treatment of metastatic hormone-sensitive prostate cancer (HSPC). This study aimed to develop and validate a novel risk model for survival in patients with de novo low- and high-burden metastatic HSPC. The retrospective observational study included men with de novo metastatic prostate cancer who were treated with primary androgen-deprivation therapy at 30 institutions across Japan between 2008 and 2017. We created a risk model for overall survival (OS) in the discovery cohort (n = 1449) stratified by the metastatic burden (low vs high) and validated its predictive ability in a separate cohort (n = 951). Based on multivariate analyses, lower hemoglobin levels, higher Gleason grades, and higher clinical T-stage were associated with poor OS in low-burden disease. Meanwhile, lower hemoglobin levels, higher Gleason grade group, liver metastasis, and higher extent of disease scores in bone were associated with poor OS in patients with high-burden disease. In the discovery and validation cohorts, the risk model using the aforementioned parameters exhibited excellent discriminatory ability for progression-free survival and OS. The predictive ability of this risk model was superior to that of previous risk models. Our novel metastatic burden-stratified risk model exhibited excellent predictive ability for OS, and it is expected to have several clinical uses, such as precise prognostic estimation., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Intractable late urinary toxicity is a serious complication after radiotherapy for patients with localized prostate cancer (LPC). We assessed clinical factors correlated with severe late urinary toxicity in LPC treated with curative image-guided intensity-modulated radiation therapy (IMRT). A total of 452 patients with LPC treated with IMRT between 2002 and 2016 were retrospectively analyzed. Among them, 432 patients received androgen deprivation therapy (ADT). The median total irradiated doses were 80 (range, 76-80) Gy. Each daily dose was 2 Gy per fraction. The median follow-up was 83 (range, 4-210) months. Late urinary toxicity was scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.03. Grade 3 late urinary toxicity was observed in 27 patients. No cases with grade ≥ 4 late urinary toxicity were observed. The 5-, 10-, and 12.5-year grade 3 late urinary toxicity-free survival rates were 97%, 91.8% and 88.1%, respectively. Age, risk classification, total irradiated dose, ADT duration, antithrombotic therapy (AT), cardiovascular disease, hypertension (HT), diabetes mellitus (DM), dyslipidemia (DL), prior transurethral resection of the prostate (TURP) and prior high-intensity focused ultrasound (HIFU) were investigated for correlations with grade 3 late urinary toxicity. In univariate analysis, AT and prior HIFU and no other studied factors, were correlated with grade 3 late urinary toxicity. AT and prior HIFU appear to be predictive of grade 3 late urinary toxicity. Patients with LPC with these relevant clinical factors should be carefully followed up by sharing detailed information with the urology department., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Background: Anemia has been a known prognostic factor in metastatic hormone-sensitive prostate cancer (mHSPC). We therefore examined the effect of anemia on the efficacy of upfront abiraterone acetate (ABI) in patients with mHSPC., Methods: We retrospectively evaluated 66 mHSPC patients with high tumor burden who received upfront ABI between 2018 and 2020 (upfront ABI group). We divided these patients into two groups: the anemia-ABI group (hemoglobin < 13.0 g/dL, n = 20) and the non-anemia-ABI group (n = 46). The primary objective was to examine the impact of anemia on the progression-free survival (PFS; clinical progression or PC death before development of castration resistant PC) of patients in the upfront ABI group. Secondary objectives included an evaluation of the prognostic significance of upfront ABI and a comparison with a historical cohort (131 mHSPC patients with high tumor burden who received androgen deprivation therapy (ADT/complete androgen blockade [CAB] group) between 2014 and 2019)., Results: We found that the anemia-ABI group had a significantly shorter PFS than the non-anemia-ABI group. A multivariate Cox regression analysis showed that anemia was an independent prognostic factor of PFS in the upfront ABI group (hazard ratio, 4.66; P = 0.014). Patients in the non-anemia-ABI group were determined to have a significantly longer PFS than those in the non-anemia-ADT/CAB group (n = 68) (P < 0.001). However, no significant difference was observed in the PFS between patients in the anemia-ABI and the anemia-ADT/CAB groups (n = 63). Multivariate analyses showed that upfront ABI could significantly prolong the PFS of patients without anemia (hazard ratio, 0.17; P < 0.001), whereas ABI did not prolong the PFS of patients with anemia., Conclusion: Pretreatment anemia was a prognostic factor among mHSPC patients who received upfront ABI. Although the upfront ABI significantly improved the PFS of mHSPC patients without anemia, its efficacy in patients with anemia might be limited.

Metastatic burden is a critical factor for therapy decision-making in metastatic hormone-sensitive prostate cancer. The present study aimed to identify prognostic factors in men with high- or low-metastatic burden treated with primary androgen-deprivation therapy. The study included 2450 men with de novo metastatic prostate cancer who were treated with primary androgen-deprivation therapy at 30 institutions across Japan between 2008 and 2017. We investigated the prognostic value of various clinicopathological parameters for progression-free survival (PFS) and overall survival (OS) in patients stratified by low- or high-metastatic burden. Among the 2450 men, 841 (34.3%) and 1609 (65.7%) were classified as having low- and high-metastatic burden, respectively. Median PFS of the low- and high-burden groups were 44.5 and 16.1 months, respectively, and the median OS was 103.2 and 62.7 months, respectively. Percentage of biopsy-positive core, biopsy Gleason grade group, T-stage, and N-stage were identified to be differentially prognostic. M1a was associated with worse PFS than was M1b in the low-burden group, whereas lung metastasis was associated with better PFS and OS than was M1b in the high-burden group. Differential prognostic factors were identified for patients with low- and high-burden metastatic prostate cancer. These results may assist in decision-making to select the optimal therapeutic strategies for patients with different metastatic burdens., (© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Epigenetic gene silencing by aberrant DNA methylation leads to loss of key cellular pathways in tumorigenesis. In order to analyze the effects of DNA methylation on prostate cancer, we established LNCaP-derived human prostate cancer cells that can pharmacologically induce global reactivation of hypermethylated genes by the methyl-CpG targeted transcriptional activation (MeTA) method. The MeTA suppressed the growth of LNCaP-derived cells and induced apoptosis. Microarray analysis indicated that PYCARD (PYD and CARD domain containing) encoding an apoptosis-inducing factor was upregulated by 65-fold or more after treatment with MeTA. We analyzed DNA methylation statuses using 50 microdissected primary prostate cancer tissues and found an extremely high frequency of tumor-specific promoter hypermethylation of PYCARD (90%, 45/50). Moreover, DNA methylation status was significantly associated with Gleason score ( P = 0.0063); the frequency of tumor-specific hypermethylation was 96% (44/46) in tumors with Gleason score ≥ 7, whereas that in tumors with Gleason score 6 was 25% (1/4). Immunohistochemical analyses using these 50 cases indicated that only 8% (4/50) of cancerous tissues expressed PYCARD, whereas 80% (40/50) of corresponding normal prostate epithelial and/or basal cells expressed PYCARD. In addition, there was no relationship between PYCARD immunostaining and the Gleason score in cancerous tissue and surrounding normal tissue. Inducible expression of PYCARD inhibited cell proliferation by induction of apoptosis. These results suggest that aberrant methylation of PYCARD is a distinctive feature of prostate cancers with Gleason score ≥ 7 and may play an important role in escaping from apoptosis in prostatic tumorigenesis., Competing Interests: The authors declare no competing financial interests., (Copyright © 2021 Toshiya Miyauchi et al.)