Influence of 1 year of androgen deprivation therapy on lipid and glucose metabolism and fat accumulation in Japanese patients with prostate cancer.

BACKGROUND: We prospectively examined influence of androgen deprivation therapy (ADT) on lipid and glucose metabolisms in Japanese patients with prostate cancer. METHODS: Patients with prostate cancer who were hormone-naive and scheduled to receive long-term ADT were recruited between 2011 and 2013. Body weight, abdominal circumference and blood testing associated with lipid and glucose metabolism were recorded every 3 months during 1 year of ADT. Computed tomography (CT) was performed to measure areas of subcutaneous and visceral fat before and after 1 year of ADT. ADT was limited to a luteinizing hormone-releasing hormone (LHRH) agonist with or without bicalutamide. RESULTS: Of 218 patients registered, data were available from 177 patients who completed 1 year of ADT. Of these, CT was performed before and after 1 year of ADT in 88 patients. Median age was 75 years (range, 49-85 years). Median PSA before ADT was 16.7 ng ml(-1) (range, 0.3-3316). Clinical stage was B (54.2%), C (23.2%) and D (20.9%). Mean increases in body weight and abdominal circumference after 1 year of ADT were 2.9 and 3.0%, respectively. Mean increases in total, low-density lipoprotein and high-density lipoprotein cholesterol and triglycerides were 10.6, 14.3, 7.8 and 16.2%, respectively. Mean increases in fasting blood sugar and hemoglobin A1c (HbA1c) were 3.9 and 2.7%, respectively. Lipid alterations were noted in patients without comorbidities, whereas changes in HbA1c were noted in patients with diabetes mellitus at baseline. These lipid and glucose alterations were prominent in the early ADT period. Both visceral and subcutaneous fat, as measured by CT, increased by >20%. The increase in subcutaneous fat was significantly greater than that in visceral fat (P=0.028). CONCLUSIONS: One year of ADT significantly changed lipid and glucose metabolism in Japanese patients with prostate cancer. Patient characteristics or comorbidities at baseline may be associated with ADT-induced metabolic changes.

Lymphovascular invasion is significantly associated with biochemical relapse after radical prostatectomy even in patients with pT2N0 negative resection margin.

BACKGROUND: The significance of lymphovascular invasion (LVI) remains controversial, and the association of LVI with biochemical relapse was investigated in men treated with radical prostatectomy according to pathological results. METHODS: Data from 1268 patients undergoing radical prostatectomy between 2000 and 2009 were retrospectively reviewed. Clinicopathological variables were compared between LVI-negative and LVI-positive patients. Multivariate analyses by Cox proportional hazard model and Kaplan-Meier method were performed to identify risk factors for biochemical relapse in all patients, patients with pT2N0 and pT2N0 negative resection margin (RM). RESULTS: LVI information was available in 1160 cases, and LVI was seen in 121 cases (10.4%). Clinicopathological variables were significantly worse in LVI-positive patients than in LVI-negative patients. On multivariate analyses, PSA⩾10 ng ml(-1), pathological Gleason score ⩾8, pathological T stage ⩾3, lymph node metastasis, positive RM and LVI were independent predictors for biochemical relapse in all patients. In patients with pT2N0, PSA⩾10 ng ml(-1), pathological Gleason score ⩾8, positive RM and LVI were independent predictors for biochemical relapse. In patients with pT2N0 negative RM, LVI and pathological Gleason score ⩾8 were independent predictors for biochemical relapse (LVI; hazard ratio 3.809, 95% confidence interval 1.900-7.635, P-value<0.001, Gleason score ⩾8; hazard ratio 2.189, 95% confidence interval 1.199-3.999, P-value=0.011). With a median follow-up of 50 months, 5-year biochemical relapse-free survival in patients with pT2N0 negative RM was 95.7% in those with negative LVI in comparison to 85.3% in those with positive LVI (P<0.001, log rank). CONCLUSIONS: LVI was consistently a significant predictor for biochemical relapse after radical prostatectomy in not only all patients but also in patients with pT2N0 and pT2N0 negative RM. These results strongly support the significance of LVI as a predictor for biochemical relapse.

Ganglioside disialosyl globopentaosylceramide is an independent predictor of PSA recurrence-free survival following radical prostatectomy.

BACKGROUND: Disialosyl globopentaosylceramide (DSGb5) is a ganglioside originally isolated from renal cell carcinoma (RCC) tissue that has been associated with RCC metastasis. However, in prostate cancer, the expression of DSGb5 has not yet been fully assessed. In this study, we investigated DSGb5 expression in prostate tissues and the relationship between DSGb5 expression and clinicopathological characteristics of prostate cancer patients. METHODS: A total of 130 patients who underwent radical prostatectomy (RP) at our hospital between January 2005 and December 2007 were analyzed in this study. The expression of DSGb5 in prostatectomy specimens was examined by immunohistochemical analysis with monoclonal antibody 5F3 (anti-DSGb5). Associations between 5F3 expression and clinicopathological findings were investigated and the factors that affected PSA failure-free survival were assessed by Kaplan-Meier analysis and a Cox regression model. RESULTS: When immunoreactivities of 5F3 were measured, negative to strong staining was observed in prostate cancer tissue, whereas strong staining was observed in benign prostate glands. These expression patterns suggest that DSGb5 may act as a differentiation antigen in cancerization. The PSA failure-free survival was significantly higher in the 5F3 intact expression group than in the 5F3 reduced expression group (log-rank P=0.0220). On multivariate analysis, 5F3 intact expression showed significantly worse PSA failure-free survival following RP. CONCLUSIONS: 5F3 expression reflects the clinical and pathological features of prostate cancer and is correlated with the outcomes following RP. Further studies are necessary to clarify the functional roles of DSGb5 and establish a novel biomarker for prostate cancer.

Impact of body mass index on clinicopathological outcome and biochemical recurrence after radical prostatectomy.

BACKGROUND: Accumulating evidence suggests that obesity is associated with tumor progression in prostate cancer (PCa) patients after radical prostatectomy (RP). We conducted a retrospective multicenter study to determine the effect of body mass index (BMI) on the clinicopathological characteristics and biochemical recurrence of PCa in Japanese men who underwent RP. METHODS: The medical records of 1257 men with PCa treated by RP without neoadjuvant therapy at four medical institutes between 2001 and 2009 were retrospectively reviewed. Patients were categorized into four groups using the World Health Organization (WHO) BMI classification and BMI quartiles. Associations of the various BMI categories with clinicopathological characteristics and biochemical recurrences were statistically evaluated. Biochemical recurrence was defined as a PSA level of >0.2 ng ml(-1). RESULTS: Of the 1257 patients, 230 (18.3%) experienced biochemical recurrence during the median follow-up period of 49 months. The median BMI was 23.8 kg m(-2), and 1.4% patients were underweight, 65.4% were of normal weight, 30.9% were overweight and 2.4% were obese (WHO classification). Preoperative PSA levels and PSA density (PSAD) tended to decrease as BMI increased. Pathological characteristics did not differ significantly among BMI categories. As per the WHO classification and quartile categories, biochemical recurrence rate was comparable among the BMI groups. After adjusting for other pre- and postoperative covariables, multivariate Cox proportional hazards analysis revealed that a high BMI did not have an independent impact on biochemical recurrence-free survival. CONCLUSIONS: Underweight Japanese PCa patients treated by RP had higher preoperative PSA levels and PSAD. High BMI was not associated with adverse pathological findings or increased biochemical recurrence rate in Japanese PCa patients treated with RP. Racial differences may exist in the relationship between obesity and outcomes of RP in PCa patients.

Probing the anharmonicity of the potential well for a magnetic vortex core in a nanodot.

The anharmonicity of the potential well confining a magnetic vortex core in a nanodot is measured dynamically with a magnetic resonance force microscope (MRFM). The stray field of the MRFM tip is used to displace the equilibrium core position away from the nanodot center. The anharmonicity is then inferred from the relative frequency shift induced on the eigenfrequency of the vortex core translational mode. An analytical framework is proposed to extract the anharmonic coefficient from this variational approach. Traces of these shifts are recorded while scanning the tip above an isolated nanodot, patterned out of a single crystal FeV film. We observe a +10% increase of the eigenfrequency when the equilibrium position of the vortex core is displaced to about one-third of its radius. This calibrates the tunability of the gyrotropic mode by external magnetic fields.

Measurement of the dynamical dipolar coupling in a pair of magnetic nanodisks using a ferromagnetic resonance force microscope.

We perform a spectroscopic study of the collective spin-wave dynamics occurring in a pair of magnetic nanodisks coupled by the magnetodipolar interaction. We take advantage of the stray field gradient produced by the magnetic tip of a ferromagnetic resonance force microscope to continuously tune and detune the relative resonance frequencies between two adjacent nano-objects. This reveals the anticrossing and hybridization of the spin-wave modes in the pair. At the exact tuning, the measured frequency splitting between the binding and antibinding modes corresponds to the strength of the dynamical dipolar coupling Ω. This accurate ferromagnetic resonance force microscope determination of Ω is measured versus the separation between the nanodisks. It agrees quantitatively with calculations of the expected dynamical magnetodipolar interaction in our sample.

[A case of idiopathic retroperitoneal fibrosis causing acute renal failure and markedly responsive to drug therapy].

We report a case of idiopathic retroperitoneal fibrosis in a 66-year-old man. He was admitted to our hospital because of acute renal failure, and emergent hemodialysis was performed. Computed tomography scanning showed a retroperitoneal mass surrounding the abdominal aorta and bilateral common iliac arteries. The mass involved bilateral ureters and acute renal failure was caused by bilateral hydronephrosis. Magnetic resonance imaging demonstrated that the mass was slightly high intensity on T2 weighted image. It was considered to be idiopathic retroperitoneal fibrosis. After inserting ureteral catheters into bilateral ureters, his renal function recovered. The layer of the fibrosis became thin by steroids and traditional Chinese medicine, and bilateral ureteral catheters could be removed two months later. At ten months after the treatment, no ureteral obstruction was observed and renal function is preserved.