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Background The association between curative treatment (CurTrt) and mortality in senior adults (≥70 years) with high‐risk prostate cancer (PCa) is poorly documented. In a population‐based cohort we report temporal trends in treatment and PCa‐specific mortality (PCSM), investigating the association between CurTrt and mortality in senior adults with high‐risk PCa, compared to findings in younger men (, Curative treatment in senior adults with high‐risk prostate cancer is associated with decreased prostate cancer‐specific and overall mortality

There is a great need to identify new and better prognostic and predictive biomarkers to stratify prostate cancer patients for optimal treatment. The aims of this study were to characterize the exp ...

The detection rate for the HT 1 (index tumour) was 92%; HT 2, 45%; and HT 3, 37%. The MRTV 1-3 vs the HTV 1-3 were 2.8 mL vs 4.0 mL (index tumour, P < 0.001), 1.0 mL vs 0.9 mL (tumour 2, P = 0.413), and 0.6 mL vs 0.5 mL (tumour 3, P = 0.492). The rate of true-positive and -negative sectors was 50% and 88%, κ= 0.39. Conclusion A combination of T2W and DW MRI detects the index tumour in 92% of cases, although MRI underestimates both TV and tumour burden compared with histology.

Objective To report the oncological and functional outcomes of hemi salvage high-intensity focused ultrasound (HSH) in patients with unilateral radiorecurrent prostate cancer. Patients and Methods Between 2009 and 2012, 48 patients were prospectively enrolled in two European centres. Inclusion criteria were biochemical recurrence (BCR) after primary radiotherapy (RT), positive magnetic resonance imaging and ≥1 positive biopsy in only one lobe. BCR was defined using Phoenix criteria (a rise by ≥2 ng/mL above the nadir prostate specific antigen [PSA] level). The following schemes and criteria for functional outcomes were used: Ingelman-Sundberg score using International Continence Society (ICS) questionnaire (A and B), International prostate symptom score (IPSS), International Index of Erectile Function-5 (IIEF-5) points, the European Organisation for the Research and Treatment of Cancer (EORTC) quality of life questionnaires (QLQ C-30). HSH was performed under spinal or general anaesthesia using the Ablatherm® Integrated Imaging device. Patients with obstructive voiding symptoms at the time of treatment underwent an endoscopic bladder neck resection or incision during the same anaesthesia to prevent the risk of postoperative obstruction. Results After HSH the mean (sd) PSA nadir was 0.69 (0.83) ng/mL at a median (interquartile range) follow-up of 16.3 (10.5–24.5) months. Disease progression occurred in 16/48 (33%). Of these, four had local recurrence in the untreated lobe and four bilaterally, six developed metastases, and two had rising PSA levels without local recurrence or radiological confirmed metastasis. Progression-free survival rates at 12, 18, and 24 months were 83%, 64%, and 52%. Severe incontinence occurred in four of the 48 patients (8%), eight (17%) required one pad a day, and 36/48 (75%) were pad-free. The ICS questionnaire showed a mean (sd) deterioration from 0.7 (2.0) to 2.3 (4.5) for scores A and 0.6 (1.4) to 1.6 (3.0) for B. The mean (sd) IPSS and erectile function (IIEF-5) scores decreased from a mean (sd) of 7.01 (5.6) to 8.6 (5.1) and from 11.2 (8.6) to 7.0 (5.8), respectively. The mean (sd) EORTC QLC-30 scores before and after HSH were 35.7 (8.6) vs 36.8 (8.6). Conclusion HSH is a feasible therapeutic option in patients with unilateral radiorecurrent prostate cancer, which offers limited urinary and rectal morbidity, and preserves health-related quality of life.

Methods for quantification of bladder outlet obstruction (BOO) are still controversial. Parameters such as detrusor opening pressure (p(det.open)), maximum detrusor pressure (p(det.max)), minimum voiding pressure (p(det.min.void)), and detrusor pressure at maximum flow rate (P(det.Qmax)) separate obstructed from nonobstructed patients to some extent, but two nomograms, the Abrams-Griffiths nomogram and the linearized passive urethral resistance relation (LinPURR), are more accepted for this purpose, along with the urethral resistance algorithm. In this retrospective, methodologic study, we evaluated the properties of these parameters with regard to test-retest reproducibility and ability to detect a moderate (pharmacologic) and a pronounced (surgical) relief of bladder outlet obstruction. We studied the pressure-flow charts of 42 patients who underwent 24 weeks of androgen suppressive therapy, 42 corresponding patients who received placebo, and 30 patients who had prostate surgery. The patients performed repeat void pressure-flow examinations before and after treatment or placebo. The various parameters were compared. Among the bladder pressure parameters, P(det.Qmax) seemed to have some advantages, supporting the belief that it is the most relevant detrusor pressure parameter to include in nomograms to quantify BOO. In assessment of a large decrease in urethral resistance, such as after TURp, resistance parameters that are based on maximum flow rate as well as detrusor pressure are preferable.

Clusterin and the terminal complement pathway synthesized by human umbilical vein endothelial cells are closely linked when detected on co-cultured agarose beads. Clusterin is a multifunctional regulatory protein rendering the terminal complement complex (TCC) soluble and unable to insert into cell membranes. The aim of the present study was to examine whether clusterin was an integral part of serum-derived TCC bound to agarose beads which activate the alternative pathway of complement. Further, we searched for evidence of clusterin synthesis in human umbilical vein endothelial cells (EC) and whether this synthesis was regulated by various proinflammatory cytokines (IL-1, IL-6, and TNF) and IFN-gamma. The clusterin and TCC on co-incubated beads were measured by radioimmunoassay based on primary anti-complement antibodies (anti-C3c, anti-TCC, anti-clusterin). We found that clusterin in serum experiments is bound to C9 in agarose bound TCC and not directly to the agarose. Addition of the protein synthesis inhibitor cycloheximide to cultured human umbilical vein cells resulted in a strong reduction (about 70%) of anti-clusterin binding to co-cultured beads, which strongly supports de novo synthesis of clusterin in EC. The results indicate that clusterin derived from the EC is linked with the TCC on the co-incubated beads for the following reasons: First, in serum experiments clusterin like vitronectin, was co-deposited with C9 in agarose-bound TCC. Second, cytokine stimulation of the EC with proinflammatory cytokines such as IL-1, IL-6 and TNF, known to increase the detection of bound TCC, also increased the amount of clusterin detected on the beads. Third, IFN-gamma, which reduces the concentration of bound TCC, exhibited the same effect on the amount of clusterin detected on such beads. There was a strong and dose-dependent reduction of anti-TCC binding from about 45% to about 95% when clusterin (5-40 micrograms/ml) was added to EC cultures. This effect was also evident (about 40-50% inhibition of bound TCC) using human serum as complement source. These results are probably mainly caused by clusterin binding to C5b-7, making this complex soluble without the capacity to bind to the agarose surface. This study supports the view that clusterin is a potent regulator of TCC at the levels of C5b-7 and C9.

In this study we demonstrate that human endothelial cells (EC) synthesize mRNA for vitronectin by using techniques based on reverse transcriptase (RT) reaction and polymerase chain reaction (PCR). The identification of vitronectin mRNA, shown by sequence analysis of PCR-amplified RT product of RNA extracted from EC, clearly demonstrates that these cells synthesize mRNA for vitronection. We further investigated whether vitronectin in serum-free EC cultures regulates the net expression of the terminal complement pathway, measured as the terminal complement complex (TCC) bound to co-cultured agarose beads which activate the alternative pathway. Presence of polyclonal F(ab')2 anti-human vitronectin (VN) antibodies, regardless of concentration (10-80 micrograms/ml), significantly reduced the binding of monoclonal anti-C3c antibodies to co-cultured beads, whereas the binding of monoclonal anti-TCC antibodies was unaltered or significantly increased compared with controls. Despite some interexperimental variation in the results, addition of vitronectin (10-80 micrograms/ml) to the EC resulted in an inversely related pattern compared with experiments using anti-VN antibodies. The binding indices of anti-C3c are comparable to the controls. On the other hand, there is a steady concentration-dependent (10-80 micrograms of vitronectin added) reduction in binding of anti-TCC up to approximately 60%. The results indicate that vitronectin regulates the expression of synthezised and surface-bound TCC in serum-free EC cultures, comparable to previous findings in serum.

The cytokine gamma-interferon (gIFN) has been reported to modulate synthesis by endothelial cells (EC) of alternative pathway complement factors (H, I, and B). However, the net effect of gIFN on the synthesis and expression of the functional alternative and terminal pathways has not yet been reported. EC cultured under serum-free conditions were treated with different concentrations of gIFN and simultaneously co-incubated with agarose beads, which activate the alternative pathway. C3b and the terminal complement complex (TCC) bound to co-incubated beads were measured by radioimmunoassay using anti-human C3c and TCC antibodies. gIFN in concentrations 500-4000 U/ml increasingly reduced the amount of C3b and TCC detected on the beads. The down-regulating effect of gIFN on EC complement biosynthesis may be physiologically relevant by locally controlling complement activation.

Objective: To evaluate health-related quality of life (HRQOL) after salvage high-intensity focused ultrasound (HIFU) for locally radiorecurrent prostate cancer (PCa). Methods: Since June 2006 we have treated 61 patients consecutively by salvage HIFU. All patients were offered the University of California, Los Angeles Prostate Cancer Index (UCLA-PCI) questionnaire at baseline and at follow-up. Scores ranged from 0 (worst) to 100 (best). Clinically significant changes were defined as a minimum difference of 10 points between the baseline score and the score at follow-up. Results: Fifty-seven patients (93%) had evaluable data at baseline, compared with 46 (75%) after treatment. The mean time lapse between HIFU treatment and questionnaire response was 17.5 months (range 6–29 months). The mean score for urinary function decreased from 79.7 ± 12.1 prior to HIFU to 67.4 ± 17.8 after HIFU (P