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Intermittent endocrine treatment or cyclic therapy of prostate cancer aims at prolonging survival by delaying progression to androgen independence and at improving quality of life by avoiding the side effects of continuous androgen ablation. In this paper we first review the available experimental data suggesting the clinical application of this therapeutic strategy and interpret them with caution. We then examine the published reports of phase II clinical studies showing the feasibility of this approach. Intermittent endocrine treatment is capable of inducing multiple apoptotic regressions; improvement in the sense of well-being and quality of life – including sexual function – is regularly reported. A period of 6–9 months on therapy is usually recommended; the mean off-therapy interval approaches 50% of the duration of the treatment cycle. The mean time to disease progression was 32 months. The definitive answer to the important question of prolonged survival awaits the completion of ongoing randomized studies.

Unfavorable prostate cancer (PCa) disease at final pathology affects at least 10 % of D’Amico low-risk patients. Thus, conservative therapies including active surveillance may be wrongfully applied. The purposes were to assess the rate of upstaging in a contemporary cohort of D’Amico low-risk PCa patients and to develop and externally validate a nomogram as upstaging prediction tool in two European cohorts. Analyses were restricted to 2007 patients who harbored low-risk PCa at ≥10-cores initial biopsy according to D’Amico classification (PSA <10.0 ng/ml, Gleason score <7 and clinical stage ≤T2a). Patients underwent radical prostatectomy at a high-volume center in Hamburg, Germany, from 2010 to 2015. The Hamburg cohort was randomly divided into development (n = 1338) and validation cohorts (n = 669). The development cohort was used to devise a nomogram predicting upstaging, defined as presence of ≥pT3 and/or lymph node invasion. The nomogram was externally validated in two European validation cohorts (Hamburg, n = 669; Milan, n = 465). Upstaging was observed in 187/1338 (14.0 %) of low-risk patients. In multivariable models, four of ten tested variables achieved independent predictor status: age (OR 1.07, 95 % CI 1.04–1.09), PSA (OR 1.21, 95 % CI 1.12–1.31), prostate volume (OR 0.97, 95 % CI 0.96–0.98) and percentage of positive cores (OR 1.02, 95 % CI 1.01–1.03). In external validation, the nomogram demonstrated 70.8 % (Hamburg) and 70.0 % (Milan) accuracy, respectively, with excellent concordance between predicted and observed values. Our proposed nomogram is capable to accurately identify D’Amico low-risk patients at risk of upstaging, utilizing four routinely available clinical variables, age, PSA, prostate volume and percentage of positive biopsy cores. Unfavorable prostate cancer disease at final pathology affects at least 10 % of D’Amico low-risk patients. Thus, we developed and externally validated a new nomogram based on contemporary low-risk prostate cancer patients to accurately identify D’Amico low-risk patients at risk of upstaging. It utilizes four routine variables, age, PSA, prostate volume and percentage of positive biopsy cores.

Few studies have evaluated prostate cancer oncologic outcomes in different ethnic groups following radical prostatectomy for clinically organ-confined disease. Existing studies lack long-term outcome data. We conducted this study to assess the impact of racial differences on risk profile and oncologic outcomes in a large cohort of patients with prostate cancer who underwent radical prostatectomy. Using our institutional review board-approved prostate cancer database, we retrospectively reviewed the records of 3437 patients who underwent radical prostatectomy with curative intent in our institution between 1987 and 2009. Based on ethnicity, patients were divided into Asian Americans (n = 133), African Americans (n = 155) and Caucasians (n = 3149). Baseline characteristics and oncologic outcomes including biochemical recurrence free, clinical recurrence free and overall survival were compared between the study groups. A total of 3437 patients with a mean age of 63 ± 9.8 years and median follow-up period of 8.7 (range 0.1–24.1) years were included in the analysis. Pathologic stage and the frequency of poorly differentiated cancer were higher in Asian Americans; however, margin status did not differ significantly. Moreover, oncologic outcomes were comparable between different ethnic groups. In multivariate analysis, both pathologic stage and grade were independent predictors of oncologic outcomes, but race was not. In this large, ethnically diverse long-term follow-up study, we noted that Asian Americans compared to African Americans and Caucasians are more likely to have high risk prostate cancer; however, race was not an independent predictor of oncologic outcome following radical prostatectomy with curative intent.

To determine whether multi-parametric magnetic resonance imaging (mpMRI) can reliably predict proximity of prostate cancer to the prostatic urethra in a contemporary series of men undergoing radical prostatectomy (RP) at two academic centers. Clinical characteristics of consecutive men undergoing pre-operative mpMRI prior to RP and whole-mount axial serial step-sectioned pathology examination at two academic centers between Jun 2016 and Oct 2018 were analyzed retrospectively. Every tumor was characterized by its pathologic minimum distance to the prostatic urethral lumen (pMDUL). Only the cancer closest to the urethra represented the prostatic urethral index lesion. The radiologic minimum distance of the index lesion to the prostatic urethral lumen was measured and noted as ≤ 5 mm versus  > 5 mm. The sensitivity, specificity, positive and negative predicting values (PPV and NPV) and area under the receivers operating characteristics curve (AUC) were calculated for performance of mpMRI for predicting pMDUL ≤ 5 mm. Of the 163 surgical specimens examined, 112 (69%) exhibited a pMDUL ≤ 5 mm. These men had significantly higher grade group (GG) and advanced pathological and clinical stage. The rates of high PI-RADS score and presence of gross extracapsular extension were also significantly greater for the group with pMDUL ≤ 5 mm. The AUC, sensitivity, specificity, PPV, and NPV were 0.641, 51.8, 76.5, 82.9, and 42.4%, respectively, for mpMRI to predict pMDUL < 5 mm. Nearly 70% of men undergoing RP present with tumor within 5 mm of the prostatic urethra. These tumors present higher risk characteristics, and mpMRI exhibited moderate performance and high PPV in their pre-operative detection. Physicians performing partial gland ablation should take these results into consideration during treatment selection and planning.

Enhancer of Zeste 2 (EZH2) is an epigenetic transcriptional repressor involved in cell cycle control and cell fate decisions. Since these processes play key roles during intact spermatogenesis, deregulation of EZH2 expression may contribute to the development and progression of benign and malignant testicular diseases. The objective of this study was to investigate the expression profile of EZH2 in testicular germ cell tumors (TGCT) and spermatogenic defects. Real-time RT-PCR was applied to quantify the m-RNA expression of EZH2 in 64 seminomas 36 non-seminomas, 4 carcinomas in situ (CIS), 40 samples harboring impaired spermatogenesis and 24 normal testicular reference biopsies. EZH2 was expressed in 99% of TGCT samples and in all biopsies with intact spermatogenesis. Its expression levels were highest in normal testicular tissue, and continuously decreased with malignant transformation to CIS and further progression to invasive TGCT (P < 0.001). EZH2 tumor levels were not related to the histological TGCT subtype or clinical tumor stage. Comparison of distinct stages of spermatogenic failure revealed an inverse association of EZH2 levels to the severity of the spermatogenic defect (P < 0.001). Our data strongly suggest that in TGCT EZH2 does not exert its often assumed oncogenic properties during malignant transformation and progression. High EZH2 levels in normal testicular tissue and the inverse association of its expression levels with the severity of spermatogenic failure point to its potential value as a molecular marker for spermatogenic defects and may indicate an important physiological role of EZH2 during intact spermatogenesis.

The aims were (1) to assess the pediatric lower urinary tract symptom score (SS) prior to treatment as a means of determining severity of overactive bladder (OAB) and (2) to investigate relationships between SS results and those of standard diagnostic modalities. Symptom scores were recorded pre- and 6 months SS for 294 children with OAB unrelated to neurological disorder. Uroflowmetry–electromyography data, total bladder capacity, and a 2-day bladder diary were also recorded, and upper urinary tract deterioration was investigated as indicated. Overactive bladder was treated with standard approaches. No response to treatment was defined as 0–49 % reduction in OAB-related symptoms based on SS results. Non-responders underwent additional evaluations as indicated. Two hundred forty-one patients (97 %; mean age 9.8 ± 2.8 years; mean follow-up 11 months; range 6–18 months) completed the study. One hundred thirteen (47 %) required ultrasonography (USG), and those with abnormal USG had a significantly higher pre- and 6 months SS (p = 0.016). All non-responders (n = 38; 16 %) underwent urodynamics evaluation, 34 underwent spinal magnetic resonance imaging (MRI), 34 underwent voiding cystourethrography (VCUG), and 34 underwent dimercaptosuccinic acid scanning (DMSA). Non-responders with terminal detrusor hyperactivity had significantly lower SS after therapy (p = 0.09). Non-responders with abnormal MRI had higher pre- and 6 months SS than those with normal MRI. Thirteen (38 %) of the non-responders who required VCUG had vesicoureteral reflux (VUR), and this subgroup had higher pre-treatment SS (p = 0.030). Seven (21 %) of the non-responders who required DMSA had scarring, and all 7 had VUR. The subgroup with scarring had higher pre-treatment SS (p = 0.030). Pediatric OAB patients with high 6 months SS have a higher incidence of additional upper urinary tract pathology. Those with low pre-treatment SS require fewer laboratory tests and other assessments. The SS tool can reduce the number of urodynamics evaluations, and other tests required to diagnose renal damage in children with OAB.

To evaluate health-related quality of life (HRQoL), anxiety and depression levels in patients with ureteral stricture (US) and to further investigate factors independently affecting this. We prospectively recruited a cohort of 275 consecutive patients with US between June 2020 and April 2021. The participants were required to provide complete sociodemographic, clinical and pathologic information. All patients were administered questionnaires to evaluate HRQoL, anxiety and depression. Multivariate linear regression analyses were performed to assess the contribution of covariates on HRQoL, anxiety and depression. Patients with US, particularly iatrogenic US, scored significantly lower than the Chinese general population in all domains of the SF-36 (all p < 0.001), except SF. Increased age, female and high education attainment were independently associated with poor HRQoL. Interestingly, iatrogenic US, nephrostomy tube placement, urinary symptoms, high anxiety and depression level independently predicted poor HRQoL. Furthermore, the percentages of anxiety and depression cases in patients with US were 31.3% and 20.7%, respectively. Iatrogenic US and urinary symptoms, specifically waist discomfort, were the strongest predictors of increased levels of anxiety and depression. Patients with US exhibited poor quality of life and emotional status. Various factors independently predicted worse HRQoL and emotion, which provide potential targets for medical, lifestyle-related, psychological interventions.

The main objective was to compare minor (Clavien I–II) and major (Clavien ≥ III) intra- and postoperative complications of living donor robotic assisted kidney transplantation (RAKT) in obese (≥ 30 kg/m2 BMI), overweight (< 30/ ≥ 25 kg/m2 BMI) and non-overweight recipients (< 25 kg/m2 BMI). For the present retrospective study, we reviewed the multi-institutional ERUS-RAKT database to select consecutive living donor RAKT recipients. Functional outcomes, intra- and postoperative complications were compared between obese, overweight and non-overweight recipients. 169 living donor RAKTs were performed, by 10 surgeons, from July 2015 to September 2018 in the 8 European centers. 32 (18.9%) recipients were obese, 66 (39.1%) were overweight and 71 (42.0%) were non-overweight. Mean follow-up was 1.2 years. There were no major intra-operative complications in either study group. Conversion to open surgery occurred in 1 obese recipient, in 2 overweight recipients and no conversion occurred in non-overweight recipients (p = 0.3). Minor and major postoperative complications rates were similar in the 3 groups. At one-year of follow-up, median eGFR was similar in all groups [54 (45–60) versus 57 (46–70) versus 63 (49–78) ml/min/1.73 m2 in obese, overweight and non-overweight recipient groups, respectively, p = 0.5]. Delayed graft function rate was similar in the 3 groups. Only the number of arteries was an independent predictive factor of suboptimal renal function at post-operative day 30 in the multivariate analysis. RAKT in obese recipients is safe, compared to non-overweight recipients and yields very good function, when it performed at high-volume referral centers by highly trained transplant teams.