Search

Despite extensive analysis of the BRCA1 and BRCA2 genes, germline mutations are detected in <20% of families with a presumed genetic predisposition for breast and ovarian cancer. Recent literature reported RAD51C as a new breast cancer susceptibility gene. In this study, we report the analysis of 410 patients from 351 unrelated pedigrees. All were referred for genetic testing and we selected families with at least one reported case of ovarian cancer in which BRCA1&2 mutations were previously ruled out. We analyzed the coding exons, intron-exons boundaries, and UTRs of RAD51C. Our mutation analysis did not reveal any unequivocal deleterious mutation. In total 12 unique sequence variations were identified of which two were novel. Our study and others suggest a low prevalence of RAD51C mutations with an exception for some founder populations. This observation is in favor of the rare allele hypothesis in the debate over the nature of the genetic contribution to individual susceptibility to breast and ovarian cancer and further genome-wide studies in high risk families are warranted. [ABSTRACT FROM AUTHOR]

Background: The incidence of papillary thyroid microcarcinomas (PMCs) has increased sharply and therefore the lack of consensus for treatment has become a clinical dilemma. Our aim was to evaluate a less-radical approach., Methods: This study includes 1,391 patients with PMC treated at a single surgical referral center in the endemic goiter area in Austria. Data, including long-term follow-up examinations with a median follow-up time of 7 years, were collected from the institutional surgery database., Results: Of the 1,391 patients, 947 (68.1%) had a near-total or total thyroidectomy; 1,090 patients (78.3%) had no lymphadenectomy, and 1,136 patients (81.7%) did not receive radioiodine treatment. Twenty-one patients (1.5%) underwent reoperation, 5 because of lymph node recurrence (0.4%), 16 with clinically benign recurrence, including 4 cases of another PMC. There were no recurrences in the thyroid bed and no disease-related deaths. Risk factors for lymph node recurrences were nonincidental finding, nodal metastases at presentation, young age, aggregate tumor size, and subcapsular tumor localization. Multifocality, sex, maximum tumor size, and the extent of surgery were not relevant factors., Conclusion: Nodal recurrence is rare and reoperation cured all patients. Micrometastases are not of clinical relevance. The postoperative findings of most PMCs suggest that, even if multifocal, a limited approach without completion thyroidectomy, lymphadenectomy and radioiodine treatment is sufficient. In case of pre- or intraoperative clinically suspected nodal metastases or postoperatively diagnosed risk factors we propose the standard radical procedure. Routine preoperative cervical lymph node sonography is advisable before any thyroid surgery., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To evaluate the frequency of bladder outlet obstruction (BOO) and detrusor overactivity (DO) in patients with castration-resistant prostate cancer (CRPC) and lower urinary tract symptoms (LUTS)., Patients and Methods: Our prospective urodynamics database was queried. Inclusion criteria were CRPC and an International Prostate Symptom Score (IPSS) ≥ 20. Exclusion criteria were previous local therapy to the prostate gland, known urethral stricture disease, and a neurological component of LUTS. Twenty-one patients were identified. Urodynamic findings were analysed and compared with those of a matched cohort of 42 patients with benign prostatic enlargement (BPE)., Results: The median age of patients in the CRPC group was 74 years, and the median prostate-specific antigen (PSA) level at the time of the urodynamic study was 90 ng/mL. According to the BOO index, three patients (14%) were obstructed, three were equivocally obstructed (14%) and 15 were unobstructed. DO was seen in 12 patients (57%). Compared with the BPE group, patients with CRPC had lower cystometric bladder capacities (P = 0.003), were less likely to have BOO (14 vs 43%, P = 0.009) and more likely to have DO (57 vs 29%, P = 0.028)., Conclusions: This study generates the hypothesis that only a minority of CRPC patients with LUTS have BOO, and that more than half of patients have DO. LUTS in CRPC may therefore be seldom attributable to BOO, but are, at least in part, related to DO and reduced cystometric capacity. A urodynamic investigation may be necessary before palliative transurethral resection of the prostate to select appropriate candidates. Larger prospective studies are needed to confirm our findings., (© 2013 The Authors. BJU International © 2013 BJU International.)

Blindness is one of the most devastating conditions affecting the quality of life. Hereditary degenerative diseases, such as retinitis pigmentosa, are characterized by the progressive loss of photoreceptors, leading to complete blindness. No treatment is known, the current state-of-the-art of restoring vision are implanted electrode arrays. As a recently discovered alternative, optical neuromodulators, such as channelrhodopsin, allow new strategies for treating these diseases by imparting light-sensitivity onto the remaining retinal neurons after photoreceptor cell death. Retinal degeneration is a heterogeneous set of diseases with diverse secondary effects on the retinal circuitry. Successful treatment strategies have to take into account this diversity, as only the existing retinal hardware can serve as substrate for optogenetic intervention. The goal is to salvage the retinal ruins and to revert the leftover tissue into a functional visual sensor that operates as optimally as possible. Here, we discuss three different successful approaches that have been applied to degenerated mouse retina.

Objective: To evaluate the prostate cancer (PCa) detection rate, PCa location, PCa significance and complications of a standardized 24-core template-guided transperineal biopsy (TPB) approach in patients with at least two negative transrectal biopsies., Methods: We prospectively recruited 50 men who had at least two negative transrectal ultrasound-guided extended biopsies in the past 24 months, a prostate-specific antigen (PSA) < 20 ng/mL, a prostate volume < 100 mL, and life expectancy of at least 90 % at 10 years. All patients underwent a standardized 24-core template-guided TPB biopsy. The PCa detection rate, PCa location, PCa significance, and complications were recorded., Results: Median age was 57.5 years and the median PSA level was 7.3 ng/ml. PCa was detected in 24 patients (48 %). The anterior zone was involved in 16 (32 %) PCa. Six PCa (25 %) were insignificant. Biopsy related complications occurred in 2 patients (4 %)., Conclusions: A 24-core TPB is a safe procedure with a high PCa detection rate. Few of the detected PCa are clinically insignificant. Men with at least two negative transrectal biopsies may be counseled to undergo TPB.

Background: Solid organ recipients have a substantial risk of developing bladder cancer, with high-risk non-muscle-invasive bladder cancer (NMIBC) being the most frequent diagnosis. Theoretically, adjuvant bacillus Calmette-Guérin (BCG) therapy is contraindicated, but limited data indicate its feasibility. The objective of this study was to evaluate the safety and efficacy of BCG following solid organ transplantation., Materials and Methods: We reviewed the data of four solid organ recipients who received adjuvant BCG for high-risk NMIBC at our institution. Additionally, individual data of 12 patients were extracted from case series and case reports, which were identified through a systematic review of the literature. A meta-analysis was performed., Results: Fourteen patients (88 %) had received a kidney, one a heart, and one a liver transplant. The median time from transplantation to bladder cancer was 60.5 months. The regimen of immunosuppression was not modified in 12 patients (75 %). Forty-two percent of patients did not receive prophylactic antibiotics, and 70 % had no side effects. Ten patients (63 %) experienced recurrence after a median of 14 months. Progression to muscle-invasive or metastatic disease was observed in two patients (13 %). Four patients (25 %) underwent radical cystectomy, and two patients died of the disease., Conclusions: BCG therapy is a safe option for patients with high-risk NMIBC following solid organ transplantation. However, there is a substantial risk of recurrence and progression. Urologists and patients considering BCG therapy should be aware of this and may consider early cystectomy. There is no evidence to support the need for prophylactic antibiotics.

Unlabelled: Study Type--Symptom prevalence (cohort) Level of Evidence 2b. What's known on the subject? and What does the study add? Depression plays an important role in pathogenesis of BPH. Our study shows that prostatic symptoms can be helpful in the screening for depression., Objective: • To evaluate the relationship between lower urinary tract symptoms (LUTS) and depression in men through validated questionnaires., Patients and Methods: • Healthy male workers (n = 673) were invited to a free health check-up. • Patients underwent a detailed medical examination. • All participants completed the International Prostate Symptom Score (IPSS) questionnaire and the Beck Depression Inventory (BDI)., Results: • Under multiple logistic regression analysis (adjusted for total testosterone and age), a significant effect of IPSS on BDI score was observed: mild depression (BDI score >9): odds ratio (OR) 1.092, 95% confidence interval (CI) 1.056-1.129; P < 0.001; moderate-to-severe depression (BDI score >19): OR 1.093, 95% CI 1.031-1.159; P = 0.003; and severe depression (BDI score >29): OR 1.176, 95% CI 1.048-1.320; P = 0.006., Conclusions: • In healthy men, LUTS are significantly associated with depression. • The treatment of LUTS is very important for the mental health of older men., (© 2012 THE AUTHORS. BJU INTERNATIONAL © 2012 BJU INTERNATIONAL.)

Purpose: We evaluated the need of routine transurethral biopsies after an induction course of intravesical bacillus Calmette-Guérin for high grade nonmuscle invasive bladder cancer., Materials and Methods: This retrospective study included 180 patients with high grade nonmuscle invasive bladder cancer who underwent a 6-week induction course of bacillus Calmette-Guérin. Cystoscopic findings, urinary cytology and pathological results of transurethral biopsy were evaluated. For cumulative meta-analysis we systematically reviewed studies indexed in MEDLINE®, EMBASE® and Web of Science®. The records of 740 patients from a total of 7 studies were finally analyzed., Results: Biopsy was positive in 58 patients (32%). Cystoscopy appeared normal in 75 patients (42%) and showed only erythema in 51 (28%) and tumor in 54 (30%), of whom 6 (8%), 11 (22%) and 41 (76%), respectively, showed positive findings at biopsy. The positive predictive value of erythema was 15% with negative cytology and 56% with positive cytology. The positive predictive value of a tumor with negative and positive cytology was 63% and 89%, respectively. A combination of negative cytology and normal cystoscopy was associated with a negative biopsy in 94% of cases. A total of 970 bladder biopsies were taken, of which 137 (14%) were positive, including 20 of 125 erythematous lesions (16%), 73 of 107 tumors (68%) and 44 of 738 normal-appearing areas (6%). Cumulative analysis findings were comparable., Conclusions: Routine transurethral bladder biopsies after a bacillus Calmette-Guérin induction course are not necessary. An individually approach is recommended, tailored from cystoscopic findings and cytology., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We studied the association of serum sex hormone levels with clinicopathological variables and biochemical recurrence in men with prostate cancer treated with radical prostatectomy., Materials and Methods: We prospectively studied preoperative serum sex hormone-binding globulin, luteinizing hormone, follicle-stimulating hormone, and free and total testosterone in 372 patients undergoing radical prostatectomy. Biochemical recurrence was analyzed in 285 patients and defined as prostate specific antigen 0.2 ng/ml or higher at least 30 days after radical prostatectomy. Median followup was 43.6 months., Results: Median sex hormone-binding globulin was 37.4 nmol/l, luteinizing hormone 4.1 mU/ml, follicle-stimulating hormone 5.9 mU/ml, and free and total testosterone 0.069 and 3.7 ng/ml, respectively. There was no significant association of sex hormone-binding globulin, luteinizing hormone, follicle-stimulating hormone or total testosterone with T and N stage, and margin status. Luteinizing hormone, follicle-stimulating hormone, and free and total testosterone were not associated with biochemical recurrence. In contrast, for each 10 U increase in sex hormone-binding globulin the risk of biochemical recurrence increased by 12% (p = 0.045). On multivariable analysis sex hormone-binding globulin achieved independent predictor status after adjusting for standard clinicopathological variables. After stepwise regression a model containing T and N stage, Gleason score, margin status, prostate weight and sex hormone-binding globulin improved the accuracy of a base model by 1.3% (79.0% vs 77.7%)., Conclusions: Preoperative serum sex hormone-binding globulin is independently associated with biochemical recurrence after radical prostatectomy and increases the predictive accuracy of a standard multivariable model. Routine assessment of sex hormone-binding globulin sex hormone-binding globulin may be a helpful adjunct to identify patients who need early adjuvant therapy., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)