Genetic and epigenetic features of neuroendocrine prostate cancer and their emerging applications.

Prostate cancer is the second most prevalent cancer in men globally. De novo neuroendocrine prostate cancer (NEPC) is uncommon at initial diagnosis, however, (treatment-induced) t-NEPC emerges in up to 25% of prostate adenocarcinoma (PRAD) cases treated with androgen deprivation, carrying a drastically poor prognosis. The transition from PRAD to t-NEPC is underpinned by several key genetic mutations; TP53, RB1, and MYCN are the main genes implicated, bearing similarities to other neuroendocrine tumours. A broad range of epigenetic alterations, such as aberrations in DNA methylation, histone post-translational modifications, and non-coding RNAs, may drive lineage plasticity from PRAD to t-NEPC. The clinical diagnosis of NEPC is hampered by a lack of accessible biomarkers; recent advances in liquid biopsy techniques assessing circulating tumour cells and ctDNA in NEPC suggest that the advent of non-invasive means of monitoring progression to NEPC is on the horizon. Such techniques are vital for NEPC management; diagnosis of t-NEPC is crucial for implementing effective treatment, and precision medicine will be integral to providing the best outcomes for patients.

The role of intra-operative void score during transurethral resection of prostate as a marker of efficacy: a feasibility study.

BACKGROUND: To assess the feasibility of a novel intra-operative void scoring technique. To determine if intra-operative void score (VS) could act as a marker for post-operative success following TURP. METHODS: Fifteen patients undergoing TURP were included in this single-centre feasibility study. All patients had indwelling urinary catheters for recurrent retention due to benign prostatic hyperplasia (BPH). In theatre, immediately before- and after TURP, an intra-operative VS was measured and graded 0-5. Primary outcomes were the feasibility of measuring intra-operative VS and its accuracy in predicting surgical outcome. RESULTS: A combined pre- and post-score with a threshold ≥6 correctly predicted 82% of those who were catheter free (sensitivity) and 100% of those who were not catheter free (specificity) at follow up and the positive predictive value was 100% and negative predictive value 60%. CONCLUSION: Intra-operative void score during TURP is simple, reproducible, fast and requires minimal resources. In TURP it may predict successful outcomes by identifying patients who will be catheter free post-operatively as opposed to those who will be catheter dependent despite the procedure.

Preparation of green synthesized copper oxide nanoparticles for efficient removal of lead from wastewaters.

Green synthesis is a clean and eco-friendly process in which metal nanoparticles can be produced by the reaction between a metal salt solution and plant organ extract. In the present study, three copper oxide nanoparticles were green synthesized from the leaf extracts of astragalus (Astragalus membranaceus), rosemary (Salvia rosmarinus), and mallow (Malva sylvestris) as predominant plant cover in the study area was characterized. The effectiveness of three green synthesized nanoparticles in the adsorption of lead ions from polluted water was studied. According to the results, the removal efficiencies of the copper oxide nanoparticles synthesized from astragalus (A-CuO-NPs), rosemary (R-CuO-NPs), and mallow leaf extract (M-CuO-NPs) especially at the highest initial concentration of lead (1.5 mM), were 88.4%, 84.9%, and 69.6%, respectively. Probably due to the smooth morphology and more uniform configuration of the M-CuO-NPs, the changes between equilibrium adsorption (qe) and equilibrium concentration (Ce) were more regular than those of the A-CuO-NPs and R-CuO-NPs. Therefore, the best fit of the data to the Langmuir and Freundlich isotherms belonged to the adsorption of lead onto the M-CuO-NPs. According to the results reported herein, the copper oxide nanoparticles synthesized from different plant covers are efficient adsorption agents for lead from wastewaters solution.

Comparison of the efficiency of copper oxide nanoparticles prepared by green synthesis method using the leaf extracts of astragalus (Astragalus membranaceus), rosemary (Salvia rosmarinus) and mallow (Malva sylvestris) plants in removing lead ions from wastewater.Astragalus, as an abundant plant cover in the study area, has a capable leaf extract for green synthesis of copper nanoparticles, which its efficiency for the removal of toxic metal ions from aqueous solutions has not been already studied in previous researches.

Awareness of European practitioners toward uncommon tropical diseases: are we prepared to deal with mass migration? Results of an international survey.

PURPOSE: The recent rise in migration from Africa through the Mediterranean basin into Europe has resulted in an increased incidence of uncommon diseases such as schistosomiasis and genito-urinary tuberculosis, which were previously largely unknown in this region. This study aimed to evaluate the insight of European urologists into diagnosing and managing these disease conditions and to determine whether they were adequately prepared to deal with the changing disease spectrum in their countries. METHODS: A survey including specific questions about the diagnosis and management of 'tropical' urological diseases was distributed among urologists working in Europe and Africa. Multivariate logistic regression models were performed to detect the continent (African or European) effect on knowledge of and insight into tropical urological diseases. RESULTS: A total of 312 surveys were administered. African and European respondents accounted for 109 (36.09%) and 193 (63.91%) respondents, respectively. The multivariate logistic regression analysis demonstrated a significant deficiency in the knowledge of tropical urological diseases in the European cohort compared with the African cohort (p < 0.05). Moreover, in the European cohort, markedly superior knowledge of tropical urological diseases was observed for respondents who had previously worked in a developing country. CONCLUSIONS: Though European urologists are not required to have the same insight as African urologists, they showed a very unsatisfactory knowledge of tropical urological diseases. The experience of working in a developing country could improve the knowledge of European urologists regarding tropical urological diseases.

Inter-rater reliability in the radiological classification of renal injuries.

INTRODUCTION: Although many radiologists invoke the surgical classification of renal injury proposed by the American Association for Surgery in Trauma (AAST), there has been only limited work on the role of the AAST system as an imaging stratification. The aim was to determine the inter-rater reliability (IRR) amongst radiologists and urologists using the AAST system. METHODS: A 1-year retrospective study of consecutive patients with computed tomography (CT) evidence of renal trauma managed at a Level 1 trauma center. Three radiologists and three urologists independently stratified the presentation CT findings according to the AAST renal trauma classification. Agreement between independent raters and mutually exclusive groups was determined utilizing weighted kappa coefficients. RESULTS: One hundred and one patients were included. Individual inter-observer agreements ranged from 54/101 (53.4%) to 62/101 (61.4%), with corresponding weighted kappa values from 0.61 to 0.69, constituting substantial agreement. Urologists achieved intra-disciplinary agreement in 49 cases (48.5%) and radiologists in 36 cases (35.6%). Six-reader agreement was achieved in 24 cases (23.7%). The AAST grade I injuries had the highest level of agreement, overall. CONCLUSION: The finding of substantial IRR amongst radiologists and urologists utilizing the AAST system supports continued use of the broad parameters of the AAST system, with some modification in specific categories with lower agreement.

Penile allotransplantation for penis amputation following ritual circumcision: a case report with 24 months of follow-up.

INTRODUCTION: Ritual circumcision complicated by gangrene is a leading cause of penile loss in young men in South Africa. This deeply rooted cultural tradition is unlikely to be abolished. Conventional reconstructive techniques using free vascularised tissue flaps with penile implants are undesirable in this often socioeconomically challenged group because donor site morbidity can hinder manual labour and vigorous sexual activity might lead to penile implant extrusion. The psychosociological effects of penile loss in a young man are devastating and replacing it with the same organ is likely to produce the maximum benefit. METHODS: We first performed a cadaver-to-cadaver penile transplantation as preparation. After approval from the Human Research Ethics Committee was obtained, we recruited potential recipients. We screened the potential participants for both physical and psychological characteristics, including penile stump length, and emotional suitability for the procedure. A suitable donor became available and the penis was harvested. We surgically prepared the penile stump of the recipient and attached the penile graft. Immunosuppression treatment with antithymyocyte globulin, methylprednisolone, tacrolimus, mycophenolate mofetil, and prednisone were commenced. Tadalafil at 5 mg once per day was commenced after 1 week as penile rehabilitation and was continued for 3 months. We collected on quality-of-life scores (Short Form 36 version 2 [SF-36v2] questionnaires) before surgery and during follow-up and measured erectile function (International Index for Erectile Function [IIEF] score) and urine flow rates at 24 months post transplant. FINDINGS: The warm ischaemia time for the graft after removal was 4 min and the cold ischaemia time was 16 h. The surgery lasted 9 h. An arterial thrombus required urgent revision 8 h after the operation. On post operative day 6, an infected haematoma and an area of proximal skin necrosis were surgically treated. The recipient was discharged after 1 month and first reported satisfactory sexual intercourse 1 week later (despite advice to the contrary). The recipient reported regular sexual intercourse from 3 months after the operation. An episode of acute kidney injury at 7 months was reversed by reducing the tacrolimus dose to 14 mg twice per day. At 8 months after surgery, the patient had a skin infection with phaeohyphomycosis due to Alternaria alternata, which we treated with topical antifungal medication. Quality-of-life scores improved substantially after the operation (SF-36v2 mental health scores improved from 25 preoperatively, to 57 at 6 months and 46 at 24 months post transplant; physical health scores improved from 37 at baseline to 60 at 6 months and 59 at 24 months post-transplant). At 24 months, measured maximum urine flow rate (16·3 mL/s from a volume voided of 109 mL) and IIEF score (overall satisfaction score of 8 from a maximum of 10) were normal, showing normal voiding and erectile function, respectively. INTERPRETATION: Penile transplantation restored normal physiological functions in this transplant recipient without major complications in the first 24 months. FUNDING: Department of Health, Western Cape Government.

Lessons learned from the world's first successful penis allotransplantation.

We performed a successful penis allotransplantation on 11 December 2014. Sharing the lessons learned might help more patients in need to be treated this way. We divided the project into manageable segments that was each overseen by an expert. The ethical review and conduct paved the way for a publically acceptable and successful project. Screening for a psychological stable recipient is important. The most difficult part of the project was finding a donor penis. This was successfully negotiated with the family of a brain dead donor by creating a neo-phallus for the donor, thereby maintaining the dignity of the donor. Working with transplant coordinators that are sympathetic to aphallic men is crucial. Surgeons versed in microvascular techniques is a critical part of the team. Transplant immunologists have to adapt to treat composite tissue transplantation patients.

Clinical (non-histological) diagnosis of advanced prostate cancer: Evaluation of treatment outcome after androgen deprivation therapy.

Introduction. Transrectal biopsy in suspected adenocarcinoma of the prostate (ACP) may cause significant morbidity and even mortality. A strong association between serum prostate-specific antigen (PSA) and tumour burden exists. If biopsy can be avoided in advanced disease, much morbidity and cost may be saved.Objective. To evaluate the reliability of using PSA and clinical features to establish a non-histological diagnosis of ACP.Methods. Androgen deprivation therapy (ADT) was used in 825 (56.2%) of 1 467 men with ACP. The diagnosis of ACP was made histologically in 607 patients (73.6%) and clinically alone in 218 (26.4%), based on a serum PSA level of >60 ng/ml, and/or clinical evidence of a T3 - T4 tumour on digital rectal examination, and/or imaging evidence of metastases. We compared two randomly selected groups treated with bilateral orchidectomy (BO) based on a clinical-only (n=90) v. histological (n=96) diagnosis of ACP.Results. There was no significant difference between the groups with regard to mean follow-up (26.1 v. 26.8 months), documented PSA relapse (70% v. 67.7%), and patients alive at last follow-up (91.1% v. 95.8%). ZAR1 068 200 (US$1 = ZAR8) was saved by treating men with advanced ACP on the basis of a clinical (non-histological) diagnosis only, and a total of ZAR24 321 000 was saved by using BO instead of luteinising hormone-releasing hormone agonists as ADT.Conclusion. A reliable clinical (non-histological) diagnosis of advanced ACP can be made based on serum PSA and clinical features. This avoids the discomfort and potentially serious complications of biopsy and saves cost.

Urological aspects of HIV and AIDS.

The use of highly active antiretroviral therapy (HAART) in HIV-infected people has led to a dramatic decrease in the incidence of opportunistic infections and virus-related malignancies such as non-Hodgkin lymphoma and Kaposi sarcoma, but not cervical or anal cancer. Advanced-stage cervical cancer is associated with a high incidence of urological complications such as hydronephrosis, renal failure, and vesicovaginal fistula. Adult male circumcison can significantly reduce the risk of male HIV acquisition. Although HAART does not completely eradicate HIV, compliance with medication increases life expectancy. HIV infection or treatment can result in renal failure, which can be managed with dialysis and transplantation (as for HIV-negative patients). Although treatment for erectile dysfunction--including phosphodiesterase 5 inhibitors, intracavernosal injection therapy, and penile prosthesis--can increase the risk of HIV transmission, treatment decisions for men with erectile dysfunction should not be determined by HIV status. The challenges faced when administering chemotherapy to HIV-infected patients with cancer include late presentation, immunodeficiency, drug interactions, and adverse effects associated with compounded medications. Nonetheless, HIV-infected patients should receive the same cancer treatment as HIV-negative patients. The urologist is increasingly likely to encounter HIV-positive patients who present with the same urological problems as the general population, because HAART confers a prolonged life expectancy. Performing surgery in an HIV-infected individual raises safety issues for both the patient (if severely immunocompromised) and the surgeon, but the risk of HIV transmission from patients on fully suppressive HAART is small.

Prevalence of histological prostatitis in men with benign prostatic hyperplasia or adenocarcinoma of the prostate presenting without urinary retention.

OBJECTIVE: To determine the prevalence of prostatitis on histopathological evaluation of prostatic tissue in men without urinary retention. DESIGN, SETTING AND SUBJECTS: The clinical data and histopathology reports of men seen from January 1999 through March 2009 at our institution were analysed using Student's t-test, the Mann-Whitney test and Fisher's exact test where appropriate. Values were expressed as means, medians and ranges (p<0.05 accepted as statistically significant). OUTCOME MEASURES: Data collected included patient age, duration of lower urinary tract symptoms and hospitalisation, findings on digital rectal examination, prostate volume, haemoglobin concentration, serum creatinine and prostate-specific antigen (PSA) levels, and histological findings. RESULTS: Prostatic tissue of 385 men without urinary retention at presentation was obtained via biopsy (48.3% of cases), transurethral prostatectomy (62.9%), retropubic prostatectomy (6.8%) or radical prostatectomy (28.3%). On histological examination, benign prostatic hyperplasia (BPH) was found to be present in 213 patients (55.3%) and adenocarcinoma of the prostate (ACP) in 172 (44.7%). Histological prostatitis was present in 130 patients (61.0%) with BPH and 51 (29.7%) with ACP (p<0.001). A previous study of 405 men presenting with urinary retention at our institution showed histological prostatitis in 98/204 (48.0%) with BPH and in 51/201 (25.4%) with ACP. The group of men with BPH alone had a significantly lower mean serum PSA at presentation (4.5 ng/ml, range 0.3 - 20.8 ng/ml) compared with the group with BPH and prostatitis (11.2 ng/ml, range 0.2 - 145 ng/ml, p=0.011). The mean PSA level at presentation did not differ significantly between the group with ACP only (40.9 ng/ml, range 0 - 255 ng/ml) and the group with ACP plus prostatitis (1 672 ng/ml, range 0.3 - 38 169 ng/ml, p=0.076). CONCLUSIONS: Among men presenting without urinary retention, histological prostatitis was significantly more prevalent in those with BPH than in those with ACP (61% v. 30%), similar to the previous study of men presenting with retention at our institution, in which histological prostatitis was significantly more prevalent in BPH than in ACP (48% v. 25%). This finding suggests that histological prostatitis is not significantly associated with the causation of ACP or urinary retention. Serum PSA at presentation was significantly higher in the group with BPH plus prostatitis compared with BPH alone, but not in the group with ACP plus prostatitis compared with ACP alone.

Inflammatory myofibroblastic tumor of the bladder in a 3-year-old boy.

Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm with unknown malignant potential that has been described in most organ systems. We present the case of a 3-year-old boy who was referred with lower urinary tract symptoms and macroscopic hematuria. An IMT was suspected after clinical, radiological, and surgical work-up, and the diagnosis was confirmed after a partial cystectomy was performed. A bladder-preserving approach is the treatment of choice, but close clinical follow-up is recommended because of the unknown biological behavior of these tumors.

Significance of histological prostatitis in patients with urinary retention and underlying benign prostatic hyperplasia or adenocarcinoma of the prostate.

OBJECTIVE: To compare the clinical features of patients having urinary retention and benign prostatic hyperplasia (BPH) with those having adenocarcinoma of the prostate (ACP) and to evaluate the significance of histological prostatitis. PATIENTS AND METHODS: The clinical data and histopathology reports of patients with retention admitted to Tygerberg Hospital between September 1998 and June 2007 were evaluated. Statistical analysis was performed with Student's t-test, Mann-Whitney test and Fisher's exact test where appropriate and P < 0.05 was considered to indicate statistical significance. RESULTS: Prostatic histology was available in 405 patients, 204 with BPH and 201 with ACP. Comparing those with BPH and those with ACP showed statistically significant differences in mean age (69.5 vs 71.9 years), serum prostate-specific antigen (PSA) level (18.6 vs 899.5 ng/mL) and histological prostatitis (48 vs 25%) but not duration of catheterization, prostate volume or urinary tract infection (UTI). Comparing those with BPH only and those with BPH plus prostatitis showed significant differences in mean age (71.9 vs 67.1 year) and PSA level (14.6 vs 22.8 ng/mL) but not prostate volume, UTI or duration of catheterization. Comparing those with ACP only and those with ACP plus prostatitis showed significant differences in stage T4 cancer (68.1 vs 35.4%) and PSA level (1123.4 vs 232.4 ng/mL) but not age, prostate volume, UTI or duration of catheterization. CONCLUSIONS: Histological prostatitis was almost twice as common in patients with urinary retention associated with underlying BPH than in patients with ACP, but there was no significant difference in the duration of catheterization, prostatic volume or presence of UTI, suggesting that histological prostatitis more often contributes to the development of retention in patients with underlying BPH than in those with ACP. In patients with BPH, histological prostatitis was associated with urinary retention at a significantly younger age and with higher serum PSA levels. In patients with ACP, histological prostatitis was associated with urinary retention at an earlier stage of cancer.

The evolution of lasers in urology.

The world's first laser was developed by Theodore Maiman in 1960. Over the course of the past five decades, this technology has evolved into a highly specialized entity, also finding a niche market in the field of urology. Lasers obtained from various lasing mediums producing amplified light of different wavelengths have been tested for urological applications. Today, these lasers are most commonly used in the surgical management of benign prostatic hyperplasia and as intracorporeal lithotripters. Other uses include ablation of various urologic tumors and incising strictures of the upper- and lower urinary tract. A continuous process of evolution of this technology is taking place, resulting in surgical lasers becoming ever safer, more effective, and more affordable.

Distant cutaneous metastases secondary to squamous carcinoma of the penis.

Penile cancer normally spreads in a predictable manner to the regional lymph nodes: first inguinal and then the pelvic nodes. We report a case where the patient presented synchronously with secondary skin metastases and primary high grade penile squamous carcinoma. In addition the patient also had pulmonary metastases, loco regional spread to the groin nodes, liver metastases and tumour erosion of a right sided rib. The skin metastases appeared nodular, were firm in consistency and appeared intradermal. Skin metastases have been described for a number of solid malignancies - the clinician must have an index of suspicion to relate a less obvious primary lesion with secondary skin lesions. The patient died before chemotherapy could be administered.