Heterogeneous genetic architectures and evolutionary genomics of prostate cancer in Sub-Saharan Africa.

Men of African descent have the highest prostate cancer (CaP) incidence and mortality rates, yet the genetic basis of CaP in African men has been understudied. We used genomic data from 3,963 CaP cases and 3,509 controls recruited in Ghana, Nigeria, Senegal, South Africa, and Uganda, to infer ancestry-specific genetic architectures and fine-mapped disease associations. Fifteen independent associations at 8q24.21, 6q22.1, and 11q13.3 reached genome-wide significance, including four novel associations. Intriguingly, multiple lead SNPs are private alleles, a pattern arising from recent mutations and the out-of-Africa bottleneck. These African-specific alleles contribute to haplotypes with odds ratios above 2.4. We found that the genetic architecture of CaP differs across Africa, with effect size differences contributing more to this heterogeneity than allele frequency differences. Population genetic analyses reveal that African CaP associations are largely governed by neutral evolution. Collectively, our findings emphasize the utility of conducting genetic studies that use diverse populations.

Uncommon Haemorrhagic Cystitis of Infectious Origin: A Narrative Review for Urologists.

Purpose: Haemorrhagic cystitis may be due to different etiologies with infectious diseases representing an insidious cause to diagnose. The aim of this narrative review is to provide a comprehensive overview of less common but difficult-to-diagnose causes of infectious haemorrhagic cystitis of bacterial, mycobacterial, and parasitic origin, Moreover, we highlight possible diagnostic tools and currently available treatment options in order to give an updated tool for urologists to use in daily practice. Patients and Methods: The search engine PubMed was used to select peer-reviewed articles published from 1/Jan/2010 to 31/Aug/2022. Results: Bacteria, fungal, TB and schistosomiasis are uncommon causes of haemorrhagic cystitis burdened by high morbidity, especially if not promptly diagnosed. Conclusion: Because haemorrhagic cystitis ranges in severity from mild dysuria associated with pelvic discomfort to severe life-threatening haemorrhage, punctual diagnosis, and immediate treatment are essential to avoid further complications.

Correlation Between Long-Term Acetylsalicylic Acid Use and Prostate Cancer Screening with PSA. Should We Reduce the PSA Cut-off for Patients in Chronic Therapy? A Multicenter Study.

Purpose: To evaluate the prostate cancer (PCa) detection rate in men with chronic use of Aspirin and to compare it with the detection rate of non-users. Patients and Methods: Prospectively maintained database regarding patients undergoing prostate biopsy over the last 10 years in five institutions. Patients were divided into two groups according to their exposure to Aspirin. We relied on multivariable linear and logistic regression models to test whether Aspirin administration was associated with lower PSA values at prostate biopsy, higher PCa diagnosis, and higher Gleason Grade Grouping (GGG) at biopsy. Results: Were identified 1059 patients, of whom 803 (76%) did not take Aspirin vs 256 (24%) were taking it. In multivariable log-linear regression analysis, Aspirin administration was associated with lower PSA levels (OR 0.83, 95% CI 0.71-0.97, p = 0.01), after controlling for age, prostate volume, smoking history, associated inflammation at prostate biopsy, presence of PCa at biopsy, and GGG. In multivariable logistic regression analysis, Aspirin administration was not found to be a predictor of PCa at prostate biopsy (OR 1.40, 95% CI 0.82-2.40, p = 0.21) after controlling for age, PSA, smoking history, prostate volume, findings at digital rectal examination and the number of biopsy cores. In patients with PCa at prostate biopsy (n = 516), Aspirin administration was found to predict higher GGG (OR 2.24, 95% CI 1.01-4.87, p = 0.04). Conclusion: Aspirin administration was found to be a predictor of more aggressive GGG. These findings suggest that a lower PSA threshold should be considered in patients taking Aspirin, as, despite low PSA levels, they might harbour aggressive PCa.

Testing the generalizability of ancestry-specific polygenic risk scores to predict prostate cancer in sub-Saharan Africa.

BACKGROUND: Genome-wide association studies do not always replicate well across populations, limiting the generalizability of polygenic risk scores (PRS). Despite higher incidence and mortality rates of prostate cancer in men of African descent, much of what is known about cancer genetics comes from populations of European descent. To understand how well genetic predictions perform in different populations, we evaluated test characteristics of PRS from three previous studies using data from the UK Biobank and a novel dataset of 1298 prostate cancer cases and 1333 controls from Ghana, Nigeria, Senegal, and South Africa. RESULTS: Allele frequency differences cause predicted risks of prostate cancer to vary across populations. However, natural selection is not the primary driver of these differences. Comparing continental datasets, we find that polygenic predictions of case vs. control status are more effective for European individuals (AUC 0.608-0.707, OR 2.37-5.71) than for African individuals (AUC 0.502-0.585, OR 0.95-2.01). Furthermore, PRS that leverage information from African Americans yield modest AUC and odds ratio improvements for sub-Saharan African individuals. These improvements were larger for West Africans than for South Africans. Finally, we find that existing PRS are largely unable to predict whether African individuals develop aggressive forms of prostate cancer, as specified by higher tumor stages or Gleason scores. CONCLUSIONS: Genetic predictions of prostate cancer perform poorly if the study sample does not match the ancestry of the original GWAS. PRS built from European GWAS may be inadequate for application in non-European populations and perpetuate existing health disparities.

Depression, Anxiety, and Their Association to Health-Related Quality of Life in Men Commencing Prostate Cancer Treatment at Tertiary Hospitals in Cape Town, South Africa.

BACKGROUND: Comorbid depression and anxiety in men with localised prostate cancer (CaP) largely go undiagnosed and untreated and their effects on health-related quality of life (HRQOL) in men with CaP should not be underestimated. We examined the prevalence of depression and anxiety and its association with HRQOL in men about to commence treatment for CaP and the differences between treatment groups, radical prostatectomy (RP) and radiation therapy (RT). METHOD: One hundred and seven participants from a longitudinal prospective observational study assessing depression, anxiety and HRQOL in men with localised CaP (DAHCaP), were used in this cross-sectional analysis. Data were collected shortly before participants were scheduled to receive their treatment. The Centre for Epidemiologic Studies Depression Scale (CES-D), the State Trait Anxiety Inventory (STAI), the Memorial Anxiety Scale for Prostate Cancer (MAX-PC), the European Organisation for Research and Treatment in Cancer Quality of Life questionnaire (EORTC QLQ-C30) and (EORTC QLQ-PR25) were used in this analysis. RESULTS: Symptoms of depression pre-treatment were noted in 39.3%, state anxiety 28%, trait anxiety 31.4% and prostate cancer anxiety in 12.1% of participants. Statistically significant correlations (P ≤ .05) with the CES-D and a cluster of symptoms on the EORTC QLQ-C30 domains for Global Health (rs = -.35), fatigue (rs = .38), pain (rs = .32), dyspnoea (rs = .28), insomnia (rs = .30) and finance (rs = .26) and EORTC QLQ-PR25 domains for urinary symptoms (rs = .43), bowel (rs = .43) and hormone replacement therapy (HRT) (rs = .41) were observed.Statistically significant correlations were also noted between the STAI-S and EORTC QLQ-C30 and EORTC QLQ-PR25. No statistically significant difference was noted between treatments. CONCLUSION: More men were depressed than anxious with significant associations with HRQOL prior to commencement of treatment. CaP treatments should focus not only on the prevailing indisposition but include a psychooncological and HRQOL assessment at pre-treatment in high-risk individuals.

The Role of Novel Bladder Cancer Diagnostic and Surveillance Biomarkers-What Should a Urologist Really Know?

The aim of this review is to analyze and describe the current landscape of bladder cancer diagnostic and surveillance biomarkers. We researched the literature from 2016 to November 2021 to find the most promising new molecules and divided them into seven different subgroups based on their function and location in the cell. Although cystoscopy and cytology are still the gold standard for diagnosis and surveillance when it comes to bladder cancer (BCa), their cost is quite a burden for national health systems worldwide. Currently, the research is focused on finding a biomarker that has high negative predictive value (NPV) and can exclude with a certainty the presence of the tumor, considering missing it could be disastrous for the patient. Every subgroup has its own advantages and disadvantages; for example, protein biomarkers cost less than genomic ones, but on the other hand, they seem to be less precise. We tried to simplify this complicated topic as much as possible in order to make it comprehensible to doctors and urologists that are not as familiar with it, as well as encourage them to actively participate in ongoing research.

Decisional Conflict is Associated with Treatment Modality and not Disease Knowledge in South African Men with Prostate Cancer: Baseline Results from a Longitudinal Prospective Observational Study.

BACKGROUND: Decisional conflict (DC) is a psychological construct that an individual experiences in making a decision that involves risk, loss, regret, or challenges to one's values. This study assessed DC in a cohort of South African men undergoing curative treatment for localised prostate cancer (LPC). The objectives were to (1) to examine the association between DC and prostate cancer knowledge (PCK), demographics, state anxiety, prostate cancer anxiety and time to treatment and (2) to compare levels of DC between treatment groups [prostatectomy (RP) and external beam radiation (RT)]. METHOD: Data, comprising the Decisional Conflict Scale (DCS), Prostate Cancer Knowledge (PCK), State-Trait Anxiety Inventory (STAI-S), the Memorial Anxiety Scale for Prostate Cancer (MAX-PC) and demographic data from 83 participants of a larger prospective longitudinal observational study examining depression, anxiety and health related quality of life (DAHCaP) were analysed. RESULTS: The mean age of participants was 63 years (RP 61yrs and RT 65yrs; p< 0.001). Most were of mixed ancestry (72.3%). The total DCS scores between the treatment groups (RP 25.00 and RT 18.75; p = 0.037) and two DCS sub-scores-uncertainty (p = 0.033), and support (p = 0.048), were significantly higher in the RP group. A statistically significant negative correlation was observed between state anxiety and time between diagnosis and treatment in the RP group (Spearman's rho = -0.368; p = 0.030). There was no correlation between the DCS score and PCK within each treatment group (Spearman's rho RP = -0.249 and RT = -0.001). CONCLUSION: Decisional conflict was higher in men undergoing RP. Men were more anxious in the RP group regarding the time treatment was received from diagnosis. No correlation was observed between DC and PCK. Pre-surgical management of DC should include shared decision making (SDM) which is cognisant of patients' values facilitated by a customised decision aid.

Reporting ChAracteristics of cadaver training and sUrgical studies: The CACTUS guidelines.

INTRODUCTION: Recent systematic reviews highlighted increasing use of cadaveric models in the surgical training, but reports on the characteristics of the models and their impact on training are lacking, as well as standardized recommendations on how to ensure the quality of surgical studies. The aim of our survey was to provide an easy guideline that would improve the quality of the studies involving cadavers for surgical training and research. METHODS: After accurate literature review regarding surgical training on cadaveric models, a draft of the CACTUS guidelines involving 10 different items was drawn. Afterwards, the items were improved by questionnaire uploaded and spread to the experts in the field via Google form. The guideline was then reviewed following participants feedback, ergo, items that scored between 7 and 9 on nine-score Likert scale by 70% of respondents, and between 1 and 3 by fewer than 15% of respondents, were included in the proposed guideline, while items that scored between 1 and 3 by 70% of respondents, and between 7 and 9 by 15% or more of respondents were not. The process proceeded with Delphi rounds until the agreement for all items was unanimous. RESULTS: In total, 42 participants agreed to participate and 30 (71.4%) of them completed the Delphi survey. Unanimous agreement was almost always immediate concerning approval and ethical use of cadaver and providing brief outcome statement in terms of satisfaction in the use of the cadaver model through a short questionnaire. Other items were subjected to the minor adjustments. CONCLUSION: 'CACTUS' is a consensus-based guideline in the area of surgical training, simulation and anatomical studies and we believe that it will provide a useful guide to those writing manuscripts involving human cadavers.

Bladder cancer histological variants: which parameters could predict the concordance between transurethral resection of bladder tumor and radical cystectomy specimens?

INTRODUCTION: The concordance rate of bladder cancer (BCa) histological variants (HV) between transurethral resection of bladder tumor (TURBT) and radical cystectomy (RC) is sub-optimal and is unclear which factors may influence it. The aim of this study was to identify factors that may be correlated to a higher TURBT-RC concordance rate. MATERIAL AND METHODS: Consecutive patients who had undergone RC between 2000 and 2019 at a single Institution with pathological evidence of HV were included. Patients with diagnosis of HV both at RC and at the previous TURBT were enlisted in the TURBT-RC Concordance Group (CG), whereas patients with only evidence of HV at RC in the TURBT-RC Non-Concordance Group (NCG). Surgical factors evaluated were the source of energy (mono- vs bipolar), surgeon's experience (10 mm represented an independent predictor of concordance [OR 2.95; CI (1.01-8.61); p = 0.048]. Tumor recurrence, focality and dimension, source of energy, surgeon's experience, performance of re-TURBT and total number of specimens at TURBT did not significantly predict the concordance. CONCLUSIONS: Longer specimens at TURBT yield a higher chance to detect HV before RC. In this light, improving the quality of bladder resection means improving the management of BCa.

Living with someone else's penis: The lived experiences of two South African penile allograft recipients: A descriptive phenomenological study.

BACKGROUND: In South Africa, penile loss is a recognised complication of ritual circumcision which has a profoundly negative effect on these men's psyches and their everyday lives. The purpose of this paper was to investigate the experiences of the first two South African penile allograft transplantation recipients in order to assess the psychosocial impact of this surgery. MATERIALS AND METHODS: A qualitative descriptive phenomenology approach was used. A total of four in-depth interviews were conducted with the two South African penile transplant recipients. The interviews were transcribed verbatim while adding the field and observational notes. Thematic analysis was used to derive meaning from the collected data. RESULTS: After the penile loss, both participants reported feeling suicidal for the following reasons: their communities shunned them and regarded them as 'dead,' they felt severely ashamed of their disfigured bodies, they were unable to develop intimate relationships and could not have children. Transplantation gave them a fully functional penis, which resolved the majority of these issues. The participants were able to build relationships and satisfy their own and their partners' sexual and relationship needs. The transplant led to complete restoration of their self-image and manhood. They were, however, still persecuted by their traditional communities as they had not successfully completed the ritual circumcision ceremony. CONCLUSION: This study emphasises the necessity of offering penile transplantation as treatment for penile loss as this is not only life enhancing but lifesaving, especially within the South African context.

The Tomato Model.

OBJECTIVES: Percutaneous renal access (PCA) is one of the most difficult intervention in endourology. Hands-on training is a useful tool for a good understanding of the puncturing technique, reducing the learning curve, and lowering risks of complications during first procedures. The ideal surgical simulator should efficiently improve trainees' skills, be easily accessible, low-cost, and realistic. We aim to present novel fluoroscopy-guided PCA simulator named TOMATO model. MATERIALS AND METHODS: The model can be easily built in few minutes using low-cost items: yoga mat, cotton wool, forceps, needle-driver, scalpel, 0 silk suture, chiba needle, small pebble (1 cm ca) and a few kidney-shaped tomatoes. The yoga mat is fold in half, sutured with silk, placed on the operating table, and thanks to the friction created between the mat and sheet underneath there is no need for other fixating methods. Once placed inside the yoga mat, the tomato is held still in the position by the cotton wool, which is placed around the vegetable. The tomato imitates the real renal structure. Therefore is ideal for this use, and there is no need for liquid-contrast enhancement. The goal is achieved when the operator manages to move the pebble with chiba needle during pulsed fluoroscopy. The model was tested 3 times by 3 endourologists and by 10 residents in training with no experience as first operators. A 7-items questionnaire (1-10 rating scale) was administered to the participants in order to evaluate the utility of the model. Trainees' kidney access time (KAT) and radiation time (RT) were assessed at the first use and after 1 hour of training (circa 15 attempts to reach the target per resident). RESULTS: The model allowed residents' significant reduction of the KAT and RT. KAT passed from 114 (144.25-89) to 72.5 (97.25-49.5) seconds (P = .04) while RAT passed from 82 (89.75-56) to 51.5 (60.25-35.75) seconds (P < .001). The residents particularly appreciated the high-fidelity reproduction of the anatomy that the model offers, and its' usefulness for learning the puncturing technique, giving it 8.5 and 10 points, while the same items were rated 7.7, and 9.3 by the experts, respectively. Trainees felt that their skills could be improved by using this model. The main issue was finding the materials mimicking the real-life tissues and their different characteristics. CONCLUSIONS: TOMATO model might be a helpful and creative way to start learning the steps of kidney puncturing using low-cost materials and we believe its' strength is being easily reproducible in all urology units.

Intensive simulation training on urological mini-invasive procedures using Thiel-embalmed cadavers: The IAMSurgery experience.

INTRODUCTION: The objective of the study was to evaluate the benefits perceived by the use of cadaver models by IAMSurgery attendees and to define indications to standardize future similar training camps. MATERIALS AND METHODS: A 25-item survey was distributed via e-mail to all the participants of previous training courses named as "Urological Advanced Course on Laparoscopic Cadaver Lab" held at the anatomy department of the University of Malta, for anonymous reply. Participants were asked to rate the training course, the Thiel's cadaveric model, and make comparison with other previously experienced simulation tools. RESULTS: The survey link was sent to 84 attendees, with a response rate of 47.6% (40 replies). There was improvement in the median self-rating of the laparoscopic skills before and after the training camp with a mean difference of 0.55/5 points in the post-training skills compared to the basal (p < 0.0001). The 72.2% of the urologists interviewed considered Thiel's HCM better than other training methods previously tried, while five urologists (27.8%) considered it equal (p = 0.00077). Globally, 77.5% (31) of attendees found the training course useful, and 82.5% (33) would advise it to colleagues. CONCLUSIONS: Thiel's fixed human cadaveric models seem to be ideal for training purposes, and their use within properly structured training camps could significantly improve the surgical skills of the trainees. An important future step could be standardization of the training courses using cadavers, and their introduction into the standardized European curriculum.

Supporting the role of penile trauma and micro-trauma in the etiology of Peyronie's disease. Prospective observational study using the electronic microscope to examine two types of plaques.

OBJECTIVES: The etiopathogenesis of Peyronie's disease (PD) remains not clearly understood. The most accepted theory attributes the histological lesions of PD to the effects of trauma to the corpora cavernosum of the penis. The aim of our study is to verify whether similar histological features exist between these two tissues, providing new evidence in favor of the traumatic theory in the etiopathogenesis of Peyronie's disease. MATERIALS AND METHODS: A prospective observational study was carried out at our institution from January 2013 to June 2018, involving patients having undergone surgery for PD and those with delayed surgery for penile trauma. Both excised PD and post-traumatic plaques were analyzed by blind pathologists with an 80kV potential acceleration electron microscope. RESULTS: Five patients were identified with a post-traumatic plaque (Group 1) and therefore an equal number of PD patients were enrolled for Group 2. The ultrastructural characteristics of the two types of preparations were very similar. In all the samples we showed an inflammatory reaction of the structure of the tunica albuginea, a production of the disorganized extracellular matrix, a proliferation of inflammatory cells and fibroblasts. Furthermore, we have found an increase in the density and collagen deposits grouped in the extracellular space and within the fibroblasts. CONCLUSIONS: These findings support the theory that attributes lesions and symptoms typical of PD to the effects of cavernous body trauma.

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.

In response to an argument against penile transplantation.

Moodley and Rennie's paper arguing against penile transplantation stated out of context arguments and wrongly quoted statements. The cost of penile transplantation is much less than portrayed. The burden of cases is much less than is communicated. The men on our penis transplantation programme represent the poorest of the poor and are one of the most discriminated against groups of humans on earth. The false hope said to be created by Moodley is indeed not false hope at all as there is a real possibility that most patients on our waiting list may be transplanted. Moodley argues that government has, in the context of penile transplantation, no duty to cure those who lost a penis after ritual circumcision, but only an obligation to prevent this from happening. A 'yuk' reaction, similarly described in facial transplantation, may be present in colleagues arguing against penile transplantation.

African KhoeSan ancestry linked to high-risk prostate cancer.

BACKGROUNDS: Genetic diversity is greatest within Africa, in particular the KhoeSan click-speaking peoples of southern Africa. South African populations represent admixture fractions including differing degrees of African, African-KhoeSan and non-African genetic ancestries. Within the United States, African ancestry has been linked to prostate cancer presentation and mortality. Together with environmental contributions, genetics is a significant risk factor for high-risk prostate cancer, defined by a pathological Gleason score ≥ 8. METHODS: Using genotype array data merged with ancestry informative reference data, we investigate the contribution of African ancestral fractions to high-risk prostate cancer. Our study includes 152 South African men of African (Black) or African-admixed (Coloured) ancestries, in which 40% showed high-risk prostate cancer. RESULTS: Genetic fractions were determined for averaging an equal African to non-African genetic ancestral contribution in the Coloured; we found African ancestry to be linked to high-risk prostate cancer (P-value = 0.0477). Adjusting for age, the associated African ancestral fraction was driven by a significant KhoeSan over Bantu contribution, defined by Gleason score ≥ 8 (P-value = 0.02329) or prostate specific antigen levels ≥20 ng/ml (P-value = 0.03713). Additionally, we observed the mean overall KhoeSan contribution to be increased in Black patients with high-risk (11.8%) over low-risk (10.9%) disease. Linking for the first time KhoeSan ancestry to a common modern disease, namely high-risk prostate cancer, we tested in this small study the validity of using KhoeSan ancestry as a surrogate for identifying potential high-risk prostate cancer risk loci. As such, we identified four loci within chromosomal regions 2p11.2, 3p14, 8q23 and 22q13.2 (P-value = all age-adjusted < 0.01), two of which have previously been associated with high-risk prostate cancer. CONCLUSIONS: Our study suggests that ancient KhoeSan ancestry may be linked to common modern diseases, specifically those of late onset and therefore unlikely to have undergone exclusive selective pressure. As such we show within a uniquely admixed South African population a link between KhoeSan ancestry and high-risk prostate cancer, which may explain the 2-fold increase in presentation in Black South Africans compared with African Americans.

Surgical Training in South Africa: An Overview and Attempt to Assess the Training System from the Perspective of Foreign Trainees.

BACKGROUND: Currently, there are no objective reports evaluating the quality of the South African surgical training. The aim of this study is to evaluate the current state of surgical training in South Africa from an external impartial point of view and to rate the experience of short-term supernumerary registrars and fellows (STSRF) within the South African training system. METHODS: A 29-item survey was distributed via e-mail and social media to non-South African trainees who worked in South Africa as STSRF for a period of at least 1 month during the past 5 years. The survey evaluated the surgical, clinical and academic training received during their elective period in a South African department. RESULTS: Sixty-four STSRF replied to the survey. Sixty-two percent of STSRF attended a trauma unit during their experience. For the majority of respondents, open and emergency surgical exposure, as well as experience as first surgeon, is significantly higher in the South African system, while minimally invasive and endoscopic surgery exposure is significantly less. Research project involvement is significantly less, for the STSRF, as opposed to lectures and teaching that constitute a higher percentage. No significant difference was found regarding exposure to hands-on activities. CONCLUSIONS: The South African system still provides excellent surgical and clinical exposure as well as teaching. However, minimally invasive surgery training and research are generally lacking for the STSRF. Exchange programs between South African and developed country institutes should be improved and encouraged in order to gain mutual benefits.

Risk factors for the delay in the diagnosis of penile lesions: results from a single center in Italy.

BACKGROUND: Early diagnosis is fundamental for the investigation and treatment of penile lesions. There is an unfortunate documented delayed in presentation and diagnosis of penile lesions. Literature is scant regarding the risk factors contributing to this delay in a Mediterranean population. Few previous reports are published in entirely different homogeneous populations. The objective of this study was to provide an analysis of the causes and risk factors related to the delay of the first medical visit in a North Italian population subgroup. METHODS: From September 2004 to September 2017, 184 consecutive patients were treated at our institute with a surgical approach for a penile lesion. The epidemiological factors and reasons for the delay to diagnosis were recorded during personal or telephonic interviews. Univariate logistic regression models were performed to screen for an effect of the clinical and demographic variables on the delay in diagnosis. Variables with a P value <0.05 were entered into multivariate analysis, where the delay in diagnosis was the dependent variable. RESULTS: One hundred and thirteen patients were enrolled. The average patient age was fifty-eight. The average delay between the appearance of the lesion and the first medical consultation was fifty-three days. The principal cause of delay was the lack of knowledge of penile lesions and secondly, the feeling of embarrassment of having to visit a doctor. The multivariate analysis reported a significant correlation between the level of education, sexual activity and extramarital affairs on the delay in presentation (P values respectively: 0.01, 0.009 and 0.04). CONCLUSIONS: Patients education regarding this pathology and its potential danger is inadequate and thus it is necessary to implement a campaign of information and prevention in order to reduce delayed diagnosis.

Clinical and histopathological features of carcinosarcoma of the renal pelvis: a systematic review of a rare tumor.

INTRODUCTION: Carcinosarcoma of the kidney pelvis (CRP) is a rare but not exceptionally unique tumor in which in literature are reported almost only case studies and small series. We aim to provide a comprehensive overview of the disease, examining epidemiology, symptoms, pathological features, treatment and outcomes which are still missing, in order to offer a landmark paper to urologists which have to manage patients with this type of disease. EVIDENCE ACQUISITION: A review of the current literature was conducted through the NCBI PubMed database in June 2017 following the updated PRISMA guidelines. The filters used for the research were: "carcinosarcoma renal pelvis," "carcinosarcoma kidney pelvis," and "urinary tract carcinosarcoma." Only studies with confirmed histological diagnosis of CRP and a description of patient characteristics (demographics and/or pathological) were included in the review. EVIDENCE SYNTHESIS: Only 15 studies fulfilled the inclusion criteria. The main symptom at presentation was macroscopic hematuria, followed by abdominal pain. The carcinomatous pattern made of transitional cell carcinoma in 73.3% of patients and squamous carcinoma in 33%, while the sarcomatoid was spindle cells in 40% of patients, chondrosarcoma and undifferentiated in 33.3%. Despite radical surgical treatment was performed in all patients, there are no articles reporting a survival rate of more than two years. CONCLUSIONS: Carcinosarcoma of the kidney is a rare tumor of which little is known, especially about pathogenesis and oncological outcomes in the different therapeutic approaches described. Current literature is almost exclusively a case report that does not provide adequate information especially about survival and progression free survival. The creation of a shared database could in a matter of years lead us to increase the information about the oncological outcomes of the various possible treatments.