Search Results (30)

Background: Magnetic resonance imaging (MRI) plays an increasingly important role in the evaluation of scrotal and penile disorders, complementing ultrasonography in cases where findings are equivocal or complex. With its superior soft-tissue contrast, multiplanar capability, and advanced functional sequences, MRI provides unparalleled anatomic and tissue characterization across a wide range of male genital pathologies. Summary: This review summarizes current clinical applications of MRI in scrotal and penile imaging and discusses its diagnostic value, protocol optimization, and interpretive features. In scrotal pathology, MRI accurately differentiates torsion, trauma, infection, and neoplasms, aiding in the distinction between benign and malignant testicular lesions and supporting testis-sparing management. Quantitative diffusion and perfusion metrics further refine lesion characterization. In andrology, MRI biomarkers such as apparent diffusion coefficient (ADC), magnetization transfer ratio (MTR), and proton spectroscopy serve as promising non-invasive indicators of spermatogenic activity in male infertility. In penile imaging, MRI enables precise local staging of carcinoma, assessment of plaque morphology and activity in Peyronie’s disease, evaluation of tissue viability in priapism, and detection of prosthesis-related complications. Conclusions: MRI has become an essential problem-solving tool in the assessment of scrotal and penile diseases, enhancing diagnostic confidence and surgical planning. Future directions include protocol standardization, quantitative parameter validation, and the integration of radiomics and artificial intelligence to improve reproducibility and clinical impact. Full article

Background/Objectives: In a series of 33 patients with advanced penile squamous cell carcinoma (PSCC), we evaluated tissue factor (TF), TROP2, and nectin-4 protein expression as potential therapeutic targets. Expression levels of these proteins were also correlated to clinicopathological characteristics, including high-risk human papillomavirus (HPV), CDKN2A (p16) status, and aberrant p53 expression. Methods: A tissue microarray (TMA) was constructed with three cores per patient tumor (99 total cores). Anti-TF antibody staining was performed by immunohistochemistry, and H-scores for membrane and cytoplasm staining were assessed (range 0–300). The percentage of cores and patient tumors staining positive for TF (≥10% of tumor cells with at least 1+ intensity in cytoplasm and/or membrane) and H-scores were described and compared with HPV and p16 status. The association of TF expression with tumor grade, presence of metastatic disease, lymphovascular invasion (LVI), perineural invasion (PNI), aberrant p53 expression, recurrence-free survival (RFS), and cancer-specific survival (CSS) was assessed. Nectin-4 and TROP2 staining and their association with clinical/pathological data were determined in a similar manner. Results: TF staining was evident in 26 (81.3%) of the cohort and was more prominent in HPV-negative tumors in both the membrane (H-score 69.6 vs. 18.8; p = 0.003) and cytoplasm (H-score 59.2 vs. 17.7, p = 0.007). Cytoplasmic (H-score 61.7 vs. 11.7, p < 0.001) and membrane TF staining (H-score 71.7 vs. 15.0, p < 0.001) favored p16-negative tumors. The p53 status was more likely to be aberrant in the higher TF staining samples (cytoplasm H-score 61.7 vs. 18.3, p = 0.012; membrane H-score 67.5 vs. 20.3, p = 0.006). We observed an association with TROP2 staining and positive p16 status (membrane H-score 120.3 vs. 85, p = 0.052; cytoplasmic H-score 135 vs. 107.5, p = 0.041). We observed an association of TROP2 staining with positive LVI (membrane H-score 136.7 vs. 66.7, p = 0.014; cytoplasmic H-score 110 vs. 93.3, p = 0.04). We found no association between TF, TROP2, or nectin-4 staining with CSS or RFS; however, we suspect that this was due to our small sample size. Conclusions: Our results indicate that TF was expressed in the majority of advanced PSCC with enhanced expression among HPV-independent, p53-aberrant tumors and may represent a novel therapy target in advanced PSCC. Full article

Background: Erectile dysfunction (ED) is a disease whose occurrence is steadily increasing worldwide. This pathology is multifactorial and often combined with other diseases. ED of organic genesis in 50–80% of men is vasculogenic. Methods: A survey was conducted of 88 men (aged 44 to 62) who complained of erectile dysfunction. It consisted of a questionnaire administered according to the protocols “International Index of Erectile Function” and “Aging Male Screening”, and was followed by a color Doppler ultrasound (Logiq 9 ExpertGE with a 7 MHz linear transducer using B mode) and penile scintigraphy (single-photon emission computed tomography). The procedures were initially performed at rest, then during pharmacologically induced erection, which was achieved through the intake of phosphodiesterase-5 (PDE5) inhibitors. Patients who did not respond to pharmacological stimulation and had IIEF scores below 5–7 were offered surgical treatment—penile prosthesis followed by histological examination of the tissue of the corpus cavernosum. Statistical analysis was carried out using Microsoft Excel and STATISTICA 10.0 software. The Mann–Whitney U test was used to assess differences between quantitative variables, with the significance level set at p ≤ 0.05. Results: Penile scintigraphy shows high sensitivity (85.2%) and specificity (83.3%), outperforming color Doppler ultrasonography in detecting vasculogenic ED. Conclusion: Penile scintigraphy is demonstrated to be a highly informative method, allowing us to analyze the condition of the magistral and organ blood flow, as well as the microcirculatory bed of the cavernous bodies of the penis. This improves the effectiveness of this method in diagnosing various types of vasculogenic erectile dysfunction (ED), which opens opportunities for its use together with ultrasound examination when the latter is less informative. Full article

Background: Peyronie’s disease (PD) is a chronic inflammatory condition that affects the penile albuginea. Oxidative stress (OS) plays a crucial role in the development of the disease, prompting us to investigate OS levels at the site of the disease and in peripheral blood. This article presents our second study in which the OS was evaluated by calculating the OS index (OSI) in blood samples taken directly from the penile corpora cavernosa of patients with PD. Our innovative diagnostic method, which focuses on the analysis of oxidative stress (OS) in the corpora cavernosa of the penis, allows us to accurately identify the “chemical” signals (OS levels) of the pathology in the area where it is present. Methods: Our study included 102 PD patients from our Peyronie’s care center and 100 control cases. To conduct a comprehensive OS analysis, we measured both the total oxidant status (TOS) and total antioxidant status (TAS) and calculated the oxidative stress index (OSI) as OSI = TOS/TAS × 100. Blood samples were collected from the penis and a vein in the upper extremity, and OS was measured using d-ROMs and PATs (FRAS kit). Results: Pearson’s analyses revealed a significant statistical correlation between penile OSI values and PD plaque volumes (p = 0.003), while no correlation was found between systemic OSI values and plaque volumes (p = 0.356). Penile OSI values decreased significantly after PD plaque removal (p < 0.0001). A comparison of penile OSI values in PD patients (post plaque removal) and the control group showed no significant differences (p = 0.418). Conclusions: The lack of correlation between systemic OSI values and Peyronie’s plaque volume suggests that direct sampling from the site of the disease is preferable for OS studies. Conducting a penile OSI study could provide a precise oxidative marker dependent on plaque volume. In addition, the penile OSI study can biochemically monitor the therapeutic result, alongside penile ultrasound imaging. Full article

Background and Objectives: The male urethra is a complex structure that plays a critical role in genitourinary health and function. Despite its importance, histological descriptions of the penile urethra, particularly its epithelial components, remain incomplete. This study offers a comprehensive histological analysis of the penile urethra, focusing on the epithelium across distinct anatomical regions, including the glans, distal and proximal fossa navicularis and spongy urethra. Materials and Methods: Utilizing five human penile specimens, we employed various staining techniques to elucidate the structural characteristics of these epithelial tissues. Results: Our findings reveal notable variations in epithelial composition, such as the presence of glycogen-rich cells in the distal fossa navicularis and the presence of mucous glands in the spongy urethra and proximal fossa navicularis. Additionally, we identified a previously underreported valvule-like structure in the distal fossa navicularis in two of the specimens. In addition, the epithelium of the glans and the distal fossa navicularis are thicker than the ones of the proximal fossa navicularis and the spongy urethra. With a similar vascular density, the orientation of the blood vessels also diverges starting with the distal fossa navicularis. Conclusions: This study provides new insights into the histological organization of the penile urethra, offering critical reference data that can enhance our understanding of urethral pathologies and improve the outcomes of surgical interventions, particularly in the context of tissue engineering and reconstructive surgery. Full article

Background: Squamous cell carcinoma (SCC) of the penis accounts for approximately 95% of penile cancers and is associated with substantial morbidity and mortality. SCC typically develops in uncircumcised men, most commonly affecting the foreskin or glans. While slow-growing, early detection is crucial to improve survival outcomes. Risk factors include advanced age, lack of circumcision, poor hygiene, HPV infection (types 16 and 18), chronic inflammation, and smoking. Methods: We conducted a retrospective, single-center study at IRCCS Hospital “G. Pascale” of Naples, Italy, involving 59 patients treated between January 2015 and January 2023. The inclusion criteria were surgically treated primary tumors, confirmed SCC pathology, and pathologically verified inguinal lymph node metastasis (ILNM). We analyzed clinical variables including lymph node involvement, lymphovascular invasion (LVI), spongiosum corpus involvement (SCI), HPV infection, and tumor differentiation. Univariate and multivariate logistic regression analyses were performed to determine independent predictors of ILNM. Results: The mean age of patients was 66.67 ± 13.97 years. ILNM was confirmed in 24 patients (40.6%), while 35 (59.3%) had no lymph node involvement. Univariate analysis identified lymph node involvement at diagnosis (p = 0.005), LVI (p = 0.003), and SCI (p = 0.003) as significant predictors of ILNM. These factors were confirmed in the multivariate analysis, with lymph node involvement (p = 0.004), LVI (p = 0.025), and SCI (p = 0.028) as independent predictors. Conclusions: Lymph node status, LVI, and SCI are significant predictors of ILNM in penile SCC. Identifying these factors can aid in risk stratification, optimizing surgical decisions, and potentially reducing unnecessary morbidity. Further large-scale studies are recommended to validate these findings and refine prognostic models. Full article

Background: Inguinal lymph node (LN) dissection (iLND) is mandatory in cN2 penile squamous cell carcinoma (PSCC). Open iLND (OIL) is often omitted due to the high rate of complications. A minimally invasive approach may reduce morbidity; however, evidence supporting its role to treat bulky nodes is limited. This study aimed to present the outcomes of the largest European single-center series of robot-assisted iLND (RAIL) for the treatment of cN2 PSCC and to compare the surgical and survival outcomes of this approach with the standard of care. Methods: A retrospective analysis was conducted on men with cT1-4N2M0 PSCC undergone either OIL or RAIL at our institution from January 2014 onwards. Baseline demographics, perioperative data, and oncologic outcomes were analyzed. Results: Overall, 47 patients were included; 38 (81%) underwent OIL. Median age was 59 years, with 23 men (48%) presenting with a ≥4 Charlson comorbidity index. Operation time was significantly longer in the robotic cohort (212 min vs. 145 min; p < 0.001), while the length of stay (p = 0.09) and time to inguinal drainage removal (p = 0.08) were not. Estimated blood loss favored the robotic approach (60 mL vs. 300 mL; p < 0.001). Post-operative complications rates were comparable in the two groups (25% vs. 47%; p = 0.17): four major complications were observed overall, and these were all in the OIL cohort. Median LN yield was comparable between the two groups (18 vs. 25; p = 0.05). Final pathology reports showed no significant differences in tumor stage distribution between the cohorts (p = 0.54). Kaplan–Meier analysis did not reveal any significant differences in RFS probabilities between the two treatment groups (Log Rank = 0.99). Conclusions: RAIL demonstrated comparable perioperative and oncologic outcomes to OIL for cN2 PSCC, with the benefit of reduced estimated blood loss. RAIL is a feasible option for cases where a minimally invasive approach is preferred, offering comparable perioperative safety and oncological outcomes. Full article

Local therapy for penile cancer provides robust survival and can preserve the penis functionally and cosmetically. Interventions must target the appropriate clinical stage. We reviewed studies regarding the primary therapy in penile cancer, from topical therapy to radical penectomy, and reconstructive techniques. Topical therapy (5-FU or Imiquimod) provides a robust oncologic response in patients with Ta or Tis disease. Multiple laser therapies are available for localized patients and those with low-grade T1 disease. There is a non-trivial risk of progression and nodal metastases in poorly selected patients. Wide local excision provides an oncologically sound option in patient with up to T1 disease; less evidence exists for Mohs microsurgery in the setting of penile cancer. Increasingly aggressive approaches include glansectomy and partial/radical penectomy, which provide 5- and 10-year cancer-specific survival rates of over 80%. Meticulous reconstruction is necessary for the durable function of the remaining penis. Preservation of voiding and sexual function occurs via penile skin grafting, glans resurfacing, creation of a functional penile stump, and phalloplasty with a penile implant. Perineal urethrostomy provides an alternative in pathology demanding extensive partial or radical penectomy, and a durable option for seated voiding. Clinical suspicion and timely diagnosis are paramount in terms of management as less-invasive options for earlier-stage disease develop. Full article

Background and Objectives: To investigate the role of preoperative albumin-to-alkaline phosphatase ratio (AAPR) in predicting pathologic node-positive (pN+) disease in penile cancer (PC) patients undergoing inguinal lymph node dissection (ILND). Materials and Methods: Clinical data of patients with squamous cell carcinoma (SCC) PC + ILND at a single high-volume institution between 2016 and 2021 were collected and retrospectively analyzed. An AAPR was obtained from preoperative blood analyses performed within 30 days from their scheduled surgery. A ROC curve analysis was used to assess AAPR cutoff, in addition to the Youden Index. Logistic regression analysis was utilized for an odds ratio (OR), 95% confidence interval (CI) calculations, and an estimate of pN+ disease. A p value < 0.05 was considered to be as statistically significant. Results: Overall, 42 PC patients were included in the study, with a mean age of 63.6 ± 12.9 years. The AAPR cut-off point value was determined to be 0.53. The ROC curve analysis reported an AUC of 0.698. On multivariable logistic regression analysis lymphovascular invasion (OR = 5.38; 95% CI: 1.47–9.93, p = 0.022), clinical node-positive disease (OR = 13.68; 95% CI: 4.37–43.90, p < 0.009), and albumin-to-alkaline phosphatase ratio ≤ 0.53 (OR = 3.61; 95% CI: 1.23–12.71, p = 0.032) were predictors of pN+ involvement. Conclusions: Preoperative AAPR may be a potentially valuable prognostic marker of pN+ disease in patients who underwent surgery for PC. Full article

The penis is a complex organ with a development cycle from the fetal stage to puberty. In addition, it may suffer from either congenital or acquired anomalies. Penile surgical reconstruction has been the center of interest for many researchers but is still challenging due to the complexity of its anatomy and functionality. In this review, penile anatomy, pathologies, and current treatments are described, including surgical techniques and tissue engineering approaches. The self-assembly technique currently applied is emphasized since it is considered promising for an adequate tissue-engineered penile reconstructed substitute. Full article

Background: Management of penile cancer patients has its grey zones. In particular, no strong evidence or recommendations exist regarding the timing of prophylactic lymphadenectomy. Here, we aim to review the impact that the timing of inguinal and pelvic prophylactic lymph node dissection has on patient outcome. Methods: All relevant databases were searched following the preferred reporting items for systematic reviews and meta-analysis guidelines. A narrative review of indications for lymph node dissection and pathological considerations precede a systematic review of the impact of prophylactic lymph node dissection timing on prognosis. The primary endpoint is disease-free and overall survival in patients undergoing early or late lymph node dissection after penile cancer diagnosis. Results: Four clinical trials, all focusing on the role of inguinal lymph node dissection, are included. Despite the lack of randomized and controlled trials, this review suggests that lymph node dissection should be performed as soon as possible after diagnosis, with 3 months as a realistic cut-off. Conclusions: Survival of penile cancer patients is strictly related to the timing of prophylactic pelvic lymph node dissection. All patients at high risk of nodal metastasis should be offered lymph node dissection within three months of diagnosis, until new predicting tools are validated. Full article

Peyronie’s disease (PD) is a benign condition caused by plaque formation on the tunica albuginea of the penis. It is associated with penile pain, curvature, and shortening, and contributes to erectile dysfunction, which worsens patient quality of life. In recent years, research into understanding of the detailed mechanisms and risk factors involved in the development of PD has been increasing. In this review, the pathological mechanisms and several closely related signaling pathways, including TGF-β, WNT/β-catenin, Hedgehog, YAP/TAZ, MAPK, ROCK, and PI3K/AKT, are described. Findings regarding cross-talk among these pathways are then discussed to elucidate the complicated cascade behind tunica albuginea fibrosis. Finally, various risk factors including the genes involved in the development of PD are presented and their association with the disease summarized. The purpose of this review is to provide a better understanding regarding the involvement of risk factors in the molecular mechanisms associated with PD pathogenesis, as well as to provide insight into disease prevention and novel therapeutic interventions. Full article

Introduction: Penile cancer (PC) is a rare malignancy with an overall incidence in Europe of 1/100,000 males/year. In Europe, few studies report the epidemiology, risk factors, clinical presentation, and treatment of PC. The aim of this study is to present an updated outlook on the aforementioned factors of PC in Spain. Materials and Methods: A multicentric, retrospective, observational epidemiological study was designed, and patients with a new diagnosis of PC in 2015 were included. Patients were anonymously identified from the Register of Specialized Care Activity of the Ministry of Health of Spain. All Spanish hospitals recruiting patients in 2015 were invited to participate in the present study. We have followed a descriptive narration of the observed data. Continuous and categorical data were reported by median (p25th–p75th range) and absolute and relative frequencies, respectively. The incidence map shows differences between Spanish regions. Results: The incidence of PC in Spain in 2015 was 2.55/100,000 males per year. A total of 586 patients were identified, and 228 patients from 61 hospitals were included in the analysis. A total of 54/61 (88.5%) centers reported ≤ 5 new cases. The patients accessed the urologist for visually-assessed penile lesions (60.5%), mainly localized in the glans (63.6%). Local hygiene, smoking habits, sexual habits, HPV exposure, and history of penile lesions were reported in 48.2%, 59.6%, 25%, 13.2%, and 69.7%. HPV-positive lesions were 18.1% (28.6% HPV-16). The majority of PC was squamous carcinoma (95.2%). PC was ≥cT2 in 45.2% (103/228) cases. At final pathology, PC was ≥pT2 in 51% of patients and ≥pN1 in 17% of cases. The most common local treatment was partial penectomy (46.9% cases). A total of 47/55 (85.5%) inguinal lymphadenectomies were open. Patients with ≥pN1 disease were treated with chemotherapy in 12/39 (40.8%) of cases. Conclusions: PC incidence is relatively high in Spain compared to other European countries. The risk factors for PC are usually misreported. The diagnosis and management of PC are suboptimal, encouraging the identification of referral centers for PC management. Full article

Sexual dysfunction can be caused by impaired neurotransmission from the peripheral to the central nervous system. Therefore, it is important to evaluate the input of sensory information from the peripheral genital area and investigate the control mechanisms in the spinal cord to clarify the pathological basis of sensory abnormalities in the genital area. However, an in vivo evaluation system for the spinal cord–penile neurotransmission mechanism has not yet been developed. Here, urethane-anesthetized rats were used to evaluate neuronal firing induced by innocuous or nociceptive stimulation of the penis using extracellular recording or patch-clamp techniques in the lumbosacral spinal dorsal horn and electrophysiological evaluation in the peripheral pelvic nerves. As a result, innocuous and nociceptive stimuli-evoked neuronal firing was successfully recorded in the deep and superficial spinal dorsal horns, respectively. The innocuous stimuli-evoked nerve firing was also recorded in the pelvic nerve. These firings were suppressed by lidocaine. To the best of our knowledge, this is the first report of a successful quantitative evaluation of penile stimuli-evoked neuronal firing. This method is not only useful for analyzing the pathological basis of spinal cord–penile neurotransmission in sexual dysfunction but also provides a useful evaluation system in the search for new treatments. Full article

Penile Squamous Cell Carcinoma (PSCC) is associated with high-risk human papillomavirus (HR-HPV). The immunohistochemical (IHC) test for p16^INK4a (p16) is highly correlated with HR-HPV expression in other SCCs. To investigate whether the expression of p16 IHC or HR-HPV is associated with survival in PSCC, we conducted a single institution analysis of 143 patients with a diagnosis of PSCC and, available tissue were tested for p16 IHC staining patterns, histological subtype, tumor grade, and lymphovascular invasion (LVI) by an experienced pathologist. HR-HPV status using the Cobas PCR Assay or the RNAScope high-risk HPV in situ hybridization kit were also assessed. Patient characteristics were summarized using descriptive statistics of clinico-pathologic variables. Kaplan–Meier was used to estimate median overall survival (OS), cancer specific survival (CSS) and correlated with HPV, p16, and other study variables. Patients with p16+ tumors had a significantly longer median CSS in comparison to the p16– group (p = 0.004), with respective 5-year CSS probability of 88% (95% CI; 0.84, 1) versus 58% (95% CI; 0.55, 0.76; p = 0.004). HPV status did not predict survival outcomes. Multivariable analysis with respect to OS and CSS, showed that p16+ status was associated with a lower risk of death (HR = 0.36, 95%CI; 0.20–0.67, p = 0.001), and improved CSS (HR = 0.20, 95% CI; 0.07–0.54, p = 0.002) after adjusting for covariates. In conclusion, tumor p16 status via IHC was an easy to perform independent prognostic factor for OS and CSS that correlates with HR-HPV expression. Full article