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Journal of Pediatric Urology Dec 2023Sex hormone imbalance in utero is hypothesized to play an important role in the pathogenesis of hypospadias. Due to its easy accessibility, foreskin samples have been...
INTRODUCTION
Sex hormone imbalance in utero is hypothesized to play an important role in the pathogenesis of hypospadias. Due to its easy accessibility, foreskin samples have been used to describe hormone receptor expression in rodents, and both adult and pediatric patients. In this study we conducted a systematic approach to assess hormone receptor expression in pediatric patients with hypospadias compared to healthy controls with a focus on age-matching and differences in severity and degree of hypospadias.
METHODS
Foreskin samples were collected from 35 children during hypospadias operations (18 distal and 17 proximal hypospadias) and compared with ventral foreskin samples of a control group of 32 children during circumcision (15 age-matched and 17 older boys). The samples were stained with H/E, androgen (AR), estrogen (ER) and progesterone receptors (PR). The receptor stainings were blindly evaluated. An Allred score was used to evaluate receptor expression in both the epithelium as well as stroma.
RESULTS
AR was detected in all cases. AR expression in the stroma was more evident than in the epithelium. AR expression in the hypospadias groups was significantly less than the age matched controls (p < 0.05). There was no significant difference between the two hypospadias groups nor between the two control groups. Older control group showed significantly elevated levels of AR expression compared to the hypospadias group (p < 0.05). ER was also detected in all cases. The stroma showed more ER than in epithelium. PR was minimal or negative in all samples.
CONCLUSION
Boys with hypospadias showed significantly weaker expression of androgen receptors than age matched controls. The severity of hypospadias did not influence hormone receptor distribution. AR expression is better observed in the stroma than in the epithelium. There was no difference in ER expression between the hypospadias group (distal or proximal) and age matched normal controls. ER was expressed in larger numbers in normal older preputial tissue. The foreskin of prepubertal boys shows little to no expression of PR.
Topics: Male; Humans; Child; Hypospadias; Foreskin; Gene Expression; Receptors, Androgen; Androgens
PubMed: 37532608
DOI: 10.1016/j.jpurol.2023.07.011 -
The Journal of Sexual Medicine Dec 2023Despite the existence of conservative therapies for Peyronie's disease (PD), surgery is commonly utilized for the treatment of bothersome curvatures due to its potential...
BACKGROUND
Despite the existence of conservative therapies for Peyronie's disease (PD), surgery is commonly utilized for the treatment of bothersome curvatures due to its potential effectiveness, although it carries intrinsic risks and may not universally lead to satisfactory outcomes.
AIM
To explore the rate and factors influencing patients' willingness to undergo surgery for PD.
METHODS
Data were prospectively collected in 5 European academic centers between 2016 and 2020. Data included age, time from PD onset, penile pain, curvature degree, difficulty at penetration, hourglass deformity, erectile dysfunction (ED), and previous treatments. All patients were offered conservative treatments, either medications or injections. Tunical shortening or lengthening procedures were offered as an alternative to conservative treatments, when indicated. Penile prosthesis was offered to those with concomitant ED. Patients' attitudes with surgery were recorded. Logistic regression analyses tested the profile of patients who were more likely to be willing to undergo surgery.
OUTCOMES
Patients' willingness to undergo surgery for PD.
RESULTS
This study included 343 patients with a median age of 57.3 years (IQR, 49.8-63.6) and a median penile curvature of 40.0° (IQR, 30.0°-65.0°). Overall, 161 (47%) experienced penetration difficulties and 134 (39%) reported ED. Additionally, hourglass deformity and penile shortening were reported by 48 (14%) and 157 (46%), respectively. As for previous treatments, 128 (37%) received tadalafil once daily; 54 (16%) and 44 (13%), intraplaque verapamil and collagenase injections; and 30 (9%), low-intensity shock wave therapy. Significant curvature reduction (≥20°) was observed in 69 (20%) cases. Only 126 (37%) patients were open to surgery for PD when suggested. At logistic regression analysis after adjusting for confounders, younger age (odds ratio [OR], 0.97; 95% CI, 0.95-1.00; P = .02), more severe curvatures (OR, 1.04; 95% CI, 1.03-1.06; P < .0001), and difficulty in penetration (OR, 1.88; 95% CI, 1.04-3.41; P = .03) were associated with a greater attitude to consider surgical treatment.
CLINICAL IMPLICATIONS
The need for effective nonsurgical treatments for PD is crucial, as is comprehensive patient counseling regarding surgical risks and benefits, particularly to younger males with severe curvatures.
STRENGTHS AND LIMITATIONS
Main limitations are the cross-sectional design and the potential neglect of confounding factors.
CONCLUSIONS
Patients with PD, having a lower inclination toward surgery, emphasize the need for effective nonsurgical alternatives and accurate counseling on the risks and benefits of PD surgery, particularly for younger men with severe curvatures.
Topics: Male; Humans; Middle Aged; Penile Induration; Cross-Sectional Studies; Penis; Treatment Outcome; Penile Implantation; Erectile Dysfunction
PubMed: 37973410
DOI: 10.1093/jsxmed/qdad145 -
Urologie (Heidelberg, Germany) Dec 2023Plastic induration of the penis (PIP, Peyronie's disease) is an acquired and chronic disease of the penis, which is characterized by penile pain, distortion and...
Plastic induration of the penis (PIP, Peyronie's disease) is an acquired and chronic disease of the penis, which is characterized by penile pain, distortion and deformation of the penis as well as the resulting impairments in sexual activity of the patient. The most probable causes are microtrauma and macrotrauma within the tunica albuginea of the corpora cavernosa, which due to an abnormal wound healing subsequently leads to the formation of fibrosis in this region. Various predisposing factors and also a genetic predisposition are discussed. The PIP occurs most frequently in the fifth to sixth decades of life. The prevalence is 0.3-20% depending on the investigated collective and the risk factors present. The PIP is subdivided into an acute inflammatory phase and a chronic postinflammatory phase. Various conservative and surgical treatment options include oral medication, penile traction therapy, intralesional injections and surgical procedures.
Topics: Male; Humans; Penile Induration; Penis; Sexual Behavior; Risk Factors; Fibrosis
PubMed: 37922029
DOI: 10.1007/s00120-023-02213-2 -
BJU International Mar 2024To examine the global disease burden and country-specific trends of penile cancer incidence by age group and investigate its associations with several factors.
OBJECTIVES
To examine the global disease burden and country-specific trends of penile cancer incidence by age group and investigate its associations with several factors.
MATERIALS AND METHODS
The Global Cancer Observatory database was interrogated for penile cancer incidence. The 10-year cancer incidence rates were collected from the Cancer Incidence in Five Continents Plus. The country-specific data were extracted from the World Health Organization Global Health Observatory and Global Burden of Disease databases for conducting risk factors analysis. The penile cancer incidence was presented using age-standardised rates. Its associations with various factors were examined by linear regression, while the incidence trend was estimated using joinpoint regression and presented as average annual percentage change with 95% confidence intervals in different age groups.
RESULTS
There were an estimated 36 068 new cases of penile cancer in 2020. There was a considerable geographical disparity in the disease burden of penile cancer, with South America reporting the highest incidence. Overall, alcohol drinking, human immunodeficiency virus (HIV) infection, and unsafe sex were positively associated with a higher penile cancer incidence, while circumcision was found to be a protective factor. There has been a mixed trend in penile cancer incidence overall, but an increasing trend was found among younger males.
CONCLUSIONS
There was a global variation in the penile cancer burden associated with prevalence of alcohol drinking, HIV infection, unsafe sex, and circumcision. The increasing penile cancer incidence in the younger population is worrying and calls for early detection and preventive interventions.
Topics: Male; Humans; Incidence; Penile Neoplasms; HIV Infections; Risk Factors; Prevalence; Global Health
PubMed: 37953505
DOI: 10.1111/bju.16224 -
International Journal of Impotence... Apr 2024Our objective was to analyze the rates of erectile dysfunction and Peyronie's disease following a penile fracture using a large, multi-institutional claims database....
Our objective was to analyze the rates of erectile dysfunction and Peyronie's disease following a penile fracture using a large, multi-institutional claims database. Inclusion criteria included men ages 15 or older with a diagnosis of penile fracture and any office visit within 5 years of the penile fracture. Exclusion criteria included prior erectile dysfunction, prescription of erectile aids, or penile prosthesis placement. Our primary outcome was the diagnosis of erectile dysfunction or prescription of phosphodiesterase-5 inhibitors within 5 years. A secondary analysis assessed rates of Peyronie's disease following penile fracture. 1242 men were identified with penile fracture and subsequently matched to men without penile fracture, resulting in equal cohorts of 1227 men. Men with a history of penile fracture were more likely to receive a diagnosis of erectile dysfunction or require phosphodiesterase-5 inhibitors (RR 3.18, 95% CI: 2.30-4.40). Men who did not undergo immediate repair had higher rates of erectile dysfunction or treatment (RR: 1.84, 95% CI: 1.22-2.78). Men over the age of 45 years who had a penile fracture were more likely to develop erectile dysfunction or treatment compared to men under 45 years (RR: 1.65, 95% CI: 1.14-2.39). Rates of Peyronie's disease were higher in men with a history of penile fracture (5.8% vs 0%, p < 0.0001). Rates of Peyronie's disease were lower if immediate repair of the fracture was performed (RR: 0.20, 95% CI: 0.10-0.41). Men over the age of 45 years with penile fracture were more likely to develop Peyronie's Disease within 5 years compared to men under the age of 45 years penile fracture (RR: 3.72, 95% CI: 1.94-7.16). Penile fracture increases the risk of both erectile dysfunction and Peyronie's disease, especially those treated with conservative measures or over the age of 45 years compared to patients under 45 years with a penile fracture.
Topics: Male; Humans; Middle Aged; Erectile Dysfunction; Penile Induration; Retrospective Studies; Cyclic Nucleotide Phosphodiesterases, Type 5; Penile Erection; Phosphodiesterase 5 Inhibitors
PubMed: 37542153
DOI: 10.1038/s41443-023-00746-w -
Human Genomics Dec 2023The effect of SPP1 in squamous cell carcinoma of the penis (PSCC) remained unknown. We attempted to clarify the function of the SPP1 gene in PSCC.
BACKGROUND
The effect of SPP1 in squamous cell carcinoma of the penis (PSCC) remained unknown. We attempted to clarify the function of the SPP1 gene in PSCC.
METHOD
Eight paired penile cancer specimens (including penile cancer tissue, paracancerous tissue, and positive lymph node tissue) subjected to whole transcriptome sequencing were analysed to identify differentially expressed genes. We used immunohistochemistry to detect the expression of SPP1 protein and immune cell related proteins in penile cancer tissue. Then, we performed weighted gene coexpression network analysis (WGCNA) to identify the genes related to SPP1 in penile cancer tissue and positive lymph node tissue. Based on the GSE57955 dataset, the CIBERSORT and ssGSEA algorithms were carried out to investigate the immune environment of PSCC. GSVA analysis was conducted to identify the signaling pathways related to SPP1 subgroups. Enzyme-linked immunosorbent assay (ELISA) method was adopted to detect SPP1 level in the serum of 60 patients with penile cancer.
RESULTS
Differential analysis indicated that SPP1 was the most differentially upregulated gene in both penile cancer tissues and positive lymph node tissues. Survival analysis suggested that the prognosis of the low-SPP1 group was significantly poorer than that of the high-SPP1 group. Subsequently, immune-related bioinformatics showed that SPP1 was significantly associated with B cells, CD8 + T cells, CD4 + T cells, macrophages, helper T cells, neutrophils and dendritic cells. The immunohistochemical results showed that the high-SPP1 group was characterized by relatively high expression of CD16 and relatively low expression of CD4. GSVA analysis indicated that high-SPP1 group was significantly associated with immune-related pathways such as PD-L1 expression and the PD-1 checkpoint pathway in cancer and the TNF signaling pathway. ELISA demonstrated that the serum level of SPP1 in patients with positive lymph node metastasis of penile cancer was significantly higher than that in patients with negative lymph node metastasis of penile cancer.
CONCLUSION
Our study shows that the SPP1 gene might be an effective biomarker for predicting the prognosis and the efficacy of immunotherapy in PSCC patients.
Topics: Carcinoma, Squamous Cell; Penile Neoplasms; Immunotherapy; Osteopontin; Biomarkers, Tumor; Gene Expression Profiling; Survival Analysis; Sequence Analysis, RNA
PubMed: 38111044
DOI: 10.1186/s40246-023-00558-5 -
Radiographics : a Review Publication of... Aug 2023Penile malignancy is the third most common male-specific genitourinary malignancy, with squamous cell carcinoma representing the most common histologic type. Squamous...
Penile malignancy is the third most common male-specific genitourinary malignancy, with squamous cell carcinoma representing the most common histologic type. Squamous cell carcinoma is an epithelial malignancy, frequently developing from the mucosal surfaces of the foreskin, glans, and coronal sulcus and manifesting as a distal infiltrative or ulcerated mass. This typically occurs in men from the 6th to 8th decades of life, and risk factors include human papillomavirus, phimosis, presence of foreskin and poor hygiene, chronic inflammatory conditions such as lichen sclerosus, trauma, and smoking. Primary urethral malignancies including urothelial carcinoma and adenocarcinoma can occur but may lack this distal predilection. Sarcoma, melanoma, leukemia or lymphoma, and metastatic disease are less common sources of penile malignancy. Because of the sensitive nature of penile malignancies, there may be delays in seeking care and in subsequent diagnosis. Recently, the staging guidelines for penile cancer have been updated concurrently with a shift toward more penile-preserving therapies, which have led to a larger role of imaging in diagnosis, staging, and treatment planning for penile malignancies. A variety of imaging modalities may play a role in the identification and staging of penile malignancy, including an increased use of MRI for local staging of tumors, CT and PET/CT for identification of nodal and distant disease, and US for image-guided biopsy. The authors discuss an imaging approach to a spectrum of penile malignancies, with an emphasis on radiologic and pathologic correlation and how knowledge of normal tissue types and anatomic structures can aid in the diagnosis and staging of these tumors. RSNA, 2023 Quiz questions for this article are available in the supplemental material.
PubMed: 37471245
DOI: 10.1148/rg.230025 -
Andrology Mar 2024Peyronie's disease (PD) is a connective tissue disorder affecting the tunica albuginea. It can cause pain and penile deformation, and its prevalence increases with age.... (Review)
Review
Peyronie's disease (PD) is a connective tissue disorder affecting the tunica albuginea. It can cause pain and penile deformation, and its prevalence increases with age. Although surgery is the gold standard for the chronic phase of the disease, there are several conservative treatment methods available, and the optimal management of the acute phase of the disease remains a matter of debate. In this article, we aim to summarize the recent trends in research on the subject of non-surgical treatment of PD. The search was performed in PubMed, Scopus, and Web of Science databases and included studies in English published between 2012 and 2022 investigating the clinical outcomes of non-surgical PD management in humans. We have identified 20 distinct conservative treatment strategies. Among the oral therapeutics, only the use of phosphodiesterase type 5 inhibitors is currently recommended for clinical use in patients with concomitant erectile dysfunction. The use of collagenase from Clostridium histolyticum is supported by the best quality evidence in terms of intralesional injections for patients suffering from significant penile curvature; however, interferon alpha-2b can also be an option in such patients. Among other non-invasive methods, extracorporeal shockwaves can be useful for pain reduction, and penile traction therapy can lead to a reduction in penile curvature and plaque size. Despite a wide range of non-surgical methods available for PD treatment, the majority are not supported by sufficient scientific evidence, and the treatment efficacy is underwhelming. Further research on the subject of non-surgical management of PD is highly warranted.
Topics: Male; Humans; Penile Induration; Penis; Treatment Outcome; Injections, Intralesional; Pain
PubMed: 37593783
DOI: 10.1111/andr.13512 -
American Journal of Men's Health 2024Numerous case reports exist on penile strangulation injuries and extrication methods; however, the care and long-term consequences of penile strangulation injuries have... (Review)
Review
Numerous case reports exist on penile strangulation injuries and extrication methods; however, the care and long-term consequences of penile strangulation injuries have been under-reported. Our aim is to investigate the long-term outcomes and sequalae following penile strangulation injuries. The PubMed Medline database was searched using the keyword string "penile strangulation," "penis strangulation," and "constriction" for all studies reporting outcomes of published penile strangulation injuries. Articles were evaluated for follow-up after strangulation injury, strangulating agent, extricating agent, and sequelae of injury. Fifty-six studies resulted with reports of 100 cases of penile strangulation and extrication from January 2000 to December 2019. The mean patient age was 41 (range: 3-86) years. Twenty-four (24/100) cases reported sequalae following extrication. Follow-up ranged from 2 weeks to 7 years with median follow-up time in the 7- to 12-month grouping. Metal rings comprised 36% (36/100) of strangulation agents and 50% of reported incidents were attributed to sexual activity. To our knowledge, this is the only study focusing on long-term outcomes after penile strangulation. This review provides a summary of 56 studies that document penile strangulation injuries over the last 20 years. Although a wide array of penile strangulation injuries have been documented in the literature, reports lack secondary management and long-term outcomes after removal of the strangulation device. We recommend that providers report long-term penile strangulation outcomes for future urologic evaluations after extrication.
Topics: Male; Humans; Child, Preschool; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Follow-Up Studies; Penis; Penile Diseases; Sexual Behavior; Constriction, Pathologic
PubMed: 38293721
DOI: 10.1177/15579883231223366 -
Journal of Clinical Oncology : Official... Nov 2023Patients with advanced penile squamous cell carcinoma have a poor prognosis (21% 2-year overall survival [OS] from diagnosis). We assessed the activity of atezolizumab...
PURPOSE
Patients with advanced penile squamous cell carcinoma have a poor prognosis (21% 2-year overall survival [OS] from diagnosis). We assessed the activity of atezolizumab (anti-PD-L1) in patients with advanced penile cancer, with or without radiotherapy (RT).
PATIENTS AND METHODS
A single-center, nonrandomized phase II study with two treatment arms was conducted in 32 patients with histologically confirmed advanced penile cancer. All patients received atezolizumab (1,200 mg) once every 3 weeks. Twenty patients, who were expected to benefit from RT for locoregional disease control, received additional irradiation. The primary end point was 1-year progression-free survival (PFS) for the complete cohort and was reached if the actual 1-year PFS was at least 35%. Secondary end points included OS, objective response rate (ORR), and tolerability. Exploratory biomarker analyses were conducted in pretreatment specimens.
RESULTS
Median follow-up was 29.1 months (IQR, 18.1-33.5). Grade 3-4 adverse events related to atezolizumab or RT were observed in 3/32 (9.4%) and 13/20 (65%) patients, respectively. One-year PFS was 12.5% (95% CI, 5.0 to 31.3), which did not meet the study's primary end point. Median OS was 11.3 months (95% CI, 5.5 to 18.7). In the objective response-evaluable population (n = 30; 93.8%), the ORR was 16.7% (95% CI, 6 to 35), including 2 (6.7%) complete responders and 3 (10%) partial responders. Improved PFS was observed in patients with high-risk human papillomavirus (hrHPV)-positive tumors ( = .003) and those with high infiltration of intratumoral CD3CD8 T cells ( = .037).
CONCLUSION
Although the primary end point of 1-year PFS was not met, durable antitumor activity to atezolizumab was observed in a subset of patients. Biomarkers, such as hrHPV and intratumoral CD3CD8 T-cell infiltration, may help to better select responders.
Topics: Male; Humans; CD8-Positive T-Lymphocytes; Penile Neoplasms; Carcinoma, Squamous Cell; Penis; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37487169
DOI: 10.1200/JCO.22.02894