-
International Braz J Urol : Official... 2021Squamous cell carcinoma (SCC) of the penis is a rare disease in developed countries but is associated with significant morbidity and mortality. A crucial prognostic... (Review)
Review
PURPOSE
Squamous cell carcinoma (SCC) of the penis is a rare disease in developed countries but is associated with significant morbidity and mortality. A crucial prognostic factor is the presence of inguinal lymph node metastases (ILNM) at the time of diagnosis. At least 25% of cases have micrometastases at the time of diagnosis. Therefore, we performed a literature review of studies evaluating factors, both clinical and pathological, predictive of lymph node metastases in penile SCC.
MATERIALS AND METHODS
Studies were identified using PubMed and search terms included the following: penile cancer, penile tumor, penile neoplasm, penile squamous cell carcinoma, inguinal lymph node metastasis, lymph node metastases, nodal metastasis, inguinal node metastasis, inguinal lymph node involvement, predictors, and predictive factor. The number of patients and predictive factors were identified for each study based on OR, HR, or RR in multivariate analyses, as well as their respective significance values. These were compiled to generate a single body of evidence supportive of factors predictive of ILNM in penile SCC.
RESULTS
We identified 31 studies, both original articles and meta-analyses, which identified factors predictive of metastases in penile SCC. The following clinical factors were predictive of ILNM in penile SCC: lymphovascular invasion (LVI), increased grade, increased stage (both clinical and pathological), infiltrative and reticular invasion, increased depth of invasion, perineural invasion, and younger patient age at diagnosis. Biochemically, overexpression of p53, SOD2, Ki-67, and ID1 were associated with spread of SCC to inguinal lymph nodes. Diffuse PD-L1 expression, increased SCC-Ag expression, increased NLR, and CRP >20 were also associated with increased ILNM.
CONCLUSIONS
A multitude of factors are associated with metastasis of SCC of the penis to inguinal lymph nodes, which is associated with poor clinical outcomes. The above factors, most strongly LVI, grade, and node positivity, may be considered when constructing a nomogram to risk-stratify patients and determine eligibility for prophylactic inguinal lymphadenectomy.
Topics: Humans; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Penile Neoplasms; Prognosis
PubMed: 33650835
DOI: 10.1590/S1677-5538.IBJU.2020.0959 -
Endocrinology, Diabetes & Metabolism Apr 2021Fibrosis is characterized by dysregulation and accumulation of extracellular matrix. Peyronie's disease and Dupuytren disease are fibroproliferative disorders of the...
INTRODUCTION
Fibrosis is characterized by dysregulation and accumulation of extracellular matrix. Peyronie's disease and Dupuytren disease are fibroproliferative disorders of the tunica albuginea of the penis and fascia of the hand, respectively. Chronic hyperglycaemia due to diabetes mellitus can also lead to tissue injury and fibrosis. A meta-analysis has shown a relationship between Dupuytren disease and diabetes (overall odds ratio, 3.1; 95% confidence interval, 2.7-3.5). This review explores commonalities in the pathogenesis of Peyronie's disease, Dupuytren disease and diabetes.
METHODS
A search of the PubMed database was conducted using the search terms "diabetes" AND "Peyronie's disease"; and "diabetes" AND "Dupuytren."
RESULTS
Genome-wide association and gene expression studies conducted with tissue from people with Peyronie's disease or Dupuytren disease identified signalling pathways associated with wingless-type mammary-tumour virus integration site signalling, extracellular matrix modulation and inflammation. Biochemical studies confirmed the importance of these pathways in the pathogenesis of fibrosis with Peyronie's disease and Dupuytren disease. Dysregulation of matrix metalloproteinase activity associated with extracellular matrix breakdown was implicated in fibroproliferative complications of diabetes and in the aetiology of Peyronie's disease and Dupuytren disease. A notable percentage of people with diabetes have comorbid Peyronie's disease and/or Dupuytren disease.
CONCLUSIONS
Studies have not been performed to identify fibroproliferative pathways that all 3 conditions might have in common, but data suggest that common pathways are involved in the fibroproliferative processes of Peyronie's disease, Dupuytren disease, and diabetes.
Topics: Chronic Disease; Diabetes Complications; Diabetes Mellitus; Dupuytren Contracture; Extracellular Matrix; Fascia; Female; Fibrosis; Genome-Wide Association Study; Hand; Humans; Hyperglycemia; Male; Matrix Metalloproteinases; Penile Induration; Penis; Signal Transduction
PubMed: 33855203
DOI: 10.1002/edm2.195 -
International Journal of Molecular... Jan 2023Current literature has indicated that Peyronie's disease (PD) could be initiated by microtrauma and the subsequent inflammation episodes that follow. PD could be sorted... (Review)
Review
Current literature has indicated that Peyronie's disease (PD) could be initiated by microtrauma and the subsequent inflammation episodes that follow. PD could be sorted into acute or chronic status, and it can differ when selecting the clinical therapeutics. PD would cause pain and penile deformity to diseased men and impair their erectile function. Occasionally, surgical revision of the penis might be needed to correct the penile curvature. We find that there are limited effective options of intra-lesion injections for the PD plaques. By searching the databases and screening the literature with the PRISMA 2020 guideline, we observed that several preclinical studies that applied stem cell therapy in treating PD were fruitful in the acute phase. Although in the chronic phase of PD, erectile parameters were not significantly improved, and therefore, future studies might be better elevated in certain aspects, such as the sites selected for harvesting stem cells or changing the centrifugation forces. In this review, we concluded the contemporary understanding of inflammatory microenvironments in PD, the stem cell therapy in PD, and our perspectives on future studies. We concluded that there may be great potential in stem cell therapy for treating both acute and chronic phases PD.
Topics: Male; Humans; Penile Induration; Penis; Penile Erection; Injections; Stem Cells
PubMed: 36614220
DOI: 10.3390/ijms24010777 -
Urologic Oncology May 2022To determine the effectiveness of adjuvant chemotherapy compared with neoadjuvant chemotherapy in patients with node-positive penile cancer in terms of overall and... (Meta-Analysis)
Meta-Analysis
Effectiveness and safety of adjuvant chemotherapy compared to neoadjuvant chemotherapy in patients with penile cancer and positive lymph nodes regarding overall survival and free disease survival: a systematic review and meta-analysis.
OBJECTIVES
To determine the effectiveness of adjuvant chemotherapy compared with neoadjuvant chemotherapy in patients with node-positive penile cancer in terms of overall and disease-free survival.
METHODS
We conducted a search strategy in MEDLINE, Embase, and Central databases. We complemented the search with unpublished literature through manual search, conferences, thesis databases, Open Grey, Google Scholar, and Clinicaltrials.gov. There were no restrictions in language. We used the MINORS tool to assess the risk of bias. Furthermore, we performed a random-effects meta-analysis according to the expected heterogeneity. The outcomes were overall survival, progression-free survival, and adverse effects. The Effect measure was hazard ratio (HR) with a confidence interval of 95%.
RESULTS
We included 1,197 patients. Seven articles reported overall survival; while 3 reported progression-free survival. The pooled overall survival HR was 1.41 (0.99-2.02), while the progression-free survival HR was 1.63 (1.09-2.44) for adjuvant vs neoadjuvant therapy. An analysis of adverse effects was not possible.
CONCLUSIONS
There were no differences when comparing adjuvant vs. neoadjuvant chemotherapy or adjuvant vs. no intervention chemotherapy. We conclude that progression-free survival had a better response with adjuvant chemotherapy when compared with neoadjuvant therapy. We suggest more studies with adequate design to offer a stronger recommendation.
Topics: Chemotherapy, Adjuvant; Disease-Free Survival; Humans; Lymph Nodes; Male; Neoadjuvant Therapy; Penile Neoplasms
PubMed: 35307290
DOI: 10.1016/j.urolonc.2022.02.014 -
Research and Reports in Urology 2020Erectile dysfunction (ED) is a common clinical condition with limited treatment options. The main aim of the present systematic review was to synthesize information on... (Review)
Review
BACKGROUND
Erectile dysfunction (ED) is a common clinical condition with limited treatment options. The main aim of the present systematic review was to synthesize information on Rho-kinase as a novel therapeutic approach for the treatment of ED.
METHODS
We performed a systematic literature study in PubMed, Google Scholar and Scopus. Included studies were original articles studied the role of Rho-kinase in the pathogenesis and/or new treatment approach for ED in animal models and clinical studies, published between 2014 and 2019. Data derived from each study were study design used, interventions applied and main treatment outcomes. The quality of the selected articles was assessed by CAMARADES criteria and data were analyzed using descriptive statistics.
RESULTS
A total of 1067 original articles were retrieved in the given period and eighteen papers met our inclusion criteria. Five articles explain the role of Rho-kinase in ED pathogenesis using different models such as cavernous nerve crush injury, heart failure-induced ED, vasculogenic and post-radical prostatectomy ED, diabetes-induced ED and age-related ED. Other ten papers explain the role of novel drugs evaluated for ED treatment by targeting Rho-kinase as a new approach for ED therapy. The rest three papers discuss the role of plant extracts used by traditional society for the treatment of ED and assess their potential function in targeting Rho-kinase in animal models. The penile erectile functional index has shown that the ratio of intracavernosal pressure to mean arterial pressure (ICP/MAP) was decreased due to age and various chronic diseases. Whilst, ROCK I and ROCK II expression were increased. Western blot findings have also shown that ROCK II and MYPT-1 phosphorylation rates increased in cavernous tissue after ED induction. Besides, compounds which can inhibit the action of Rho-kinase activity showed relaxation of the corpus cavernosum, decrease in corporal fibrosis, and alleviate increased apoptosis and caspase-3 activity in an NO-independent manner. Moreover, histological and molecular dysregulation have been improved by inhibition of Rho-kinase.
CONCLUSION
Targeting Rho-kinase may be a possible target for the treatment of ED secondary to specific causes, and Rho-kinase inhibitors may be a new drug family for the treatment of ED. However, this requires further studies for in-depth understanding.
PubMed: 32766173
DOI: 10.2147/RRU.S255743 -
Indian Journal of Urology : IJU :... 2022The management options for regional lymph nodes (LNs) in men with penile cancer include surveillance, surgery, and chemotherapy. The use of radiotherapy (RT) for nodal... (Review)
Review
INTRODUCTION
The management options for regional lymph nodes (LNs) in men with penile cancer include surveillance, surgery, and chemotherapy. The use of radiotherapy (RT) for nodal disease follows tradition and single-institution policies. We aimed to analyse the existing evidence regarding the management of penile cancer patients with suspected or known metastatic pelvic LNs using pelvic LN dissection (PLND) with RT versus PLND or RT alone.
METHODS
A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, with no filters for language or time. The search was conducted in EMBASE, MEDLINE/PubMed, and Cochrane Library. Inclusion criteria were adult men with penile cancer and suspected metastatic pelvic LNs, undergoing PLND with or without RT or RT alone. Primary outcomes included disease-specific survival and locoregional recurrence. Secondary outcomes included overall survival and complications of therapy.
RESULTS
A total of 552 articles were identified. Only eight retrospective studies were eligible for inclusion (including 406 patients). All studies had a high risk of bias. None of the studies reported the use of neoadjuvant RT. Indications for PLND varied but were usually two or more clinically positive inguinal nodes with or without extracapsular extension. Adjuvant RT was mainly used in positive pelvic LNs or pN2/pN3 stages. The rate of locoregional recurrence following adjuvant RT was 70%. Complications of treatment were reported in two studies only.
CONCLUSIONS
There is insufficient evidence to recommend the use of adjuvant RT following PLND in penile cancer patients. The quality of evidence is low due to the retrospective design and high risk of bias. Randomized clinical trials are required to assess the efficacy and safety of adjuvant RT and PLND.
PubMed: 35400869
DOI: 10.4103/iju.iju_453_21 -
International Journal of Molecular... Dec 2021Penile squamous cell carcinoma (PSCC) is a rare but aggressive neoplasm with dual pathogenesis (human papillomavirus (HPV)-associated and HPV-independent). The...
Penile squamous cell carcinoma (PSCC) is a rare but aggressive neoplasm with dual pathogenesis (human papillomavirus (HPV)-associated and HPV-independent). The development of targeted treatment is hindered by poor knowledge of the molecular landscape of PSCC. We performed a thorough review of genetic alterations of PSCC focused on somatic mutations and/or copy number alterations. A total of seven articles have been identified which, overall, include 268 PSCC. However, the series are heterogeneous regarding methodologies employed for DNA sequencing and HPV detection together with HPV prevalence, and include, in general, a limited number of cases, which results in markedly different findings. Reported top-ranked mutations involve , , , and . Numerical alterations involve gains in and , as well as amplifications in HPV integration loci. A few genes including , , and harbor both somatic mutations and copy number alterations. Notch, RTK-RAS and Hippo pathways are frequently deregulated. Nevertheless, the relevance of the identified alterations, their role in signaling pathways or their association with HPV status remain elusive. Combined targeting of different pathways might represent a valid therapeutic approach in PSCC. This work calls for large-scale sequencing studies with robust HPV testing to improve the genomic understanding of PSCC.
Topics: Carcinoma, Squamous Cell; DNA Copy Number Variations; Geography; Humans; Male; Molecular Targeted Therapy; Mutation; Papillomaviridae; Penile Neoplasms; Prognosis; Signal Transduction
PubMed: 35008677
DOI: 10.3390/ijms23010251 -
Archivio Italiano Di Urologia,... May 2023Penile fracture (PF) with associated urethral injury has been described as a rare condition yet a serious urological emergency. We conducted this systematic review to...
PURPOSES
Penile fracture (PF) with associated urethral injury has been described as a rare condition yet a serious urological emergency. We conducted this systematic review to address the current literature concerning the etiology, presentations, intra-operative findings, site of injury, and complications of PF with associated urethral injury, Materials and Methods: The present systematic review was limited to human-based studies published in English language, and reporting clinical data on PF cases with associated urethral injuries. A comprehensive search of the literature was conducted on five electronic databases from their inception to May 2022: Medline via PubMed, Web of Science, Google Scholar, Scopus, and EBSCO host.
RESULTS
A total of 15 studies were included encompassing 1671 patients with PF. Out of 1665 patients with PF retrieved from the case series studies, 65 patients had associated urethral injuries giving a point prevalence of 3.9%. The vast majority of the patients had blood on the meatus and hematuria suggestive of urethral injury (57/59; 96.6%). Forty patients had partial urethral disruption and the rest of the patients had a complete rupture. All patients received primary urethroplasty as the main modality of treatment. The median hospital stay was two days and the median duration of transurethral catheterization was 21 days. Five patients (8.5%) developed urethral stricture; other complications included penile curvature (6.7%), palpable fibrosis (6.7%), and erectile dysfunction (3.4%).
CONCLUSIONS
Urethral injuries are uncommon, but serious findings, in patients with PF. Primary urethroplasty appears to achieve satisfactory outcomes with a low incidence of short and long-term complications.
Topics: Male; Humans; Penile Diseases; Urethra; Penis; Erectile Dysfunction; Urethral Stricture; Rupture
PubMed: 37259814
DOI: 10.4081/aiua.2023.11082 -
World Journal of Urology Jul 2023False penile fractures (FPF) represent a rare sexual emergency characterized by blunt trauma of penis in the absence of albuginea's injury, with or without lesion of... (Meta-Analysis)
Meta-Analysis
PURPOSE
False penile fractures (FPF) represent a rare sexual emergency characterized by blunt trauma of penis in the absence of albuginea's injury, with or without lesion of dorsal penile vein. Their presentation is often indistinguishable from true penile fractures (TPF). This overlapping of clinical presentation, and lack of knowledge about FPF, can lead surgeons often to proceed directly to surgical exploration without further examinations. The aim of this study was to define a typical presentation of false penile fractures (FPF) emergency, identifying in absence of "snap" sound, slow detumescence, penile shaft ecchymosis, and penile deviation main clinical signs.
METHODS
We performed a systematic review and meta-analysis based on Medline, Scopus and Cochrane following a protocol designed a priori, to define sensitivity of "snap" sound absence, slow detumescence and penile deviation.
RESULTS
Based on the literature search of 93 articles, 15 were included (73 patients). All patients referred pain, most of them during coitus (n = 57; 78%). Detumescence occurred in 37/73 (51%), and all patients described detumescence occurrence as "slow". The results show that single anamnestic item have a high-moderate sensibility in the diagnosis of FPF, and the highest sensitive item was penile deviation (sensibility = 0.86). However, when more than one item is present, overall sensitivity increases greatly, closing to 100% (95% Confidence Interval 92-100).
CONCLUSION
Surgeons can consciously decide between additional exams, a conservative approach, and rapid intervention using these indicators to detect FPF. Our findings identified symptoms with excellent specificity for FPF diagnosis, giving clinicians more useful tools for making decisions.
Topics: Male; Humans; Rupture; Penile Diseases; Penis; Coitus; Pelvis
PubMed: 37326652
DOI: 10.1007/s00345-023-04456-2 -
Translational Andrology and Urology Jun 2021The pudendal nerve is considered as the main nerve of sexuality. Pudendal neuralgia is an underdiagnosed disease in clinical practice. The aim of this systematic review... (Review)
Review
BACKGROUND
The pudendal nerve is considered as the main nerve of sexuality. Pudendal neuralgia is an underdiagnosed disease in clinical practice. The aim of this systematic review is to highlight the role of pudendal neuralgia on sexual dysfunction in both sexes.
METHODS
A PubMed search was performed using the following keywords: "Pudendal" AND "Sexual dysfunction" or "Erectile dysfunction" or "Ejaculation" or "Persistent sexual arousal" or "Dyspareunia" or "Vulvodynia". The search involved patients having sexual dysfunction due to pudendal neuralgia. Treatment received was also reported.
RESULTS
Five case series, seven cohort studies, two pilot studies, and three randomized clinical trials were included in this systematic review. Pudendal nerve and/or artery entrapment, or pudendal neuralgia, is a reversible cause of multiple sexual dysfunctions. Interventions such as anesthetic injections, neurolysis, and decompression are reported as potential treatment modalities. There are no studies describing the role of pudendal canal syndrome in the pathophysiology or treatment of delayed ejaculation or penile shortening.
DISCUSSION
Pudendal neuralgia is an underestimated yet important cause of persistent genital arousal, erectile dysfunction (ED), premature ejaculation (PE), ejaculation pain, and vulvodynia. Physicians should be aware of this entity and examine the pudendal canal in such patients before concluding an idiopathic cause of sexual dysfunction.
PubMed: 34295736
DOI: 10.21037/tau-21-13