-
The Urologic Clinics of North America Aug 2024Penile cancer (PC), although rare, poses significant challenges in both diagnosis and treatment. Penile squamous cell carcinoma (PSCC) represents the most common... (Review)
Review
Penile cancer (PC), although rare, poses significant challenges in both diagnosis and treatment. Penile squamous cell carcinoma (PSCC) represents the most common histologic subtype of PC, accounting for approximately 95% of cases. With limited therapeutic options available, systemic therapies have emerged as critical components in the management of advanced PSCC. Recent developments in clinical research have revealed the effectiveness of new therapeutic strategies. By elucidating the mechanism of action and clinical evidence supporting these treatments, we strive to offer insights into optimizing treatment strategies and enhancing the quality of care for patients affected by this complex disease.
Topics: Humans; Penile Neoplasms; Male; Carcinoma, Squamous Cell; Antineoplastic Agents
PubMed: 38925737
DOI: 10.1016/j.ucl.2024.03.013 -
The Urologic Clinics of North America Aug 2024Penile cancer with bulky inguinal metastasis has a high probability of harboring pathologically involved lymph nodes best managed in a multidisciplinary care setting.... (Review)
Review
Penile cancer with bulky inguinal metastasis has a high probability of harboring pathologically involved lymph nodes best managed in a multidisciplinary care setting. Appropriate staging with cross-sectional imaging and fine-needle aspirate cytology of suspicious nodes guide decision-making for the use of platinum-based neoadjuvant chemotherapy followed by inguinal lymph node dissection. Surgical resection plays an important diagnostic, therapeutic, and guiding role in disease management. Patients with adverse pathologic features, especially those with extranodal disease extension, may derive additional benefit from adjuvant radiotherapy.
Topics: Humans; Lymphatic Metastasis; Inguinal Canal; Male; Penile Neoplasms; Lymph Node Excision; Lymph Nodes; Pelvis; Neoplasm Staging
PubMed: 38925736
DOI: 10.1016/j.ucl.2024.03.012 -
The Urologic Clinics of North America Aug 2024Penile cancer is a rare cancer, where patients not only need to deal with the anxiety around a cancer diagnosis, but also manage the consequences of treatment on their... (Review)
Review
Penile cancer is a rare cancer, where patients not only need to deal with the anxiety around a cancer diagnosis, but also manage the consequences of treatment on their self-esteem, body image, and intimate relationships. Many find it embarrassing and difficult to talk to family and friends. Due to this, changes in urination and other physical effects of treatment, many will withdraw from social activities too. Patients need psychosocial support and more needs to be done to address this unmet need. Holistic and multidisciplinary approaches in clinic, with access to counseling, may help patients adjust to their new situation.
Topics: Humans; Male; Communication; Penile Neoplasms; Psychosocial Support Systems; Social Interaction; Spouses; Suicide; Recurrence; Counseling
PubMed: 38925735
DOI: 10.1016/j.ucl.2024.03.004 -
The Urologic Clinics of North America Aug 2024The landscape of squamous cell carcinoma of the penis (SCC-P) has undergone a significant transformation since the new World Health Organization classification of... (Review)
Review
The landscape of squamous cell carcinoma of the penis (SCC-P) has undergone a significant transformation since the new World Health Organization classification of genitourinary cancers and recent European Association of Urology/American Association of Clinical Oncology guidelines. These changes emphasize the necessity to categorize SCC-P into 2 groups based on its association with human papillomavirus (HPV) infection. This shift has major implications, considering that prior knowledge was derived from a mix of both groups. Given the distinct prognosis, treatment options, and staging systems observed for HPV-associated tumors in other body areas, the question now arises: will similar patterns emerge for SCC-P?
Topics: Humans; Penile Neoplasms; Male; Carcinoma, Squamous Cell; Papillomavirus Infections; Neoplasm Staging; Prognosis
PubMed: 38925734
DOI: 10.1016/j.ucl.2024.03.003 -
Andrology Jun 2024Peyronie's disease is characterized by the formation of fibrotic plaques in the penile tunica albuginea. Effective treatments are limited, warranting the investigation...
BACKGROUND
Peyronie's disease is characterized by the formation of fibrotic plaques in the penile tunica albuginea. Effective treatments are limited, warranting the investigation of new promising therapies, such as the application of microRNAs that regulate fibrosis-related genes.
OBJECTIVE
We aimed to investigate the therapeutic potential of mimicking microRNA-29b in a fibrin-induced rat model of Peyronie's disease.
MATERIAL/METHODS
The study was designed in two phases. To establish an optimal Peyronie's disease model, rats received either human fibrin and thrombin or saline solutions into the tunica albuginea on days 0 and 5. The animal model validation was done through expression and histopathological analyses, the latest by an experienced uropathologist. After validation, we performed microRNA-29b treatment on days 14, 21, and 28 of the study. This phase had control (normal saline) and scramble (microRNA scramble) groups. The mid-penile shaft was removed on day 30 for histological examination and molecular analyses in both study stages.
RESULTS
The control group displayed typical tunica albuginea histologic architecture in the animal model validation. In Peyronie's disease group, the Hematoxylin and eosin and Masson Trichrome staining methods demonstrated an interstitial inflammatory process with concomitant dense fibrotic plaques as well as disarrangement of collagen fibers. Additionally, we found out that reduced microRNA-29b (p = 0.05) was associated with significantly increased COL1A1 and transforming growth factor β1 genes and proteins (p > 0.05) in the Peyronie's disease group. After treatment with mimic microRNA-29b stimulation, the Hematoxylin & eosin and Masson Trichrome staining revealed a discrete and less dense fibrotic plaque. This result was associated with significantly decreasing expression of COL1A1, COL3A1, and transforming growth factor β1 genes and proteins (p < 0.05).
DISCUSSION
The fibrin-induced animal model showed significant histopathological and molecular changes compared to the Control group, suggesting that our model was appropriate. Previous findings have shown that increased expression of microRNA-29b was associated with decreased pathological fibrosis. In the present study, treatment with microRNA-29b decreased the gene and protein expression of collagens and transforming growth factor β1. This study reveals the therapeutic potential for Peyronie's disease involving molecular targets.
CONCLUSION
MicroRNA-29b application on the rat's tunica albuginea attenuated fibrosis, arising as a novel potential strategy for Peyronie's disease management.
PubMed: 38925608
DOI: 10.1111/andr.13672 -
Urology Jun 2024To analyze current standards in urethroplasty by urologists employing buccal mucosal grafts (BMG) for treating urethral stricture disease (USD).
OBJECTIVES
To analyze current standards in urethroplasty by urologists employing buccal mucosal grafts (BMG) for treating urethral stricture disease (USD).
METHODS
An IRB-approved online survey was distributed to members of the Society of Genitourinary Reconstructive Surgeons (GURS) between July and October 2022 to assess BMG utilization in urethroplasty. Questions covered surgeon experience, graft harvest site, graft length, surgical technique, and perceived success rates.
RESULTS
Of 350 invited GURS members, 134 responded (38%). 69% were GURS fellowship-trained, performing 10-30 urethroplasties annually. 95% harvested their own grafts, with 99% preferring buccal mucosa as the primary site. Buccal mucosa was favored over fasciocutaneous flap for penile urethroplasty, regardless of circumcision status (95% with, 84% without). For bulbar urethroplasty with BMG, dorsal graft placement was favored (66%) over ventral (34%). Most surgeons (90%) preferred multiple BMGs over combined graft/flap for panurethral strictures. When harvesting long grafts, 56% preferred using both cheeks. Anastomotic urethroplasty was preferred over buccal graft urethroplasty for short bulbomembranous stenosis post-radiotherapy (63% vs. 37%). Surgeons reported a success rate of 80-90% (53%).
CONCLUSIONS
The expanded scope of reconstructive urology has led to increased use of BMG in diverse urethral reconstructions. Buccal grafts are now preferred for penile, bulbar, and panurethral strictures, demonstrating high perceived success rates in the reconstructive community.
PubMed: 38925372
DOI: 10.1016/j.urology.2024.06.019 -
International Urology and Nephrology Jun 2024Mohs micrographic surgery (MMS) is a low-risk penile cancer management option. However, contemporary patients' short-term oncologic control and preoperative...
PURPOSE
Mohs micrographic surgery (MMS) is a low-risk penile cancer management option. However, contemporary patients' short-term oncologic control and preoperative characteristics predicting reconstruction needs are undefined. This study assesses MMS's oncologic efficacy for low-risk penile cancer and identifies baseline predictors of post-resection reconstruction referral.
METHODS
We retrospectively reviewed 73 adult males with 78 penile cutaneous malignancies treated with MMS from 2005 to 2019. Patients underwent MMS with or without surgical reconstruction. Demographic information, MMS operative details, lesion pathology, and short-term outcomes were recorded. Descriptive statistics for all variables were calculated, and logistic regression identified predictive factors for urologic referral for complex reconstruction.
RESULTS
Seventy-three men with 78 lesions, all staged ≤ cT1a prior to MMS, were identified. Twenty-one men were found to have invasive SCC. Median follow-up was 2.0 years (IQR 0.8-5.2 years). MMS was able to clear the disease in 90.4% of cases. One patient had disease related death following progression. Dermatology closed primarily in 68% of patients. Twenty percent of patients had a complication, most commonly poor wound healing. On univariate and multivariate linear regression analysis, lesion size > 3 cm and involvement of the glans independently predicted the need for referral to a reconstructive surgeon.
CONCLUSIONS
MMS for penile cancer appears to provide sound oncologic control in the properly selected patient. Involvement of a reconstructive surgeon may be needed for glandular and large lesions, necessitating early referral to a comprehensive multidisciplinary care team.
PubMed: 38922534
DOI: 10.1007/s11255-024-04121-6 -
Minerva Urology and Nephrology Jun 2024Inguinal lymph nodes dissection (ILND) is recommended in patients presenting with high-risk penile (PC) or vulvar cancers (VC). Though, this surgical procedure is... (Review)
Review
INTRODUCTION
Inguinal lymph nodes dissection (ILND) is recommended in patients presenting with high-risk penile (PC) or vulvar cancers (VC). Though, this surgical procedure is underused because of its anticipated morbidity. Minimally invasive approaches were proposed to minimize complications associated with open surgery. In this review, we analyze current available data exploring intra and perioperative outcomes of robot-assisted ILND (RAIL).
EVIDENCE ACQUISITION
On April 9, 2023, a literature search was conducted using the PubMed and Scopus databases. The search employed the combination of the following terms: ("robotic assisted" OR "robot-assisted" OR "robotic") AND ("inguinal lymph node dissection" OR "lymphadenectomy") AND ("penile cancer" OR "vulvar cancer"). Out of the 404 identified articles, 18 were used for the present scoping review and their results were reported according to the PRISMA statement.
EVIDENCE SYNTHESIS
Data on 171 patients, ranging in age from 32 to 85 years, were obtained. Most of them (90.6%) harbored a penile squamous cell carcinoma and presented with no palpable nodes (85%). Operation time (OT) ranged between 45 and 300 min. Estimated blood loss varied from 10 to 300 mL. One single intra-operative complication was reported and one conversion to open was recorded. The lymph nodes (LNs) count spanned from 3 to 26 per groin, with 17 studies reporting a median yield >7 nodes. Hospital stay was 1-7 days, while the duration of drainage ranged from 4 to 72 days. Post-operative complications included lymphocele (22.2%; 0-100%), lymphedema (13.4%; 0-40%), cellulitis (11.1%; 0-25%), skin necrosis (8.7%; 0-15.4%). seroma (3.5%; 0-20%) and wound breakdown/wound infection (2.9%; 0-10%). Out of the included studies, 7 provided at least a 12-month follow-up, with recurrence-free rates ranging from 50% to 100% in patients affected by penile cancer and from 92% to 100% in vulvar cancer patients.
CONCLUSIONS
The available evidence on RAIL for the treatment of PC and VC is limited. The approach appears to be safe and effective, as it provides an adequate lymph node yield while ensuring a minimally morbid postoperative course and a short hospital stay.
Topics: Humans; Penile Neoplasms; Lymph Node Excision; Male; Vulvar Neoplasms; Female; Robotic Surgical Procedures; Inguinal Canal
PubMed: 38920009
DOI: 10.23736/S2724-6051.24.05532-0 -
Reproductive Biology and Endocrinology... Jun 2024Erectile dysfunction (ED) is a common male sexual dysfunction, with an increasing incidence, and the current treatment is often ineffective.
BACKGROUND
Erectile dysfunction (ED) is a common male sexual dysfunction, with an increasing incidence, and the current treatment is often ineffective.
METHODS
Vascular endothelial growth factor (VEGFA) was used to treat bone marrow-derived mesenchymal stem cells (BM-MSCs), and their cell migration rates were determined by Transwell assays. The expression of the von Willebrand Factor (vWF)VE-cadherin, and endothelial nitric oxide synthase(eNOS) endothelial markers was determined by qRT‒PCR and Western blot analyses. The MALAT1-induced differentiation of BM-MCs to ECs via the CDC42/PAK1/paxillin pathway was explored by transfecting VEGFA-induced BM-MSC with si-MALAT1 and overexpressing CDC42 and PAK1. The binding capacity between CDC42, PAK1, and paxillin in VEGFA-treated and non-VEGFA-treated BM-MSCs was examined by protein immunoprecipitation. MiR-206 was overexpressed in VEGFA-induced BM-MSC, and the binding sites of MALAT1, miR-206, and CDC42 were identified using a luciferase assay. Sixty male Sprague‒Dawley rats were divided into six groups (n = 10/group). DMED modelling was demonstrated by APO experiments and was assessed by measuring blood glucose levels. Erectile function was assessed by measuring the intracavernosa pressure (ICP) and mean arterial pressure (MAP). Penile erectile tissue was analysed by qRT‒PCR, Western blot analysis, and immunohistochemical staining.
RESULTS
MALAT1 under VEGFA treatment conditions regulates the differentiation of BM-MSCs into ECs by modulating the CDC42/PAK1/paxillin axis. In vitro experiments demonstrated that interference with CDC42 and MALAT1 expression inhibited the differentiation of BM-MSCs to ECs. CDC42 binds to PAK1, and PAK1 binds to paxillin. In addition, CDC42 in the VEGFA group had a greater ability to bind to PAK1, whereas PAK1 in the VEGFA group had a greater ability to bind to paxillin. Overexpression of miR-206 in VEGFA-induced BM-MSCs demonstrated that MALAT1 competes with the CDC42 3'-UTR for binding to miR-206, which in turn is involved in the differentiation of BM-MSCs to ECs. Compared to the DMED model group, the ICP/MAP ratio was significantly greater in the three BM-MSCs treatment groups.
CONCLUSIONS
MALAT1 facilitates BM-MSC differentiation into ECs by regulating the miR-206/CDC42/PAK1/paxillin axis to improve ED. The present findings revealed the vital role of MALAT1 in the repair of BM-MSCs for erectile function and provided new mechanistic insights into the BM-MSC-mediated repair of DMED.
Topics: Male; Animals; RNA, Long Noncoding; MicroRNAs; Cell Differentiation; cdc42 GTP-Binding Protein; Rats, Sprague-Dawley; Signal Transduction; Rats; p21-Activated Kinases; Mesenchymal Stem Cells; Erectile Dysfunction; Paxillin; Endothelial Cells; Cells, Cultured; Vascular Endothelial Growth Factor A
PubMed: 38918809
DOI: 10.1186/s12958-024-01240-8 -
Clinical Genitourinary Cancer May 2024Penile squamous cell carcinoma (PSCC) can develop from human papillomavirus (HPV) infection. This study investigates if the prognostic value of the TNM stage groups or...
INTRODUCTION
Penile squamous cell carcinoma (PSCC) can develop from human papillomavirus (HPV) infection. This study investigates if the prognostic value of the TNM stage groups or the components tumor stage (pT), grade of differentiation (Grade), lymphovascular invasion (LVI), and nodular stage (pN) depend on HPV status. Also, whether the value of tumor parameters (pT, Grade, and LVI) for predicting node-positive disease depends on HPV status was investigated.
PATIENTS AND METHODS
Stored tumor tissue from 226 patients treated for PSCC in Western Norway between 1973 and 2023 was investigated for HPV DNA. Histopathological variables were reevaluated according to the current TNM classification. Disease course was registered from hospital records. Inclusion of an interaction term between HPV and TNM stage groups in Cox regression enabled analysis of whether cancer-specific survival (CSS) of the stage groups depended on HPV status. This was also done separately for pT, Grade, LVI, and pN. Logistic regression with interaction terms between HPV and the tumor parameters were used to investigate if their predictive value depended on HPV status.
RESULTS
HPV DNA was detected in 43% of the tumors. Stratified by HPV status, there was no significant interaction term in the Cox regression between HPV status and TNM stage groups (P = .74). Similar results were found for pT (P = .94), Grade (P = .08), LVI (P = .91) and pN (P = .77). Moreover, there were no significant interaction terms in the logistic regression between HPV status and the tumor parameters pT, Grade, and LVI (all P > .2).
CONCLUSIONS
This study found that prognosis of the TNM stage groups and the components pT, Grade, LVI, and pN were not modified by HPV in PSCC. The value of pT, Grade, and LVI for predicting lymph node-positive disease was not affected by HPV status.
PubMed: 38918085
DOI: 10.1016/j.clgc.2024.102127