Primary urethral carcinoma: Recommendations of the oncology committee of the French Urology Association.

Primary urethral carcinoma (PUC) is defined as a tumor process arising within the urethra, with no history of other urinary tract localization or synchronous tumor of the urinary tract. The most common histological types are urothelial carcinoma (UC), squamous cell carcinoma (SCC) and adenocarcinoma (AC). In men, UC predominates, while AC is rare. In women, AC affects around one in two patients, while EC and UC are equally divided between the remaining cases. Diagnosis is often delayed, and requires endoscopic examination with biopsies. MRI is the gold standard for local staging. FDG-PET scan can help in cases of doubt about regional or distant extension. The prognosis remains unfavorable despite aggressive surgical treatment. Multimodal management combining surgery, radiotherapy and chemotherapy appears to improve prognosis in severe forms.

Sexual Structure Sparing for Prostate Cancer Radiotherapy: A Systematic Review.

CONTEXT: Erectile dysfunction represents a major side effect of prostate cancer (PCa) treatment, negatively impacting men's quality of life. While radiation therapy (RT) advances have enabled the mitigation of both genitourinary and gastrointestinal toxicities, no significant improvement has been showed in sexual quality of life over time. OBJECTIVE: The primary aim of this review was to assess sexual structures' dose-volume parameters associated with the onset of erectile dysfunction. EVIDENCE ACQUISITION: We searched the PubMed database and ClinicalTrials.gov until January 4, 2023. Studies reporting the impact of the dose delivered to sexual structures on sexual function or the feasibility of innovative sexual structure-sparing approaches were deemed eligible. EVIDENCE SYNTHESIS: Sexual-sparing strategies have involved four sexual organs. The mean penile bulb doses exceeding 20 Gy are predictive of erectile dysfunction in modern PCa RT trial. Maintaining a D100% of ≤36 Gy on the internal pudendal arteries showed preservation of erectile function in 88% of patients at 5 yr. Neurovascular bundle sparing appears feasible with magnetic resonance-guided radiation therapy, yet its clinical impact remains unanswered. Doses delivered to the testicles during PCa RT usually remain <2 Gy and generate a decrease in testosterone levels ranging from -4.6% to -17%, unlikely to have any clinical impact. CONCLUSIONS: Current data highlight the technical feasibility of sexual sparing for PCa RT. The proportion of erectile dysfunction attributable to the dose delivered to sexual structures is still largely unknown. While the ability to maintain sexual function over time is impacted by factors such as age or comorbidities, only selected patients are likely to benefit from sexual-sparing RT. PATIENT SUMMARY: Technical advances in radiation therapy (RT) made it possible to significantly lower the dose delivered to sexual structures. While sexual function is known to decline with age, the preservation of sexual structures for prostate cancer RT is likely to be beneficial only in selected patients.

Current management and future perspectives of penile cancer: An updated review.

Penile cancer (PeCa) is a rare disease worldwide, accounting for less than one percent of all malignancies in men. It usually presents as a painless ulcer or lump on the head of the penis. Squamous cell carcinoma represents the most common histological subtype of PeCa, with pathogenesis intimately linked to chronic Human Papilloma Virus (HPV) infection. Surgery is the cornerstone for the treatment of primary PeCa with potential mutilating outcome depending on the nodal extension of the disease. However, in case of extensive lymph node involvement, multidisciplinary treatment including perioperative chemotherapy and inclusion in clinical trial should be considered. To date, advanced or metastatic disease still have poor prognosis and are a therapeutic challenge with limited options, highlighting the need of new treatments and further investigations. Growing efforts to identify molecular alterations, understand the role of HPV and characterize immune contexture have expanded over the past years, providing further perspectives in prognostication, predictive biomarkers and therapeutic intervention. In this review, we provide an updated overview of current management of PeCa focusing on perioperative strategy. We discuss about new insights of the biology of PeCa and comment future directions in the field.

Testicular tumours discovered during infertility workup are predominantly benign and could initially be managed by sparing surgery.

BACKGROUND AND OBJECTIVES: To evaluate the pathological features and recurrence of incidental testis tumours treated by partial orchiectomy in a population of infertile men. METHODS: We retrospectively pooled, from four andrology referral centres, 32 patients diagnosed with testis mass during regular infertility workup. Patients included had an impaired sperm analysis and testis sparing surgery was performed to prevent secondary azoospermia or androgen therapy. RESULTS: Mean age was 36 (IQR, 32 to 37). The mean largest tumoral diameter was 8.5 mm (IQR, 5 to 10). A total of 25% (8 of 32) of patients had a malignant tumour (seminoma, 7 of 32, 22%; teratoma, 1 of 32, 3%) and 75% (24 of 32) had a benign lesion (Leydig cell tumour, 23 of 32, 72%; scar tissue, 1 of 32, 3%). Malignant tumours were then managed by total orchiectomy (six of eight) or by radiotherapy (two of eight). With a mean follow up of 26 months (IQR, 8 to 32), one patient (3%) had an homolateral recurrence, which was a Leydig cell tumour. Not a single patient developed metastasis. CONCLUSION: Seventy-five per cent of the tumours discovered during infertility management were of a benign pathology. A conservative approach could be proposed initially to avoid unnecessary orchiectomies. Orchiectomy and radiotherapy could be discussed as salvage therapies for malignant lesions.

Tunica albuginea allograft: a new model of LaPeyronie's disease with penile curvature and subtunical ossification.

The pathophysiology of LaPeyronie's disease (PD) is considered to be multifactorial, involving genetic predisposition, trauma, inflammation and altered wound healing. However, these factors have not yet been validated using animal models. In this study, we have presented a new model obtained by tunica albuginea allograft. A total of 40, 16-week-old male rats were used. Of these, 8 rats served as controls and underwent a 10 × 2-mm-wide tunical excision with subsequent autografting, whereas the remaining 32 underwent the same excision with grafting of the defect with another rat's tunica. Morphological and functional testing was performed at 1, 3, 7 and 12 weeks after grafting. Intracavernous pressure, the degree of penile curvature and elastic fiber length were evaluated for comparison between the allograft and control groups. The tissues were obtained for histological examination. The penile curvature was significantly greater in the allografted rats as compared with the control rats. The erectile function was maintained in all rats, except in those assessed at 12 weeks. The elastin fiber length was decreased in the allografted tunica as compared to control. SMAD2 expression was detected in the inner part of the allograft, and both collagen-II- and osteocalcin-positive cells were also noted. Tunica albuginea (TA) allograft in rats is an excellent model of PD. The persistence of curvature beyond 12 weeks and the presence of ossification in the inner layer of the TA were similar to those observed in men with PD. Validation studies using this animal model would aid understanding of the PD pathophysiology for effective therapeutic interventions.

Testicular-sparing surgery for bilateral or monorchide testicular tumours: a multicenter study of long-term oncological and functional results.

OBJECTIVE: To review long-term oncological and functional outcomes of testicular-sparing surgery (TSS) in men presenting with bilateral or monorchide testicular tumours at one of five reference centres for testicular neoplasm and infertility. PATIENTS AND METHODS: We review 25 cases of bilateral synchrone and metachrone testicular tumours treated in five academic centres between 1984 and 2013. Clinical, biological, ultrasonography and pathological tumour findings, overall survival (OS) times, local or metastatic recurrence, pre- and postoperative hormonal profile, paternity and the need for androgen substitution were assessed. RESULTS: Eleven patients with a bilateral synchrone tumour and 14 patients with a testicular tumour on a solitary testicle underwent a tumorectomy. The mean (sem) patient age was 31.9 (1.04) years, total testosterone level was 4.5 (0.57) ng.mL and tumour size was 11.66 (1.49) mm. Tumour types were as follows: 11 seminoma, nine non-seminomatous or mixed germ cell tumours, four Leydig tumours, and one hamartoma. Frozen-section examination was performed in 14 patients, and matched the final pathological analysis in 11 patients. There was an OS rate of 100% and three patients (12%) presented with a local recurrence after a mean follow-up of 42.7 months. Radical orchiectomy was performed for six patients. No patient with a preserved testicle required androgen therapy; the mean postoperative total testosterone level was 4.0 ng/mL. No patient remained fertile after radiation therapy. CONCLUSIONS: TSS for bilateral testicular tumour is safe and effective in selected patients, and should be considered to avoid definitive androgen therapy. Adjuvant radiotherapy remains poorly described in the literature, leading to adjuvant treatment heterogeneity for testicular tumours.

Effects of low-energy shockwave therapy on the erectile function and tissue of a diabetic rat model.

Introduction. Low-energy shockwave therapy (LESWT) has been shown to improve erectile function in patients suffering from diabetes mellitus (DM)-associated erectile dysfunction (ED). However, the underlying mechanism remains unknown. Aim. The aim of this study is to investigate whether LESWT can ameliorate DM-associated ED in a rat model and examine the associated changes in the erectile tissues. Methods. Newborn male rats were intraperitoneally injected with 5-ethynyl-2-deoxyuridine (EdU; 50 mg/kg) for the purpose of tracking endogenous mesenchymal stem cells (MSCs). Eight weeks later, eight of these rats were randomly chosen to serve as normal control (N group). The remaining rats were injected intraperitoneally with 60 mg/kg of streptozotocin (STZ) to induce DM. Eight of these rats were randomly chosen to serve as DM control (DM group), whereas another eight rats were subject to shockwave (SW) treatment (DM+SW group). Each rat in the DM+SW group received 300 shocks at energy level of 0.1 mJ/mm(2) and frequency of 120/minute. This procedure was repeated three times a week for 2 weeks. Another 2 weeks later, all 24 rats were evaluated for erectile function by intracavernous pressure (ICP) measurement. Afterward, their penile tissues were examined by histology. Main Outcome Measures. Erectile function was measured by ICP. Neuronal nitric oxide synthase (nNOS)-positive nerves and the endothelium were examined by immunofluorescence staining. Smooth muscle and MSCs were examined by phalloidin and EdU staining, respectively. Results. STZ treatment caused a significant decrease in erectile function and in the number of nNOS-positive nerves and in endothelial and smooth muscle contents. These DM-associated deficits were all partially but significantly reversed by LESWT. MSCs (EdU-positive cells) were significantly more numerous in DM+SW than in DM rats. Conclusion. LESWT can partially ameliorate DM-associated ED by promoting regeneration of nNOS-positive nerves, endothelium, and smooth muscle in the penis. These beneficial effects appear to be mediated by recruitment of endogenous MSCs. Qiu X, Lin G, Xin Z, Ferretti L, Zhang H, Lue TF, and Lin C-S. Effects of low-energy shockwave therapy on the erectile function and tissue of a diabetic rat model. J Sex Med 2013;10:738-746.

Efficacy of BloodSTOP iX, surgicel, and gelfoam in rat models of active bleeding from partial nephrectomy and aortic needle injury.

OBJECTIVE: To compare the bleeding time using 3 different hemostatic agents in a rat model of partial nephrectomy and aortic needle injury. METHODS: Bilateral partial nephrectomy was performed in 20 rats with a total bleeding surface of 1.5 cm(2) without vascular clamping. Surgicel (n = 10) or BloodSTOP iX (n = 10) matrix was applied on each kidney cut surface. Finger pressure was applied to the parenchyma with transparent plastic bubble wrap to allow for visualization of the site and monitor the bleeding time. Pressure was applied until the bleeding stopped and then released to assess the presence of active bleeding for 5 minutes. An additional 24 rats underwent aortic trauma with a 25-gauge needle puncture, and the efficacy of the topical hemostatic agents were compared among Gelfoam (n = 8), Surgicel (n = 8), and BloodSTOP iX (n = 8). RESULTS: After partial nephrectomy, the mean bleeding time with BloodSTOP iX and Surgicel treatment was 83.70 ± 13.73 seconds and 168.8 ± 19.41 seconds, respectively, a statistically significant difference (P = .002). After aortic injury, the mean bleeding time was 157.5 ± 31.44 seconds, 187.5 ± 23.20 seconds, and 66.00 ± 13.74 seconds in the Gelfoam, Surgicel, and BloodSTOP groups, respectively, which was statistically significant (P = .004). CONCLUSION: The BloodSTOP iX hemostatic surgical matrix was more effective in reducing the bleeding time than Surgicel in a rat model of partial nephrectomy. Similarly, in an aortic needle injury model, BloodSTOP iX achieved hemostasis faster than Gelfoam or Surgicel.

Effects of intravenous injection of adipose-derived stem cells in a rat model of radiation therapy-induced erectile dysfunction.

INTRODUCTION: Radiation therapy (RT) for prostate cancer is frequently associated with posttreatment erectile dysfunction (ED). AIM: To investigate whether injection of adipose-derived stem cells (ADSCs) can ameliorate RT-associated ED. METHODS: Thirty male rats were divided into three groups. The control + phosphate-buffered saline (PBS) group received tail-vein injection of PBS. The radiation + PBS group received radiation over the prostate and tail-vein injection of PBS. The radiation + ADSC group received radiation over the prostate and tail-vein injection of ADSCs, which were labeled with 5-ethynyl-2-deoxyuridine (EdU). Seventeen weeks later, erectile function was evaluated by intracavernous pressure (ICP) in response to electrostimulation of cavernous nerves (CNs). Penile tissue and major pelvic ganglia (MPG) were examined by immunofluorescence (IF) and EdU staining. MAIN OUTCOME MEASURES: Erectile function was measured by ICP. Protein expression was examined by IF, followed by image analysis and quantification. RESULTS: Radiation over the prostate caused a significant decrease in erectile function and in the expression of neuronal nitric oxide synthase (nNOS) in penis and MPG. Cavernous smooth muscle (CSM) but not endothelial content was also reduced. Injection of ADSCs significantly restored erectile function, nNOS expression, and CSM content in the irradiated rats. EdU-positive cells were visible in MPG. CONCLUSIONS: Radiation appears to cause ED via CN injury. ADSC injection can restore erectile function via CN regeneration.

Scaffoldless tissue engineering of stem cell derived cavernous tissue for treatment of erectile function.

INTRODUCTION: As one-third of erectile dysfunction (ED) patients do not respond to phosphodiesterase-5 inhibitors, there is great demand for new therapeutic options. Adipose tissue-derived stem cells (ADSCs) represent an ideal source for new ED treatment. AIM: To test if ADSCs can be differentiated into smooth muscle cells (SMCs) and endothelial cells (ECs), if these differentiated cells can be used to engineer cavernous tissue, and if this engineered tissue will remain for long time after implantation and integrate into corporal tissue. METHOD: Rat ADSCs were isolated and differentiated into SMC and ECs. The differentiated cells were labeled with 5-ethynyl-2-deoxyuridine (EdU) and used to construct cavernous tissue. This engineered tissue was implanted in penises of normal rats. The rats were sacrificed after 1 and 2 months; penis and bone marrow were collected to assess cell survival and inclusion in the penile tissues. MAIN OUTCOME MEASURES: The phenotype conversion was checked using morphology, immunocytochemistry (immunohistochemistry [IHC]), and Western blot for SMC and EC markers. The cavernous tissue formation was assessed using rat EC antibody (RECA), calponin, and collagen. The implanted cell survival and incorporation into penis were evaluated with hematoxylin and eosin, Masson's trichrome, and IHC (RECA, calponin, and EdU). RESULTS: The phenotype conversion was confirmed with positive staining for SMC and EC markers and Western blot. The formed tissue exhibited architecture comparable to penile cavernous tissue with SMC and ECs and extracellular matrix formation. The implanted cells survived in significant numbers in the penis after 1 and 2 months. They showed proof of SMC and EC differentiation and incorporation into penile tissue. CONCLUSIONS: The results showed the ability of ADSCs to differentiate into SMC and ECs and form cavernous tissue. The implanted tissue can survive and integrate into the penile tissues. The cavernous tissue made of ADSCs forms new technology for improvement of in vivo stem cell survival and ED treatment.

Both immediate and delayed intracavernous injection of autologous adipose-derived stromal vascular fraction enhances recovery of erectile function in a rat model of cavernous nerve injury.

BACKGROUND: Intracavernous injection of cultured adipose-derived stem cells (ADSCs) effectively restores erectile function in cavernous nerve (CN)-injured rats when administered at the time of injury. However, culturing exposes ADSCs to the risk of contamination and dedifferentiation. OBJECTIVE: Explore the effect of uncultured autologous adipose-derived stromal vascular fraction (SVF) on improving erectile function in a rat model of CN injury when administered at the time of injury or 4 wk after injury. DESIGN, SETTING, AND PARTICIPANTS: Eighty-nine male Sprague Dawley rats were randomly divided into four groups. CN injury or sham surgery was performed at the start of the study, and rats were treated with either SVF or vehicle. Functional testing and histologic analysis were performed 12 wk after CN crush or sham surgery. INTERVENTION: We used intracavernous injection of saline immediately after CN crush (n=23), intracavernous injection of SVF immediately after CN crush (n=17), intracavernous injection of SVF 4 wk after CN crush (n=23), or sham surgery (n=26). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We studied intracavernous pressure (ICP) response to CN electrostimulation and performed histologic examination of midpenile cross-sections. Data were analyzed using one-way analysis of variance followed by the Tukey-Kramer test. RESULTS AND LIMITATIONS: Both immediate and delayed treatment with SVF resulted in a significantly increased ICP-to-mean arterial pressure ratio compared with the vehicle-treated group. Both immediate and delayed treatment with SVF significantly increased expression of neuronal nitric oxide synthase and neurofilament in dorsal penile nerves compared to the vehicle group. Furthermore, the smooth muscle-to-collagen ratio within the corpus cavernosum was significantly improved in both of the SVF groups compared to vehicle-treated rats. The main limitation of the study is the lack of determination of the SVF components. CONCLUSIONS: Uncultured autologous SVF injected immediately or 4 wk after CN crush improved erectile function, promoted nerve regeneration, and prevented fibrosis of the corpus cavernosum following CN injury.

Adipose tissue-derived stem cells ameliorate diabetic bladder dysfunction in a type II diabetic rat model.

Diabetes mellitus is associated with a broad constellation of voiding complaints that are often multifactorial and resistant to currently available therapies. The leading causes of diabetic bladder dysfunction (DBD) include alterations in the bladder smooth muscle, neuronal degeneration, and urothelial dysfunction. Adipose tissue-derived stem cells (ADSCs), a type of mesenchymal stromal cells, have shown promise as a novel tissue regenerative technique that may have utility in DBD. The aim of this study is to determine the efficacy and mechanism by which ADSCs may ameliorate DBD in rats fed a high-fat diet and treated with low-dose streptozotocin to induce type II diabetes. Improved voiding function was noted in ADSCs-treated rats as compared with phosphate-buffered saline-treated rats. Though some ADSCs differentiated into smooth muscle cells, paracrine pathway seems to play a main role in this process, thus resulting in reduction of apoptosis and preservation of "suburothelial capillaries network."

Tissue engineering for penile surgery: comparative study of noncellular and cell-seeded synthetic grafts for tunica albuginea replacement.

INTRODUCTION: Surgical treatment outcomes in Peyronie's disease remain controversial because of high rates of recurrence. AIM: The aim of this study was to engineer in vitro a new type of tunica albuginea (TA) autologous graft obtained by culture of autologous fibroblast on a polyglycolic acid (PGA) scaffold. This engineering graft was compared with PGA with morphological and functional outcomes for TA replacement, 4 months after graft upon corpus cavernosum in a rat model. METHODS: Thirty-nine Sprague Dawley adult male rats were divided into four groups: (i) control group (C) with resection and resuture of a 5 mm long and 2 mm large piece of original TA; (ii) PGA scaffold group (P) with the same resection of TA and suture of PGA scaffold; (iii) autologous fibroblast-seeded on PGA scaffold graft after resection of the same piece of TA (F + P); and (iv) sham group for functional and histological comparison. MAIN OUTCOME MEASURE: The main outcome measure was assessment of graft size variation at 4 months and comparison between the three test groups. The secondary objective is assessment of erectile function by measuring erectile response to cavernous nerve electrical stimulation in each group. RESULTS: At 4 months, there was a significant difference in graft area retraction between the groups (P = 0.0081) with higher retraction in P group vs. in C or F + P groups. Erectile response to cavernous nerve stimulation significantly differed between the groups and was sham equivalent to C equivalent to F + P superior to P group. CONCLUSIONS: This study provides experimental evidence for the feasibility and the functionality of fibroblast-seeded scaffold compared with acellular graft for TA replacement.

Effect of a local delivery of triiodothyronine (T3) within neuroregenerative guide on recovery of erectile function in a rat-model of cavernous nerve injury.

INTRODUCTION: A promoting effect of thyroid hormones has been established on the maturation of central and peripheral nervous systems. However, effects on autonomic nerves have never been experimentally investigated. AIM: To assess the effect of a local treatment combining silicone guides and local administration of Triiodothyronine (T3) on the erectile function and the histological neuroregeneration of crushed cavernous nerves (CNs) in rats. METHODS: Forty-five rats were divided into five equal groups: SHAM surgery, guide without crush, crush, crush + guide, crush + guide + T3. All surgical procedures were bilateral. CNs were crushed with microvascular bulldog clamp of 100 g/cm(2). A silicone guide was placed around the nerves. The guides were filled with T3 neuroregenerative solution. MAIN OUTCOME MEASURES: Erectile function was assessed 10 weeks post-operatively. Intra-cavernous pressure (ICP) and mean arterial pressure (MAP) were monitored during electrical stimulation of CNs at various frequencies. The main outcome was hardness of erection defined as DeltaICP/MAP. Fluorescent immunohistochemical analysis of CNs was performed to assess regeneration of nerves morphologically. RESULTS: Electrophysiological data showed increased recovery of erectile function in the group with guide + T3 neuroregenerative solution compared with the empty guide. Immunohistochemical analysis of cavernous nerves demonstrated in morphology that regenerated axons were straighter in nerves with guide and more regular if guides had been filled with T3. CONCLUSION: The use of guides prevented axonal sprouting, facilitated functional neuroregeneration and enabled a local delivery of thyroid hormones. Triiodothyronine improved neuroregeneration and recovery of erectile function after a nerve-sparing-like injury in a rat model.

[Traumatic complete isthmic rupture of horseshoe kidney]. / Rupture isthmique complete post-traumatique d'un rein en fer a cheval.

The authors report the case of a 14-year-old boy with complete isthmic rupture of a horseshoe kidney after a bicycle accident. The imaging diagnosis was difficult because of the presence of a massive retroperitoneal haematoma. However, sonography and CT should be sufficient to detect associated signs, such as malrotation of the renal hila and low-lying kidneys. Laparotomy was indicated because of the unstable haemodynamic state, allowing haemostasis and suture of the two isthmic sections.