Primary mucinous adenocarcinoma of the urethra: A contemporary clinicopathologic analysis of 17 patients.

Mucinous adenocarcinoma of the urethra is rare. Here we performed a contemporary clinicopathologic analysis of this entity in both male and female patients. All cases with secondary tumors involving the urethra were excluded. Clinicopathologic parameters and follow up was obtained. Seventeen patients were included in the study, 9/17 (53 %) male and 8/17 (47 %) female. The mean patient age was 68 years (range: 53-88 years). The majority (11/17, 65 %) of patients were African American, with an even greater incidence (7/8, 87 %) in female patients. In male patients, prostatic urethra was the most common part of the urethra (6/9, 67 %) where the tumor arose from. Immunohistochemical stains were performed in 11/17 (65 %) tumors and were positive for CK20 (11/11, 100 %), CDX2 (11/12, 92 %), CK7 (8/9, 88 %), GATA3 (3/8, 37 %) and negative for NKX3.1, PSA, p63, PAX8, and Beta-Catenin. In resection specimens, tumors were categorized as pT2 (3/11, 27 %), pT3 (1/11, 9 %), and pT4 (7/11, 64 %). Lymph node status was categorized as pN0 (6/9, 67 %), pN1 (1/9, 11 %), and pN2 (2/9, 22 %). Available follow up data showed 7/13 (54 %) patients developed recurrence after surgical resection and chemotherapy, of which 3/7 (43 %) died of widespread metastatic disease. It is critical for pathologists and urologic oncologists to be aware of this entity in both male and female patients in view of potential diagnostic pitfalls, prognosis, and therapeutic implications.

Primary mucinous adenocarcinoma of the urethra: A clinicopathological analysis of 35 cases.

AIM: Primary mucinous adenocarcinoma of the urethra represents an extremely rare entity. We sought to characterise further these tumours' clinicopathological, immunohistochemical and molecular features. METHODS AND RESULTS: Thirty-five cases were identified, occurring in 18 males and 17 females. The mean age at diagnosis was 65 years (28-89 years). The main presentation symptoms were haematuria and urinary outlet obstruction. Microscopic analysis revealed that all 35 tumours have stromal dissection by mucin. Ten tumours showed villoglandular dysplasia, nine showed mucinous metaplasia, two showed adenocarcinoma in situ and four showed signet ring cell features. All tumours were immunopositive for CEA, while immunonegative for nuclear ß-catenin; 19 of 23 (83%) expressed high molecular weight cytokeratin; 19 of 33 (58%) CK7; 28 of 34 (82%) CK20; 32 of 35 (91%) CDX2; 22 of 27 (81%) cadherin-17 (CDH-17); 26 of 29 (90%) SATB2; and one of 31 (3%) GATA3. Mismatch repair gene products, including MLH1, PMS2, MSH2 and MSH6, were immunopositive, suggesting the MSI-low genotype of mucinous adenocarcinoma of the urethra. BRAF V600E and ALK rearrangements were not detected. During the mean follow-up of 20 months, nine patients either developed distant metastasis or succumbed to the illness. CONCLUSION: Our study, encompassing the most extensive series of 35 cases of primary mucinous adenocarcinoma of the urethra, provides crucial insights into its precise diagnosis, management and potential targeted treatments. We found a greater CDX2, SATB2 and CDH17 sensitivity in these urethral tumours for the first time, to our knowledge. We identified characteristics such as an MSI-low profile, non-V600E BRAF mutations and an absence of ALK rearrangements.

Urethral Tissue Reconstruction Using the Acellular Dermal Matrix Patch Modified with Collagen-Binding VEGF in Beagle Urethral Injury Models.

OBJECTIVES: Urethral tissue reconstruction for hypospadias is challenging for urologists. In this study, bovine acellular dermal matrix (ADM) patch loading with collagen-binding vascular endothelial growth factor (CBD-VEGF) was used to repair the urethral injury in beagles. METHODS: The safety and effectiveness of the scaffold implantation were carefully evaluated by comparing among the urethral injury control group, ADM implantation group, and ADM modified with CBD-VEGF implantation group during 6 months. Urodynamic examination, urethral angiography, and pathological examination were performed to evaluate the recovery of urethral tissue. RESULTS: Stricture, urethral diverticulum, and increased urethral closure pressure were observed in the control group. Fistula was observed in one animal in the ADM group. By contrast, no related complications or other adverse situations were observed in animals treated with ADM patch modified with CBD-VEGF. The average urethra diameter was significantly smaller in the control animals than in scaffold implantation groups. Pathological examination revealed more distribution of proliferative blood vessels in the animals treated with ADM modified with CBD-VEGF. CONCLUSIONS: Overall, ADM patches modified with CBD-VEGF demonstrated an optimized tissue repair performance in a way to increase tissue angiogenesis and maintain urethral function without inducing severe inflammation and scar formation.

Urethra-inspired biomimetic scaffold: A therapeutic strategy to promote angiogenesis for urethral regeneration in a rabbit model.

Limited angiogenesis and epithelialization make urethral regeneration using conventional tissue-engineered grafts a great challenge. Consequently, inspired from the native urethra, bacterial cellulose (BC) and bladder acellular matrix (BAM) were combined to design a three dimensional (3D) biomimetic scaffold. The developed BC/BAM scaffold was engineered for accelerating urethral regeneration by enhancing angiogenesis and epithelialization. The BC/BAM scaffold reveals the closest mimic of native urethra in terms of the 3D porous nanofibrous structure and component including collagen, glycosaminoglycans, and intrinsic vascular endothelial growth factor (VEGF). In vitro studies showed that the bioinspired BC/BAM scaffold promoted in vitro angiogenesis by facilitating human umbilical vein endothelial cells (HUVECs) growth, expression of endothelial function related proteins and capillary-like tube formation. Effect of the BC/BAM scaffold on angiogenesis and epithelialization was studied by its implantation in a rabbit urethral defect model for 1 and 3 months. Results demonstrated that the improved blood vessels formation in the urethra-inspired BC/BAM scaffold significantly promoted epithelialization and accelerated urethral regeneration. The urethra-inspired BC/BAM scaffold provides us a new design approach to construct grafts for urethral regeneration. STATEMENT OF SIGNIFICANCE: Findings in urethral regeneration demonstrate that an ideal tissue-engineered urethra should have adequate angiogenesis to support epithelialization for urethral regeneration in vivo. In this study, inspired from the native urethra, a bioinspired bacterial cellulose/bladder acellular matrix (BC/BAM) scaffold was developed to promote angiogenesis and epithelialization. The designed scaffold showed the closest physical structure and component to natural urethra, which is beneficial to angiogenesis and regeneration of urethral epithelium. This is the first time to utilize BC and dissolved BAM to develop biomimetic scaffold in urethral tissue engineering. Our biomimetic strategy on urethra graft design provided enhanced angiogenesis and epithelialization to achieve an accelerated and successful rabbit urethral repair. We believe that our urethra-inspired biomimetic scaffold would provide new insights into the design of urethral tissue engineering grafts.

Clarification of the Innervation of the Bladder, External Urethral Sphincter and Clitoris: A Neuronal Tracing Study in Female Mongrel Hound Dogs.

Many studies examining the innervation of genitourinary structures focus on either afferent or efferent inputs, or on only one structure of the system. We aimed to clarify innervation of the bladder, external urethral sphincter (EUS) and clitoris. Retrograde dyes were injected into each end organ in female dogs. Spinal cord, mid-bladder, and spinal, caudal mesenteric, sympathetic trunk and pelvic plexus ganglia were examined for retrograde dye-labeled neurons. Neurons retrogradely labeled from the bladder were found primarily in L7-S2 spinal ganglia, spinal cord lateral zona intermedia at S1-S3 levels, caudal mesenteric ganglia, T11-L2 and L6-S2 sympathetic trunk ganglia, and pelvic plexus ganglia. The mid-bladder wall contained many intramural ganglia neurons labeled anterogradely from the pelvic nerve, and intramural ganglia retrogradely labeled from dye labeling sites surrounding ureteral orifices. Neurons retrogradely labeled from the clitoris were found only in L7 and S1 spinal ganglia, L7-S3 spinal cord lateral zona intermedia, and S1 sympathetic trunk ganglia, and caudal mesenteric ganglia. Neurons retrogradely labeled from the EUS were found in primarily at S1 and S2 spinal ganglia, spinal cord lamina IX at S1-S3, caudal mesenteric ganglia, and S1-S2 sympathetic trunk ganglia. Thus, direct inputs from the spinal cord to each end organ were identified, as well as multisynaptic circuits involving several ganglia, including intramural ganglia in the bladder wall. Knowledge of this complex circuitry of afferent and efferent inputs to genitourinary structures is necessary to understand and treat genitourinary dysfunction. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc.

Rat animal model for preclinical testing of microparticle urethral bulking agents.

OBJECTIVES: To develop an economic, practical and readily available animal model for preclinical testing of urethral bulking therapies, as well as to establish feasible experimental methods that allow for complete analysis of hard microparticle bulking agents. METHODS: Alumina ceramic beads suspended in hyaluronic acid were injected into the proximal urethra of 15 female rats under an operating microscope. We assessed overall lower urinary tract function, bulking material intraurethral integrity and local host tissue response over time. Microphotographs were taken during injection and again 6 months postoperatively, before urethral harvest. Urinary flow rate and voiding frequency were assessed before and after injection. At 6 months, the urethra was removed and embedded in resin. Hard tissue sections were cut using a sawing microtome, and processed for histological analysis using scanning electron microscopy, light microscopy and immunohistochemistry. RESULTS: Microphotographs of the urethra showed complete volume retention of the bulking agent at 6 months. There was no significant difference between average urinary frequency and mean urinary flow rate at 1 and 3 months postinjection as compared with baseline. Scanning electron microscopy proved suitable for evaluation of microparticle size and integrity, as well as local tissue remodeling. Light microscopy and immunohistochemistry allowed for evaluation of an inflammatory host tissue reaction to the bulking agent. CONCLUSIONS: The microsurgical injection technique, in vivo physiology and novel hard tissue processing for histology, described in the present study, will allow for future comprehensive preclinical testing of urethral bulking therapy agents containing microparticles made of a hard material.

Development of the human male urethra: a histochemical study on human embryos.

PURPOSE: Controversy persists regarding the formation of human penile urethra. The classic fusion theory for the development of the spongy urethra and ectodermal ingrowth or endodermal transformation theories for the development of the glanular urethra do not explain the wide spectrum of anomalies seen in patients with hypospadias. This histological study was made to clarify the mechanism of urethral development. MATERIALS & METHODS: 15 human male embryos ranging from 6 to 14 weeks were studied. The phalluses were examined microscopically and photographed. Tissues were prepared as serial histological sections and stained with haematoxylin and eosin and with special immuno-histochemical stains. RESULTS: 1) The penile urethra: At 6 weeks of gestation, the urethral plate which is solid distally and partially grooved proximally becomes grooved distally and has fused proximally by 8 weeks. At 14 weeks of gestation; the urethral opening migrates only to the middle of the shaft. 2) The glanular urethra: At the 6th week of gestation, a solid epithelial plate reached the tip of the genital tubercle, and a glans cannot be identified. At the 7th week, a central vacuolation appears and the penile urethral groove does not reach the tip of the phallus. At the 8th week; coronal sulcus starts to appear, and a well defined blind central canal was evident in the 13th week. During the 14th week, the floor of the glanular canal degenerated to form a glanular groove. CONCLUSIONS: Our observations suggest that the spongy urethra passes through 3 stages of development: a solid epithelial plate, deep urethral groove, and fused urethra. The glanular urethra passes through 4 developmental stages: a solid epithelial plate, a blind central canal, a deep glanular groove, and the floor from the preputial lamella. There was no evidence of ectodermal ingrowth. These observations raise serious questions to the current theories for human urethra development. Further studies on fresh human embryos are needed.

Altered neuronal and endothelial nitric oxide synthase expression in the bladder and urethra of cyclophosphamide-treated rats.

Increased nitric oxide (NO) production seems to play a key role in cyclophosphamide (CYP)-induced cystitis, although the underlying mechanisms and the relative involvement of the different NO synthase (NOS) isoforms remain to be elucidated. Moreover, the role of the urethra in this process is also unclear. In this study, we have analyzed the changes in the expression and distribution of the inducible (iNOS), endothelial (eNOS) and neuronal (nNOS) isoforms of NOS, and the alterations in nerve-mediated contractility in the bladder and urethra of CYP-treated rats. Accordingly, Wistar rats were treated with 150 mg kg(-1) CYP for 4 (acute treatment) or 48 h (intermediate treatment), or with 70 mg kg(-1) CYP every 3 days for 10 days (chronic treatment), and the changes in protein expression were assessed by immunohistofluorescence and in Western blots, while mRNA expression was assessed by conventional and quantitative PCR. Similarly, nerve-mediated contractility was analyzed in vitro. Unexpectedly, no iNOS expression was detected in CYP-treated animals, while a transient downregulation of nNOS expression and a progressive upregulation of eNOS was observed, although the eNOS accumulated was not in the active phosphorylated form. Qualitative changes in mRNA expression were also observed in the bladder and urethra, although contractility only diminished in the bladder and this change was not dependent on NOS activity. These findings suggest that spatiotemporal alterations in NO production by constitutive NOS may be involved in the pathogenicity of CYP. Further studies will be necessary to understand the contribution of eNOS to the increases in NO associated with bladder inflammation, or that of free radicals.

The application of tissue-engineered preputial matrix and fibrin sealant for urethral reconstruction in rabbit model.

BACKGROUND: To introduce the role of fibrin sealant and preputial acellular matrix (PAM) as a new source of inert collagen matrix for urethral reconstruction. METHODS: A ventral urethral segmental defect was created in 24 male rabbits divided into four groups. In group 1 (G1), urethrotomy was closed in layers. In group 2 (G2), closure was followed by applying fibrin sealant. In groups 3 (G3) and 4 (G4), urethroplasty was performed with a patch graft of PAM, and in G4, fibrin sealant was also applied. Serial urethrography was performed before and after the operation. Then, the animals were euthanized, and their urethra was excised 1, 3, and 9 months postoperatively for further electron microscopic examination, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) technique, and immunohistochemical (IHC) staining with CD34, CD31, desmin, SMA, and α-actin. RESULTS: In G1 and G2, the fistula repair failed in all the time points. In G3 and G4, serial urethrography confirmed the maintenance of a wide urethral caliber without signs of strictures or extravasations. Satisfactory vascularity was observed in G3 and G4 during the whole study, which was more significant in G4 after 9 months of follow-up. The presence of a complete transitional cell layer was confirmed over the graft in G3 and G4 in all time points. IHC staining confirmed the effectiveness of fistula repair in G3 and G4, 3 months postoperatively. CONCLUSION: This rabbit model showed that PAM combined with fibrin sealant may herald a reliable option for repairing segmental urethral defects.

Differential expression of microRNAs in periurethral vaginal wall tissues of postmenopausal women with and without stress urinary incontinence.

OBJECTIVE: The aims of this study were to investigate microRNA (miRNA) expression profiles in the periurethral vaginal wall tissues of postmenopausal women with and without stress urinary incontinence (SUI) and to explore the putative target genes associated with SUI via miRNA-messenger RNA (mRNA) pair prediction. METHODS: Periurethral vaginal wall tissues of postmenopausal women with SUI (n = 13) and matched continent postmenopausal women (n = 13) were collected during transvaginal surgical operation. Total RNAs were extracted and miRNAs were profiled by TaqMan Array Human MicroRNA assays in three case-control pairs. TargetScanS, PicTar, and miRanda were used to obtain the putative miRNA-mRNA pairs based on sequence data, and three pairs were predicated. The relative expression levels of miRNAs in predicated miRNA-mRNA pairs were quantified in 10 other case-control pairs by real-time polymerase chain reaction. The expression levels of mRNAs and corresponding proteins were estimated via real-time polymerase chain reaction and Western blot analysis. RESULTS: Twelve miRNAs were identified to be differentially expressed between two groups: the significantly up-regulated let-7a, miR-101#, miR-125b-2#, miR-190b, and miR-892b, and the down-regulated miR-124, miR-330-3p, miR-485-3p, miR-517b, miR-523, miR-589, and miR-93#. Moreover, three miRNA-mRNA pairs of interest were established via computational algorithms: miR-124 and growth factor receptor-bound protein 2; miR-330-3p and bicaudal D homolog 2; and miR-93# and signal transducer and activator of transcription 3. The expression levels of the three miRNAs were quantified, and a reduction in SUI was revealed. On the other hand, increased expression levels of predicated mRNAs and their protein products were detected. CONCLUSIONS: This study reports the differential expression of 12 miRNAs in SUI and predicates three miRNA-mRNA pairs. Interestingly, all three predicated target genes are associated with neurodegenerative conditions, indicating the potential significance of neurodegenerative mechanisms in the etiology of SUI.

Immunohistochemical analysis of estrogen receptors in the urethra of sexually intact, ovariectomized, and estrogen-substituted ovariectomized sheep.

INTRODUCTION AND HYPOTHESIS: Urinary incontinence is prevalent in postmenopausal women and spayed dogs and is associated with decreased estrogen plasma concentrations. The objective of the study was to investigate the expression of estrogen receptors (ER) in the urethra of sexually intact, ovariectomized, and estrogen-substituted ovariectomized ewes. METHODS: Paraffin cross-sections from each urethral quarter were immunohistochemically analyzed. The reactivity of ER was semiquantitatively assessed employing an immunoreactive score (IRS). RESULTS: In contrast to ERß, ERα was identified in all urethral compartments; the highest IRS was detected in the epithelium of the distal urethra. The immunoreactivity and distribution of ERα did not differ among groups. Highly significant differences in ERα concentrations were observed between consecutive urethral quarters in each group. CONCLUSIONS: Neither ovariectomy nor ovariectomy and estrogen substitution seem to have a significant effect on overall urethral ERα concentration. The results demonstrate that the precise location of the investigated urethral part is crucial to the reliable evaluation or possible comparison of ERα concentrations.

Coexistence of elastic fibers with hyaluronic acid in the human urethral sphincter complex: a histological study.

PURPOSE: To promote the prevention and treatment of urethral sphincteric dysfunction, we examined the distribution of elastic fibers around the urethral sphincter complex and the histological localization of hyaluronic acid in relation to elastic fiber architecture. MATERIALS AND METHODS: Using elastica-Masson staining as well as biotinated hyaluronic acid binding protein, we examined specimens of the urethral sphincter complex obtained from 14 elderly Japanese cadavers, including 10 men and 4 women. As a control, we also observed other striated muscles in male cadavers. RESULTS: Elastic fibers were densely distributed throughout the submucosal and smooth muscle layers along the entire length of the male urethra, including the prostatic urethra. The levator ani fascia and rhabdosphincter also contained abundant elastic fibers. An intramuscular elastic net was seen in the rhabdosphincter but not in other striated muscles. Strong staining for hyaluronic acid was evident in the submucosa and smooth muscle sphincter of the urethra but not in the levator ani fascia or rhabdosphincter, suggesting that elastic fibers and hyaluronic acid might interact at the former sites. Gender related differences in the distribution of elastic fibers and hyaluronic acid were noted with a much lower density of elastic fibers and hyaluronic acid staining in women than in men. CONCLUSIONS: Urethral sites where elastic fibers and hyaluronic acid coexist could be targeted for the prevention and treatment of urethral sphincteric insufficiency. These findings should improve our understanding of the human urethral sphincter complex.

Stereological and biochemical analysis of the urethral edges in patients submitted to end-to-end anastomosis for bulbar urethral stricture.

PURPOSE: To study the morphologic alterations in the proximal and distal urethral edges from patients submitted to end-to-end bulbar urethroplasty. MATERIALS AND METHODS: We analyzed 12 patients submitted to anastomotic urethroplasty to treat bulbar strictures less than 2.0 cm in length. After excision of the fibrotic segment to a 28Fr urethral caliber, we obtained biopsies from the spongious tissue of the free edges (proximal: PROX and distal: DIST). Controls included normal bulbar urethras obtained from autopsies of 10 age matched individuals. The samples were histologically processed for smooth muscle cells (SMC), elastic system fibers and collagen. Stereological analysis was performed to determine the volumetric density (Vv) of each element. Also, a biochemical analysis was performed to quantify the total collagen content. RESULTS: Vv of SMC was reduced in PROX (31.48 ± 7.01 p < 0.05) and similar in DIST when compared to controls (55.65 ± 9.60%) with no statistical difference. Elastic fibers were increased in PROX (25.70 ± 3.21%; p < 0.05) and were similar to controls in DIST (15.87 ± 4.26%). Total collagen concentration in PROX (46.39 ± 8.20 µg/mg), and DIST (47.96 ± 9.42 µg/mg) did not differ from controls (48.85 ± 6.91 µg/mg). Type III collagen was similarly present in all samples. CONCLUSIONS: After excision of the stenotic segment to a caliber of 28Fr, the exposed and macroscopically normal urethral edges may present altered amounts of elastic fibers and SMC, but are free from fibrotic tissue. When excising the peri-stenotic tissue, the surgeon should be more careful in the proximal end, which is the most altered.

Stereological and biochemical analysis of the urethral edges in patients submitted to end-to-end anastomosis for bulbar urethral stricture

PURPOSE: To study the morphologic alterations in the proximal and distal urethral edges from patients submitted to end-to-end bulbar urethroplasty. MATERIALS AND METHODS: We analyzed 12 patients submitted to anastomotic urethroplasty to treat bulbar strictures less than 2.0 cm in length. After excision of the fibrotic segment to a 28Fr urethral caliber, we obtained biopsies from the spongious tissue of the free edges (proximal: PROX and distal: DIST). Controls included normal bulbar urethras obtained from autopsies of 10 age matched individuals. The samples were histologically processed for smooth muscle cells (SMC), elastic system fibers and collagen. Stereological analysis was performed to determine the volumetric density (Vv) of each element. Also, a biochemical analysis was performed to quantify the total collagen content. RESULTS: Vv of SMC was reduced in PROX (31.48 ± 7.01 p < 0.05) and similar in DIST when compared to controls (55.65 ± 9.60%) with no statistical difference. Elastic fibers were increased in PROX (25.70 ± 3.21%; p < 0.05) and were similar to controls in DIST (15.87 ± 4.26%). Total collagen concentration in PROX (46.39 ± 8.20 μg/mg), and DIST (47.96 ± 9.42 μg/mg) did not differ from controls (48.85 ± 6.91 μg/mg). Type III collagen was similarly present in all samples. CONCLUSIONS: After excision of the stenotic segment to a caliber of 28Fr, the exposed and macroscopically normal urethral edges may present altered amounts of elastic fibers and SMC, but are free from fibrotic tissue. When excising the peri-stenotic tissue, the surgeon should be more careful in the proximal end, which is the most altered.

Expression and localization of translationally controlled tumor protein in rat urinary organs.

This study describes the very first assessment of the expression and localization of translationally controlled tumor protein (TCTP) in adult rat urinary organs. TCTP expression levels in kidneys, urinary bladder, and urethra were evaluated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting, and its cellular localization was examined immunohistochemically in paraffin sections of various urinary organs. TCTP was found in all urinary organs. Its expression was high in the urethra and low in the bladder. TCTP was localized in glomerular podocytes, epithelium of proximal and distal renal tubules, in the loop of Henle, and in the transitional epithelium of the bladder and urethra, mostly in basal cell layers). The subcellular localization of TCTP in these urinary organs was cytoplasmic. These findings suggest that TCTP may be involved in urine formation and excretion.

Unusual findings on cystoscopy in a patient with detrusor overactivity.

BACKGROUND: Chronic lithium ingestion has been shown to cause polyuria and polydipsia in 20% to 40% of patients, secondary to diabetes insipidus. However, it has not been reported to cause lithium deposition in the bladder. CASE: A 77-year-old woman presented to our clinic with complaints of urinary incontinence, urinary urgency, and nocturnal enuresis for the past 3 to 4 years. She denied polydipsia. Her medical history was significant for bipolar disorder for which she had been on lithium therapy for more than 10 years. Metallic deposition was noted in the suburothelium of a urethral biopsy by gross inspection. CONCLUSION: Suburothelial deposition of metal may act as a bladder irritant and account for this patient's overactive bladder symptoms.

[Effects of delivery and oophorectomy on urethral collagen: an experimental study]. / Efectos del parto y ooforectomía sobre el colágeno uretral: estudio experimental.

OBJECTIVE: Stereological evaluation of the concentration of type I and III collagen fibers in the urethral tissue of rats subjected to simulated labor and oophorectomy. To compare the concentrations of collagen between oophorectomized and non-oophorectomized rats. MATERIAL AND METHOD: Sixty adult Wistar rats were divided into six groups. A group made up of virgin rats was used as control group and another group was made up of oophorectomized rats. Two groups underwent vaginal distention for 30 and 120 minutes, respectively. The two other groups were subjected to the same distension periods, followed by oophorectomy. Sixty days later, euthanasia and removal of urethral tissue was carried out for stereological analysis of type I and III collagen after staining with hematoxylin and eosin and picrosirius red. RESULTS: A decrease in estrogen levels was observed in the oophorectomized rats. There was a reduction of type III collagen in the oophorectomized control group compared to the control group when analyzed independently. No significant differences were observed among the other groups. Type I collagen decreased in all groups compared to the control group. However, in the prolonged vaginal distension and oophorectomy group, these fibers increased. CONCLUSION: In normal rats, simulation of labor does not alter the collagen III levels. In hypoestrogenic rats, the concentration of collagen type I and III decreased, except in those undergoing prolonged labor simulation in which collagen I increased.

Small cell carcinoma arising from the bulbar urethra: a case report and literature review.

Primary neuroendocrine carcinomas of the genitourinary tract are rare and aggressive tumors carrying a bad prognosis. With squamous cell and transitional cell carcinoma being the most commonly reported urethral malignancies, primary small cell carcinoma (SCC) of the urethra is extremely rare. To date, only 5 cases have been reported in the literature. We present the first case of primary SCC occurring in the bulbar urethra in an 89-year-old male. We discuss the clinical, histological and immunohistochemical features of SCC of the urethra. Furthermore, we summarize the available literature and discuss the possible treatment options for this rare yet aggressive neoplasm.

Absolute measurement of androgen receptor mRNA in peripheral blood mononuclear, preputial skin and urethral mucosa cells of control individuals with phimosis using qRT-PCR / Valor absoluto do mRNA do receptor androgênico em células mononucleares do sangue periférico e células da pele do prepúcio e mucosa uretral em indivíduos controle com fimose, determinado por meio de qRT-PCR

INTRODUCTION: Androgen actions are exerted upon the androgen receptor (AR), and complete genital virilization of normal 46,XY individuals depends on adequate function and expression of the AR gene in a tissue-specific manner. OBJECTIVE: Standardization of normal ARmRNA in androgen-sensitive tissues. MATERIALS AND METHODS: In this study, we determined the quantitative amounts of ARmRNA in peripheral blood mononuclear, urethral mucosa and preputial skin cells of control subjects with phimosis by using RT-PCR. RESULTS: The mean (SD) values of AR expression in blood, urethra and prepuce were: 0.01 (0.01); 0.43 (0.32); 0.31 (0.36), respectively. CONCLUSION: The AR expression is low in blood and equivalent in urethral mucosa and preputial skin, which may be useful in the diagnosis of individuals with abnormal external genitalia.

INTRODUÇÃO: As ações androgênicas são exercidas por meio do receptor androgênico (AR), e a completa virilização genital de indivíduos 46,XY normais depende de adequada expressão do gene AR de forma tecido específica. OBJETIVO: Padronizar valores normais de ARmRNA em tecidos sensíveis aos andrógenos. MATERIAIS E MÉTODOS: Neste estudo, determinamos as quantidades de ARmRNA em células mononucleares do sangue periférico e em células da mucosa uretral e pele do prepúcio de indivíduos controles com fimose, utilizando RT-PCR. RESULTADOS: A média (dp) dos valores de expressão do AR em sangue, uretra e prepúcio foram: 0,01 (0,01); 0,43 (0,32); 0,31 (0,36), respectivamente. CONCLUSÃO: A expressão do AR é baixa em sangue periférico e equivalente em mucosa uretral e pele prepucial, sendo sua quantificação útil no diagnóstico de indivíduos com alterações da genitália externa.

Expression of pleiotrophin in the prostate is androgen regulated and it functions as an autocrine regulator of mesenchyme and cancer associated fibroblasts and as a paracrine regulator of epithelia.

BACKGROUND: Androgens and paracrine signaling from mesenchyme/stroma regulate development and disease of the prostate, and gene profiling studies of inductive prostate mesenchyme have identified candidate molecules such as pleiotrophin (Ptn). METHODS: Ptn transcripts and protein were localized by in situ and immunohistochemistry and Ptn mRNA was quantitated by Northern blot and qRT-PCR. Ptn function was examined by addition of hPTN protein to rat ventral prostate organ cultures, primary human fetal prostate fibroblasts, prostate cancer associated fibroblasts, and BPH1 epithelia. RESULTS: During development, Ptn transcripts and protein were expressed in ventral mesenchymal pad (VMP) and prostatic mesenchyme. Ptn was localized to mesenchyme surrounding ductal epithelial tips undergoing branching morphogenesis, and was located on the surface of epithelia. hPTN protein stimulated branching morphogenesis and stromal and epithelial proliferation, when added to rat VP cultures, and also stimulated growth of fetal human prostate fibroblasts, prostate cancer associated fibroblasts, and BPH1 epithelia. PTN mRNA was enriched in patient-matched normal prostate fibroblasts versus prostate cancer associated fibroblasts. PTN also showed male enriched expression in fetal human male urethra versus female, and between wt male and ARKO male mice. Transcripts for PTN were upregulated by testosterone in fetal human prostate fibroblasts and organ cultures of female rat VMP. Ptn protein was increased by testosterone in organ cultures of female rat VMP and in rat male urethra compared to female. CONCLUSIONS: Our data suggest that in the prostate Ptn functions as a regulator of both mesenchymal and epithelial proliferation, and that androgens regulate Ptn levels.