Urethral stricture, a fibrotic condition causing lumen narrowing, lacks effective pharmacological treatments, with autologous grafts facing donor-site limitations. Tissue engineering strategies, particularly anisotropic hydrogels, offer promising alternatives but remain unexplored in urethral repair. Here, we developed a multifunctional anisotropic polyvinyl alcohol/tannic acid (APVA/TA) hydrogel via mechanical training and hydrogen-bond crosslinking for urethral reconstruction. The APVA/TA hydrogel exhibited enhanced crystallinity, mechanical strength, and anti-swelling properties, with TA conferring potent antioxidant and broad-spectrum antibacterial activity. In vitro, TA suppressed LPS-induced inflammatory responses, while the anisotropic structure synergistically promoted endothelial cell migration and angiogenesis. In a rabbit urethral stricture model, the APVA/TA2.5 hydrogel significantly reduced stricture recurrence (12.6% obstruction rate) and facilitated improved repair through enhanced epithelial regeneration (pan-CK), vascularization (CD31), and smooth muscle regeneration (α-SMA). This study demonstrates the dual role of anisotropic structure and TA in enabling functional urethral reconstruction, providing a novel tissue-engineered solution for stricture management.

Detrusor underactivity (DU) is a prevalent bladder dysfunction for which effective treatment is lacking. A series of studies have shown that the 5-HT2A receptor is involved in the regulation of micturition, but its role in DU remains unknown. Besides, transient receptor potential vanilloid 4 (TRPV4) agonist has been demonstrated to improve bladder function in BPNI rats by increasing afferent signals and the 5-HT/5-HT2A receptor are functionally associated with TRPV4 in several pathophysiological processes. In the current study, we established a bilateral pelvic nerve injury (BPNI) model. Tissue staining and cystometry were performed and the results showed that the BPNI model exhibited DU in both histological and urodynamic manifestations. Intrathecal injection of the 5-HT2A receptor agonist TCB2 could facilitate the micturition reflex in BPNI rats, reducing intercontraction interval (ICI), residual volume (RV), and bladder capacity (BC), which could be reversed by the TRPV4 antagonist HC-067047. Western blot and immunofluorescence analyses revealed there was no significant difference in the expression of the 5-HT2A receptor in the L6-S1 dorsal root ganglia (DRG) and spinal dorsal horn between sham-operated and BPNI rats, whereas the expression of TRPV4 was significantly decreased in BPNI rats. Calcium imaging of DRG neurons showed an increased calcium influx induced by TCB2, which was blocked by HC-067047. These findings suggest that the 5-HT2A receptor agonist can improve bladder dysfunction in BPNI rats by regulating the micturition reflex via TRPV4. The 5-HT2A receptor may be a potential therapeutic target for the treatment of DU.

Background Penoscrotal Paget's disease (PPD) is a rare malignant skin tumor, and consensus on reconstruction, treatment strategies, and prognosis remains elusive. We aimed to elucidate the clinical features, surgical outcomes, and prognosis, proposing a tailored Perineal Reconstruction (PR) strategy. Methods We conducted a retrospective cohort study using pathologically confirmed 233 PPD cases from a large tertiary hospital pathology registry between May 2004 and February 2021. Clinical features, surgical treatment patterns, sexual function, and prognosis were analyzed. Kaplan-Meier analysis, univariate and multivariate Cox regression were performed to identify prognostic factors. Results PR strategy-based reconstruction was applied on all postsurgical defects. Kaplan-Meier analysis indicated worse disease free-survival (DFS) in the high-PR score (≥4) group compared to the low-PR score (≤3) group. Age, tumor thickness, and lymph node invasion emerged as independent predictors of overall survival (OS). Conclusions Early evaluation and intervention are crucial to prevent vertical and lymph node invasion. Wide local excision provides low recurrence, high overall survival rates, and acceptable sexual function. The PR strategy serves as a promising approach to assess lesions, guide reconstruction, and predict prognosis, potentially improving treatment and management of this rare malignancy.

The nasty urine microenvironment (UME) impedes neourethral regeneration by inhibiting angiogenesis and inducing an excessive inflammatory response. Cellular adaptation to hypoxia improves regeneration in numerous tissues. In this study, heterogeneous porous hypoxia-mimicking scaffolds were fabricated for urethral reconstruction via promoting angiogenesis and modulating the inflammatory response based on sustained release of dimethyloxalylglycine (DMOG) to promote HIF-1α stabilization. Such scaffolds exhibit a two-layered structure: a dense layer composed of electrospun poly (l-lactic acid) (PLLA) nanofibrous mats and a loose layer composed of a porous gelatin matrix incorporated with DMOG-loaded mesoporous silica nanoparticles (DMSNs) and coated with poly(glycerol sebacate) (PGS). The modification of PGS could significantly increase rupture elongation, making the composite scaffolds more suitable for urethral tissue regeneration. Additionally, sustained release of DMOG from the scaffold facilitates proliferation, migration, tube formation, and angiogenetic gene expression in human umbilical vein endothelial cells (HUVECs), as well as stimulates M2 macrophage polarization and its regulation of HUVECs migration and smooth muscle cell (SMCs) contractile phenotype. These effects were downstream of the stabilization of HIF-1α in HUVECs and macrophages under hypoxia-mimicking conditions. Furthermore, the scaffold achieved better urethral reconstruction in a rabbit urethral stricture model, including an unobstructed urethra with a larger urethral diameter, increased regeneration of urothelial cells, SMCs, and neovascularization. Our results indicate that heterogeneous porous hypoxia-mimicking scaffolds could promote urethral reconstruction via facilitating angiogenesis and modulating inflammatory response.

OBJECTIVE:To investigate the clinical effect of pulsed thulium laser (PTL) combined with triamcinolone acetonide injection in the treatment of failed posterior urethral anastomosis (FPUA). METHODS:This retrospective study included 35 male patients treated in Gongli Hospital for failed posterior urethral anastomosis from January 2018 to December 2023. All the patients underwent direct-vision internal urethrotomy (DVIU) with transurethral PTL (the PTL group, n = 15) or transurethral plasma (the TUP group, n = 20), and all received intralesional injection of triamcinolone acetonide. We followed up the patients for a median of 21 months, recorded the age, length of urethral stricture, operation time, pre- and post-operative maximum urinary flow rate (Qmax), postoperative complications and recurrence of urethral stricture, and compared the data obtained between the two groups. RESULTS:All the patients smoothly completed the treatment procedures. No statistically significant differences were observed in the age, length of urethral stricture, operation time and postoperative complications between the two groups (P > 0.05). The median follow-up time for the thulium laser group and plasma group was 21.0 months (IQR 16.0－24.0) and 21.0 months (IQR 17.0－25.0), respectively, with a statistically significant difference observed in the maximum urine flow rate before and after surgery at the 12-month mark (P < 0.01). No significant disparity was found in terms of relapse-free survival between the two groups (P = 0.398) Conclusion: Pulsed thulium laser combined with triamcinolone acetonide injection can effectively maintain a short-term cicatricial stability of the urethral stricture and satisfactory urethral patency, obviously superior to plasmotomy as a remedial treatment of urethral stricture after failed posterior urethral anastomosis.

The precise determination of surgical margins is essential for the management of multifocal cutaneous cancers, including extramammary Paget’s disease. This study introduces a novel strategy for precise margin identification in such tumors, employing multichannel autofluorescence lifetime decay (MALD), fluorescence lifetime imaging microscopy (FLIM), and machine learning, including confidence learning algorithms. Using FLIM, 51 unstained frozen sections were analyzed, of which 13 (25%) sections, containing 5003 FLIM patches, were used for training the residual network model (ResNet–FLIM). The remaining 38 (75%) sections, including 16 918 patches, were retained for external validation. Application of confidence learning with deep learning reduced the reliance on extensive pathologist annotation. Refined labels obtained by ResNet–FLIM were then incorporated into a support vector machine (SVM) model, which utilized fiber-optic-based MALD data. Both models exhibited substantial agreement with the pathological assessments. Of the 35 MALD-measured tissue segments, six (17%) segments were selected as the training dataset, including 900 decay profiles. The remaining 29 segments (83%), including 2406 decay profiles, were reserved for external validation. The ResNet–FLIM model achieved 100% sensitivity and specificity. The SVM–MALD model demonstrated 94% sensitivity and 83% specificity. Notably, fiber-optic-MALD allows assessing 12 sites per patient and delivering predictions within 10 min. Variations in the necessary safe margin length were observed among patients, highlighting the necessity for patient-specific approaches to determine surgical margins. This innovative approach holds potential for wide clinical application, providing a rapid and accurate margin evaluation method that significantly reduces a pathologist’s workload and improves patient outcomes through personalized medicine.

Long-segment lichen sclerosus (LS) urethral stricture is a challenge for urologists. Limited data are available for surgeons to make a surgical decision between Kulkarni and Asopa urethroplasty. In this retrospective study, we investigated the outcomes of these two procedures in patients with LS urethral stricture. Between January 2015 and December 2020, 77 patients with LS urethral stricture underwent Kulkarni and Asopa procedures for urethroplasty in the Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine (Shanghai, China). Of the 77 patients, 42 (54.5%) underwent the Asopa procedure and 35 (45.5%) underwent the Kulkarni procedure. The overall complication rate was 34.2% in the Kulkarni group and 19.0% in the Asopa group, and no difference was observed ( P = 0.105). Among the complications, no statistical difference was observed in the incidence of urethral stricture recurrence ( P = 0.724) or glans dehiscence ( P = 0.246) except for postoperative meatus stenosis ( P = 0.020). However, the recurrence-free survival rate between the two procedures was significantly different ( P = 0.016). Cox survival analysis showed that antiplatelet/anticoagulant therapy use ( P = 0.020), diabetes ( P = 0.003), current/former smoking ( P = 0.019), coronary heart disease ( P < 0.001), and stricture length ( P = 0.028) may lead to a higher hazard ratio of complications. Even so, these two techniques can still provide acceptable results with their own advantages in the surgical treatment of LS urethral strictures. The surgical alternative should be considered comprehensively according to the patient characteristics and surgeon preferences. Moreover, our results showed that antiplatelet/anticoagulant therapy use, diabetes, coronary heart disease, current/former smoking, and stricture length may be contributing factors of complications. Therefore, patients with LS are advised to undergo early interventions for better therapeutic effects.

You have accessJournal of UrologyCME1 Apr 2023MP33-09 GLANSECTOMY AND NEOGLANS RECONSTRUCTION USING SPLIT-THICKNESS SKIN GRAFT / ACELLULAR DERMAL MATRIX FOR PENILE CANCER Haijun Yao, Dachao Zheng, Jianshu Ni, Xiang Wan, and Zhong Wang Haijun YaoHaijun Yao More articles by this author , Dachao ZhengDachao Zheng More articles by this author , Jianshu NiJianshu Ni More articles by this author , Xiang WanXiang Wan More articles by this author , and Zhong WangZhong Wang More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003266.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Penectomy as the traditional surgical treatment of penile cancer has substantial adverse functional and psychological impact. Organ-sparing surgery is recommended in selected penile cancer patients.Glansectomy and Neoglans reconstruction aims to provide curative resection while maximizing functional outcomes and minimizing psychological harm.To show the efficacy and safety of glansectomy and neoglans reconstruction using split-thickness skin graft (STSG) and Acellular Dermal Matrix (ADM). METHODS: Using our prospectively derived database, we identified 25 patients with penile squamous-cell carcinoma involving the glans, who were treated using glansectomy and neoglans reconstruction between March 2015 and December 2021. All the patients underwent total glansectomy and reconstruction of a new glans, of whom 18 (82%) with STSG and 7 with ADM. Deep spongiosal biopsies are taken to exclude invasion as a standard practice. The glans is excised and a neoglans is created using STSG/ADM. These 25 patients represent the subject of our study (mean age 57 years, range 45 to 71 years). RESULTS: 92% of patients (23/25) reported to be fully satisfied with the postoperative aesthetic appearance. The apex of corpora cavernosa was transected in 5 cases due to local invasion. Positive surgical margins were no detected in all the cases. 2 patients (8%) experienced local recurrence during the follow-up period. 4 patients had early partial loss of the graft (STSG 2 vs ADM 2). Two late complications occurred with urethral meatus stricture. CONCLUSIONS: Glansectomy and Neoglans reconstruction using STSG/ADM comprise a safe procedure in terms of oncologic control and complications for patients with penile cancer confined to the glans. Further studies are required to assess functional and sexual outcomes in these patients.The overall satisfaction rate and recovery of the sexual function are acceptable, and it can be considered an ideal procedure to treat superficial penile cancer. Source of Funding: The Project of Biobank (No. YBKB202119) from Shanghai 9th People's Hospital,Shanghai Jiao Tong University,School of Medicine © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e453 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Haijun Yao More articles by this author Dachao Zheng More articles by this author Jianshu Ni More articles by this author Xiang Wan More articles by this author Zhong Wang More articles by this author Expand All Advertisement PDF downloadLoading ...

Given that there is lack of effective therapies for castration-resistant prostate cancer (CRPC), the combination of photothermal (PTT), photodynamic (PDT), and chemical therapy (CT) has emerged as a prominent strategy. Tumor-targeted delivery and controlled release of antitumor drug are key-elements of any combined therapy. Considering these important elements, we designed and constructed tumor microenvironment (TME)-activated nanoprobes (PGP/CaCO3@IR820/DTX-HA). The CaCO3 shell could efficiently entrap the photosensitizer IR820 and the chemotherapeutic docetaxel (DTX) on the surface of pentagonal gold prisms (PGPs) to prevent elimination from the circulation, and it could act as a TME-trigger to achieve TME-responsive drug release. After modification with hyaluronic acid, PGP/CaCO3@IR820/DTX-HA was capable of synergistic TME-triggered PTT/PDT/CT and tumor-targeted delivery. Our in vitro and in vivo studies demonstrate that PGP/CaCO3@IR820/DTX-HA could achieve synergistic antitumor effects following near-infrared (NIR)-light irradiation. In addition, using the NIR fluorescence signal from IR820 and the photoacoustic (PA) signal from PGPs, i.e., through multimodal fluorescence/photoacoustic imaging, we could monitor the in vivo distribution and excretion of PGP/CaCO3@IR820/DTX-HA. Therefore, it can be concluded that PGP/CaCO3@IR820/DTX-HA shows promising clinical translational potential as a treatment for CRPC. STATEMENT OF SIGNIFICANCE: Utilizing pentagonal gold prisms (PGPs), we constructed a multifunctional nanoplatform (PGP/CaCO3@IR820/DTX-HA) for effectively delivering agents into the tumor microenvironment (TME) for the diagnosis and therapy of castration-resistant prostate cancer (CRPC). The synthetic nanoplatform can satisfy TME-activated synergistic photothermal therapy (PTT)/photodynamic therapy (PDT)/chemical therapy (CT) and NIR fluorescence imaging/photoacoustic (PA) imaging. Hyaluronic acid (HA) on the surface of nanoplatform allowed the specific tumor-targeting capacity and biocompatibility. In conclusion, PGP/CaCO3@IR820/DTX-HA could be a promising integrated nanoplatform for CRPC diagnosis and treatment.

Skin shortages and scar contractures are common complications following penile trauma and tumor surgery, resulting in significant pain and erectile dysfunction. Currently, skin grafts and scrotal flaps are widely used to reconstruct skin shortages. However, various limitations still exist; for instance, the skin graft may cause severe scarring in patients, and the traditional scrotal flap usually requires a two-stage procedure due to the large skin defect. To treat the shortage of foreskin, a modified bilateral scrotal pedicled flap is used. In this procedure, flaps located on each side of the midline of the scrotum, which was pedicled from the anterior scrotal artery, are harvested. Subsequently, these bilateral scrotal flaps, like a butterfly, can successfully cover the foreskin defect. In this study, seven patients underwent this procedure, and satisfactory outcomes were obtained. Only two patients developed necrosis in some small areas of the flaps, which were recovered after wound care. Postoperative penile length significantly increased compared to the preoperative status in both flaccid and erectile states. We believe that modified bilateral scrotal flaps are a simple and effective solution to penile skin shortages and scar contractures.

Skin shortages and scar contractures are common complications following penile trauma and tumor surgery, resulting in significant pain and erectile dysfunction. Currently, skin grafts and scrotal flaps are widely used to reconstruct skin shortages. However, various limitations still exist; for instance, the skin graft may cause severe scarring in patients, and the traditional scrotal flap usually requires a two-stage procedure due to the large skin defect. To treat the shortage of foreskin, a modified bilateral scrotal pedicled flap is used. In this procedure, flaps located on each side of the midline of the scrotum, which was pedicled from the anterior scrotal artery, are harvested. Subsequently, these bilateral scrotal flaps, like a butterfly, can successfully cover the foreskin defect. In this study, seven patients underwent this procedure, and satisfactory outcomes were obtained. Only two patients developed necrosis in some small areas of the flaps, which were recovered after wound care. Postoperative penile length significantly increased compared to the preoperative status in both flaccid and erectile states. We believe that modified bilateral scrotal flaps are a simple and effective solution to penile skin shortages and scar contractures.

General recommendations regarding surgical techniques are not always appropriate for all Peyronie's disease (PD) patients. Therefore, the purpose of this study was to investigate the effects of plication procedures in PD patients with severe penile curvature and the effects of early surgical correction in patients who no longer have progressive deformities. The clinical data from 72 patients who underwent plication procedures were analyzed in this study. Patients were divided into Groups A and B according to the curvature severity (≤60° or >60°) and Groups 1 and 2 according to the duration of disease stabilization (≥3 months or <3 months). At the 1-year follow-up, 90.0% (36/40) and 90.6% (29/32) patients reported complete penile straightening, and 60.0% (24/40) and 100.0% (32/32) patients reported penile shortening in Groups A and B, respectively. No curvature recurrence occurred in any patient, and no significant differences were observed in postoperative International Index of Erectile Function–Erectile Function domain (IIEF-EF), erectile pain, sensitivity, or suture knots on the penis whether such outcomes were grouped according to the curvature severity or the duration of stabilization. However, the duration from symptom onset to surgical management in Group 1 was significantly longer than that in Group 2 (mean ± standard deviation [s.d.]: 20.9 ± 2.0 months and 14.3 ± 1.2 months, respectively, P < 0.001). The present study showed that the plication procedures seemed to be an effective choice for the surgical treatment of PD patients with severe penile curvature. In addition, the early surgical treatment seemed to benefit those patients who already had no erectile pain and no longer exhibited progressive deformity.

BACKGROUNDOral medication therapies are more conventional than other non-surgical therapies in the acute phase of Peyronie's disease (PD). Although the commonly used oral drugs for PD have shown poor or indeterminate outcomes, most patients prefer oral medications. The aim of this study was to evaluate the efficacy and safety of Scutellaria baicalensis extract for treating acute-phase PD patients and examine the practicality of treatment strategies for PD according to the disease course.METHODSThis retrospective study was performed at our institution from 2005 to 2015 and analyzed the data of 261 patients with PD. The acute-phase PD patients received Scutellaria baicalensis extract for 6 months. After oral treatment, the patients with persistent curvature underwent surgical correction during the stable phase.RESULTSDuring this study period, 183 patients received oral treatment with Scutellaria baicalensis, and 78 patients did not. Compared to the untreated patients, treatment with Scutellaria baicalensis had a significant effect in improving the symptoms of acute-phase PD. The mean time required for stabilization also showed a significant statistical difference. Treatment with Scutellaria baicalensis was safe and well-tolerated. After the disease stabilized, 70 and 31 patients with significant penile curvature underwent surgical correction by 16- dot plication and great saphenous vein grafting procedures, respectively. At the one-year follow-up, complete penile straightening and penile length shortening were observed in 92.86% and 41.43% of the patients after 16-dot plication and in 87.10% and 25.81% of the patients after grafting procedures, respectively. The postoperative Erectile Function domain of the International Index of Erectile Function scales were maintained in all patients after the 16-dot plication procedure and decreased in 54.84% of the patients after the grafting procedure. Overall, 92.86% and 83.87% of the patients who received 16-dot plication and grafting procedures, respectively, were satisfied with the final surgical results.CONCLUSIONSTreatment with extract of Scutellaria baicalensis seems to be beneficial for improvements in symptoms of acute phase PD and acceleration of the disease stabilization. The 16-dot plication and great saphenous vein grafting procedure seem effective options in the surgical management of the stable phase after Scutellaria baicalensis administration in the acute phase of PD.

BACKGROUND:Erectile dysfunction (ED) has often been observed in patients with obstructive sleep apnea (OSA). Research on adipose-derived mesenchymal stem cell (ADSC)-derived exosomes has shown that they have significant therapeutic effects in many diseases including ED.METHODS:In this study, ED was induced in Sprague Dawley (SD) rats using chronic intermittent hypoxia (CIH) exposure. CIH-mediated influences were then measured in the corpus cavernous smooth muscle cells (CCSMCs).RESULTS:Our data showed that miR-301a-3p-enriched exosome treatment significantly recovered erectile function in rats and CCSMCs by promoting autophagy and inhibiting apoptosis. The treatment also significantly recovered the level of alpha smooth muscle actin (α-SMA) in rats and CCSMCs. Bioinformatics predicted that phosphatase and tensin homolog (PTEN) and Toll-like receptor 4 (TLR4) might be targets of miR-301a-3p.CONCLUSIONS:Our results indicate that PTEN-overexpression vectors or TLR4-overexpression vectors reverse the therapeutic effects achieved by miR-301a-3p in CCSMCs indicating that PTEN/hypoxia-inducible factor-1 alpha (HIF-1α) and TLR4 signaling pathways play key roles in the progression of ED. The findings in this study suggest that miR-301a-3p should be considered a new therapeutic target for treating ED associated with OSA.

Background: This study describes and compares three surgical procedures for the construction of urethral stricture (US) models in rabbits. Methods: Forty adult male rabbits were allocated to four groups: 36 rabbits were randomly assigned to three experimental groups, while the remaining 4 were assigned to a sham group. The penis was separated from the rectum. Then along the ventral midline, a longitudinal penile skin incision was made while ensuring that the urethral mucosa was intact and the muscular layer was not completely incised. In group 1 (n=12), ventral semi-circumferential mucosa electrocoagulation of a 1-cm length of the anterior urethra was performed until ulceration occurred. In group 2 (n=12), the ventral urethral mucosa was incised, and electrocoagulation of the dorsal semi-circumferential mucosa was performed. In group 3 (n=12), whole circumferential mucosa electrocoagulation was performed. In group 4 (n=4), no special treatment was performed. Four weeks later, urethrography, urethroscopy, and histological evaluation were carried out. Results: The weights of the rabbits in the four groups were comparable. There was no significant difference between groups 2 and 3 with regard to operative time, but the operative time in these groups was significantly longer than that in group 1 (group 2 vs. group 1: P<0.05, group 3 vs. group 1: P<0.001). After the surgery, urinary fistula with infection occurred in one rabbit in group 1, and one rabbit died due to urethral atresia in group 3. According to the urethrography and urethroscopy findings, 9 out of 12 rabbits in group 1, 5 out of 12 rabbits in group 2, and 11 out of 11 rabbits in group 3 developed US, while no rabbits in the sham group developed US. Histopathological examination revealed injury to the urothelium, inflammatory infiltration, a decrease in the amount of blood vessels and smooth muscle fibers, and a decrease in the amount of collagen fibers. Conclusions: Compared with the semi-circumferential procedures, the whole-circumferential procedure had a higher success rate. Therefore, this procedure seems to have potential for the construction of long segment rabbit US models.

Background Extramammary Paget's disease (EMPD) is a rare malignant intraepidermal adenocarcinoma that is poorly understood. Regulatory long noncoding RNAs (lncRNAs) are characterized in many species and shown to be involved in processes such as development and pathologies, revealing a new layer of regulation in different diseases, especially in cancer studies. In the present study, we used high-throughput sequencing to reveal the lncRNA-mRNA interaction network in extramammary Paget's disease. Methods High-throughput sequencing was used to identify differentially expressed lncRNA and mRNA profiles between EMPD patients and healthy controls. Then, a series of bioinformatics analyses were conducted to construct the lncRNA-mRNA interaction network, which was finally confirmed in vitro. Results Six pairs of EMPD tumor and normal skin samples were collected and sequenced to identify the differentially expressed lncRNA and mRNA profiles between EMPD and healthy controls. A total of 997 differentially expressed mRNAs and 785 differentially expressed lncRNAs were identified. The GO and KEGG analyses show that epidermal development and cell adhesion play important roles in EMPD. The results of the lncRNA-mRNA interaction network analysis suggested that NEAT1, PGAP1, FKBP5 and CDON were the pivotal nodes of the network and that lncRNA NEAT1 might regulate mRNA PGAP1, FKBP5 and CDON. The results of the quantitative real-time RT-PCR performed in ten other patients for NEAT1, PGAP1, FKBP5 and CDON were consistent with those of the sequencing analysis. Moreover, an in vitro experiment confirmed the interactions between NEAT1 and PGAP1, FKBP5 and CDON in human immortalized keratinocytes. Conclusion These findings suggest that the lncRNA-mRNA interaction network based on four pivotal nodes, NEAT1, PGAP1 FKBP5 and CDON, may play an important role in EMPD, which will contribute to a deeper understanding of the pathogenesis of EMPD.

Subject: Collagen And Calcium Binding EGF Domains 1 (CCBE1) is a coding protein which plays a significant role in extracellular matrix remodeling and migration and is involved in the development of Hennekam syndrome and lymphangiogenesis. Here, we investigate its prognostic value in prostate cancer based on TCGA database and its antioncogenic role in prostate cancer.Methods: Wilcoxon rank sum test, Pearson χ2 test, and logistic regression analysis were utilized to evaluate the correlation between CCBE1 and clinicopathological variables. Kaplan-Meier and Cox regression analysis were used to reveal the relation between CCBE1 and survival rates. The role of CCBE1 in prostate cancer was investigated using CCK-8 assay, EdU assay, and transwell experiments, respectively.Results: Here, we found that CCBE1 expression is down-regulated in prostate cancer tissue dramatically in TCGA database. Furthermore, high CCBE1 expression predicted a good prognosis in patients with prostate cancer. High expression level of CCBE1 in PRAD cohort was prominently correlated with T classification (OR =0.49 for T3&T4 vs T2, P<0.001), Gleason score (OR = 0.42 for8&9&10 vs. 6&7, P<0.001). Kaplan-Meier and Cox regression analysis showed that prostate cancer patients with high CCBE1 expression had a better progression-free interval (hazard ratio [HR]:0.50; 95% confidence interval [CI]: 0.33-0.77; P = 0.002) and overall survival (hazard ratio [HR]:0.38; 95% confidence interval [CI]: 0.15-0.92; P = 0.032). In vitro experiments indicated that overexpressed CCBE1 inhibited prostate cancer cell proliferation, migration, and invasion.Conclusion: CCBE1 plays a pivotal role in the progression of prostate cancer and up-regulated CCBE1 expression inhibits prostate cancer tumorgenicity.

Abstract BackgroundLichen sclerosus (LS) is a chronic, inflammatory disease of unknown cause which occurs in the male genital area and can affect the external genital and the anterior urethra. Nowdays, urethral stricture associated with LS is still a challenge to urologists and different surgical options are employed according to surgeons’ personal preferences. In this study, we report our experience of surgical treatments for genital lichen sclerosus urethral stricture and try to share our surgical algorithm. MethodsBetween March 2013 and March 2018, 55 patients with LS urethral strictures underwent three different surgical techniques including of Kulkarni technique, Bracka technique and perineal urethrostomy (PU). Approaches were chosen according to the evaluation of the degree of spongiofibrosis and patients’ wishes. ResultsThe overall success rate was 74.55%. Kulkarni technique was performed in 37 patients with a success rate of 78.38%. 12 patients who were planned for staged substitution urethroplasty, developed a 50% success rate, including 3 local graft contractures following the first stage, 2 fistulas and 1 dehiscence following the urethroplasty respectively. PU was chosen as the primary treatment in 6 patients and performed as salvage surgery on 4 patients, which resulted a 100% success rate. Comparing to the Kulkarni and Bracka techniques, PU offers the highest degree of success and could be considered as a final salvage for all patients and statistic difference was found between three techniques (P=0.0082). ConclusionThe staged urethroplasty by excising corpus spongiosum consumed more cost of time and money but could not provide similar therapeutic effects as the Kulkarni technique and PU. Therefore, the evaluation of corpus spongiosum is a necessary step in the surgical decision making which can make surgeons avoid unsuitable decisions and improve the success rate.

You have accessJournal of UrologyTrauma/Reconstruction/Diversion: External Genitalia Reconstruction and Urotrauma (including transgender surgery) I (MP29)1 Apr 2020MP29-01 THE CLASSIFICATION AND MANAGEMENT FOR EXTRAMAMMARY PAGET’S DISEASE Hai-jun Yao*, Da-chao Zheng, Min-kai Xie, Yue-qing Jiang, and Zhong Wang Hai-jun Yao*Hai-jun Yao* More articles by this author , Da-chao ZhengDa-chao Zheng More articles by this author , Min-kai XieMin-kai Xie More articles by this author , Yue-qing JiangYue-qing Jiang More articles by this author , and Zhong WangZhong Wang More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000868.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Extramammary Paget’s disease (EMPD) is a rare cancer which involves the skin and apocrine glands. It involves perianal region, scrotum, penis, and axilla. The primary disease originates from intraepidermal cells and secondary originates from underlying neoplasm. Up to now, no clear guidelines have been established for the diagnosis, treatment, and follow-up. Surgical excision is the standard treatment, but results in mutilating procedures in patients with the advanced or recurrent disease. This study aimed to evaluate the classification and choose the treatment strategy of EMPD. METHODS: All 192 cases of EMPD, diagnosed between 2003 and 2017, were selected from Shanghai 9th People's Hospital, Shanghai JiaoTong University, School of Medicine. All cases of biopsy-proven penoscrotalEMPD were included in this retrospective analysis. Factors reported to be associated with survival such as positive surgical margins, local recurrence, distant metastasis, lymph node (LN) metastasis, and primary tumor status were evaluated using the log-rank test. The surgical resection with clear margins is considered to be the standard of care and provides good outcomes. However, if surgery is not feasible other treatment options like imiquimod 5% or 5-Fu topical cream may be offered. RESULTS: We enrolled 192 EMPD patients, of whom 34 had remote metastases (10 had both distant and LN metastasis; 5, distant metastasis only; and 19, LN metastasis only) and the remaining 158 patients had no remote metastasis. Patients who had no remote metastasis and tolerable anesthesia were treated with surgical therapy (Wide local excision). Flaps or Graft were needed if there were massive defect after appropriate wide excision, primarily when the tumor was very extensive. According to the PISA method, we choose the strategy to reconstruct the penile and scrotum with flap or skin graft. Other treatment options like imiquimod 5% or 5-Fu topical cream may be offered. The size of the wound after radical resection is a significant challenge for reconstruction. Distant metastasis (M1), 2 or more LN metastases (N2), tumor thickness of over 4 mm or lymphovascularinvasion showed worse survival (P < 0.01). CONCLUSIONS: Based on TNM classification and stage, the treatment strategy is more conducive to the treatment and prognosis of EMPD, and significantly improves the quality of life. Based on the treatment of advanced disease with visceral adenocarcinoma, topical drug and systemic chemotherapeutic are remedial measures. We propose a TNM staging system for EMPD using simple factors for classification that could provide relevant prognostic information in managing EMPD. Source of Funding: no © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e429-e429 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hai-jun Yao* More articles by this author Da-chao Zheng More articles by this author Min-kai Xie More articles by this author Yue-qing Jiang More articles by this author Zhong Wang More articles by this author Expand All Advertisement PDF downloadLoading ...