Penile keloid formation post-circumcision: A case series and review of literature.

The formation of penile keloid after circumcision is an uncommon complication. Herein, we report two pediatric cases of large circumferential keloids that developed post-circumcision and were successfully treated by surgical excision and intralesional triamcinolone injections. In addition, we provide a comprehensive review of the reported cases of penile keloids that developed after circumcision in the literature to highlight the various presentations, treatment options, and outcomes for this condition.

Critical elements of pediatric testicular germ cell tumors surgery.

Children, adolescents and young adults with testicular germ cell tumors require appropriate surgical care to insure excellent outcomes. This article presents the most critical elements, and their basis in evidence, for surgery in this population. Specifically, the importance of inguinal radical orchiectomy for malignant tumors, partial orchiectomy for prepubertal tumors and normal serum tumor markers, and the appropriate use of post-chemotherapy retroperitoneal lymph node dissection in those with residual retroperitoneal masses.

Posterior urethral valves in patients with trisomy 21: Similar renal outcomes and rates of volitional voiding.

INTRODUCTION: Posterior urethral valves (PUV) occur in patients with Down Syndrome (DS) at a rate of 3-4%; far higher than the general population. Our understanding of the relationship between PUVs and DS is in its infancy, with the majority of the literature consisting of case reports. In this study, we present the largest known series of DS patients with PUVs. AIM: We hypothesized that patients with DS and PUVs would have worse functional bladder outcomes and renal outcomes when compared to PUV patients without DS. STUDY DESIGN: We queried our prospectively managed multi-institutional database of PUV patients from 1990 to 2021. We identified patients with a concomitant diagnosis of DS and PUV. In addition, we performed a systematic review of the literature describing the presentation of children with PUV and DS. Patient demographics, renal outcomes, voiding habits, surgical interventions, and radiologic images were aggregated and analyzed. RESULTS: Out of the 537 patients in our PUV database, we identified 18 patients with a concomitant diagnosis of PUV and DS, as well as 14 patients with a concomitant diagnosis of PUV and DS from the literature. DS and non-DS patients had a similar age at presentation, 31.5 days (2-731) and 17 (4-846), and length of follow up 6.32 years (2-11.2) and 6.98 (1-13). Both groups had similar nadir creatinines DS 0.43 (0.4-0.8), non-DS 0.31 (0.2-0.5) and similar rates of renal failure (DS 11.1% and non-DS 14.5%). With respect to bladder outcomes, a similar percentage of patients were volitionally voiding at last follow up (DS 72.2% and non-DS 72.3%). Our literature review corroborated these findings. CONCLUSIONS: Patients with DS and PUV have similar renal outcomes to other PUV patients in terms of renal function, progression to renal failure, and probability of volitional voiding with continence. Given the increased rate of PUVs in the DS population, physicians should have a high index of suspicion for PUV when patients with DS present with voiding dysfunction.

Automated Society of Fetal Urology (SFU) grading of hydronephrosis on ultrasound imaging using a convolutional neural network.

INTRODUCTION: Grading of hydronephrosis severity on postnatal renal ultrasound guides management decisions in antenatal hydronephrosis (ANH). Multiple systems exist to help standardize hydronephrosis grading, yet poor inter-observer reliability persists. Machine learning methods may provide tools to improve the efficiency and accuracy of hydronephrosis grading. OBJECTIVE: To develop an automated convolutional neural network (CNN) model to classify hydronephrosis on renal ultrasound imaging according to the Society of Fetal Urology (SFU) system as potential clinical adjunct. STUDY DESIGN: A cross-sectional, single-institution cohort of postnatal renal ultrasounds with radiologist SFU grading from pediatric patients with and without hydronephrosis of stable severity was obtained. Imaging labels were used to automatedly select sagittal and transverse grey-scale renal images from all available studies from each patient. A VGG16 pre-trained ImageNet CNN model analyzed these preprocessed images. Three-fold stratified cross-validation was used to build and evaluate the model that was used to classify renal ultrasounds on a per patient basis into five classes based on the SFU system (normal, SFU I, SFU II, SFU III, or SFU IV). These predictions were compared to radiologist grading. Confusion matrices evaluated model performance. Gradient class activation mapping demonstrated imaging features driving model predictions. RESULTS: We identified 710 patients with 4659 postnatal renal ultrasound series. Per radiologist grading, 183 were normal, 157 were SFU I, 132 were SFU II, 100 were SFU III, and 138 were SFU IV. The machine learning model predicted hydronephrosis grade with 82.0% (95% CI: 75-83%) overall accuracy and classified 97.6% (95% CI: 95-98%) of the patients correctly or within one grade of the radiologist grade. The model classified 92.3% (95% CI: 86-95%) normal, 73.2% (95% CI: 69-76%) SFU I, 73.5% (95% CI: 67-75%) SFU II, 79.0% (95% CI: 73-82%) SFU III, and 88.4% (95% CI: 85-92%) SFU IV patients accurately. Gradient class activation mapping demonstrated that the ultrasound appearance of the renal collecting system drove the model's predictions. DISCUSSION: The CNN-based model classified hydronephrosis on renal ultrasounds automatically and accurately based on the expected imaging features in the SFU system. Compared to prior studies, the model functioned more automatically with greater accuracy. Limitations include the retrospective, relatively small cohort, and averaging across multiple imaging studies per patient. CONCLUSIONS: An automated CNN-based system classified hydronephrosis on renal ultrasounds according to the SFU system with promising accuracy based on appropriate imaging features. These findings suggest a possible adjunctive role for machine learning systems in the grading of ANH.

How Female Is the Future of Urology? Projecting Various Trajectories of the United States Urology Workforce.

OBJECTIVE: To project the number and proportion of women in the urology workforce using recent demographic trends and develop an app to explore updated projections using future data. METHODS: Demographic data were obtained from AUA Censuses and ACGME Data Resource Books. The proportion of female graduating urology residents was characterized with a logistic growth model. "Stock and Flow" models were used to project future population numbers and proportions of female practicing urologists, accounting for trainee demographics, retirement trends, and growth in the field. RESULTS: Assuming growth in urology graduate numbers and continued logistic growth in the proportion of women, 10,957 practicing urologists (38%) will be female by 2062. If the rate of women entering urology residency stagnates, 7038 urologists (24%) will be female. If the retirement rates for women in urology change to mirror those of men and the proportion of female residents continues to experience logistic growth, 11,178 urologists (38%) will be female. An interactive app was designed to allow for a range of assumptions and future data: https://stephenrho.shinyapps.io/uro-workforce/. CONCLUSION: Workforce projections should incorporate recent growth in numbers of female residents. If current growth continues, 38% of urologists will be female by 2062. The app allows for exploration of different scenarios and can be updated with new data. The projections demonstrate the need for targeted efforts to recruit women into urology, address disparities within the field, and work toward retaining female urologists. We must continue working toward an equitable future workforce that can address the impending shortage of urologists.

Characterization of Changes in Penile Microbiome Following Pediatric Circumcision.

BACKGROUND: While microbiome and host regulation contribute independently to many disease states, it is unclear how circumcision in pediatric population influences subsequent changes in penile microbiome. OBJECTIVE: Our study aims to analyze jointly paired taxonomic profiles and assess pathways implicated in inflammation, barrier protection, and energy metabolism. DESIGN, SETTING, AND PARTICIPANTS: We analyzed 11 paired samples, periurethral collection, before and after circumcision, to generate microbiome and mycobiome profiling. Sample preparation of 16S ribosomal RNA and internal transcribed spacer sequencing was adapted from the methods developed by the National Institutes of Health Human Microbiome Project. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We obtained the predictive functional attributes of the microbial communities between samples using Silva-Tax4Fun and the Greengenes-Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) approach. The predictive functioning of the microbial communities was determined by linearly combining the normalized taxonomic abundances into the precomputed association matrix of Kyoto Encyclopedia of Genes and Genomes orthology reference profiles. RESULTS AND LIMITATIONS: Several notable microbiome and mycobiome compositional differences were observed between pre- and postcircumcision patients. Pairwise comparisons across taxa revealed a significant decrease (p < 0.05, false discovery rate corrected) of microbiome organisms (Clostridiales, Bacteroidales, and Campylobacterales) and mycobiome (Saccharomycetales and Pleosporales) following circumcision. A total of 14 pathways were found to differ in abundance between the pre- and postcircumcision groups (p < 0.005, false discovery rate <0.1 and linear discriminant analysis score >3; five enriched and nine depleted). The pathways reduced after circumcision were mostly involved with amino acid and glucose metabolism, while pathways prior to circumcision were enriched in genetic information processing and transcription processes. As expected, enrichment in methyl-accepting chemotaxis protein, an integral membrane protein involved in directed motility of microbes to chemical cues and environment, occurred prior to circumcision, while the filamentous hemagglutinin pathway (a strong immunogenic protein) was depleted after circumcision CONCLUSIONS: Our results offer greater insight into the host-microbiota relationship of penile circumcision and may serve to lay the groundwork for future studies focused on drivers of inflammation, infection, and oncogenesis. PATIENT SUMMARY: Our study showed a significant reduction in bacteria and fungi after circumcision, particularly anaerobic bacteria, which are known to be potential inducers of inflammation and cancer. This is the first study of its kind showing the changes in microbiome after circumcision, and some of the changes that occur in healthy infants after circumcision that may explain the differences in cancer and inflammatory disorders in adulthood.

A systematic review of underlying genetic factors associated with ureteropelvic junction obstruction in stenotic human tissue.

OBJECTIVE: Genetic factors are implicated in the development of ureteropelvic junction obstruction (UPJO). The aims of this study were: 1) condense and examine the existing data in studies containing information regarding differential gene expression in tissues from patients with UPJO and 2) investigate associations between genetic markers and their related pathways. MATERIALS AND METHODS: A systematic review of studies published between January 2000 and September 2021 was conducted using the following databases: Ovid/Medline, PubMed, Wiley Cochrane Central Register of Controlled Trials, Web of Science, and Scopus. Of 249 studies, 10 were included in the final analysis. The search was performed using the terms "ureteropelvic junction obstruction", "genetic", "gene", and "gene expression". Literature pertaining to differential gene expression in UPJO patients as compared to healthy controls was identified. Studies containing gene expression and quantification of molecular data carried out directly on stenotic tissue samples were selected for analysis. Gene network connections and functional analyses were then determined using MetaScape software. RESULTS: From the ten studies identified for analysis, fifteen genes were noted as differentially expressed. In UPJO patients, nine genes were upregulated (ET1, ACTA2, MCP-1, TGFB1, NFKB1, IL-6, HIF1A, S100A1, SYP) and six were downregulated (ADM, NOS2, EGF, PDGFRA, UCHL1, NGFR). These genes were principally involved in HIF-1 signaling pathway, blood vessel development, positive regulation of signaling receptor activity, and Ras signaling pathway. CONCLUSIONS: A potential link exists between genes related to hypoxia, excessive fibrous tissue formation, and inflammation in the development of UPJO, and these connections merit more detailed, tissue level investigations in UPJO patients. The outcomes of this systematic review may lay the groundwork for the development of future targeted therapies and novel biomarker detection for treatments, early detection, and possible prediction and prevention of development of UPJO.

Duplex renal collecting system presenting with hydroureteronephrosis following pelvic organ prolapse and sacrocolpopexy in an adult female.

Duplex collecting systems are common congenital abnormalities of the urinary tract but are infrequently reported in adult populations. This abnormality can present with hydroureteronephrosis secondary to urinary tract obstruction or concomitant vesicoureteral reflux (VUR), recurrent urinary tract infections (UTIs), and urinary incontinence. Options for surgical management include common-sheath ureteral reimplantation, uretero-ureterostomy, pyelostomy, and heminephroureterectomy. We report the case of a 39-year-old female with a duplex kidney who presented with severe hydroureteronephrosis following a sacrocolpopexy.

Where to draw the line? Understanding preferences in mucosal collar length after circumcision: A crowdsourced survey from the U.S. general population.

INTRODUCTION: Male circumcision is a polarizing and prevalent procedure. Little understanding exists regarding patient preferences for circumcision appearance. Our objective was to elicit how mucosal collar length may be perceived in terms of overall cosmesis and desirability among adults. METHODS: A questionnaire using REDCap was created and distributed through Amazon Mechanical Turk. Respondents provided demographic information and circumcision status before being challenged with artistic representations of circumcised penises with increasing lengths of mucosal collar. Participants were asked to select the most and least esthetically pleasing image, as well as rate the "importance of appearance" from 0-100. Responses were analyzed with ordinal regression models. RESULTS: Preference for shorter mucosal collars were seen in respondents with a postgraduate education (p=0.013) and no religious affiliation (p=0.034). In contrast, participants reporting a religious affiliation preferred longer mucosal collars (p=0.034). Circumcised males rated appearance as being more important (p=0.001) in contrast to uncircumcised males who did not (p=0.001). Circumcised fathers were more likely to circumcise their sons relative to uncircumcised fathers (p<0.05) and women preferred circumcision (p<0.05). CONCLUSIONS: Our study revealed polarized esthetic preferences in the sample as a whole, with large proportions of respondents selecting the longest or shortest collar length. Preferences regarding mucosal collar length appear to be most influenced by education and religion. Overall, our study did not observe a predominant preference for mucosal collar length following circumcision. Surgeons should engage patients and/or caregivers/parents preoperatively in discussions regarding preferences and desired cosmetic outcomes.

Quadratus Lumborum Block for Upper Tract Urological Surgery in Pediatric Patients / Bloqueo del cuadrado lumbar para cirugía urológica del tracto superior en pacientes pediátricos

Objective Among regional blocks, the quadratus lumborum fascial plane block (QLB) has been well described, but the description of its use and efficacy for pediatric patients undergoing upper abdominal urologic surgery is limited. We present a case series examining the use of the QLB for postoperative pain management in children undergoing upper tract surgery. Methods From August 2019 to August 2020, through a chart review, we identified 5 patients who had undergone a QLB for upper urinary tract surgery via a flank incision. Posterior QLB was performed after induction of general anesthesia. A single injection of 0.5mL/kg of either 0.25% or 0.5% ropivacaine with 1mcg/kg of clonidine was administered. Patients received fentanyl IV (1 mcg/kg), and acetaminophen IV (15mg/kg) as adjuvants during the operation. Postoperative pain was managed with oral acetaminophen and ibuprofen. Results The average postoperative pain score during the entire admission was 1, with the lowest being 0 and highest, 3. No administration of rescue narcotics was required in the postanesthesia care unit or on the floor. The average length of stay ranged from 0 to 1 day. No complications associated with the regional QLB were identified. Conclusions Our series suggests the QLB may be considered as a regional anesthetic option to minimize narcotic requirements for children undergoing upper abdominal urological surgery via flank incision. Additional studies are needed to compare the efficacy of the QLB versus alternate regional anesthetic blocks for upper tract urological surgery via flank incision in children and to determine effective dosing and use of adjuvants

Objetivo Entre los bloqueos regionales, el bloqueo del plano fascial del cuadrado lumbar (BCL) ha sido bien descrito; sin embargo, tiene una descripción limitada de su uso y eficacia en pacientes pediátricos sometidos a cirugía urológica abdominal superior. Presentamos una serie de casos que examinan el uso del BCL en el manejo del dolor posoperatorio en niños sometidos a cirugía urológica del tracto superior. Métodos De agosto de 2019 a agosto de 2020, mediante revisión de historias clínicas, se identificaron 5 pacientes sometidos al BCL para cirugía del tracto urinario superior por incisión en el flanco. El BCL posterior se realizó después de la inducción de la anestesia general. Solo se administró una inyección de 0,5 ml/kg de ropivacaína al 0,25% o al 0,5% con 1 mcg/kg de clonidina. Los pacientes recibieron fentanilo IV (1 mcg/kg) y acetaminofén IV (15 mg/kg) como adyuvantes durante la operación. El dolor posoperatorio se manejó con acetaminofén e ibuprofeno oral. Resultados El puntaje promedio de dolor posoperatorio para todo el ingreso fue de 1, siendo el más bajo 0 y el más alto, 3. No se requirieron administraciones de narcóticos de rescate en la unidad de recuperación posanestésica ni en la planta de hospitalización. La estancia media fue de 0 a 1 día. No se identificaron complicaciones asociadas con el BCL regional. Conclusiones Nuestra revisión sugiere que el BCL puede ser considerado una opción anestésica regional para minimizar los requerimientos de narcóticos en niños sometidos a cirugía urológica abdominal superior por incisión en el flanco. Se necesitan estudios adicionales para comparar la eficacia de BCL en comparación con la de los bloqueos anestésicos regionales alternativos para la cirugía urológica del tracto superior por incisión en el flanco en niños y para determinar la efectividad de la dosificación y del uso de adyuvantes.

Prenatal ultrasound findings of covered bladder exstrophy and persistent cloaca.

Unlike classic exstrophy, covered bladder exstrophy is a rare variant characterized by a cycling bladder and intact abdominal wall. We present a case of covered bladder exstrophy diagnosed prenatally and associated persistent cloaca (PC) noted only after delivery. This case report demonstrates that prenatal diagnosis of covered bladder exstrophy is possible and PC can present without any abdominal cysts, bowel, or renal findings. Covered bladder exstrophy should be considered in the differential of cystic protrusion of the bladder to the abdominal wall.

Fertility potential in adult men treated for uncorrected bilateral cryptorchidism: A systematic literature review and analysis of case reports.

OBJECTIVE: Reports of adult orchidopexy for bilateral undescended testicles (bUDT) are sparse, and fertility outcomes are not well established. Our aim was to determine prognosis for restoration of spermatogenesis among adult men (≥18 years) undergoing orchidopexy for bUDT. METHODS: A systematic literature review, conforming to the PRISMA statement, was conducted using the PubMed/MEDLINE and EMBASE databases through March 2020 using search terms "adult" AND "bilateral orchidopexy" OR "bilateral cryptorchidism." Relevant referenced articles from non-indexed journal were identified by Google Scholar search and additionally included. RESULTS: Fifty-seven publications including adult men with uncorrected bilateral UDTs were identified. Baseline semen analysis was reported in 157 men, all of whom demonstrated azoospermia. Testosterone values were reported in 82 cases and were normal in 89%. Germ cells could not be identified in 72.6% of histologic specimens from 62 testicles. Abdominal testicles more frequently lacked germ cells (90%, p = 0.038) on univariate analysis. Eleven cases identified ejaculated spermatozoa following adult bilateral orchidopexy (8 publications). Sperm extraction (TESE) during orchidopexy or orchiectomy was reported in 13 men without success. Delayed TESE (median 10 months) was performed in 22 persistently azoospermic men with success in 10 (45.5%), none of whom had abdominal testicles prior to orchidopexy. Six men experienced successful paternity via natural conception (3) or assisted reproduction (3). CONCLUSION: Fertility is possible in adult men with inguinal bUDT following orchidopexy. Subsequent sperm retrieval may involve ejaculated specimens or delayed TESE. TESE performed prior to or at time of orchidopexy is unlikely to be of benefit.

Partial orchiectomy vs. radical orchiectomy for pediatric testis tumors.

While radical orchiectomy remains the gold standard for testicular cancer, partial orchiectomy has become a well-accepted organ-sparing approach for benign testicular tumors in pre-pubertal patients. The aims of testicular-sparing surgery include prevention of over-treatment, preservation of future hormonal and reproductive function, and provision of a durable cure. For pre-pubertal patients, who have a high likelihood of benign lesions, partial orchiectomy provides effective treatment, owing to the high reliability of scrotal ultrasound (US) and intraoperative frozen section. In adolescent and young adult patients, who are more likely to harbor malignant pathology, the role of partial orchiectomy is less clear. Testis-sparing surgery is being reported with greater frequency in the adult literature for small testicular masses and for situations in which radical orchiectomy would result in an anorchia. More recently, a testis-sparing approach has also been described for carefully-selected post-pubertal pediatric patients. This review will highlight the role of partial orchiectomy in pediatric patients (<18 years old).

Impact of trauma center designation in pediatric renal trauma: National Trauma Data Bank analysis.

INTRODUCTION: The pediatric kidney is the most common urinary tract organ injured in blunt abdominal trauma. Trauma care in the United States has been established into a hierarchical system verified by the American College of Surgeons (ACS). Literature evaluating management of pediatric renal trauma across trauma tier designations is scarce. OBJECTIVE: To examine the differences in the management and outcomes of renal trauma in the pediatric population based on trauma level designation across the United States. STUDY DESIGN: We performed a review of the ACS - National Trauma Data Bank database. Pediatric patients (age 0-18 years) who were treated for renal injury between years 2011-2016 were identified. Our primary outcome was the difference in any complication rate amongst Level I versus Non-Level I trauma centers. Management strategies were evaluated as secondary outcomes. Propensity score matching (PSM) was utilized to adjust for baseline differences between cohorts. Multivariable regression analysis was performed to determine the independent effects of individual factors on complications, operative intervention, minimally invasive procedure, and blood transfusions. RESULTS: Overall, 12,097 pediatric patients were diagnosed with renal trauma between 2011 and 2016 using target ICD-9 and AAST codes. After PSM, there was a total of 1623 subjects withing each group. No difference was identified between groups for occurrence on any complication [105 (6.5%) vs 114 (7.0%), p = 0.576. There were no differences in the rate of minimally invasive interventions [67 (4.1%) vs 48 (3.0%), p = 0.087], operative intervention [58 (3.6%) vs 68 (4.2%), p = 0.413], or nephrectomy [42 (2.6%) vs 47 (2.9%), p = 0.667] between Level I and Non-Level I trauma designations, respectively. Length of stay was longer in the Level I cohort compared to Non-Level I (days (SD)) [6.9 (8.8) vs 6.2 (7.9), p = 0.024. When specifically looking at risk factors associated with operative intervention, higher renal injury grade and injury severity score were highly correlated, whereas, trauma level designation was not found to be predictive for more aggressive management. DISCUSSION & CONCLUSION: Our results corroborate with previous literature that renal injury grade and injury severity score are strong predictors of morbidity, invasive management, and complications. Pediatric renal trauma was managed similarly across trauma center designations, with the rate of complication and intervention more prevalent in patients with high grade renal injuries and concomitant injuries. Further studies are necessary to identify patients who will benefit most from transfer to a level I center.

Testicular Torsion Postorchiopexy: A Case of Twisted Hammock.

We herein report an unusual case of testicular torsion a decade after orchiopexy. An occurrence of postorchiopexy testicular torsion is an exceedingly rare event, infrequently reported in literature. Previously placed anchoring sutures in the inferior pole resulted in a "hammock" testicular torsion, resulting in twisting of cord with involvement of the sutures themselves.

The Need for Improved Detection of Urinary Tract Infections in Young Children.

BACKGROUND AND OBJECTIVES: An estimated 400,000 urinary tract infections (UTIs) are diagnosed annually in children aged <3 years in the United States; yet >50% of febrile UTIs may be missed in this population. Here, we explored possible barriers to diagnosing febrile UTIs in very young children through social research of community pediatricians. METHODS: Following qualitative interviews, a quantitative survey was developed that included a high-risk case for febrile UTI, presented before prompting for the topic of the survey, to gauge practice of delayed testing. Factors associated with delay were explored using univariate logistic regression. The final survey link was sent to three populations via email, with the largest response from a survey sent to pediatricians in Pennsylvania, which formed the basis of our primary results. RESULTS: Of the 218 evaluable responses, 59.6% of physicians would initially test urine in the high-risk case patient, while 21.6% would choose to continue fever reducer and follow-up in 2 days. In the knowledge-based questions, 67.5, 34.0, and 35.6% of respondents identified the correct prevalences in total population, Caucasian girls, and uncircumcised boys, respectively. Many pediatricians (59.5%) believed that delays in detection are common in clinical practice. Physicians who chose to delay testing were more likely to be female, in practice for <25 years, to underestimate prevalence of febrile UTIs and have greater number of children seen per week (all P ≤ 0.02). CONCLUSION: Our findings support the need for improved communication and education about prevalence in higher risk populations, outcomes associated with delayed diagnosis, and optimal skills for collection of urine in young patients.

The role of testis-sparing surgery in children and adolescents with testicular tumors.

Organ-sparing approaches have been applied to the treatment of a variety of urologic tumors in both the realms of adult and pediatric urology, with the goals of minimizing overtreatment of benign lesions, preserving function, and providing durable cure. The predominance of benign tumors in prepubertal patients and the reliability of both ultrasound and intraoperative frozen sections have resulted in a marked shift toward testis-sparing approaches over the last few decades. The role of testis sparing in the adolescent population is presently unclear, although there have been increasing reports of successful organ-sparing surgery for testis tumors in the adult literature. This review presents recent trends in testis-sparing approaches for both pediatric and adolescent patients, the operative technique, and some of the controversies related to testis-sparing surgery.

Impact of parturition on chemokine homing factor expression in the vaginal distention model of stress urinary incontinence.

PURPOSE: Human childbirth simulated by vaginal distention is known to increase the expression of chemokines and receptors involved in stem cell homing and tissue repair. We hypothesized that pregnancy and parturition in rats contributes to the expression of chemokines and receptors after vaginal distention. MATERIALS AND METHODS: We used 72 age matched female Lewis rats, including virgin rats with and without vaginal distention, and delivered rats with and without vaginal distention. Each rat was sacrificed immediately, or 3 or 7 days after vaginal distention and/or parturition, and the urethra was harvested. Relative expression of chemokines and receptors was determined by real-time polymerase chain reaction. Mixed models were used with the Bonferroni correction for multiple comparisons. RESULTS: Vaginal distention up-regulated urethral expression of CCL7 immediately after injury in virgin and postpartum rats. Hypoxia inducible factor-1α and vascular endothelial growth factor were up-regulated only in virgin rats immediately after vaginal distention. CD191 expression was immediately up-regulated in postpartum rats without vaginal distention compared to virgin rats without vaginal distention. CD195 was up-regulated in virgin rats 3 days after vaginal distention compared to virgin rats without vaginal distention. CD193 and CXCR4 showed delayed up-regulation in virgin rats 7 days after vaginal distention. CXCL12 was up-regulated in virgin rats 3 days after vaginal distention compared to immediately after vaginal distention. Interleukin-8 and CD192 showed no differential expression. CONCLUSIONS: Vaginal distention results in up-regulation of the chemokines and receptors expressed during tissue injury, which may facilitate the spontaneous functional recovery previously noted. Pregnancy and delivery up-regulated CD191 and attenuated the expression of hypoxia inducible factor-1α and vascular endothelial growth factor in the setting of vaginal distention, likely by decreasing hypoxia.

Mesenchymal stem cell recruitment and improved bladder function after bladder outlet obstruction: preliminary data.

PURPOSE: Mesenchymal stem cells have various therapeutic benefits in various organ injury models. Bladder outlet obstruction causes smooth muscle hypertrophy and fibrosis, leading to lowered compliance, increased storage pressures and renal injury. Decreased blood flow and hypoxia may contribute to obstruction related bladder decompensation. We used a mouse model to determine whether mesenchymal stem cell recruitment occurred after bladder outlet obstruction and whether this was associated with changes in bladder hypoxia, histology and function. We also identified potential chemokines involved in mesenchymal stem cell recruitment. MATERIALS AND METHODS: A total of 20 female mice underwent bladder outlet obstruction. Three days later 2 million green fluorescent protein labeled mesenchymal stem cells were intravenously administered. After 4 weeks urodynamic and histological evaluation was performed. Quantitative reverse transcriptase-polymerase chain reaction was done to determine relative expression of the chemokines CCL2, CCL20, CCL25, CXCL9 and CXCL16. We simultaneously studied mice with bladder outlet obstruction only without mesenchymal stem cell injection and a control group. RESULTS: In 10 of 15 surviving mesenchymal stem cell injected mice mesenchymal stem cells were identified in the detrusor, and decreased hypoxia, hypertrophy and fibrosis was seen. Nine of 10 mice with mesenchymal stem cell engraftment had improved compliance compared to those without engraftment (mean±SD 9.6±5.1 vs 3.9±2.6 µl/cm H2O, p=0.012). Polymerase chain reaction revealed a 2-fold increase in CCL2 expression but there were no significant changes in other chemokine levels. CONCLUSIONS: Mesenchymal stem cell recruitment to the bladder after bladder outlet obstruction appears to be associated with increased blood flow and decreased tissue hypoxia, which may contribute to improvement in histopathological and functional parameters. Mesenchymal stem cell recruitment may be related to CCL2 over expression. Additional studies in larger samples are needed but these initial results suggest a potential role for mesenchymal stem cell based therapy for bladder outlet obstruction related bladder injury.