Sacral neuromodulation device biofilm differs in the absence and presence of infection, harbors antibiotic resistance genes, and is reproducible in vitro.

INTRODUCTION/PURPOSE: Sacral neuromodulation (SNM) is effective therapy for overactive bladder refractory to oral therapies, and non-obstructive urinary retention. A subset of SNM devices is associated with infection requiring surgical removal. We sought to compare microbial compositions of explanted devices in the presence and absence of infection, by testing phase, and other clinical factors, and to investigate antibiotic resistance genes present in the biofilms. We analyzed resistance genes to antibiotics used in commercially-available anti-infective device coating/pouch formulations. We further sought to assess biofilm reconstitution by material type and microbial strain in vitro using a continuous-flow stir tank bioreactor, which mimics human tissue with an indwelling device. We hypothesized that SNM device biofilms would differ in composition by infection status, and genes encoding resistance to rifampin and minocycline would be frequently detected. MATERIALS/METHODS: Patients scheduled to undergo removal or revision of SNM devices were consented per IRB-approved protocol (IRB 20-415). Devices were swabbed intraoperatively upon exposure, with controls and precautions to reduce contamination of the surrounding field. Samples and controls were analyzed with next-generation sequencing and RT-PCR, metabolomics, and culture-based approaches. Associations between microbial diversity or microbial abundance, and clinical variables were then analyzed using t-tests and ANOVA. Reconstituted biofilm deposition in vitro using the bioreactor was compared by microbial strain and material type using plate-based assays and scanning electron microscopy. RESULTS: Thirty seven devices were analyzed, all of which harbored detectable microbiota. Proteobacteria, Firmicutes and Actinobacteriota were the most common phyla present overall. Beta-diversity differed in the presence versus absence of infection (p = 0.014). Total abundance, based on normalized microbial counts, differed by testing phase (p < 0.001), indication for placement (p = 0.02), diabetes mellitus (p < 0.001), cardiac disease (p = 0.008) and history of UTI (p = 0.008). Significant microbe-metabolite interaction networks were identified overall and in the absence of infection. 24% of biofilms harbored the tetA tetracycline/minocycline resistance gene and 53% harbored the rpoB rifampin resistance gene. Biofilm was reconstituted across tested strains and material types. Ceramic and titanium did not differ in biofilm deposition for any tested strain. CONCLUSIONS: All analyzed SNM devices harbored microbiota. Device biofilm composition differed in the presence and absence of infection and by testing phase. Antibiotic resistance genes including to rifampin and tetracycline/minocycline, which are used in commercially-available anti-infective pouches, were frequently detected. Isolated organisms from SNM devices demonstrated the ability to reconstitute biofilm formation in vitro. Biofilm deposition was similar between ceramic and titanium, materials used in commercially-available SNM device casings. The findings and techniques used in this study together provide the basis for the investigation of the next generation of device materials and coatings, which may employ novel alternatives to traditional antibiotics. Such alternatives might include bacterial competition, quorum-sensing modulation, or antiseptic application, which could reduce infection risk without significantly selecting for antibiotic resistance.

Ureteral Stents Harbor Complex Biofilms With Rich Microbiome-Metabolite Interactions.

PURPOSE: We sought to determine microbe-metabolite composition and interactions within indwelling ureteral stent biofilms, determine their association with patient factors including infection, and reconstitute biofilm formation on relevant surface materials in vitro. MATERIALS AND METHODS: Upon ureteral stent removal from patients, proximal and distal ends were swabbed. Samples were analyzed by 16S next-generation sequencing and metabolomics. A continuous-flow stir-tank bioreactor was used to reconstitute and quantify in vitro biofilm formation from stent-isolated bacteria on stent-related materials including silicone, polytetrafluoroethylene, polyurethane, polycarbonate, and titanium. Diversity, relative abundance, and association with clinical factors were analyzed with ANOVA and Bonferroni t-tests or PERMANOVA. Biofilm deposition by microbial strain and device material type were analyzed using plate counts and scanning electron microscopy following bioreactor incubation. RESULTS: All 73 samples from 37 ureteral stents harbored microbiota. Specific genera were more abundant in samples from stents wherein there was antibiotic exposure during indwelling time (Escherichia/Shigella, Pseudomonas, Staphylococcus, Ureaplasma) and in those associated with infection (Escherichia/Shigella, Ureaplasma). The enriched interaction subnetwork in stent-associated infection included Ureaplasma and metabolite 9-methyl-7-bromoeudistomin. Strains identified as clinically relevant and central to interaction networks all reconstituted biofilm in vitro, with differential formation by strain (Enterococcus faecalis most) and material type (titanium least). CONCLUSIONS: Ureteral stent biofilms exhibit patterns unique to stent-associated infection and antibiotic exposure during indwelling time. Microbes isolated from stents reconstituted biofilm formation in vitro. This work provides a platform to test novel materials, evaluate new coatings for anti-biofilm properties, and explore commensal strain use for bacterial interference against pathogens.

Biofilms on Indwelling Artificial Urinary Sphincter Devices Harbor Complex Microbe-Metabolite Interaction Networks and Reconstitute Differentially In Vitro by Material Type.

The artificial urinary sphincter (AUS) is an effective treatment option for incontinence due to intrinsic sphincteric deficiency in the context of neurogenic lower urinary tract dysfunction, or stress urinary incontinence following radical prostatectomy. A subset of AUS devices develops infection and requires explant. We sought to characterize biofilm composition of the AUS device to inform prevention and treatment strategies. Indwelling AUS devices were swabbed for biofilm at surgical removal or revision. Samples and controls were subjected to next-generation sequencing and metabolomics. Biofilm formation of microbial strains isolated from AUS devices was reconstituted in a bioreactor mimicking subcutaneous tissue with a medical device present. Mean patient age was 73 (SD 10.2). All eighteen artificial urinary sphincter devices harbored microbial biofilms. Central genera in the overall microbe−metabolite interaction network were Staphylococcus (2620 metabolites), Escherichia/Shigella (2101), and Methylobacterium-Methylorubrum (674). An rpoB mutation associated with rifampin resistance was detected in 8 of 15 (53%) biofilms. Staphylococcus warneri formed greater biofilm on polyurethane than on any other material type (p < 0.01). The results of this investigation, wherein we comprehensively characterized the composition of AUS device biofilms, provide the framework for future identification and rational development of inhibitors and preventive strategies against device-associated infection.

The Natural History and Composition of Urinary Catheter Biofilms: Early Uropathogen Colonization with Intraluminal and Distal Predominance.

PURPOSE: We sought to determine the composition and initiation site of bacterial biofilm on indwelling urinary catheters and to track biofilm progression with time. MATERIALS AND METHODS: Indwelling urinary catheters were collected from 2 tertiary care centers following removal from patients. Indwelling time was noted and catheters were de-identified. Catheters were sectioned, stained for biofilms and analyzed by spectrophotometry and visualization. Biofilm colonization patterns were analyzed using descriptive statistical analysis and bacterial composition was determined using next generation sequencing. RESULTS: We collected and analyzed a total of 33 catheters from 26 males and 7 females with indwelling time ranging from 15 minutes to 43 days. Biofilm colonization was consistently high on the region of the balloon for all indwelling times. After week 1 the distal third of the catheter had higher biofilm colonization than the proximal third (week 2 p=0.034). At all indwelling times the intraluminal surface of the catheter had greater biofilm colonization than the outer surface. Next generation sequencing detected potential uropathogenic bacteria in all 10 analyzed samples. CONCLUSIONS: The catheter balloon, its distal aspect and its lumen were the predominant locations of biofilm comprising uropathogenic bacteria. Strategies to prevent or treat biofilm should be targeted to these areas.

Impact of Age and Comorbidities on Use of Sacral Neuromodulation.

PURPOSE: We investigated the influence of patient age on sacral nerve stimulation trial outcomes, device implantation and treatment durability. MATERIALS AND METHODS: We analyzed a database of all sacral nerve stimulation procedures performed between 2012 and 2014 at a high volume institution for associations of patient age with sacral nerve stimulation indication, trial stimulation success, device revision and device explantation. RESULTS: In a cohort of 356 patients those with nonobstructive urinary retention and urgency-frequency were younger than patients with urgency urinary incontinence. Trial stimulation success did not differ by age in stage 1 and percutaneous nerve evaluation trials (p = 0.51 and 0.84, respectively). Logistic regression identified greater odds of trial success in females compared to males (OR 2.97, 95% CI 1.32-6.04, p = 0.009) and for urgency urinary incontinence compared to urgency-frequency (OR 3.02, 95% CI 1.39-6.50, p = 0.006). In analyzed patients there were 119 surgical revisions, including battery replacement, and 53 explantations. Age was associated with a decreased risk of revision with 3% lower odds per each additional year of age (OR 0.97, 95% CI 0.95-0.98, p <0.0001). While age did not influence explantation, for each body mass index unit there was a 5% decrease in the odds of explantation (OR 0.95, 95% CI 0.91-0.98). CONCLUSIONS: In contrast to previous studies, older patients experienced no difference in the sacral nerve stimulation response in stimulation trials and no difference in the implantation rate. Furthermore, age was modestly protective against device revision. This suggests that age alone should not negatively predict sacral nerve stimulation responses.

Does Size Matter? Measured and Modeled Effects of Suprapubic Catheter Size on Urinary Flow.

OBJECTIVE: To quantify the effects of catheter size and urinary sediment on catheter drainage, and to determine the French size at which catheter upsizing yields a diminished marginal return in flow. MATERIALS AND METHODS: Latex Foley catheters (12-26 French [Fr]) were connected to a simulated bladder. Passive drainage times of 450 mL water were measured over 5 successive trials for each catheter size. The effect of sediment was modeled by adding 2g of infant rice cereal to the water. Measurements were repeated in half-length catheters to assess the effect of catheter length. A computational model of resistance was compared to measured data. Percent differences in catheter resistance based on measured catheter dimensions were determined. RESULTS: Catheter resistance significantly decreased (P < .001) with increasing catheter size. All catheter sizes had significantly faster (P < .001) drainage times after being shortened, except for the 16 Fr catheter. All catheter sizes exhibited significantly prolonged (P < .001) drainage times after the addition of sediment, except for the 16 Fr catheter. Beyond 18 Fr, larger catheter sizes provided diminishing marginal returns in flow; upsizing from 18 Fr to 20 Fr reduced measured resistance by 19%, which was the lowest improvement in resistance between 2 catheter sizes. The coefficient of determination (R2) between measured and modeled resistances was 0.9754, confirming that the model of catheter performance was accurate. CONCLUSION: Marginal improvement in urine flow occurs with catheter upsizing after 18 Fr; however, shortening catheter lengths may serve as another means of improving flow.

Transvaginal neobladder vaginal fistula repair after radical cystectomy with orthotopic urinary diversion in women.

AIM: We present the surgical management and outcomes of patients who underwent transvaginal neo-bladder vaginal fistula (NBVF) repair at our institution. METHODS: Between 2002 and 2012, eight patients underwent transvaginal NBVF repair. The surgical management entailed placing a Foley catheter into the fistula tract. A circumferential incision was made around the fistula tract after which a plane between the serosa of the neobladder and the vaginal epithelium was created. Interrupted polyglycolic acid sutures were used to close the fistula. An additional layer of vaginal wall, Martius, or omental flap was interposed before vaginal wall closure. A urethral catheter was placed for a minimum of 14 days and removed after a negative cystogram and pelvic exam with retrograde neobladder filling without leakage. RESULTS: All patients presented with a fistula following radical cystectomy with orthotopic ileal neobladder. Two patients had failed two prior transvaginal fistula repairs. A unilateral Martius flap was used in five patients and an omental flap was used in one patient. The surgery was successful in all patients. After a mean follow up of 33 months [4-117], five patients underwent or are waiting to undergo management of stress urinary incontinence with bulking agents. No patient had a recurrent fistula. CONCLUSIONS: Management of NBVF is challenging but cure is possible using a transvaginal approach. Most patients will suffer from incontinence after the repair because of a short and incompetent urethra. Patients should be counseled about the high probability of requiring a secondary procedure to achieve continence.

Is there an association between polypropylene midurethral slings and malignancy?

OBJECTIVE: To examine any association between polypropylene mesh used in midurethral slings and malignancy in humans. Macroporous, monofilament polypropylene midurethral slings have been established as a safe and effective treatment for stress urinary incontinence. However, despite long-term studies supporting the efficacy and safety of midurethral slings, there have been concerns regarding the general risks of using mesh in transvaginal surgery. In addition, concerns have recently been raised about synthetic midurethral slings and a possible link with malignancy. Therefore, the goal of this work was to further assess any association between polypropylene mesh slings and malignancy. MATERIALS AND METHODS: All sling procedures performed at our institution from 2004 to 2013 were retrospectively reviewed. From within this group, the International Classification of Disease codes for urethral cancer, vaginal cancer, and bladder cancer were reviewed. RESULTS: From 2004-2013, 2545 procedures were performed. Of these, 2361 (96.3%) underwent polypropylene midurethral sling placement. Average follow-up after sling placement was 42.0 ± 38.6 months, with follow-up extending up to 122.3 months. The rate of bladder cancer after the sling procedure was 1 of 2361 (0.0%), with the same rate of vaginal cancer. No sarcomas were noted. CONCLUSION: Overall, the rate of malignancy after polypropylene mesh midurethral sling placement in our series was 0.0% (2 of 2361). With a mean follow-up of almost 4 years and follow-up extending up to a maximum of 122.3 months, our series does not support any association between the polypropylene mesh used for midurethral slings and the development of malignancy in humans.

Increasing patient preparedness for sacral neuromodulation improves patient reported outcomes despite leaving objective measures of success unchanged.

PURPOSE: We assessed how a group shared appointment influenced patient preparedness for sacral nerve stimulation for refractory overactive bladder and/or urge urinary incontinence. We also evaluated subjective and objective outcomes. MATERIALS AND METHODS: Patients considering sacral nerve stimulation were prospectively enrolled and invited to attend a group shared appointment. This 75-minute presentation included a question and answer period with an implanting surgeon and an implanted patient. Control patients received standard office counseling. A patient preparedness questionnaire was completed after the group shared appointment or office counseling. Response to treatment was determined using the postoperative satisfaction questionnaire, Patient Global Impression of Improvement (PGI-I) and voiding diaries. RESULTS: In our study 36 women with a mean ± SD age of 61 ± 15 years underwent sacral nerve stimulation. There was no significant difference in patient demographics between the 19 women who attended the group shared appointment and the 17 controls. Overall preparedness was greater in the shared appointment group (p = 0.043) with better understanding of the purpose of (p = 0.003) and alternatives to (p = 0.043) sacral nerve stimulation. Significantly more women in the shared appointment group than controls felt completely prepared (78.9% vs 29.4%, p = 0.003) and completely satisfied (78.9% vs 35.3%, p = 0.003) with sacral nerve stimulation as well as very much better (68.4% vs 17.6%, p = 0.002) according to the PGI-I. There was no difference between the groups in the number of women with a 50% or greater symptom reduction on voiding diary. CONCLUSIONS: Participating in a group shared appointment before sacral nerve stimulation improved patient preparedness and perceived outcomes of treatment, although there was no difference in objective outcomes based on voiding diary.

Patterns of hardware related electrode failures in sacral nerve stimulation devices.

PURPOSE: Abnormal electrical impedance in sacral nerve stimulation devices is a cause of device failure. Currently, there is scant literature evaluating the incidence and management of this problem. We evaluated the presentation, characteristics and management of sacral nerve stimulation devices with abnormal electrical impedance. MATERIALS AND METHODS: A total of 565 patients were permanently implanted with sacral nerve stimulation devices using a tined lead between 2003 and 2011. Devices were interrogated postoperatively and at followup. Abnormal electrical impedance was classified as open circuit--impedance greater than 4,000 Ω or short circuit--impedance less than 50 Ω and/or equivalence of impedance. Details on presentation, characteristics and management were recorded. RESULTS: Of the 565 patients 72 (12.7%) experienced a total of 86 abnormal electrical impedance events, of which 57 (66.2%) were open circuits and 28 (32.5%) were short circuits. One event (1.1%) was a simultaneous open and short circuit. Short circuits presented earlier than open circuits (median 3.5 months, IQR 2-7.5 vs 15, IQR 5.5-30.5, p <0.0001) and required surgical intervention more often (75.0% vs 54.3%, p = 0.09). Patient specific factors, such as trauma history and change in body mass index class, were not associated with abnormal electrical impedance. No electrode failure patterns could be identified. CONCLUSIONS: Abnormal electrical impedance occurred in approximately 13% of cases permanently implanted in our series. Short circuits presented earlier and often required surgical intervention. Open circuits presented later and may have potentially been secondary to microfractures that accumulate with time at the sacral plate, resulting in later presentation. Almost a third of patients with abnormal electrical impedance associated with clinical inefficacy were treated conservatively, primarily with reprogramming.

Purely transvaginal/perineal management of complications from commercial prolapse kits using a new prostheses/grafts complication classification system.

PURPOSE: Commercial prolapse mesh kits are increasingly used in the management of pelvic organ prolapse. We present our experience with the transvaginal/perineal management of synthetic mesh related complications from prolapse kits. In addition, we used the new ICS/IUGA (International Continence Society/International Urogynecological Association) prostheses/grafts complication classification system to report on our contemporary series. MATERIALS AND METHODS: A retrospective chart review of all patients who underwent surgical removal of transvaginal mesh for mesh related complications after prolapse kit use from November 2006 to April 2010 at 1 institution was performed. We report our contemporary series of mesh complications using the new ICS/IUGA prostheses/grafts complication classification system. Postoperative pain, degree of improvement and presence of continued symptoms were reported by patients at last followup. RESULTS: A total of 23 patients underwent transvaginal removal of mesh during the study period. Mean patient age was 61 years. Median period of latency to mesh related complication was 10 months (range 1 to 27). Indications for mesh removal included vaginal/pelvic pain (39%), dyspareunia (39%), vaginal mesh extrusion/exposure (26%), urinary incontinence (35%), recurrent pelvic organ prolapse (22%), bladder mesh perforation with recurrent urinary tract infection (22%), rectal mesh perforation (4%), ureteral perforation injury (4%), retained foreign body (surgical sponge) in the bladder (4%) and vesicovaginal fistula (9%), with most patients citing more than 1 reason. CONCLUSIONS: Although technically difficult in some cases, purely transvaginal mesh excision appears to be safe with resolution of almost all presenting symptoms. Although slightly cumbersome, the new ICS/IUGA prostheses/graft complication classification system can be used to report and more accurately characterize mesh complications.

Improvement of bowel dysfunction with sacral neuromodulation for refractory urge urinary incontinence.

INTRODUCTION AND HYPOTHESIS: Sacral nerve stimulation (SNS) is approved for urologic indications in the USA and, recently, fecal incontinence. This study described concomitant bowel dysfunction and improvements in bowel and urinary symptoms and quality of life (QOL) in women with refractory urge urinary incontinence (UUI) receiving SNS. METHODS: Women (N = 36) with refractory UUI receiving SNS were prospectively enrolled. Surveys and exams were completed at baseline and follow-up, with symptom and QOL scores measured using validated scales (0-100, none-worst). RESULTS: A total 24 women were followed up at a median of 4.0 months post-implantation. Of these, 20 (83%) had bowel dysfunction, 13 (54%) used bowel medications at baseline, and 11 (45%) continued them after SNS. The mean/median urinary (54.8 to 32.6) and bowel (23.4 to 14.1) symptom scores improved significantly, as did urinary (64.2 to 14.3) but not bowel (2.4 to 0.0) QOL scores. CONCLUSIONS: Bowel dysfunction is common in women with refractory UUI. SNS improves urinary symptoms and QOL, but improvement in bowel symptoms does not translate into significant QOL changes.

Improved sexual and urinary function in women with sacral nerve stimulation.

OBJECTIVES: Urinary and sexual function improve following sacral nerve stimulation (SNS) for refractory overactive bladder. No significant associations between these changes have been found. Whether improvements in sexual function are independent of or secondary to improvements in urinary function remains unclear. The aim of this study was to analyze changes in urinary and sexual function in a homogeneous sample of patients undergoing SNS for urge urinary incontinence and subsequently identify associations between the two. MATERIALS AND METHODS: A prospective database was created. Enrollees underwent a full history and physical examination at the first office visit. Multiple-day voiding diaries with validated and investigator-designed questionnaires were administered at baseline and follow-up as standard implantation procedures and to assess changes in urinary and sexual function, respectively. Analyses were completed using data from patients who were sexually active at baseline and follow-up. RESULTS: Statistically significant improvements in urinary and sexual function occurred according to multiple metrics. Patient global impression scales categorized all patients' urinary conditions as improved, with most being less severe. Validated urinary symptom and quality of life scores improved significantly. After treatment, most patients were incontinent less often with sexual activity and felt less restricted from sexual activity by fear of incontinence. Validated quantification of sexual function demonstrated significant improvements in overall sexual function, arousal, and satisfaction. No significant associations between changes in urinary and sexual function were noted; however, trends appeared to exist between the two. CONCLUSIONS: Improved sexual function was not significantly associated with improved urinary function after SNS despite apparent trends between the two. Larger samples are required to definitively demonstrate this conclusion.

Force of stream after sling therapy: safety and efficacy of rapid discharge care pathway based on subjective patient report.

PURPOSE: We evaluated the safety of a mid urethral sling postoperative care pathway using patient subjective reporting of force of stream to minimize length of stay and catheter placement. MATERIALS AND METHODS: Women undergoing solitary mid urethral sling surgery were prospectively enrolled in our study. Force of stream after the sling therapy protocol consisted of retrograde bladder filling with 300 ml fluid within 1 hour after surgery. Patients rated force of stream compared to baseline on a visual analog scale. Those with a force of stream of 50% or greater were immediately discharged home regardless of post-void residual urine volume. Only those unable to void and those rating force of stream less than 50% with post-void residual urine volume greater than 500 ml were discharged home with a catheter. Patients were telephoned within 1 week of surgery and seen 4 to 6 weeks postoperatively. The primary outcome was unexpected visits to the emergency room or office for voiding dysfunction or urinary retention. RESULTS: A total of 114 women were prospectively enrolled in our study, of whom 105 (92.1%) passed the protocol and were discharged home without a catheter. Of the patients 14 were discharged home with increased post-void residual urine volume (range 152 to 427 ml) but no catheter, representing those who would have been discharged with a catheter by many traditional voiding protocols. According to protocol 9 patients were discharged with a catheter. No patient presented to the emergency room or office in urinary retention or with voiding dysfunction before the scheduled visit. CONCLUSIONS: Patients who report a force of stream of 50% or greater can be safely and rapidly discharged home after an uncomplicated mid urethral sling procedure regardless of post-void residual urine volume. Scanned post-void residual urine volume does not add much value in those who can void. By following the force of stream after sling therapy protocol patients can be discharged home less than 3 hours after mid urethral sling surgery.

Surgically corrected urethral diverticula: long-term voiding dysfunction and reoperation rates.

OBJECTIVES: To present the largest reported cohort of women with urethral diverticula and to evaluate the surgical outcomes and long-term voiding symptoms after urethral diverticulectomy. Studies evaluating the outcomes after urethral diverticulectomy have been limited by small patient numbers and short-term follow-up. METHODS: Women who had undergone diverticulectomy at our institution from 1996 to 2008 were mailed surveys. Urinary bother was assessed using the Urogenital Distress Inventory 6-item questionnaire, and patients were asked to report subsequent urethral or vaginal surgery and the number of urinary tract infections within the previous year. To determine the rate of surgical recurrence, the charts of women not responding to the survey were reviewed. RESULTS: A total of 122 women were identified as having undergone urethral diverticulectomy during the study period. Of these, 13 (10.7%) had an eventual recurrence that required repeat surgical excision. Patients with a proximal diverticulum, multiple diverticula, or previous pelvic or vaginal surgery (excluding previous diverticulectomy) were more likely to develop recurrence (P = .01, P = .03, and P < .001, respectively). For the 61 women (50%) responding to our survey, the mean follow-up was 50.4 months. Of these 61 women, 24 (39.3%) had had a urinary tract infection within the previous year, with 14 (23%) women having had ≥3 within the previous year. Also, 16 (26.2%) had persistent pain or discomfort with urination. The mean ± SD total Urogenital Distress Inventory-6 score was 31.1 ± 25.5 for the survey responders. CONCLUSIONS: To our knowledge, our study represents the largest study with the longest follow-up after urethral diverticulectomy. Patients with proximal or multiple diverticula and those with previous pelvic surgery should be counseled appropriately regarding the risks of recurrence and persistent voiding dysfunction.

An hTERT-immortalized human urothelial cell line that responds to anti-proliferative factor.

Studies of the urothelium, the specialized epithelial lining of the urinary bladder, are critical for understanding diseases affecting the lower urinary tract, including interstitial cystitis, urinary tract infections and cancer. However, our understanding of urothelial pathophysiology has been hampered by a lack of appropriate model systems. Here, we describe the isolation and characterization of a non-transformed urothelial cell line (TRT-HU1), originally explanted from normal tissue and immortalized with hTERT, the catalytic subunit of telomerase. We demonstrate responsiveness of the cells to anti-proliferative factor (APF), a glycopeptide implicated in the pathogenesis of interstitial cystitis. TRT-HU1 carries a deletion on the short arm of chromosome 9, an early genetic lesion in development of bladder cancer. TRT-HU1 urothelial cells displayed growth and migration characteristics similar to the low-grade papilloma cell line RT4. In contrast, we observed marked differences in both phenotype and gene expression profiles between TRT-HU1 and the highly malignant T24 cell line. Together, these findings provide the first demonstration of a non-transformed, continuous urothelial cell line that responds to APF. This cell line will be valuable for studies of both benign and malignant urothelial cell biology.

Fallopian tube prolapse presenting as a peritoneovaginal fistula.

INTRODUCTION: Peritoneovaginal fistula is an extremely rare cause of persistent vaginal leakage following a hysterectomy. Likewise, fallopian tube prolapse is an uncommon but known complication of hysterectomy. Fallopian tube prolapse resulting in peritoneal leakage has yet to be reported in the literature. CLINICAL CASE: A 27-year-old female presented with a two year history of continuous leakage per vagina. The leakage started shortly after an abdominal hysterectomy. Examination noted clear fluid emanating from a vaginal lesion located at the level of the vaginal cuff. An extensive workup ruled out vesicovaginal and ureterovaginal fistula. Surgical exploration noted that the lesion was a prolapsed fallopian tube, which was resected vaginally. DISCUSSION: This is the first reported case of peritoneovaginal fistula associated with a prolapsed fallopian tube. CONCLUSION: Vaginal resection of the fallopian tube remnant and reclosure of the vaginal cuff results in cure of the leakage.

Clinical and magnetic resonance imaging characteristics of vaginal and paraurethral leiomyomas: can they be diagnosed before surgery?

OBJECTIVE: To describe the clinical and magnetic resonance imaging (MRI) characteristics of vaginal and paraurethral leiomyomas. PATIENTS AND METHODS: All patients with pathologically confirmed paraurethral and vaginal wall leiomyomas from January 2006 to August 2007 were reviewed. Patients with no preoperative MRI of the pelvis were excluded. RESULTS: Five patients were identified; all had a firm, smooth, non-tender, non-fluctuant mass. MRI showed a well-circumscribed shape, a homogeneous signal that was hypointense or isointense to muscle on T1- and hyperintense or isointense to muscle on T2-weighted images, and uniform enhancement. In all cases, MRI excluded urethral diverticulae, and pathology showed leiomyoma, of which one had atypical features. CONCLUSION: Paraurethral and vaginal wall leiomyomas can be identified before surgery with a reasonable degree of certainty, based on their clinical and MRI characteristics.