Does total testicular volume predict testicular volume difference in adolescent males with varicocele?

INTRODUCTION: We evaluated the relationship between total testicular volume (TTV) and testicular volume differential (TVD) in adolescent males with varicocele. Both low TTV and high TVD have been independently associated with higher incidences of infertility later in life, but a predictive relationship between TTV and TVD directly has yet to be described. MATERIALS AND METHODS: We retrospectively analyzed a database of Tanner 5 boys ages 16-21 who presented with varicocele at a single institution between 2009 and 2017. All patients had a scrotal sonogram prior to surgical intervention. TTV and TVD were calculated for each individual and four non-exclusive groupings of patients were created for statistical analysis. We chose 30 cc as a cut off value for low TTV based on prior studies. RESULTS: 209 patients met our inclusion criteria. Mean age was 18.3 years (16-21, SD 1.7) with a mean total testicular volume of 36 cc (13.5-78.2, SD 11.1). Cut off points of TVD of 20% and TTV of 30 cc were used to separate patients. There were 65 boys (31%) with TTV < 30 cc and 58 boys (28%) with TVD ≥ 20%. Among males with TTV < 30 cc, 23 (35%) had a TVD ≥ 20%. Among males with TTV ≥ 30 cc, 35 (24%) had a TVD ≥ 20%. The relationship between TVD and TTV was found to be non-significant (p > 0.05). DISCUSSION: Adolescent varicoceles continue to pose a challenge to pediatric urologists. The dilemma of over-aggressive treatment has proven difficult to balance with the risk of infertility. We hoped that elucidating the relationship between TTV and TVD could be useful in identifying patients who are at greater risk for infertility while decreasing the need for more intrusive testing, such as semen analysis, in an adolescent population. We looked at the direct relationship between low TTV and high TVD. In our population, there was a non-significant relationship between TTV < 30 cc and TVD ≥ 20% (p > 0.05) indicating that in adolescents with varicocele, TTV and TVD are independent variables. Our study limitations include the inherent user dependent bias of ultrasound measurements and data collection at a single institution with high ethnic diversity, possibly not comparable to all patient populations. CONCLUSIONS: Low TTV (< 30 cc) itself is not predictive of high TVD (≥ 20%) in adolescent boys with varicocele, despite their reported independent associations with impaired fertility in other studies.

Does total testicular volume predict testicular volume difference in adolescent males with varicocele?

ABSTRACT Introduction: We evaluated the relationship between total testicular volume (TTV) and testicular volume differential (TVD) in adolescent males with varicocele. Both low TTV and high TVD have been independently associated with higher incidences of infertility later in life, but a predictive relationship between TTV and TVD directly has yet to be described. Materials and Methods: We retrospectively analyzed a database of Tanner 5 boys ages 16-21 who presented with varicocele at a single institution between 2009 and 2017. All patients had a scrotal sonogram prior to surgical intervention. TTV and TVD were calculated for each individual and four non-exclusive groupings of patients were created for statistical analysis. We chose 30 cc as a cut off value for low TTV based on prior studies. Results: 209 patients met our inclusion criteria. Mean age was 18.3 years (16-21, SD 1.7) with a mean total testicular volume of 36 cc (13.5-78.2, SD 11.1). Cut off points of TVD of 20% and TTV of 30 cc were used to separate patients. There were 65 boys (31%) with TTV < 30 cc and 58 boys (28%) with TVD ≥ 20%. Among males with TTV < 30 cc, 23 (35%) had a TVD ≥ 20%. Among males with TTV ≥ 30 cc, 35 (24%) had a TVD ≥ 20%. The relationship between TVD and TTV was found to be non-significant (p > 0.05). Discussion: Adolescent varicoceles continue to pose a challenge to pediatric urologists. The dilemma of over-aggressive treatment has proven difficult to balance with the risk of infertility. We hoped that elucidating the relationship between TTV and TVD could be useful in identifying patients who are at greater risk for infertility while decreasing the need for more intrusive testing, such as semen analysis, in an adolescent population. We looked at the direct relationship between low TTV and high TVD. In our population, there was a non-significant relationship between TTV < 30 cc and TVD ≥ 20% (p > 0.05) indicating that in adolescents with varicocele, TTV and TVD are independent variables. Our study limitations include the inherent user dependent bias of ultrasound measurements and data collection at a single institution with high ethnic diversity, possibly not comparable to all patient populations. Conclusions: Low TTV (< 30 cc) itself is not predictive of high TVD (≥ 20%) in adolescent boys with varicocele, despite their reported independent associations with impaired fertility in other studies.

Metastatic neuroblastoma presenting as a scrotal mass in an infant.

OBJECTIVE: Neuroblastoma is a common malignancy of infancy and childhood. The scrotum and paratesticular tissues are rare sites of presentation. We report the case of an infant who presented with a scrotal mass that proved to be a metastatic neuroblastoma. PATIENT AND RESULTS: A previously healthy 4-month-old boy presented with a scrotal mass. Ultrasound and surgery showed a well circumscribed, 1.2-cm nodule in the inferior scrotum, associated with dartos fascia. Intraoperative frozen section revealed a small round blue cell tumor, prompting a wider excision. Final diagnosis was poorly differentiated neuroblastoma with unfavorable histology. Further imaging revealed a large adrenal mass, with hepatic and pleural metastases. CONCLUSION: Metastatic and primary neuroblastomas are rare causes of scrotal mass in infants and children. Treatment and prognosis depend on factors including patient age, histology and stage. Stem-cell-supported chemotherapy is the current treatment of choice for high-stage, high-risk neuroblastoma, as in this case. The differential diagnosis of pediatric scrotal neoplasms is broad, and several small round blue cell tumors can present in the scrotum and paratesticular tissues. Preoperative ultrasound of the scrotum and abdomen may assist in diagnosis and surgical planning. Intraoperative frozen section may assist in diagnosis and tissue triage.

Updated experience with the Monti catheterizable channel.

OBJECTIVES: The Monti catheterizable channel is used as an integral part of continent bladder reconstruction in children. We have updated our ongoing experience at Riley Children's Hospital with 199 patients. METHODS: We identified 199 patients for retrospective review, including all patients for whom a Monti ileovesicostomy was created from January 1997 to August 2004. We assessed the complications, surgical procedures, and stomal continence. RESULTS: At mean follow-up of 28 months, we found that 194 of 199 patients (97.5%) continued to use their Monti catheterizable channel for bladder drainage. Early surgical complications occurred in 7 patients (3.5%), usually in those who had undergone simultaneous bladder augmentation (5 of 7). Revision was required in 16 patients (8%) for stomal stenosis (n = 11), prolapse (n = 2), or superficial stomal problems (n = 3). Of the 199 patients, 17 (8.5%) required 19 bladder or channel revisions. The primary indications were related to elongation and angulation of the channel in 7 and deficient tunnel length in 8. Minor difficulty with catheterization was noted in 16 patients (8%), and endoscopy with minor procedures was required in 4 patients (2%). Leakage from the channel was uncommon, occurring in only 4 of 115 patients (3.5%). CONCLUSIONS: With increasing demand for simultaneous appendicocecostomy for stool continence at bladder reconstruction, we continue to use the Monti ileovesicostomy for bladder drainage. Our experience with nearly 200 patients has demonstrated the durability and success of this technique.

A comparison of the Monti and Casale (spiral Monti) procedures.

PURPOSE: We present our long-term followup and comparison of outcomes between the Monti and Casale (spiral Monti) procedures in a large group of children and young adults. MATERIALS AND METHODS: A retrospective chart review was done, including all patients undergoing the Monti or Casale procedure at our institution with a minimum followup of 6 months. Age at surgery, the bowel segment used, stomal location, the number and type of revisions or endoscopic procedures required after channel creation, problems catheterizing and channel continence were documented, and a database was created. RESULTS: Of 188 patients identified with at least 6 months of followup 109 underwent a Monti procedure, while 79 underwent a Casale procedure. Patient age at surgery was 10 months to 31 years (mean 10.2 years). Mean followup was 43 months for the entire cohort, and 47.2 and 37.2 months for the Monti and Casale groups, respectively. A total of 43 open revisions were required in 36 patients (19.1%). Stomal revisions accounted for 18 procedures, while subfascial revisions accounted for 25 in 17 (9.0%) and 21 (11.2%) patients, respectively. A total of 21 endoscopic procedures requiring anesthesia were performed in 17 patients (9.0%). In the Monti group stomal revision was required in 11 patients (10.1%), while subfascial revisions were required in 9 (8.3%). In the Casale group stomal revision was required in 6 patients (7.6%), while subfascial revisions were required in 12 (15.2%). Of the channels 98% were completely continent at the stoma. CONCLUSIONS: In a large population of children and young adults we report durable and reliable long-term results with the Monti and Casale procedures, including continence at the stoma. The only significant difference noted between the 2 procedures was a higher incidence of subfascial revisions for umbilical stomas in each group. The need for subfascial revision is highest in spiral Monti channels placed in the umbilicus.

Alternative uses of dextranomer/hyaluronic acid copolymer: the efficacy of bladder neck injection for urinary incontinence.

PURPOSE: Urinary continence in children with neuropathic bladder and other urological disorders depends on a bladder with adequate low pressure storage capacity and a competent outlet. Various procedures are performed with the goal of achieving continence in these patients. Recently, dextranomer/hyaluronic acid copolymer (Dx/H) has been introduced for the correction of vesicoureteral reflux. We evaluated the efficacy of submucosal bladder neck (BN) injection of Dx/H for urethral incontinence in children. MATERIALS AND METHODS: We retrospectively reviewed continence status after Dx/H injection into the BN for incontinence. Parameters examined include gender, underlying disease, prior BN surgery and means of emptying the bladder. Continence was described by the patients and/or their parents as unchanged (no change in requirements for diapers or pads), improved (longer dry intervals or requiring fewer pads/diapers) or dry (requiring no pads and dry in underwear). RESULTS: A total of 6 males and 10 females underwent injections for treatment of incontinence. Mean followup was 9.5 months (range 3 to 24). Volumes injected ranged from 0.8 to 4.4 ml (mean 1.88). Of the patients 3 achieved dryness after injection, all of whom had catheterizable urinary stomas and two-thirds had undergone bladder augmentations. All 5 patients who improved had undergone augmentation and had catheterizable channels. No improvement was seen in 8 patients. CONCLUSIONS: Injection at the BN is well tolerated and relatively easy to perform. Success rates may be better in females and in patients with neuropathic incontinence. Despite limited success it remains an option for all patients who are poor surgical candidates and those who want to avoid extensive BN reconstruction.

The colon flap/extension Malone antegrade continence enema: an alternative to the Monti-Malone antegrade continence enema.

PURPOSE: In situations where the appendix is not available for the Malone antegrade continence enema (MACE) procedure a Yang-Monti channel or a colon flap conduit can be created. We report our experience with colonic flap conduits used for the MACE. MATERIALS AND METHODS: A total of 169 MACE procedures were performed between February 1997 and March 2003. In 11 patients 12 colon flaps or cecal extensions were used to construct the MACE conduit. Diagnoses included myelomeningocele (8 patients), caudal regression (1), sacral agenesis (1) and gunshot wound (1). Mean age at creation of MACE was 11.3 years (range 4.4 to 16.9). Seven cecal flaps, 1 descending colon flap and 4 cecal extension flaps were created. RESULTS: Average followup was 22.8 months (range 2.6 to 34.6). Indications for colon flap MACE were appendicovesicostomy (6 patients), short appendix (2), shortened mesentery (1), retrocecal appendix (1), prior appendectomy (1) and right hemicolectomy (1). Initially all patients easily catheterized and flushed the MACE once daily. All 11 patients achieved fecal continence. Complications occurred in 3 cases. One obese patient could not visualize the umbilical stoma and it stenosed, requiring conversion to a spiral Monti-MACE. One patient with a cecal extension had development of a false passage, resulting in complete channel stenosis. One patient had development of stomal leakage, which was successfully treated with dextranomer/hyaluronic acid copolymer injection. CONCLUSIONS: A colon flap MACE conduit is a simple technique to provide access to the colon for irrigation. When faced with situations were the appendix is not available for the MACE procedure the colon flap can be a good option.

Small intestinal submucosa bladder neck slings for incontinence associated with neuropathic bladder.

PURPOSE: We assess the results using small intestinal submucosa (SIS) for neuropathic urinary incontinence in a large single institutional experience. Ambulatory status was considered as a possible predictor of success. MATERIALS AND METHODS: We retrospectively reviewed the charts of patients treated with SIS bladder neck sling procedures for neuropathic urinary incontinence with a leak point pressure less than 25 cm H2O and a minimum of 6 months followup. Continence was defined as wet (requiring pads or diapers) or dry (requiring no pads and dry underwear). Patients were classified as ambulatory (able to ambulate without assistance or using braces, crawling at home) or nonambulatory (confined to a wheelchair). Results were analyzed with regard to patient sex, ambulatory status and simultaneous bladder neck repair. RESULTS: A total of 21 females and 15 males 3 to 10 years old (mean age 9 years) were treated with SIS bladder neck slings (sling alone 27, bladder neck repair with SIS sling 9). Slings were performed along with reconstructive surgery in all cases (all had creation of urinary catheterizable channels and simultaneous or prior bladder augmentations). Minimum followup was 6 months (mean 15, range 6 to 42). Overall, 27 of the 36 patients (75%) are dry following bladder neck sling. In patients treated with the sling procedure alone 6 of 8 (75%) nonambulatory females and 8 of 10 (80%) ambulatory females were continent, and 3 of 4 (75%) nonambulatory males and 2 of 5 (40%) ambulatory males were dry. CONCLUSIONS: SIS has equivalent rates of continence compared to series using rectus fascia in patients with neuropathic urinary incontinence. The ambulatory status of males should be considered when determining which treatment option is best for the patient with myelodysplasia and neuropathic sphincteric incontinence, as in our series ambulatory males undergoing sling placement alone had a poor outcome.

Upper and lower urinary tract outcome after surgical repair of cloacal malformations: a three-decade experience.

OBJECTIVE: To report the urological outcome of the surgical correction of persistent cloaca, which is technically demanding and may require many procedures in an effort to preserve renal function and provide urinary continence. PATIENTS AND METHODS: A retrospective chart review from 1971 to 2003 identified 23 patients with cloacal malformations (two posterior, 21 classical) that were reconstructed. The confluence of the urethra, vagina and rectum was noted to be high in 16, low in five and unknown in two; one patient was a conjoined twin. RESULTS: The mean (range) follow-up was 9.3 (0.4-31.6) years. Urinary anomalies included 14 patients with renal anomalies (six solitary kidneys, four renal dysplasia, two pelvi-ureteric junction, one each duplex and crossed fused) and two duplicated bladders. Vesico-ureteric reflux was present in 13 patients (57%), hydronephrosis at birth in 13, a bony vertebral abnormality in 14 and the VACTERL association in four. Total urogenital mobilization (TUM) was used in six patients and spinal cord untethering in four; a nephrectomy was required in three and partial nephrectomy in one. Upper tract dilation was still present in six patients. Age-adjusted creatinine levels were abnormal in four (18%) patients and borderline in another six (26%). In the nine patients with a solitary kidney (six solitary, three after nephrectomy), the age-adjusted creatinine level was abnormal in two and borderline in four. A vesicostomy was initially performed in 11 patients. The method of bladder emptying is known in 22; 10 void, 11 require clean intermittent catheterization (five abdominal stoma, six urethral) and one was diverted with a conduit. Of the 18 patients aged > 47 months 15 were continent (14 complete > 4 h, one partial 2-4 h), and three are wet (one conduit). Reconstruction of the lower urinary tract included four bladder augmentations (one ureteric, one ileal, two colon), five bladder neck procedures (two artificial sphincter, one each bladder neck repair, sling, bladder neck division) and six catheterizable channels (one now with a colon conduit). The ureters were re-implanted in 12 patients. CONCLUSION: Although the surgical correction of this rare malformation is complex, the upper urinary and lower urinary tract outcome can be favourable, albeit after several reconstructive procedures. TUM has emerged as the primary method for vaginal reconstruction, but the long-term lower tract outcome after this procedure is awaited.

Intravesical phallus in cloacal exstrophy.

We report a case of a fused phallus located within the urinary bladder in a child with cloacal exstrophy. Surgical exploration revealed a phallus formed by fusion of the left and right corpus cavernosum and completely covered by bladder urothelium. The phallus was surgically separated from the bladder and mobilized to a more normal position and a neourethra created from tubularized bladder urothelium. Skin coverage was done using perineal skin flaps to cover the penile shaft, with the bladder urothelium covering the tip of the phallus being left intact to provide the appearance of a glans penis.

Long-term outcome of the surgical treatment of concealed penis.

PURPOSE: The term concealed penis describes a spectrum of disorders ranging from penoscrotal webbing to a completely buried penis. A number of surgical procedures have been described to correct this condition but little has been written about long-term results. We report our long-term results of the surgical correction of concealed penis based on a survey of parents. MATERIALS AND METHODS: A retrospective review of patients treated from 1995 to 1999 identified 18 males with a minimum of 21 months of followup whose parents were available for evaluation via telephone interview. The parents were questioned about the initial problems that they associated with concealed penis, such as appearance and accessibility of the penis, ease of hygiene, severity of concealment and negative feelings about the appearance of the penis. Parents were also questioned about the results of surgery and how the surgical result improved or failed to improve their concerns. Specifically, they were questioned about whether the surgery helped to alleviate negative concerns, improve hygiene and make the penis more assessable. RESULTS: Of the 18 patients 14 were infants/toddlers (group 1) and 4 were adolescents (group 2). Group 1 patients with a mean age of 2 years were evaluated at a mean of 41.7 (range 21 to 76) months and group 2 patients with a mean age of 12 years were evaluated at a mean of 38.8 (25 to 63) months after surgery. Before surgery 57% of patients in group 1 and 50% in group 2 complained of difficulty with hygiene. Of the parents 64% of group 1 and 75% of group 2 described their child as having a completely hidden penis. On the other hand, only 57% of parents in group 1 expressed negative feelings about the appearance of the penis compared to all parents in group 2. Following surgery group 1 patients fared better reporting improvements in hygiene (87%), accessibility (86%) and improved appearance of the penis (100%). Results from surgical intervention were less successful in group 2, with improved hygiene in 50%, improved penile accessibility in 75% and improved appearance in 50% of patients. Interestingly, all group 2 parents would still recommend the same surgery to a friend with the same problem despite less than perfect results compared to 79% of group 1 parents who would recommend surgery to others. CONCLUSIONS: Our long-term outcome survey data demonstrate that surgical correction of concealed penis addresses an array of presenting complaints. According to the parents of patients surgery is almost uniformly successful in toddlers and less often successful in adolescents. However, despite its limited success in older patients, most parents thought that surgery was a positive intervention and would recommend it to a friend with a similar condition.

Use of a Monti channel for administration of antegrade continence enemas.

PURPOSE: Success with Malone antegrade continence enemas (MACE) requires reliable access to the colon and a customized enema regimen. Use of the appendix in situ provides a natural and well-vascularized conduit. When the appendix is absent or inadequate, alternative techniques are required. We report our experience using Monti channels to administer antegrade continence enemas. MATERIALS AND METHODS: Of the 106 MACE procedures performed in 53 months a Monti-MACE was created in 13. Indications for use of ileum, technique, ease of catheterization and incidence of complications were reviewed. RESULTS: Mean followup was 21.7 months. Two patients had transient difficulty advancing the catheter into the cecum. Stoma revisions were required for critical stenosis in 2 patients (15.4%). Stoma leakage occurred in 1 patient after multiple stoma revisions. CONCLUSIONS: The Monti-MACE provides continent access to the colon for antegrade enemas. The rate of stomal revision is only slightly higher than that reported for appendicocecostomy. While use of the appendix in situ remains our preference, reconfigured ileum is a reliable substitute in patients without a suitable appendix.

Percutaneous cystolithotomy in the pediatric augmented bladder.

PURPOSE: Bladder stones are a common problem following augmentation cystoplasty. With the addition of Mitrofanoff channels for intermittent catheterization and more aggressive bladder neck tightening procedures, the incidence of stones has increased and endoscopic access to the bladder has become more complicated. We present our results of percutaneous endoscopic cystolithotomy in children with bladder augmentation. MATERIALS AND METHODS: We performed percutaneous extraction of bladder calculi in 13 children with bladder augmentation. All patients performed catheterization either via a Mitrofanoff channel, artificial urinary sphincter or plicated ileal limb of an ileocecal reservoir. The prior suprapubic tube site was dilated with an Amplatz set for access, and stones were removed intact or fragmented by laser or electrohydraulic lithotripsy. RESULTS: Percutaneous extraction was successful in 12 of the 13 patients (92%). The remaining patient had a small posterior bladder perforation and open cystolithotomy was performed. All patients were discharged home in 24 to 36 hours, and there have been no stone recurrences with a mean followup of 24 months. CONCLUSIONS: Percutaneous stone removal using the previous suprapubic tract is a simple, effective and minimally invasive option for removing stones in an augmented bladder. This technique avoids potential injury to the continence mechanism of the reconstructed bladder neck or Mitrofanoff channel. Percutaneous stone removal has become our procedure of choice for managing calculi in the augmented bladder.

Long-term followup and outcome of continent catheterizable vesicocstomy using the Rink modification.

PURPOSE: Multiple techniques have been described to create a Mitrofanoff channel in the pediatric population. A small subset of patients only requires creation of a catheterizable channel without bladder augmentation. These patients are ideal candidates for a procedure that avoids the use of intestine, especially in the absence of a suitable appendix. We used a modification of the Casale vesicostomy, as described by Rink, to create a continent vesicostomy in these children. We report our long-term experience with this technique. MATERIALS AND METHODS: We retrospectively reviewed the medical records of all patients who underwent continent vesicostomy at our institution between 1992 and 2000. Patient diagnosis, stomal site, associated bladder procedures, stomal continence, followup and complications associated with continent vesicostomy were documented. RESULTS: Of the 31 patients who underwent continent vesicostomy, as described by Rink, 14 were female and 17 were male. Average age was 9 years (range 2.5 to 22). Primary diagnosis included neuropathic bladder in 15 cases, the prune-belly syndrome in 6, cloacal exstrophy/anomaly in 5 and other in 5. The stoma was placed in the lower abdomen in 17 patients, in the umbilicus in 7 and in a neoumbilicus in 7. Simultaneous procedures included ureteral reimplantation in 8 cases, bladder augmentation in 5, bladder neck surgery in 4 and reduction cystoplasty in 2. Mean followup was 41 months. All patients achieved excellent stomal continence. Complications included stomal stenosis requiring revision in 14 cases (45%). Stenosis developed in 60% of the patients with neuropathic bladder and in 86% with an umbilical stoma. Eventually 6 patients underwent conversion to an alternative catheterizable channel. CONCLUSIONS: Continent vesicostomy can be performed successfully when there is any underlying bladder pathology with 100% stomal continence. Despite the higher rate of stomal problems with this type of Mitrofanoff channel we think that continent vesicostomy is a reasonable alternative in patients with a large bladder requiring only catheterizable channel creation. Because of the excellent results reported with the Monti-Yang technique, we would currently recommend this procedure over continent vesicostomy when bowel is used for bladder reconstruction.

Continence and classic bladder exstrophy treated with staged repair.

PURPOSE: Urinary continence rates after reconstruction of the urinary tract for classic bladder exstrophy are variable. We review our experience with procedures required to optimize continence. MATERIALS AND METHODS: We retrospectively reviewed the charts of patients with classic bladder exstrophy undergoing staged reconstruction between 1976 and 2001. Continence was reviewed and associated with the procedures performed. Patients were considered continent if dry for greater than 3 hours with no stress incontinence and dry at night. Partial continence required dryness for 1 to 3 hours, minor stress incontinence and occasional nighttime leakage. Incontinent patients were dry for less than 1 hour, had significant stress incontinence or were wet at night. Patients were followed for a median of 12.5 years. RESULTS: Continence was achieved in 43 of 48 patients (90%), partial continence in 4 (8%) and 1 (2%) remains incontinent. Continence occurred before bladder neck repair in 4 patients. Bladder neck repair alone (without augmentation) was performed in 38 patients at a median of 4.25 years, resulting in continence in 13 patients (34%). However, 6 of these 13 patients later required augmentation. Augmentation was performed in 33 patients, with 30 (91%) attaining continence after this procedure. Of those continent patients 10 void per urethra, and 8 void and use clean intermittent catheterization. Of the patients treated with bladder augmentation 93% required clean intermittent catheterization. CONCLUSIONS: Continence can be achieved in most patients with classic bladder exstrophy. However, augmentation was required in 30 of 43 patients (70%). Bladder neck reconstruction alone resulted in continence in only a third of the cases.

Lipopolysaccharide and inflammatory cytokines cause an inducible nitric oxide synthase-dependent bladder smooth muscle fibrotic response.

PURPOSE: Bladder wall fibrosis is a sequela of recurrent urinary tract infection (UTI). Inducible nitric oxide synthase (iNOS) has been shown to mediate the fibrotic response to inflammation in other tissues. We determined if iNOS could be involved in the fibrotic response to recurrent UTI. MATERIALS AND METHODS: Human bladder smooth muscle cells (SMC) were treated with bacterial lipopolysaccharides (LPS) and a mixture of inflammatory cytokines. The level of collagen type III, and the levels of iNOS mRNA, protein and activity were determined. The effect of the iNOS inhibitor aminoguanidine on collagen type III expression was then assessed. RESULTS: Expression of collagen type III, iNOS mRNA and iNOS protein as well as iNOS activity were increased in bladder SMC treated with the combination of LPS and cytokines. The increase in collagen type III expression was inhibited by pretreatment of cells with aminoguanidine. CONCLUSIONS: LPS and inflammatory cytokines induce collagen type III expression in an iNOS dependent manner in human bladder SMC. This finding suggests that iNOS may be a critical mediator of the bladder wall fibrotic response to chronic UTI and iNOS inhibitors may be of therapeutic value in patients with chronic UTI.