Evidence for Early Cyclosporine Treatment for Hunner Lesion Interstitial Cystitis.

OBJECTIVES: The objective of this study was to evaluate our experience using cyclosporine A (CyA) in the treatment of Hunner lesion interstitial cystitis (HLIC). METHODS: Retrospective chart review was performed on patients with HLIC treated with CyA from August 2012 to September 2019. Demographic and clinical variables, number of interstitial cystitis therapies, frequency, nocturia, and bladder pain visual analog scores before and after CyA treatment were collected, as well as the Global Response Assessment (GRA) and the Interstitial Cystitis Symptom Index and Interstitial Cystitis Problem Index. CyA responders were defined as those with moderately or markedly improved GRA scores. RESULTS: A total of 51 patients with HLIC treated with CyA were identified. Mean follow-up was 3 years (0.36-6.8 years). Seventy-six percent (28 of 37) were female; mean age was 68 years (51-84 years). Before CyA treatment, an average of 8 previous therapies were tried and patients reported an average of 8 of 10 bladder pain. Daytime frequency was 11-20 times per day, and nocturia was 7 times per night. Per the GRA, 84% (31 of 37) were considered CyA responders. Posttherapy Interstitial Cystitis Symptom Index and Interstitial Cystitis Problem Index scores were lower in responders compared with nonresponders (8.9 ± 5.7 vs 21.3 ± 7.0, P = 0.001). Bladder pain, number of hydrodistentions/fulgurations, nocturia, and daytime frequency improved significantly after CyA treatment. CONCLUSIONS: The cyclosporine A response rate was 84%, with most of these patients reporting marked improvement. Bladder pain, daytime frequency, and nocturia were significantly improved after CyA treatment, and the number of interventions after CyA treatment decreased. Cyclosporine A should be considered earlier than fifth-line therapy in HLIC.

Placement of mid-urethral mesh slings at the time of vaginal prolapse repair does not affect post-operative sexual function or orgasm.

INTRODUCTION AND HYPOTHESIS: Because of the relationship between the clitoral neurovascular supply and the urethra, the dissection for placement of mid-urethral slings (MUS) may negatively impact orgasmic function. We aimed to analyze the role of MUS in orgasmic and overall sexual function in patients undergoing prolapse surgery. METHODS: A single institution retrospective review was performed on 157 patients undergoing prolapse surgery with and without MUS from 2008 to 2014. Pelvic Organ Prolapse Incontinence Sexual Questionnaires (PISQ-12) scores at baseline, 6, and 12 months post-operatively were compared. The difference in overall mean post-operative PISQ-12 scores at 6 and 12 months in those undergoing POP with or without MUS placement was assessed using Wilcoxon rank tests. RESULTS: Of 157 women who underwent prolapse surgery, 81 (52%) had concomitant MUS. Mean baseline PISQ-12 scores were 32 in both groups (p = 0.98). Post-operative PISQ-12 scores between the two groups did not differ at 6 (p = 0.96) or 12 months (p = 0.65). Within the MUS group, mean overall PISQ-12 scores improved at 6 (p = 0.05) and 12 months (p < 0.01). Mean overall PISQ-12 scores did not improve in patients who did not have slings placed at 6 (p = 0.10) or 12 months (p = 0.15). Orgasm frequency and intensity did not differ between the two groups at 6 (p = 0.39, p = 0.91, respectively) or 12 months (p = 0.11, p = 0.44, respectively). CONCLUSION: MUS at the time of prolapse repair did not affect orgasmic or overall sexual function. PISQ-12 scores improved after prolapse surgery with concomitant MUS placement. Our findings may help counsel patients regarding the risk of MUS placement affecting sexual function.

Sacral Neuromodulation: Determining Predictors of Success.

OBJECTIVE: To determine predictors of success for sacral neuromodulation in women with overactive bladder, urinary retention, and fecal incontinence. METHODS: A retrospective chart review was performed on women who underwent a staged sacral neuromodulation implantation between 2007 and 2018. Clinical and procedural characteristics were recorded. Presence of intraoperative motor responses in either all 4 or <4 electrodes were used to group women. Endpoints included completion of stage II implant, tined lead revision, and patient-reported success. RESULTS: In 198 women with a mean age of 62.9 years (SD+/- 14.7), completion of stage II implant occurred in 92.4% of women, and 83.3% of these women reported success at the first postoperative visit. Continued success at 6 months was reported in 70.3%. Lead revision was noted in 23.0%. Age >65 years (odds ratio [OR] = 0.2, 95% confidence interval [CI] = 0.06-0.8) and prior onabotulinumtoxinA (onaBoNT-A) (OR = 0.2, 95% CI = 0.06-0.9) were negative predictors for completion of stage II implant on multivariable analysis. Also, prior pelvic floor physical therapy was a significant negative predictor of postoperative patient-reported success on multivariable analysis (OR = 0.25, 95% CI = 0.1-0.6). There were no differences seen in women who had motor responses with either all 4 electrodes or <4 electrodes in any endpoint (P > .05). CONCLUSION: Patient age >65 and history of prior onaBoNT-A were associated with failure to complete stage II implant. Women with prior pelvic floor physical therapy were less likely to report success after sacral neuromodulation. Motor responses in <4 electrodes during lead testing did not impact patient-reported success.

The clinical rate of antibiotic change following empiric treatment for suspected urinary tract infections.

PURPOSE: To determine the rate of antibiotic change in an outpatient setting following empiric treatment of culture proven UTI and to identify risk factors associated with change. METHODS: Patients with suspected UTI and urine culture were reviewed (January 2016-June 2016). Those with a positive culture were categorized by whether or not they were treated empirically. Empiric treatment was evaluated for associations with clinical-demographic data, symptoms and urinalysis (UA). Antibiotic change was evaluated with clinical-demographic data, urine culture, and resistance patterns. RESULTS: 916 urine cultures (636 patients) were included. 391 (43%) cultures were positive, and 164 (42%) were treated empirically. Clinical-demographic data did not differ between groups. Those treated empirically had more documented UTI symptoms (93 vs 58%, P < 0.001), and UA abnormalities including positive nitrites (51 vs 29%, P < 0.001), 3 + leukocyte esterase (27 vs 19%, P = 0.002) and 3 + blood (13 vs 4%, P = 0.005). Of those treated empirically, 42/164 (26%) required an antibiotic change, and this was associated with immunosuppression (12 vs 2%, P = 0.027) resistance to > 3 antibiotics (33 vs 20%, P = 0.039) and also resistance to fluoroquinolone (50 vs 30%, P = 0.016), monobactam (19 vs 7% P = 0.042) and TMP-SMX (52 vs 19%, P < 0.001). CONCLUSIONS: Almost one-quarter of patients treated empirically required antibiotic change. This was driven largely by bacterial resistance. New technologies allowing rapid bacterial identification and sensitivity may improve patient care.

Characterization of the T-cell response to polypropylene mesh in women with complications.

BACKGROUND: Polypropylene mesh is used widely for surgical treatment of pelvic organ prolapse and stress urinary incontinence. Although these surgeries demonstrate favorable functional and anatomic outcomes, their use has been limited by complications, the 2 most common being exposure and pain. Growing evidence suggests that T lymphocytes play a critical role in the regulation of the host response to biomaterials. OBJECTIVE: The purpose of this study was to define and characterize the T-cell response and to correlate the response to collagen deposition in fibrotic capsules in mesh tissue complexes that are removed for the complications of pain vs exposure. STUDY DESIGN: Patients who were scheduled to undergo a surgical excision of mesh for pain or exposure at Magee-Women's Hospital were offered enrollment. Forty-two mesh-vagina tissue complexes were removed for the primary complaint of exposure (n=24) vs pain (n=18). Twenty-one patients agreed to have an additional vaginal biopsy away from the site of mesh that served as control tissue. T cells were examined via immunofluorescent labeling for cell surface markers CD4+ (Th), CD8+ (cytotoxic) and foxp3 (T-regulatory cell). Frozen sections were stained with hematoxylin-eosin for gross morphologic condition and picrosirius red for collagen fiber analysis. Interrupted sodium-dodecyl sulfate gel electrophoresis was used to quantify the content of collagens type I and III, and the collagen III/I ratio. Transforming growth factor-ß and connective tissue growth factor, which are implicated in the development of fibrosis, were measured via enzyme-linked immunosorbent assays. Data were analyzed with the Student's t tests, mixed effects linear regression, and Spearman's correlation coefficients. RESULTS: Demographic data were not different between groups, except for body mass index, which was 31.7 kg/m2 for the exposure group and 28.2 kg/m2 for pain (P=.04). Tissue complexes demonstrated a marked, but highly localized, foreign body response. We consistently observed a teardrop-shaped fibroma that encapsulated mesh fibers in both pain and exposure groups, with the T cells localized within the tip of this configuration away from the mesh-tissue interface. All 3 T-cell populations were significantly increased relative to control: CD4+ T helper (P<.001), foxp3+ T regulatory (P<.001), and CD8+ cytotoxic T cell (P=.034) in the exposure group. In the pain group, only T-helper (P<.001) and T-regulatory cells (P<.001) were increased, with cytotoxic T cells (P=.520) not different from control. Picrosirius red staining showed a greater area of green (thin) fibers in the exposure group (P=.025) and red (thick) fibers in the pain group (P<.001). The ratio of area green/(yellow + orange + red) that represented thin vs thick fibers was significantly greater in the exposure group (P=.005). Analysis of collagen showed that collagen type I was increased by 35% in samples with mesh complications (exposure and pain) when compared with control samples (P=.043). Strong correlations between the profibrosis cytokine transforming growth factor-ß and collagen type I and III were found in patients with pain (r≥0.833; P=.01) but not exposure (P>.7). CONCLUSION: T cells appear to play a critical role in the long-term host response to mesh and may be a central pathway that leads to complications. The complexity of this response warrants further investigation and has the potential to broaden our understanding of mesh biology and clinical outcomes.

An Update on Fluoroquinolones: The Emergence of a Multisystem Toxicity Syndrome.

INTRODUCTION: The FDA (U.S. Food and Drug Administration) recently revised the boxed warning on fluoroquinolones to address serious safety concerns. This action was prompted by a growing number of reports involving patients with a constellation of symptoms now called fluoroquinolone associated disability. METHODS: Internet and literature searches were performed to identify previous reports of quinolone induced multisystem toxicity syndromes. The 3 terms fluoroquinolone toxicity, quinolone toxicity syndrome and fluoroquinolone associated disability were used to query PubMed® and Google's search engine for available information. RESULTS: Four primary sources emerged, including a recent FDA review, 2 case series and robust social media platforms. The FDA identified 1,122 fluoroquinolone disability reports from November 1, 1997 to May 30, 2015. A total of 178 cases qualified as fluoroquinolone associated disability after applying inclusion and exclusion criteria. Some estimate that there are as many as 45,000 cases of fluoroquinolone toxicity syndrome in the United States. All sources agree the affected population is generally young (mean age 40s to 50s), previously healthy and predominantly female. The FDA analysis revealed that average symptom duration was 14 months and longest duration was 9 years at the time of the review. CONCLUSIONS: Fluoroquinolone toxicity syndromes do not affect the majority of exposed patients but are likely underappreciated. As providers seeking to heal and avoid harm to our patients, diligent prescribing practices are paramount, as are early recognition and discontinuation of the antibiotic.

Current management of paratesticular rhabdomyosarcoma.

OBJECTIVES: Paratesticular rhabdomyosarcoma accounts for 7-10% of genitourinary rhabdomyosarcoma tumors and is the 3rd most common after RMS of the prostate and bladder. Though most (60%-80%) patients with paratesticular rhabdomysarcoma present with localized disease, assessment of systemic disease is vital. The treatment of paratesticular rhabdomyosarcoma has evolved over several decades; the current standard of care is multimodal treatment including surgery, chemotherapy, and radiation. We give insight into the evolution of treatment, present the oncologic outcomes of seminal studies, and summarize the current recommendations for the management of these patients. METHODS: A comprehensive search of the literature on the electronic databases PubMed was conducted for management of paratesticular rhabdomyosarcoma. Case reports were excluded, clinical trials from all the oncologic society were reviewed and relevant articles are included in the review. RESULTS: The treatment regimen is based on following principles: (1) local control of the primary site with radical orchiectomy and (2) assessment of local control and distant sites. Further treatment is directed according to disease stage, histology, and age of the patient. The goal of treatment is to achieve cure or maximum tumor control while minimizing toxicity. CONCLUSIONS: With the changing landscape in the management of paratesticular rhabomyosarcoma, significant improvement is evident in the oncologic outcomes. Further advance in genomic testing would lead us to tailor treatment based on individual risk factors and minimize long-term side effects.

Using the Native Afferent Nervous System to Sense Bladder Fullness: State of the Art.

The regulation of micturition involves complex neurophysiologic pathways, and its understanding has grown immensely over the past decade. Alternative approaches and applied technologies in the treatment of bladder dysfunction have minimized the complications that result from neurogenic bladder. The use of natural bladder mechanoreceptors and electroneneurographic (ENG) signal recordings from afferent nerves to chronically monitor bladder volume is a promising concept, but the technology to accomplish this has proven to be a great biomedical engineering challenge. The focus of this paper will be to describe the current state of ENG signal recording as a method to detect bladder fullness.

Dorsal Lumbotomy Incision for Partial Nephrectomy in Patients With Small Posterior Renal Masses.

OBJECTIVE: To describe our single-surgeon experience with dorsal lumbotomy, an uncommonly utilized muscle-sparing incision, for open partial nephrectomy. MATERIALS AND METHODS: We retrospectively identified patients who underwent partial nephrectomy through dorsal lumbotomy incision by a single surgeon from September 2012 through April 2014. Clinicopathologic characteristics were recorded along with early postoperative outcomes including hospital length of stay and narcotic requirement. RESULTS: Twenty-four patients were identified for analysis. Median operative time was 71 minutes (interquartile range [IQR]: 63-91 minutes), and median estimated blood loss was 250 mL (IQR: 100-438 mL). Median length of stay was 1.2 days (IQR: 0.94-2.0 days) and median narcotic requirement was 17 mg of oral morphine equivalents (IQR: 4.9-43 mg). Overall perioperative complication rate was 25% including 1 major (Clavien III-V) complication. CONCLUSION: Partial nephrectomy via dorsal lumbotomy incision is a safe and feasible option for small posterior renal masses when performed by an experienced surgeon. The drawbacks of this approach are limited access to the renal hilum and risk of injury to the iliohypogastric or subcostal nerves. Dorsal lumbotomy is associated with postoperative outcomes equivalent to or better than standard operative approaches and should be considered a viable surgical approach in selected cases.

Large Bladder Clot-An Unusual Presentation of Neonatal Bilateral Renal Vein Thrombosis-Case Report and Review of Literature.

A 1-day-old boy born at 37 weeks gestation presented with hematuria, thrombocytopenia, and palpable irregular right flank mass. Renal ultrasound demonstrated large clot within the bladder, bilateral kidney masses with loss of corticomedullary differentiation, and reversal of diastolic flow. The patient was diagnosed with bilateral renal vein thrombosis and was managed conservatively. There was complete resolution of the bladder clot with restoration of corticomedullary differentiation bilaterally. We report the first case of renal vein thrombosis associated with a large bladder clot in a neonate.