Successfully treated urethral condyloma acuminatum utilizing intraurethral self-application of 5-fluorouracil via Q-tip.

Condyloma acuminatum is a benign genital lesion associated with low-risk human papillomavirus subtypes. Approximately 20% of HPV-associated genital warts occur in the urethra. Topical treatment of urethral condyloma in women can be challenging to treat due to difficulty applying the medication such that it maintains contact with the urethra long enough to be effective. We present a case of a successfully cleared urethral condyloma acuminatum treated via self-application using a Q-tip.

Therapeutic Efficacy of Urethral Sphincteric Botulinum Toxin Injections for Female Sphincter Dysfunctions and a Search for Predictive Factors.

External urethral sphincter (EUS) dysfunction is a common, bothersome female voiding dysfunction. This study aims to analyze the characteristics of different types of female EUS dysfunction, as well as to determine the outcome predictors of sphincteric botulinum toxin A (BoNT-A) injection. Women receiving sphincteric BoNT-A injections for refractory EUS dysfunction were retrospectively reviewed. A comparison of the baseline clinical, urodynamic parameters and the treatment responses were made for patients with different EUS dysfunctions. A total of 106 females were included. Significantly increased detrusor overactivity, detrusor contracting pressure and the bladder outlet obstruction index with decreased urge sensation were noted in patients diagnosed with dysfunctional voiding or detrusor sphincter dyssynergia comparing to those diagnosed with poor relaxation of the external urethral sphincter. The average subjective improvement rate was 67% for the injection. The therapeutic effect was not affected by the type of EUS dysfunction. The multivariate analysis revealed that bladder neck narrowing and catheterization history were predictive of negative outcomes. There is a distinct urodynamic presentation for each type of female EUS dysfunction. Sphincteric BoNT-A injection provides a good therapeutic outcome for refractory EUS dysfunction. A narrowing bladder neck and a history of catheterization suggest poor therapeutic outcomes.

Treatment of Urethral Pain Syndrome (UPS) in Sweden.

BACKGROUND: Urethral Pain Syndrome (UPS) in women is a recurrent urethral pain without any proven infection or other obvious pathology. There are few studies on UPS, and evidence-based treatment is lacking. The primary aim was to study what treatments are used, and to compare the treatment tradition of UPS in Sweden in 2018, with what was used in 2006. METHODS: A questionnaire on the treatment of women with UPS was sent to all public gynecology, urology, gynecologic oncology and venereology clinics, and one public general practice in each county in Sweden in 2018. Private practice clinics in gynecology responded to the survey in 2017. Comparisons were made with the same survey sent to gynecology and urology clinics in 2006. FINDINGS: Of 137 invited clinics in 2018, 99 (72.3%) responded to the survey. Seventy-seven (77.8%) of them saw women with UPS and 79.2% (61/77) of these clinics treated the patients using 19 different treatment methods. Local corticosteroids and local estrogens were the methods most used. Treatments were similar in gynecology and urology clinics in 2006 and 2018, although strong corticosteroids had increased in use in the treatment regimens of 2018. More than half of the clinics used antibiotics. INTERPRETATION: Since there is no evidence-based treatment of UPS, a wide spectrum of treatments is used, and different specialties use different treatment strategies. Despite the lack of proven infection, a large number of clinics also treated the syndrome with antibiotics. There is thus a need for well-designed randomized controlled clinical trials to find evidence-based treatments of UPS.

Septic shock caused by the under-recognized bacterium Eggerthella lenta in a 61-year-old male with a periurethral abscess: a case report.

Eggerthella lenta is a gram-positive anaerobic bacillus that has been associated with life-threatening infections. Bacteremia is always clinically significant and is mostly but not always associated with gastrointestinal disease. We present a unique case of abrupt deterioration and rapid development of septic shock secondary to periurethral abscess caused by E. lenta infection. This case highlights the atypical clinical presentation, risk factors, uncommon source of infection, challenges in therapy, and outcome of this infrequent infection. There is still a gap in the understanding of E. lenta pathogenicity, and more literature is needed to establish clear management recommendations.

New concepts in regenerative medicine approaches to the treatment of female stress urinary incontinence.

PURPOSE OF REVIEW: Update on recent regenerative medicine approaches to the treatment of stress urinary incontinence (SUI) caused by intrinsic sphincter deficiency (ISD). RECENT FINDINGS: In the treatment of female SUI/ISD, results using different types of cellular therapy have been disappointing, and new approaches are desirable. To advance our regenerative medicine approaches to SUI/ISD, it is critical to utilize animal models that best parallel the pathophysiology of this disease in women. Many current animal models mimic acute SUI/ISD. However, SUI/ISD in women is usually a chronic condition resulting from previous muscle and nerve sphincter damage during parturition or muscle loss during aging. Similar to women, a nonhuman primate (NHP) model of chronic SUI/ISD has demonstrated only modest response to cell therapy. However, treatment with stromal cell-derived factor 1 (SDF1), also known as C-X-C motif chemokine 12 (CXCL12) restored continence in this model. SUMMARY: As a potential therapeutic approach, the use of a well characterized chemokine, such as CXCL12, may by-pass the lengthy and expensive process of cell isolation, expansion, and injection. Recent findings in this new NHP model of chronic SUI/ISD may open up the field for noncell-based treatments.

5-aminolevulinic acid photodynamic therapy for condyloma acuminatum of urethral meatus.

Objectives: Condyloma acuminatum are the most common sexually transmitted diseases worldwide, and they are closely associated with human papillomavirus (HPV) infection. Urethral meatus is one of the places that warts occur. Many treatments for uretheral warts have limitations. In this study, we performed 5-aminolevulinic acid-photodynamic therapy (ALA-PDT) on patients and investigated the effectiveness of reducing HPV viral loads. Materials and Methods: In our study, 21 patients diagnosed with urethral condyloma acuminatum were included. After 4 h treatment of ALA, patients received PDT. Each patient received HPV test before every PDT cycle. The frequency of PDT was dependent on viral load changes. Results: All patients achieved complete clinical remission after the last session of ALA-PDT. There were significant differences in HPV viral loads between pretherapy and after one or three rounds of PDT treatment. Conclusions: ALA-PDT is a safe and effective method for treatment of condyloma acuminatum in urethra meatus. Dynamic monitoring of HPV viral loads can more objectively demonstrate the effectiveness and guide the treatment of PDT.

Septic shock caused by the under-recognized bacterium Eggerthella lenta in a 61-year-old male with a periurethral abscess: a case report

Abstract Eggerthella lenta is a gram-positive anaerobic bacillus that has been associated with life-threatening infections. Bacteremia is always clinically significant and is mostly but not always associated with gastrointestinal disease. We present a unique case of abrupt deterioration and rapid development of septic shock secondary to periurethral abscess caused by E. lenta infection. This case highlights the atypical clinical presentation, risk factors, uncommon source of infection, challenges in therapy, and outcome of this infrequent infection. There is still a gap in the understanding of E. lenta pathogenicity, and more literature is needed to establish clear management recommendations.

The effect of neutralization of nerve growth factor (NGF) on bladder and urethral dysfunction in mice with spinal cord injury.

AIMS: To investigate the role of nerve growth factor (NGF) in lower urinary tract dysfunction in mice with spinal cord injury (SCI). METHODS: Using 4-week SCI mice, single-filling cystometry and external urethral sphincter (EUS)-electromyography were performed under an awake condition. In some SCI mice, anti-NGF antibodies (10 µg/kg/h) were administered for 1 or 2 weeks before the urodynamic study. NGF levels in the bladder and L6/S1 spinal cord were assayed by ELISA. The transcript levels of P2X receptors and TRP channels in L6/S1 dorsal root ganglia (DRG) were measured by RT-PCR. RESULTS: In SCI mice, the area under the curve of non-voiding contractions (NVCs) during the storage phase was significantly decreased in both 1- and 2-week anti-NGF antibody-treated SCI groups. However, EUS-electromyogram parameters during voiding were not altered by the treatment. Bladder mucosal and spinal NGF levels were decreased after 2 weeks of anti-NGF antibody treatment. TRPA1 and TRPV1 transcripts in L6/S1 DRG were significantly decreased after 1- or 2-week anti-NGF treatment. CONCLUSIONS: In SCI mice, NGF is involved in the emergence of NVCs in association with increased expression of TRP receptors that are predominantly found in C-fiber afferent pathways. Thus, NGF targeting treatments could be effective for treating storage problems such as detrusor overactivity after SCI.

Effectiveness of syndromic management for male patients with urethral discharge symptoms in Amazonas, Brazil

Abstract: Background: Urethral discharge syndrome (UDS) is characterized by the presence of purulent or mucopurulent urethral discharge.The main etiological agents of this syndrome are Neisseria gonorrhoeae and Chlamydia trachomatis. Objectives: To evaluate the effectiveness of the syndromic management to resolve symptoms in male urethral discharge syndrome cases in Manaus, Amazonas, Brazil. Methods: Retrospective cohort of male cases of urethral discharge syndrome observed at a clinic for sexually transmitted disease (STD) in 2013. Epidemiological and clinical data, as well as the results of urethral swabs, bacterioscopy, hybrid capture for C.trachomatis, wet-mount examination, and culture for N.gonorrhoeae, were obtained through medical chart reviews. Results: Of the 800 urethral discharge syndrome cases observed at the STD clinic, 785 (98.1%) presented only urethral discharge syndrome, 633 (79.1%) returned for follow-up, 579 (91.5%) were considered clinically cured on the first visit, 41(6.5 %) were considered cured on the second visit, and 13(2.0%) did not reach clinical cure after two appointments. Regarding the etiological diagnosis, 42.7% of the patients presented a microbiological diagnosis of N.gonorrhoeae, 39.3% of non-gonococcal and non-chlamydia urethritis, 10.7% of C.trachomatis and 7.3% of co-infection with chlamydia and gonococcus. The odds of being considered cured in the first visit were greater in those who were unmarried, with greater schooling, and with an etiological diagnosis of gonorrhea. The diagnosis of non-gonococcal urethritis reduced the chance of cure in the first visit. Study limitation: A study conducted at a single center of STD treatment. Conclusion: Syndromic management of male urethral discharge syndrome performed in accordance with the Brazilian Ministry of Health STD guidelines was effective in resolving symptoms in the studied population. More studies with microbiological outcomes are needed to ensure the maintenance of the syndromic management.

Topical ALA-PDT as alternative therapeutic option in treatment-recalcitrant dermatosis: Report of 4 cases.

BACKGROUND: Topical Photodynamic therapy (PDT) is widely acknowledged for its safety and effectiveness in treating oncologic skin diseases such as basal cell carcinoma, actinic keratosis and squamous cell carcinoma in situ. Despite its broad applications in dermatology, this method is a relatively new therapeutic option for treating inflammatory/infectious skin diseases. OBJECTIVES: To determine whether topical PDT is a safe and effective treatment option in treating treatment-recalcitrant dermatosis. OBSERVATIONS: We presented one of each case of Acne Vulgaris, facial flat warts, urethral meatus Condyloma Acuminatum and extramammary Paget's disease, where other treatment options were either ineffective or not feasible, then those patients underwent topical PDT and showed significant improvement with minimal side effects. CONCLUSIONS: Topical PDT therapy may be applied in cases of Acne Vulgaris, facial flat warts, urethral meatus Condyloma Acuminatum and extramammary Paget's disease, where other treatment has shown no or minimal improvement, or in whom ablative or invasive procedure is to be avoided or not well tolerated.

Urethrovaginal fistula following vaginal prolapse of a pedunculated uterine myoma: a case report.

BACKGROUND: Urethrovaginal fistulas are usually secondary to a foreign body in the vagina or to vaginal gynecologic surgeries. We present a case of an urethrovaginal fistula secondary to vaginal prolapse of a huge pedunculated submucosal uterine myoma. CASE PRESENTATION: A 25-year-old black African woman with a past history of huge uterine fibroids and an uncomplicated vaginal delivery 5 weeks prior to presentation consulted for a difficult micturition that occurred 2 days earlier. A vaginally prolapsed huge uterine myoma was diagnosed. The fibroid was easily twisted off per vagina. Around 9 days after prolapse of the fibroid or 5 days after its removal, she complained of a vaginal leaking of urine during micturition. An urethrovaginal fistula was diagnosed using a blue dye test. The fistula was successfully repaired with polyglactin and she was discharged on day 15. CONCLUSIONS: To the best of our knowledge, this is the first case of urethrovaginal fistula secondary to delivered uterine myoma. We recommend close postpartum follow-up of women carrying huge uterine fibroid and urgent management of a vaginally prolapsed uterine fibroid to reduce the risk of urethrovaginal fistula.

Efficacy and Initial Safety Profile of CXCL12 Treatment in a Rodent Model of Urinary Sphincter Deficiency.

Disappointing results of skeletal muscle precursor cell (skMPC) therapy for women with intrinsic urinary sphincter deficiency (ISD) associated urinary incontinence has increased interest in alternative sphincter regenerative approaches. This study was to measure the safety and efficacy of the cell homing chemokine CXCL12 versus skMPCs in a rat model of ISD. Thirty-six adult female Sprague Dawley rats were divided into 6 treatment (Tx) conditions: (a) no ISD/noTx [Control]; (b) ISD/noTx; (c) ISD + skMPCs; (d) ISD + 3.5 mg CXCL12; (e) ISD + 7mg CXCL12; and (f) ISD + 14 mg CXCL12. Tx's were injected directly into the sphincter complex 30 days post ISD and rats euthanized 30 days post Tx. Blood samples for measurements of kidney and liver function, white and red blood cell counts, were taken at baseline and at euthanasia. Leak point pressures (LPP) were measured prior to, and sphincter collagen/muscle content measured after, euthanasia. There were no effects of treatments on white or red/white blood cell counts, kidney/liver function tests or histopathology of the urinary sphincter complex or surrounding tissues. ISD lowered LPP 35% and sphincter muscle content by 17% versus control rats. CXCL12, but not skMPC injections, restored both LPP to control values in a dose-dependent fashion. Both skMPCs and CXCL12 restored sphincter muscle content to control values. This chemokine approach may represent a novel therapeutic option for ISD and appears, at least short-term, to produce little clinical or tissue pathology. Stem Cells Translational Medicine 2017;6:1740-1746.

Effectiveness of syndromic management for male patients with urethral discharge symptoms in Amazonas, Brazil.

BACKGROUND: Urethral discharge syndrome (UDS) is characterized by the presence of purulent or mucopurulent urethral discharge.The main etiological agents of this syndrome are Neisseria gonorrhoeae and Chlamydia trachomatis. OBJECTIVES: To evaluate the effectiveness of the syndromic management to resolve symptoms in male urethral discharge syndrome cases in Manaus, Amazonas, Brazil. METHODS: Retrospective cohort of male cases of urethral discharge syndrome observed at a clinic for sexually transmitted disease (STD) in 2013. Epidemiological and clinical data, as well as the results of urethral swabs, bacterioscopy, hybrid capture for C.trachomatis, wet-mount examination, and culture for N.gonorrhoeae, were obtained through medical chart reviews. RESULTS: Of the 800 urethral discharge syndrome cases observed at the STD clinic, 785 (98.1%) presented only urethral discharge syndrome, 633 (79.1%) returned for follow-up, 579 (91.5%) were considered clinically cured on the first visit, 41(6.5 %) were considered cured on the second visit, and 13(2.0%) did not reach clinical cure after two appointments. Regarding the etiological diagnosis, 42.7% of the patients presented a microbiological diagnosis of N.gonorrhoeae, 39.3% of non-gonococcal and non-chlamydia urethritis, 10.7% of C.trachomatis and 7.3% of co-infection with chlamydia and gonococcus. The odds of being considered cured in the first visit were greater in those who were unmarried, with greater schooling, and with an etiological diagnosis of gonorrhea. The diagnosis of non-gonococcal urethritis reduced the chance of cure in the first visit. STUDY LIMITATION: A study conducted at a single center of STD treatment. CONCLUSION: Syndromic management of male urethral discharge syndrome performed in accordance with the Brazilian Ministry of Health STD guidelines was effective in resolving symptoms in the studied population. More studies with microbiological outcomes are needed to ensure the maintenance of the syndromic management.

Effects of botulinum toxin A injections in spinal cord injury patients with detrusor overactivity and detrusor sphincter dyssynergia.

OBJECTIVE: To evaluate the safety and effect of botulinum toxin A injection in the detrusor and external urethral sphincter in male patients with detrusor overactivity (DO) and detrusor external sphincter dyssynergia (DESD) secondary to spinal cord injury. METHODS: A multicentre trial was conducted from June 2012 to August 2015. A total of 65 spinal cord injury patients with DO and DESD participated in the study. Of these, 59 received 200 U botulinum toxin Aintradetrusor and 100 U external urethral sphincter injections. The effective outcomes included maximum detrusor pressure at first DO and DESD, VDO-DESD, maximum urethral closure pressure, duration of first DO and DESD, Incontinence-Specific Quality-of-Life Instrument, voiding volume, urinary incontinence episodes and complete dryness. Adverse events were recorded. RESULTS: All patients experienced a significant mean reduction in PdetmaxDO -DESD (46.60%), maximum urethral closure pressure (29.61%), duration of first DO and DESD (42.93%) and a significant mean increase in VDO-DESD (38.11%) 12-weeks post-injection. Significant (p < 0.001) improvement in mean Incontinence-Specific Quality-of-Life Instrument, voiding volume, urinary incontinence episodes and complete dryness were found in all patients at 2 weeks and were sustained at 8 weeks and 16 weeks. CONCLUSION: Botulinum toxin A injection in the detrusor and external urethral sphincter is an effective treatment to protect the upper urinary tract and improve quality of life for patients with DO and DESD secondary to spinal cord injury.

Cell versus Chemokine Therapy in a Nonhuman Primate Model of Chronic Intrinsic Urinary Sphincter Deficiency.

PURPOSE: Mixed efficacy results of autologous skeletal muscle precursor cell therapy in women with chronic intrinsic urinary sphincter deficiency have increased interest in the therapeutic value of alternative regenerative medicine approaches. The goal of this study was to compare the effects of the cell homing chemokine CXCL12 (C-X-C motif chemokine 12) and skeletal muscle precursor cells on chronic urinary sphincter regeneration in chronic intrinsic urinary sphincter deficiency. MATERIALS AND METHODS: Five million autologous skeletal muscle precursor cells or 100 ng CXCL12 were injected in the urinary sphincter complex of adult female cynomolgus monkeys with chronic (6-month history) intrinsic urinary sphincter deficiency. These treatment groups of 3 monkeys per group were compared to a group of 3 with no intrinsic urinary sphincter deficiency and no injection, and a group of 3 with intrinsic urinary sphincter deficiency plus vehicle injection. Maximal urethral pressure was measured at rest, during stimulation of the urinary sphincter pudendal nerves at baseline and again 6 months after treatment. The monkeys were then necropsied. The urinary sphincters were collected for tissue analysis of muscle and collagen content, vascularization and motor endplates. RESULTS: CXCL12 but not skeletal muscle precursor cells increased resting maximal urethral pressure in nonhuman primates with chronic intrinsic urinary sphincter deficiency compared to that in monkeys with intrinsic urinary sphincter plus vehicle injection (p >0.05). Skeletal muscle precursor cells and CXCL12 only partially restored pudendal nerve stimulated increases in maximal urethral pressure (p >0.05), sphincter vascularization and motor endplate expression in monkeys with chronic intrinsic urinary sphincter deficiency. Additionally, CXCL12 but not skeletal muscle precursor cell injections decreased collagen and increased the muscle content of urinary sphincter complex in monkeys with chronic intrinsic urinary sphincter deficiency compared to those with intrinsic urinary sphincter plus vehicle injection and no intrinsic urinary sphincter plus no injection (p <0.05 and >0.05, respectively). CONCLUSIONS: These results raise questions about cell therapy for chronic intrinsic urinary sphincter deficiency and identify a chemokine treatment (CXCL12) as a potential alternative treatment of chronic intrinsic urinary sphincter deficiency.