Intravesical gentamicin instillation for the treatment and prevention of urinary tract infections in complex paediatric urology patients: evidence for safety and efficacy.

BACKGROUND: Little has been reported to date on the instillation of antimicrobials directly into the bladder in children. Children with complex urinary tract anomalies struggle frequently with recurrent urinary tract infections (UTI), with frequent emergence of antibiotic resistance. Gentamicin bladder instillation to treat and prevent UTI was described in children since 2006. OBJECTIVE: We adopted gentamicin bladder instillation in 2016 and evaluate herein our intermediate-term experience with it. STUDY DESIGN AND METHODS: This study is a retrospective review of a prospectively initiated database and a clinical audit of our practice. The gentamicin bladder instillation was employed in 24 cases. A treatment regime was initiated for symptomatic documented UTI when resistance patterns precluded an oral alternative (14 cases), avoiding hospitalisation for parenteral antibiotics. A prophylaxis regime (19 cases-including 9 of the 14 who received an initial treatment regime) followed at least one breakthrough UTI while receiving oral prophylactic antibiotics. Two instillation volumes (8 mg gentamicin in 20 mL 0.9% NaCl or 20 mg gentamicin in 50 mL 0.9% NaCl) were used to suit different bladder capacities. The irrigation is given twice a day for 7 days in the treatment regime or once a day, every other day, in the prophylactic regime. Gentamicin serum levels (all cases) and audiology/audiometry testing (17/24 cases) were checked to assess the safety of this method. RESULTS: The median age when either the treatment course or prophylaxis regime was started was 3.8 years. The treatment regime was 86% successful (12/14) to suppress an acute UTI. The mean duration of prophylaxis was 252 days (median: 256 days). The percentage of patients on the prophylactic regime who had no breakthrough UTI was 58%. No serum gentamicin was detectable secondary to the intravesical instillation. No attributable cases of sensorineural hearing loss were detected. Gentamicin resistance emerged in one case (4.16%). DISCUSSION: Intravesical administration was feasible via various routes for a spectrum of complex lower urinary tract abnormalities (see Summary Figure). Concerns regarding systemic absorption, nephrotoxicity or ototoxicity were investigated and safety ensured. Limitations include being a small series of non-identical pathologies, albeit categorically similar and being a single-arm study, however, statistical significance was proven descriptively and analytically. CONCLUSION: In selected cases and with the appropriate specialist support and logistics, intravesical gentamicin instillation is well-tolerated and safe to treat and/or prevent urinary tract infections in pateints with complex bladder conditions and lower urinary tract pathologies.

Distribution of Semen Parameters Among Adolescent Males Undergoing Fertility Preservation in a Multicenter International Cohort.

OBJECTIVE: To determine the distribution of semen parameters among adolescent and adult males presenting for fertility preservation. METHODS: A retrospective, cross-sectional cohort study of adolescent males age 11-19 who underwent semen analysis for fertility preservation at 3 centers in 2 countries with a comparison cohort of adult men presenting for fertility preservation. Prevalence of azoospermia and distribution of semen parameters was compared across groups. RESULTS: A total of 197 adolescents and 95 adults underwent semen analysis for fertility preservation. Azoospermia was present in 17 (8.6%) adolescents and 3 (3.2%) adults. There was decline in the prevalence of azoospermia with increasing age. After exclusion of patients with azoospermia, the adolescent and adult cohorts were comprised of 180 and 92 patients, respectively. Median age at presentation among adolescents vs adults was 16.5years (interquartile range [IQR] 15.2-17.6) and 30.8years (IQR 22.7-43.8), respectively. Median semen volume was 1.0mL (IQR 0.5-2.0) vs 2.5mL (IQR 1.5-3.5), P <.001. Median sperm concentration was 30million/mL (IQR 10-57) vs 39million/mL (IQR 14-57), P = .2. Median sperm motility was 39% (IQR 20-55) vs 45% (IQR 35-55), P = .01. Median total motile sperm count was 11million (IQR 1.4-33) for adolescents vs 29million (IQR 13-69) for adults, P <.001. CONCLUSION: Young adolescent males had higher prevalence of azoospermia and lower semen parameters compared to adults. In conjunction with physical examination, Tanner stage, and specific clinical context, these data can help to inform patients and their families about potential for fertility preservation, even in very young adolescent patients.

Sperm concentration and forward motility are not correlated with age in adolescents with an idiopathic varicocele and symmetrical testicular volumes.

AIM: Idiopathic varicocele is a common condition that may impair fertility. Its treatment in children and adolescents is reserved for those patients who develop symptoms or testicular growth arrest. We evaluated the trends in sperm parameters among adolescent varicocele patients with symmetrical testicular volumes who have not undergone varicocelectomy. METHOD: Data were prospectively collected from a single institution (2009 to 2014). Post-pubertal patients aged 12 to 17years produced semen samples by masturbation. Outcomes measured were semen volume, sperm concentration, and forward motility. Additional variables recorded included: a) testicular volume (ultrasound measurement), b) clinical varicocele grade, c) venous Doppler grading. Linear regression analysis was performed using Fisher's transformation. P<0.05 was considered significant, and data are presented as median (IQ range). RESULTS: Forty-one patients with a median age of 15.4 (15.0-15.9) years each provided a sperm sample during the study period. Thirty-five had grade 3 (visible) varicocele, and 6 had grade 2 (palpable) varicocele. All patients had spontaneous venous reflux on Doppler ultrasound, and none had undergone varicocelectomy prior to producing the sperm sample. Table 1 summarizes the sperm parameters according to patient age. The overall median sperm concentration was 37 (16-64) millions/ml and was not correlated with age. The overall median forward motility was 55% (44-64) and was not correlated with age. Thirty-four patients had normal sperm parameters, which remained within the WHO range of normality. CONCLUSIONS: Following the European Association of Urology guidelines does not cause progressive deterioration of sperm parameters between the age of 12 and 17years.

Chemical stability of heparin, isopropanol, and ethanol line lock solutions.

BACKGROUND: Ethanol line locks are used in the US to prevent catheter associated bloodstream infections. Heparin precipitates in solution with ethanol. However, isopropanol may reduce precipitate formation. We aimed to determine the chemical stability of heparin, isopropanol, and ethanol line lock for a 10 day period at 2-8°C and 25°C. METHODS: Forty samples were prepared for analysis. Each sample was prepared identically using a 5 ml syringe capped with a Combi-stopper: 1 ml 70% isopropanol, 1 ml 70% ethanol, and 1 ml heparin sodium 10 IU/ml. Twenty syringes were stored at 2-8°C and 20 at 25°C. Analysis was carried out on days 1, 3, 6, 8, and 10 with a single syringe from each condition being tested in duplicate. Samples were assessed visually. Sub-visible particle count analysis was carried out using a CLIMET particle counting system. Heparin concentration was analysed using an anti-Xa assay. Ethanol and isopropanol concentrations were analysed by gas chromatography. RESULTS: Samples remained clear and colourless throughout the study. Sub-visible particle counts remained within limits specified in British Pharmacopoeia 2013 when stored at 2-8°C and 25°C, 60% humidity for up to 10 days. There was no significant change in ethanol or isopropanol concentration during the study. However, heparin activity fell by >10% after 1 day storage and to 65% of original activity after 10 days. CONCLUSIONS: This study shows that addition of isopropanol to heparin and ethanol prevents precipitation. However, this solution shows a progressive decline in heparin activity over time making it unsuitable for extended shelf life.

Intravenous methylene blue venography during laparoscopic paediatric varicocelectomy.

INTRODUCTION: One of the challenges of varicocele surgery is to prevent hydrocele formation while still ensuring success. Methylene blue has been used to identify and preserve lymphatic vessels, and venography has been a standard component of sclerotherapy and percutaneous retrograde techniques. The authors have combined both approaches during laparoscopic varicocelectomy and report their experience. METHODS: A prospective study was performed of adolescents with idiopathic varicocele and spontaneous venous reflux on Doppler ultrasound. A pampiniform plexus vein was cannulated via scrotal incision before creating the pneumoperitoneum. A mixture of methylene blue and Omnipaque™ was injected into the pampiniform plexus with fluoroscopic screening. Laparoscopic selective vein ligation was then performed using 5mm endoscopic clips or a bipolar vessel sealing device such as Plasmakinetic™ or Ligasure™. Venography was repeated to confirm complete ligation of the internal testicular veins. Patients were followed-up at 3, 6, and 9 months post-surgery with clinical examination and Doppler ultrasound. Data are presented as median (interquartile range). RESULTS: Twenty-four patients underwent laparoscopic selective vein ligation with venography and methylene blue injection. The median age was 14.7 (14.6-15.7) years. The recurrence rate was 12%. No patients developed a hydrocele. The length of surgery was 120 (100-126) minutes. CONCLUSION: Intra-operative intra-venous methylene blue injection and venography helps to identify venous duplications of the internal testicular veins and enhances the success rate of laparoscopic selective vein ligation. This approach prevents hydrocele formation but has a 12% recurrence rate, which appears to be higher than some techniques described in the literature.

Shortened pubic bones in bladder exstrophy: a congenital or acquired phenomenon?

OBJECTIVE: It is accepted that the length of the anterior segment of the pelvis in classic bladder exstrophy is shorter than that of controls. However, studies performed involve children with a wide range of ages. By studying children with classic bladder exstrophy under the age of 1 year, the authors aim to ascertain if there is a congenital pubic bone length discrepancy associated with bladder exstrophy. MATERIAL AND METHODS: Fourteen classic bladder exstrophy patients under 1 year of age and 14 age-matched controls were identified. Three-dimensional (3D) computerized tomography was used to measure the length of the superior pubic ramus bilaterally. In the exstrophy group, scans were performed before bladder closure. The Mann-Whitney U test was used and p < 0.05 was considered significant. RESULTS: There was no significant difference (p = 0.76) in the median age in cases (72 days) and controls (64 days). The median superior pubic ramus length was 19.1 mm in the exstrophy group and 20 mm in the control group (p = 0.99). CONCLUSIONS: Superior pubic ramus length in children under 1 year of age with classic bladder exstrophy is not statistically different from that in control subjects. Therefore, the authors hypothesize that the previously described shortening of the pubic bones is an acquired phenomenon, which may develop after the first year of life.

Sperm banking in the United Kingdom is feasible in patients 13 years old or older with cancer.

PURPOSE: Assisted reproductive technologies are increasingly being used to treat infertility. Male adolescents with cancer are particularly encouraged to bank semen to preserve fertility before beginning chemotherapy or radiotherapy. We evaluated the feasibility of semen preservation in 12 to 17-year-old patients with cancer. MATERIALS AND METHODS: We retrospectively collected data from the sperm banking database at our institution for the years 1995 to 2009. Outcomes measured were histological diagnosis, success rate, sperm concentration and sample volume. RESULTS: A total of 180 patients with a mean age of 16.1 years (range 13.2 to 17.9) were referred for cryopreservation during the study period. Underlying diagnoses included lymphoma (64 patients), leukemia (50), bone tumors (18), testicular tumors (13), soft tissue sarcoma (13), brain tumor (6), germ cell tumors (6) and other cancers (10). Of the patients 119 (66%) successfully banked sperm. A total of 26 patients did not attend their appointment. Of those who attended 15 (10%) were unable to provide a sample and 20 (13%) had azoospermia. A total of 20 patients died after banking sperm and their specimens were subsequently destroyed. CONCLUSIONS: Cryopreservation of semen of acceptable quality for future use in assisted conception is feasible for most adolescents from age 13 years onward.

Testicular volume and semen parameters in patients aged 12 to 17 years with idiopathic varicocele.

PURPOSE: Varicocele is potentially a progressive condition that may affect fertility. The authors have encouraged sperm banking for their postpubertal patients with varicocele and aim to evaluate the sperm parameters in this cohort of patients. METHODS: With institutional ethical approval, sperm variables (volume, concentration, and forward motility) of patients with postpubertal varicocele who opted for sperm banking were prospectively recorded. The following parameters were also acquired: (a) ultrasound measurement of testicular volume, (b) clinical grade, and (c) venous Doppler. Patients were divided into 2 groups: symmetrical testis (group A) and asymmetrical testis (group B). Testicular asymmetry was defined as greater than 20% difference in testicular volume compared with contralateral testis. Sperm parameters were compared between groups A and B using Mann-Whitney U test and P < .05. RESULTS: Fifteen patients were included: 10 in group A and 5 in group B. Median semen concentration in group B was significantly lower than group A (3 vs 26 million/mL; P = .04). One hundred percent of group B failed World Health Organisation adult criteria for normal spermiograms compared with 50% of group A. CONCLUSIONS: Sperm concentration and quality was lower in patients with asymmetrical testis. Testicular dysfunction may be present before the onset of testicular hypotrophy. When testicular hypotrophy is present, testicular dysfunction is very likely.