Parenchymal echotexture changes as a predictor of viability in testicular torsion.

INTRODUCTION: Preoperative test that can predict the salvageability of the torsed testis may add essential information to the surgeon managing testicular torsion (TT), this can assist with patients' and parents' expectations, particularly with nonviable testes. We aimed to examine if parenchymal echotexture changes in preoperative ultrasound can predict irreversible hemorrhagic necrosis. MATERIALS AND METHODS: Preoperative ultrasound studies of 154 patients with TT were reviewed by 3 raters (2 radiologists and 1 urologist). The raters were asked to categorize the affected testicular parenchymal echotexture into one of the following categories: (1) normal (identical to the contra-lateral testis), (2) homogenous hypoechoic, or (3) focal heterogeneous echotexture. Testis non-viability was defined macroscopically during surgical exploration and correlated with the US results. Sensitivity, specificity, and positive and negative predicting values of the proposed diagnostic test were calculated. Cohen's kappa coefficient was used to determine inter-rater agreement. RESULTS: A total of 54/154 patients had a nonviable testis. Mean of 59.5% cases was classified as category 1, 27.3% cases as category 2, and 13.2% cases as category 3. Testicular necrosis was 12%, 34%, and 92% in each category, respectively. Category 3 classified non-viability with a mean specificity of 99.3% and with a high inter-rater agreement level (Cohen's kappa coefficient of 0.830). Mean positive predictive value of 97% and mean negative predictive value of 74.3%. The mean sensitivity of this test however was low 39.7%. CONCLUSION: Ultrasound finding of focal parenchymal echotexture heterogeneous changes is highly specific although not sensitive, for nonviable testis. The presence of this finding reassures non-viability in over 99%.

BactoSpin: Novel Technology for Rapid Bacteria Detection and Antibiotic Susceptibility Testing.

Inappropriate use of antibiotics is one of the leading causes of the increasing numbers of resistant bacteria strains, resulting in 700,000 deaths worldwide each year. Reducing unnecessary use of antibiotics and choosing the most effective antibiotics instead of broad-spectrum drugs will slow the arms race between germs and humans. Urinary tract infections (UTIs) are among the most common bacterial infections. Currently, accurate diagnosis of UTI requires approximately 48 h from the time of urine sample collection until antibiotic susceptibility test (AST) results. This work presents a rapid bacterial detection device that integrates a centrifuge, microscope, and incubator. Two disposable microfluidic chips were developed. The first chip was designed for bacteria concentration, detection, and medium exchange. A second multi-channel chip was developed for AST. This chip contains superhydrophobic and hydrophilic coatings to ensure liquid separation between the channels without the need for valves. The designed chips supported the detection of E. coli at a concentration as low as 5 × 103 cells/mL within 5 min and AST in under 2 h. AST was also successfully performed with Klebsiella pneumonia isolated from a human urine sample. In addition, machine-learning-based image recognition was shown to reduce the required time for AST and to provide results within 1 h for E. coli cells. Thus, the BactoSpin device can serve as an efficient and rapid platform for UTI diagnostics and AST.

[NEOADJUVANT CHEMOTHERAPY BEFORE RADICAL CYSTECTOMY - MIGHT IT BE OFFERED SELECTIVELY?]

INTRODUCTION: Neoadjuvant cisplatin-based chemotherapy prior radical cystectomy is the standard of care in patients with a muscle invasive bladder cancer. It is intended to treat micro-metastases. However, most patients do not develop metastases even without chemotherapy and are receiving this treatment in vain. In this study, we looked for pre-operative risk factors for developing metastases that can triage the patients that really need neoadjuvant therapy. METHODS: From 1998 to 2018, 285 patients underwent radical cystectomy without neoadjuvant chemotherapy. During a median follow-up of 42.5 months, 99 patients (34%) developed recurrent disease after a median duration of 12 months. The study compared 10 different preoperative parameters of patients who developed or did not develop recurrence. RESULTS: An increased risk of metastases was found in older patients (39.8% in older than 69 years vs. 33.3% in younger patients, p=0.045), in patients with a high Charlson Comorbidity index (46.2% in 5 and above vs. 28.2% when lower than 4, p=0.003), and in patients with large tumor diameter (p=0.01). No difference was found in the other variables examined including: gender, primary versus secondary tumor, tumor stage, presence of histological variant, hydronephrosis, carcinoma in situ (CIS) or sarcomatoid differentiation. CONCLUSIONS: Older age, comorbidity, and large tumor diameter predict the risk of recurrence after radical cystectomy. However, overlap between the groups precludes the use of these parameters for clinical decisions. Therefore, neoadjuvant chemotherapy treatment should currently be offered to all candidates for radical cystectomy. Hopefully, future molecular markers will be able to predict the risk of metastases.

A study of prostate volumes in patients with spinal cord injury.

AIMS: To evaluate the development of benign prostatic hyperplasia (BPH) in patients with spinal cord injury (SCI) and to deduce the role of the nervous system in this process. METHODS: Prostate volumes (PVs) of 65 men older than 30 years of age who sustained SCI were determined from CT scans. Correlations of PVs with SCI level, age, age during SCI and duration of paralysis were calculated. RESULTS: Average patient's age during SCI was 37.7 (±19) years and during measurement of PV 54.8 (±15.3) years. PVs of patients with SCI were similar to expected age-adjusted volumes (29.7 ± 24 mL vs 29.9 ± 5.7 mL, P = 0.95). We dichotomized the cohort into two groups: High SCI (T5 and above) and low SCI (T6 and below) with almost identical: number of patients, age of SCI and duration of paralysis. Patients with lower injuries, had significantly smaller PVs when compared both to patients with higher injuries (19.4 ± 6.3 and 39.8 ± 30, P = 0.0006) and to age-adjusted normal PVs (19.4 ± 6.3 and 29.2 ± 5.8, P = 0.0005). Correlation of PV with age was found in patients higher injuries (R2 = 0.26, p = 0.003) but not in patients with lower (R2 = 0.08, P = 0.11). Moreover, patients with lower SCI had significantly smaller prostate even compared to expected PVs during SCI (18.7 ± 4.6 cc vs 27.8 ± 6.9 cc, P = 0.00006). CONCLUSIONS: Low SCI stops and reverses age related increase in PV. This phenomenon does not occur in high SCIs. This suggests that continuous support of the nervous system is essential for sustaining BPH and raises the possibility of finding a non-hormonal pharmacological intervention for reversing BPH.

'Very-low-risk' bladder tumours - a new entity?

OBJECTIVE: To evaluate the homogeneity of the 'low-risk' bladder cancer group in an attempt to optimise follow-up protocols. PATIENTS AND METHODS: Between June 1998 and December 2008, 211 patients (mean [sd] age of 66.7 [12.8] years) underwent transurethral resection of low-risk bladder cancer. Postoperative follow-up included cystoscopy at 3 and 12 months after surgery, then annually for a total of 5 years, and then annual ultrasonography indefinitely. RESULTS: After a median follow-up of 10 years, 65 patients (30.7%) developed tumour recurrence and three (1.4%) stage progressions. In all, 84 patients (40%) had tumours of ≤1 cm; these patients were significantly younger than patients with 1.1-3 cm tumours (64.6 vs 68.3 years, P = 0.03). Their 5-year recurrence-free survival rate was significantly higher (92% vs 70% in patients with larger tumours, P < 0.001). The median time to recurrence was 5.7 years in patients with smaller tumours and 3.6 years in patients with larger tumours (P = 0.03). Only 43.7% of the recurrences in patients with small tumours occurred within 5 years, compared to 75.5% in patients with larger tumours. CONCLUSIONS: Patients with low-risk bladder cancer make an inhomogeneous group. They can be stratified according to tumour size. Patients with tumours of ≤1 cm are younger, have lower risk of tumour recurrence, and most of their recurrences arise beyond the recommended 5-year surveillance period. It seems that these patients can be classified separately to a 'very-low-risk' group. Follow-up in these cases can be based on prolonged non-invasive evaluations.

[ACTIVE SURVEILLANCE IN RECURRENT LOW-RISK BLADDER TUMORS].

OBJECTIVES: To report our experience with the active surveillance policy in patients with recurrent low-risk bladder tumors. METHODS: The files of 52 patients who underwent active surveillance instead of immediate surgical resection were reviewed. Different variables concerning tumor growth rate were evaluated. RESULTS: A total of 75 surveillance periods were documented in 52 patients (mean age 75.6 years S.D. 10.45 years, 37 males and 14 females), Mean surveillance period length was 16.5 months (S.D. 16.1). All tumors resected after surveillance were found in stage Ta and in low-grade except one tumor which was high-grade; 70 active surveillance periods ended with tumor resection, and 5 patients were still under surveillance when the research ended; 27 surveillance periods (37.7%) ended because of the growth of additional tumors. Active surveillance therefore spared 27 surgeries. The rate of tumor growth during surveillance depended on the tumor's largest diameter at the beginning of surveillance. If initial tumor diameter was smaller than 5 mm (68 cases), the median tumor growth rate was 1.12 mm3/month (IRQ: 0-6.55). If the initial tumor diameter was ≥5 mm (7 cases), the median tumor growth rate was 137.14 mm3/month (IRQ: 2.21-1787.5, p < 0.05). CONCLUSIONS: Small, recurrent papillary bladder tumors pose minimal risk to the patient. An active surveillance policy, without immediate resection of the tumor is safe, can spare surgeries and can be considered in patients presenting with small papillary recurrence.

[PERCUTANEOUS TREATMENT OF SMALL RENAL TUMORS BY THERMAL ABLATION].

INTRODUCTION: Kidney cancer accounts for approximately 2-3 % of all types of cancers. Renal tumors prevalence and especially the prevalence of small renal tumors, is on the rise. About half of the tumors currently diagnosed are smaller than 4 cm. Minimally invasive methods of radiofrequency ablation technology were recently developed for the treatment of small renal tumors and are characterized by reducing the surgical and anesthetic risk. The ablation is performed with a percutaneous approach guided by ultrasound, CT or MRI. We reviewed the results of this treatment. METHODS: A total of 75 patients with a mean age of 69.5 years (27 - 90) were treated using RF during the period 2007-2014. The average tumor diameter was 28.4 mm (11-58 mm); 40 tumors were exophytic and 30 were central. Monitoring protocol after treatment included imaging after 1, 3, 6, 12 months subsequent to treatment and later annually; median follow-up time was 21 months (1 - 97). RESULTS: Evidence of tumor recurrence was observed in 9 patients (11.4%); 8 were treated successfully by another RF session. Cases in which recurrence was observed were characterized by a tumor larger than 30 mm (5/9) and adjacent to renal cysts (3/9); 5 of the lesions were central (endophytic) (P=0.5). One patient died due to metastatic RCC and a metastatic disease developed in two additional patients who died of other causes. CONCLUSIONS: It is possible to destroy most of the small renal tumors by RF ablation. When the tumor size is up to 30 mm, a 94% long-term cure may be reached. In the event of renewed growth of the tumor, the treatment can be repeated with good results. In light of short-term experience, it is recommended to limit this treatment to older patients, with a short life expectancy or when anesthetic risks prohibit surgery.

Home Urodynamic Pressures and Volume Measurement for the Neurogenic Bladder: Initial Validation Study.

PURPOSE: We evaluated the ability of a bladder pressure/volume diary to identify patients at risk for increased intravesical pressures. MATERIALS AND METHODS: Patients dependent on clean intermittent catheterization used ruler based manometry to measure intravesical pressures before leakage or scheduled drainage at home. We prospectively collected clinical, urodynamic and bladder pressure/volume diary data in patients with spina bifida who were optimized on anticholinergic therapy and clean intermittent catheterization. Measurements were taken with patients in the supine position with relaxed abdominal muscles. We defined increased pressure as detrusor pressure greater than 30 cm water as measured by urodynamics. ROCs were plotted to correlate bladder pressure/volume diary variables with abnormal intravesical pressures, and the most sensitive variable in determining abnormal intravesical pressures was sought as the end point. RESULTS: A total of 30 patients with a mean age of 10 years (range 1 to 20) were included. Home pressures measured at maximal clean intermittent catheterization volume and mean bladder pressure/volume diary pressures were most reliable in predicting urodynamic pressures greater than 30 cm water (AUC 0.93 and 0.87, respectively). Home pressures measured at maximal clean intermittent catheterization volumes less than 20 cm water were associated with normal bladder pressures (less than 30 cm water) on urodynamics, with a sensitivity of 100% and a specificity of 80%. CONCLUSIONS: Home manometry less than 20 cm water provides a reliable measurement of safe pressures. A bladder pressure/volume diary is feasible and can aid in monitoring pressures at home without the additional cost and morbidity of urodynamics. A bladder pressure/volume diary may be a useful tool to help identify patients who would benefit from urodynamic testing.

Pregnancy Rates after Testicular Torsion.

PURPOSE: To our knowledge the effect of testicular torsion on the pregnancy rate is unknown. In this study we focused on the pregnancy rate, which is the ultimate index of fertility status. MATERIALS AND METHODS: We reviewed the records of 273 patients who presented to our emergency room with testicular torsion between 1994 and 2014. Study inclusion criteria included being in a relationship with the intent to conceive for at least 1 year, age greater than 25 years and a normal contralateral testis. Patients with primary infertility, those who were unwilling to participate or unreachable and those with a history of undescended testis and/or varicocele were excluded from analysis. Patients were contacted by telephone and interviewed according to a standardized questionnaire. Pregnancy rates in the orchiopexy and orchiectomy groups were compared to each other and to the accepted pregnancy rate in the literature. RESULTS: A total of 63 patients met study inclusion criteria, including 41 and 22 in the orchiopexy and orchiectomy groups, respectively. The pregnancy rate in the orchiopexy and orchiectomy groups was 90.2% and 90.9%, respectively (p = 1.0). The accepted pregnancy rate in the general population is 82% to 92%. Mean ± SD time to pregnancy in the orchiopexy and orchiectomy groups was 6.6 ± 5.50 and 7.2 ± 5.4 months, respectively (p = 0.27). CONCLUSIONS: Several studies suggest decreased fertility potential in patients with a history of testicular torsion. However, in the current study in couples in which the male had a history of testicular torsion the pregnancy rate and the interval to pregnancy were within the accepted range of the general population.

Development, reliability and validation of a neurogenic bowel dysfunction score in pediatric patients with spina bifida.

OBJECTIVE: To develop a reliable and valid questionnaire to monitor neurogenic bowel symptoms in children. PATIENTS: Thirty-four children aged 6-18 with neurogenic bowel and their caregivers. Eighteen control patients. METHODS: An expert panel generated a domain of observables and formative/reflective content. Response options were scaled following Likert-type items. Key informant interviews revised the measures. A final questionnaire was given to patients twice to calculate intra-rater reliability using Cohen's Kappa Coefficient (k) and paired t-test. Blinded interviews were conducted after physical examination and health assessment and questionnaires completed by a nurse to determine construct validity and inter-rater reliability using k and Spearman's rank-order correlation. Control patients completed the questionnaire once, their results were used to determine discriminate validity and a receiver operating characteristic (ROC) curve. RESULTS: Intra-rater reliability showed 85% of the questionnaires having k >0.6. Paired t-test results of t(33) = 1.997, P = 0.054, d = 0.53, confirmed there was not a significant difference between the scores of the two completed questionnaires. Inter-rater reliability showed 97% of the questionnaires having k >0.6 between the nurse and the patient/caregiver responses. Scores had a strong positive correlation at rs (32) = 0.943, P < 0.0005. Mean score with neurogenic bowel was 15.18(STD ± 5.77) and control group 4.68(STD ± 2.98). ROC analysis showed an area under the curve of 0.9. A score of 8.5 correlated with presence of neurogenic bowel with sensitivity of 94% and specificity of 87%. CONCLUSION: The questionnaire shows positive reliability and validity when used for pediatric neurogenic bowel patients. The questionnaire differentiates between normal and neurogenic patients. Larger studies are necessary to conduct further validation.

Timing of Orchidopexy for Undescended Testis in Israel: A Quality of Care Study.

BACKGROUND: Strong evidence suggests that in order to prevent irreversible testicular damage surgical correction (orchidopexy) for undescended testis (UDT) should be performed before the age of 1 year. OBJECTIVES: To evaluate whether orchidopexy is delayed in our medical system, and if so, to explore the pattern of referral for orchidopexy as a possible contributing factor in such delays. METHODS: We conducted a retrospective chart review of all children who underwent orchidopexy for UDT between 2003 and 2013 in our institution. We collected data on the age at surgery and the child's health insurance plan. We also surveyed pediatricians from around the country regarding their pattern of UDT patient referral to a pediatric urologist or surgeon for surgical correction. RESULTS: A total of 813 children underwent orchidopexy in our institute during the study period. The median age at surgery was 1.49 years (range 0.5-13). Only 11% of the children underwent surgery under the age of 1 year, and 53% between the ages of 1 and 2 years. These findings were consistent throughout the years, with no difference between the four health insurance plans. Sixty-three pediatricians who participated in the survey reported that they referred children to surgery at a median age of 1 year (range 0.5-3 years). CONCLUSIONS: Our results demonstrate delayed orchidopexy in our medical system. There is a need to improve awareness for early specialist consultation in order to facilitate earlier surgery and better care.

[FACTORS PREDICTING OVERALL AND DISEASE-FREE SURVIVAL AFTER SURGERY FOR INVASIVE BLADDER CANCER].

OBJECTIVES: To evaluate the prognosis of patients who underwent surgery for invasive bladder cancer and to search for prognostic factors. METHODS: The files of all the patients who underwent radical or partial cystectomy for invasive bladder cancer between 1992 and 2014 were reviewed. The effect of various prognostic factors was evaluated by uni- and multivariate analyses. RESULTS: A total of 160 patients were included in the study and were followed for a median period of 25.5 months after surgery. The overall 2 years and 5 years survival rates were 70% and 61.2% respectively. The disease-free 2 years and 5 years survival rates were 64.4% and 61.9% respectively. The overall 2 years and 5 years survival rates of patients with disease limited to the bladder (≥T2N0) were 88.2% and 82.4% and of patients with disease extending beyond the bladder (≤T3N0) 56.5% and 45.7% respectively. Factors that were found to be significantly associated with overall survival were: TNM stage, co-morbidity (Charlson 6-11) and the tumor's diameter. No association was found between: disease presentation, smoking habits, positive cytology, the tumor being primary or secondary, variant histology, the presence of endophytic growth pattern, the presence of CIS, hydronephrosis, positive lymph nodes on pre-operative imaging, surgery type (radical or partial cystectomy) and adjuvant chemotherapy. CONCLUSIONS: The survival rates of the locally treated patients match the reported rates in the literature. Tumors' T stage were found to be the strongest prognostic factor. Tumors' diameter was found to be an independent prognostic factor. This is reported here for the first time in the literature.

Predicting the Risk of Breakthrough Urinary Tract Infections: Primary Vesicoureteral Reflux.

PURPOSE: We constructed a risk prediction instrument stratifying patients with primary vesicoureteral reflux into groups according to their 2-year probability of breakthrough urinary tract infection. MATERIALS AND METHODS: Demographic and clinical information was retrospectively collected in children diagnosed with primary vesicoureteral reflux and followed for 2 years. Bivariate and binary logistic regression analyses were performed to identify factors associated with breakthrough urinary tract infection. The final regression model was used to compute an estimation of the 2-year probability of breakthrough urinary tract infection for each subject. Accuracy of the binary classifier for breakthrough urinary tract infection was evaluated using receiver operator curve analysis. Three distinct risk groups were identified. The model was then validated in a prospective cohort. RESULTS: A total of 252 bivariate analyses showed that high grade (IV or V) vesicoureteral reflux (OR 9.4, 95% CI 3.8-23.5, p <0.001), presentation after urinary tract infection (OR 5.3, 95% CI 1.1-24.7, p = 0.034) and female gender (OR 2.6, 95% CI 0.097-7.11, p <0.054) were important risk factors for breakthrough urinary tract infection. Subgroup analysis revealed bladder and bowel dysfunction was a significant risk factor more pronounced in low grade (I to III) vesicoureteral reflux (OR 2.8, p = 0.018). The estimation model was applied for prospective validation, which demonstrated predicted vs actual 2-year breakthrough urinary tract infection rates of 19% vs 21%. Stratifying the patients into 3 risk groups based on parameters in the risk model showed 2-year risk for breakthrough urinary tract infection was 8.6%, 26.0% and 62.5% in the low, intermediate and high risk groups, respectively. CONCLUSIONS: This proposed risk stratification and probability model allows prediction of 2-year risk of patient breakthrough urinary tract infection to better inform parents of possible outcomes and treatment strategies.

Mixed high and low grade bladder tumors--are they clinically high or low grade?

PURPOSE: The pathological grade of bladder cancer has an immense impact on patient treatment and prognosis. While most bladder tumors show pure high or low grade patterns, some show a mixed pattern. We explored the incidence and clinical significance of this phenomenon. MATERIALS AND METHODS: A total of 642 patients with a mean age of 67.5 years underwent transurethral resection of nonmuscle invasive bladder tumors between June 1998 and December 2008, including 156 and 454 with low and high grade lesions, respectively. In 32 patients (5%) mixed grade tumors were found, defined as low grade tumors with 10% or less of a high grade component. All patients were followed a median of 60 months postoperatively. RESULTS: Mean age, the proportion of men and the proportion of stages Ta/T1 in patients with mixed grade tumors were between those of the high and low grade groups. Five-year recurrence-free survival was similar for high, low and mixed grade tumor types (56.9%, 63.8% and 66.4%, respectively, p=0.252). Five-year progression-free survival was significantly lower in patients with high grade disease (73.9%, p<0.0001) but similar in those with high and mixed grade tumors (99% and 96.9%, respectively, p=0.167). Similarly, disease specific survival was significantly worse in patients with high grade tumors (p<0.0001) but similar in those with high and mixed grade lesions (p=0.679). CONCLUSIONS: Mixed grade is found in about 5% of nonmuscle invasive tumors, representing a patient group with unique clinical features. The clinical course of patients with mixed grade tumors parallels that of patients with low grade tumors.

Is the appearance of the dextranomer/hyaluronic acid mound predictive of reflux resolution?

PURPOSE: After endoscopic correction of vesicoureteral reflux, we correlated the appearance of the Deflux® mound with the outcome. MATERIAL AND METHODS: We created an online survey based on 11 primary vesicoureteral reflux cases, including 6 failed and 9 successful procedures in a total of 15 renal units. Cases were selected randomly from our video library. All cases were performed by a single surgeon using the double hydrodistention implantation technique until a satisfactory mound was achieved and corrected. An online survey questionnaire was e-mailed to 234 members of the Society for Pediatric Urology. Each survey question contained a preoperative voiding cystourethrogram image as well as images of the ureteral orifice before and after injection. Respondents were asked to predict whether they thought that the appearance of the Deflux mound would be associated with successful reflux resolution on voiding cystourethrogram 3 months postoperatively. We analyzed the percent of correctly answered questions as well as the sensitivity, specificity and predictive value of the ability of experts to predict the outcome. RESULTS: A total of 104 pediatric urologists responded to the survey. Overall, 66.4% of respondents predicted reflux resolution based on mound appearance, including 66% and 67% who correctly predicted success and failure, respectively. Mean outcome predictability per respondent was 66% (range 26% to 86%). CONCLUSIONS: The appearance of the Deflux mound and lack of hydrodistention at the completion of the procedure are not reliable predictors of outcome. Based on this experience, postoperative voiding cystourethrogram is still required to truly determine reflux resolution.

The natural history of secondary muscle-invasive bladder cancer.

BACKGROUND: The management of patients with high-grade non muscle invasive bladder cancer (NMIBC) brings diagnostic and therapeutic challenges. In the current study, we sought to study the natural history of progression to "secondary" muscle-invasive bladder cancer (MIBC)-cancer that developed during follow up of patients presenting with non-muscle invasive bladder cancer (NMIBC). METHODS: Between 1998 and 2008, 760 patients were treated for bladder cancer. Primary MIBC (>=T2) tumors (present upon presentation) were diagnosed in 114 patients. All patients with high-grade NMIBC were treated with intravesical BCG. Mean follow-up was 44 months. RESULTS: Forty patients (6.1%) developed secondary MIBC after a mean period of 21 months from initial diagnosis of bladder cancer. The 2- and 5-year disease-specific survival rates were better for patients with secondary MIBC (90% and 56% compared to 69% and 42% for patients with primary disease, p=0.03). The Kaplan-Meier curves of the two groups were parallel but displaced by approximately 2 years. CONCLUSION: In the current series, MIBC progression occurred among initially presenting patients with NMIBC in 6.1%. In most patients, the initial diagnosis of NMIBC is correct and muscle invasion occurs after a mean period of about 2 years. This supports a non-radical approach in patients with high-grade T1, Ta or Tis. Meticulous follow-up with liberal biopsy of any suspicious lesion may provide early diagnosis of invasive disease.

Peripheral Cannabinoid-1 Receptor Blockade Ameliorates Cystitis Severity.

Background: The endocannabinoid system (ECS) plays a key physiological role in bladder function and it has been suggested as a potential target for relieving lower urinary tract symptoms (LUTSs). Whereas most studies indicate that activating the ECS has some beneficial effects on the bladder, some studies imply the opposite. In this study, we investigated the therapeutic potential of peripheral cannabinoid-1 receptor (CB1R) blockade in a mouse model for LUTSs. Materials and Methods: To this end, we used the cyclophosphamide (CYP; 300 mg/kg, intraperitoneal)-induced cystitis model of bladder dysfunction, in which 12-week-old, female C57BL/6 mice were treated with the peripherally restricted CB1R antagonist, JD5037 (3 mg/kg), or vehicle for three consecutive days. Bladder dysfunction was assessed using the noninvasive voiding spot assay (VSA) as well as the bladder-to-body weight (BW) ratio and gene and protein expression levels; ECS tone was assessed at the end of the study. Results: Peripheral CB1R blockade significantly ameliorated the severity of CYP-induced cystitis, manifested by reduced urination events measured in the VSA and an increased bladder-to-BW ratio. Moreover, JD5037 normalized CYP-mediated bladder ECS tone imbalance by affecting both the expression of CB1R and the endocannabinoid levels. These effects were associated with the ability of JD5037 to reduce CYP-induced inflammatory response, manifested by a reduction in levels of the proinflammatory cytokine, tumor necrosis factor alpha (TNFα), in the bladder and serum. Conclusions: Collectively, our results highlight the therapeutic relevance of peripheral CB1R blockade in ameliorating CYP-induced cystitis; they may further support the preclinical development and clinical use of peripherally restricted CB1R antagonism for treatment of LUTSs.

Urinary tract injuries during cesarean delivery: long-term outcome and management.

OBJECTIVE: Urinary tract injury during cesarean delivery is a rare but severe complication. Due to the high prevalence of cesarean delivery, this injury may pose a high burden of morbidity. We reviewed the cases of lower urinary tract injuries identified during cesarean delivery in a tertiary medical center and identified diagnosis and treatment methods, as well as short and long-term outcomes, to establish a protocol of care for such cases. METHODS: We included women with urinary tract injury during cesarean delivery between 2004 and 2018. The cases were identified according to ICD-9 codes, as well as free text in the medical report and discharge letter. Data were collected retrospectively. Telephone interviews were conducted to obtain additional data regarding long-term outcomes. RESULTS: In14 years, a total of 17,794 cesarean deliveries were performed at our institution (17.5% of all deliveries), 14 cases of bladder injury, and 11 cases of ureteral injury were identified featuring an incidence of 0.08 and 0.06%, respectively. All bladder injuries were diagnosed and repaired intra-operatively. Six (55%) cases of ureteral injury were diagnosed in the post-operative period, and 3 of these patients required further surgery for definitive treatment. None of the patients suffered long-term adverse effects. Most bladder injuries occurred in women with previous cesarean delivery in the presence of abdominal adhesions. In contrast, most ureteral injuries occurred in women with emergency cesarean delivery during the second stage of labor, and were accompanied by an extension of the uterine incision. All women had normal kidney function in follow up and did not suffer from long term sequelae. CONCLUSION: Urinary tract injury is an uncommon complication of cesarean delivery. A high index of suspicion is recommended to avoid late diagnosis and complications. We propose a comprehensive protocol for the management of these injuries.

Is there a correlation between meatal stenosis severity, lower urinary tract symptoms and uroflowmetry?

INTRODUCTION: We have recently validated a meatal Stenosis (MS) severity grading system that is based on physical examination. OBJECTIVES: The study objective was to examine the correlation between this grading system, patients' urinary symptoms, uroflowmetry and postvoid residual parameters. STUDY DESIGN: Patients referred for our clinic for urinary and non-urinary complaints, were prospectively enrolled. Urinary symptoms questionnaire, uroflowmetry parameters and post-voiding residuals (PVR) were assessed, and photographs of the urethral meatus were taken for each patient. The photographs were graded blindly according to the previously validated grading system and correlated with urinary symptoms, uroflowmetry parameters and PVR. RESULTS: Overall, 75 patients were assessed (20 grade 0, 23 grade 1 and 32 grade 2). When using grade 0 as a reference, the odds ratio (OR) for reporting narrow stream was 6.4 (95%CI 1.65-24.77) and 4 (95%CI 1.18-14.16) for grade 1 and 2 respectively. OR for prolonged urination was 6 (95% CI 1.47-24.89) for Grade 1 and 2; OR for upward stream deviation was10.08 (95%CI -2.43-41.82) for grade 1 and 15.12 (95%CI - 3.74-61.17) for grade 2. Uroflowmetry results showed lower Qmax from 16.8(SD ± 8.0) ml/sec in grade 0-9.6 ml/s on grade 1 and 2 (p < 0.001) (Figure 1). PVR was not statistically different in the three groups. DISCUSSION: Our main findings were that meatal stenosis severity grade is associated with narrow stream as reported by parent, prolonged urination, and upward deviation of urinary stream, with increasing severity with worsening stenosis. MS grade was also associated with significant worsening of uroflow measures: a lower Qmax, Qmean and a longer time-to-Qmax. Post-void residual volume was not significantly different between the different severity grades. This study showed the clinical significance of the grading system. With subjective and objective measures. The implementation of this grading system in clinics, may aid in decision making regarding surgical intervention in the appropriate patients, and avoid unnecessary procedures. CONCLUSION: The Severity of MS seen on physical examination correlates well with obstructive symptoms and decrease of urine stream seen on uroflowmetry. These findings confirm the importance of the grading system in the evaluation of patients with MS and may be additional measure that assist in consulting parents on the indications to meatotomy.