Medications mostly associated with hematuria: assessment of the EudraVigilance and Food and Drug Administration pharmacovigilance databases entries.

BACKGROUND: Drugs may have a direct causative role in triggering hematuria. The range of medications which may be responsible for hematuria is wide, but little is known on those which are most frequently involved. The aim of our study was to identify and compare drugs mostly related with hematuria. METHODS: The Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database and the EudraVigilance (EV) database were queried to identify the drugs which were associated the most with hematuria individual reports till 30 September 2021. Rivaroxaban, aspirin, warfarin sodium, clopidogrel bisulfate, dabigatran etexilate mesylate, apixaban, warfarin, cyclophosphamide, lansoprazole, enoxaparin sodium, and ibuprofen were analyzed. Analysis per gender, age and severity was performed. Disproportional analysis was performed to compare drugs. RESULTS: Overall, 15,687 reports of hematuria were recorded in the FDA database and 15 007 in the EV database. Rivaroxaban and Warfarin appear to be the most dangerous medications in terms of hematuria when compared to the other medications (PRR>1, P<0.05) while apixaban is the safest one (PRR<1, P<0.05) when compared to the other medications. In terms of severity only 162/15 007 (1.08%) were fatal. Between the drugs analyzed cyclophosphamide 7.2%, enoxaparin (3%) and dabigatran (2.5%) presented a higher number of fatal hematuria episodes when compared to the other drugs (<1%). CONCLUSIONS: Anticoagulants and antiplatelets are more frequently related to hematuria episodes however some differences exist between them. Particularly warfarin and rivaroxaban should be prescribed with caution in patients at increased risk of hematuria. Prescribers should inform those treated with these medications about the risk of hematuria and its sequelae.

A New Technique for Continent Urinary Diversion: Initial Experience and Description of the Technique.

PURPOSE: Orthotopic neobladder is a well-established surgical solution for continent urinary diversion after radical cystectomy. Nevertheless, it still represents a challenging surgery. Some critical issues of orthotopic bladder substitution include relevant complication rates, renal function impairment, urinary incontinence and patient quality of life. We present a new ileal neobladder technique, Vesuvian Orthotopic Neobladder (VON), performed for the first time at our institution in 2020. The main purpose of this new surgical procedure is to simplify and speed up the reservoir reconstruction through a ten standardized technical steps and obtain an appropriate bladder capacity at the same time.   METHODS: Inclusion criteria were muscle-invasive bladder carcinoma or non muscle-invasive high risk bladder cancer patients fit for bladder substitution. The exclusion criteria were locally advanced cancer, presence of hydronephrosis, renal or hepatic impairment. A chest-abdominal CT scan and urinary cytology were performed before the procedure. Patients received neoadjuvant chemotherapy, as required. Overall, operative time, bladder reconfiguration time, hospitalization time, catheterization time were recorded. All complications associated with the procedure were classified according to the Clavien Dindo score. The bladder volume was evaluated by ultrasound three months after the surgery.   RESULTS: A total of six male patients diagnosed with non-metastatic muscle-invasive or high-risk non-muscle invasive bladder cancer who underwent radical cystectomy followed by VON reconfiguration were included in the study. Mean age was 62.8 (±4.9) years; all selected patients enjoyed good health conditions (Charlson Comorbidity Index 4-6). One patient presented with high-risk non-muscle invasive bladder cancer. Four patients received neoadjuvant chemotherapy. Mean overall operative time was 273.3 (±18.6) minutes. Average time for neobladder reconstruction was 63.7 (±16.1) minutes. There were no intraoperative complications. A single case of urethral anastomosis leakage occurred and was treated conservatively. Bladder volume on ultrasound evaluation ranged between 250 and 290 ml.  Day time and nocturnal continence were observed in four and three patients, respectively.   CONCLUSION: The new VON technique is a good alternative to traditional orthotopic bladder procedures. VON reconstruction seems to offer the advantage of speeding up the procedure, reducing intestinal compromise with good storage capacity. The ten surgical steps can be considered a good starting point for further improvements in surgical technique. More robust data regarding the number of procedures and the duration of follow-up is required.

Adverse events related to antimuscarinics and beta-3-agonist: "real-life" data from the Eudra-Vigilance Database.

BACKGROUND: Antimuscarinic (AM) and beta-3-agonist (B3A) treatment are the standard first-line pharmacological treatment used to manage overactive bladder (OAB) patients. Aim of our study was to analyze real-life data of adverse events related to AMs and B3A reported on Eudra-Vigilance (EV) Database. METHODS: EV database is the system for managing and analyzing information on suspected adverse reactions to medicines which have been authorized or being studied in clinical trials in the European Economic Area (EEA). We recorded the number of AEs for antimuscarinic and beta-3-agonist per category and severity until January 2021. RESULTS: Overall, 2313 AEs were reported for oxybutinin, 5129 for solifenacin, 2483 for tolterodine, 3523 for fesoterodine, 787 for trospium, 621 for propiverine and 7213 for mirabegron. Urinary retention was higher for fesoterodine (43%) and tolterodine (23%) when compared to solifenacin (10%), mirabegron (11%) and oxybutinin (4%). Cognitive disorder was uncommon for all the analyzed drugs analyzed. Regarding anticolinergic AEs: vision blurred, dry mouth and constipation were higher for AMs when compared to mirabegron. Their prevalence was higher in female patients. Mirabegron presented a higher risk of hypertension (7%) when compared to oxybutinin (2%, P<0.01), solifenacin (2%, P<0.01), tolterodine (2%, P<0.01) and fesoterodine (1%, P<0.01); the rate of hypertension was higher in females (63%) than males (29%) (P<0.01). The risk of acute urinary retention was also significantly higher (15% vs. 10%, P<0.01) in older patients (>85 years). CONCLUSIONS: Real life data is consistent with registry studies regarding the rate of AEs related to antimuscarinic and beta-3-agonist. However some differences were observed. Female patients present higher rates of AEs when compared to male patients. The risk of acute urinary retention was particularly evident in the octogenarians.

Diffuse Leukoplakia of the Bladder Ostium-Sparing in Patient Treated with Leuprorelin for Breast Cancer.

CASE: A 55-year-old woman came to our attention in April 2020 referring haematuria, frequency and urgency. The patient referred previous treatment with leuprorelin 3.75 mg/2 ml for breast cancer three years ago. Urine culture was performed and resulted always negative for pathogens. Cystoscopy revealed a whitish plaque lesion on the fundus, dome, trigone, and left lateral wall of the bladder. Histology of the biopsy confirmed the diagnosis of leukoplakia of the bladder. The plan is to follow her up repeating a cystoscopy every three months and biopsy in 6 months. Literature search revealed very little information on pathogenesis and prognosis of this condition due to its rare occurrence. The main objective of our case study was to describe individual situation of a woman affected by diffuse leukoplakia of the bladder ostium-sparing with a previous treatment with leuprorelin 3.75 mg/2 ml for breast cancer and to show safety of follow-up by cystoscopy and biopsy. CONCLUSIONS: We showed a case of a woman treated with leuprorelin and with diffuse leukoplakia of the bladder. We support the recommended long-term follow-up and surveillance based on the literature review by cystoscopy with or without biopsy.

A new transportable shock-wave lithotripsy machine for managing urinary stones: a single-centre experience with a dual-focus lithotripter.

OBJECTIVE: To assess the efficacy and safety of a transportable extracorporeal shock wave lithotripsy (ESWL) machine, the Modulith SLX-F2(TM) (Storz Medical Italia, Rome, Italy), in the management of solitary urinary calculi. PATIENTS AND METHODS: The study included 233 patients (mean age 51 years; 172 male, 61 female) with symptomatic solitary renal (group A, 170, mean diameter 15.5 mm) or ureteric stones (group B, 63, mean diameter 9.5 mm) treated in a tertiary care institution. Exclusion criteria for the analysis were: pelvi-ureteric junction obstruction, multiple stones, stone diameter >2 cm, stones in a lower calyx with unfavourable anatomy, active infection, or impacted ureteric stones. Selected patients had ureteric stenting before treatment, and all patients were treated with no anaesthesia. Hospitalization, complications and subsequent auxiliary procedures were evaluated. Patients were assessed after a single ESWL session and after 3 months by a plain abdominal film and renal ultrasonography. Stone-free status was defined as no evidence of calculi, and clinical success as the presence of stone fragments of <4 mm. An efficiency quotient (EQ) was calculated for the ESWL treatment. Pain was assessed using a visual analogue scale. RESULTS: The mean number of shocks used was 3779 and the mean (range) treatment time was 35 (5-55) min. The overall clinical success rate after one ESWL session was 83.7% and 82.5% for renal and ureteric stones, respectively, and the overall 3-month stone-free rate was 77% and 74.6%, respectively; the overall EQ was 0.64. When risk factors for persistent calculi were analysed simultaneously in a logistic regression model, only stones of >1 cm were statistically significant (P < 0.05). Most patients reported that pain during ESWL was mild to moderate and easily tolerated. Only minor complications occurred, with an overall complication rate of 3.8%. CONCLUSIONS: This transportable lithotripter is a safe and effective device for managing solitary stones throughout the urinary tract. Its main advantage is represented by the dual-focus system. Moreover, it shares with other contemporary machines several important features such as outpatient setting, no need for anaesthesia, easy patient positioning, and the capability of ancillary procedures.

The forgotten stent: late complication in a patient with neobladder.

Encrustation constitutes a serious complication of ureteral stent use and can result in difficult stent removal. We report the case of a patient with a retained ureteral stent for 3 years following a radical cystectomy.

Medical expulsive treatment of distal-ureteral stones using tamsulosin: a single-center experience.

PURPOSE: To evaluate the efficacy of the addition of tamsulosin to our standard expulsive pharmacologic therapy for the treatment of distal-ureteral stones. PATIENTS AND METHODS: A series of 96 patients referred to our department for the management of symptomatic distal-ureteral calculi were randomly divided into group 1 (N = 46) who received diclofenac (100 mg/daily) plus aescin (80 mg/daily) and group 2 (N = 50) who received the same therapy plus tamsulosin (0.4 mg/daily) for a maximum of 2 weeks. There were no differences between the groups with respect to age, sex, or stone size. The primary endpoint was the expulsion rate. Expulsion time, need for analgesics, need for hospitalization, and drug side effects were the secondary endpoints. RESULTS: The expulsion rate was significantly higher in group 2 (90%) than in group 1 (58.7%; P = 0.01), and group 2 achieved stone passage in a shorter time (mean 4.4 v 7.5 days, respectively; P = 0.005). Lower analgesic use was found in group 2 (P = 0.003), as well as significantly fewer hospitalizations for recurrent colic (P = 0.01). Both groups experienced few side effects associated with expulsive therapy. CONCLUSIONS: A conservative approach should be considered as an option in the management of uncomplicated distal-ureteral stones. Even if the best pharmacologic expulsive regimen remains to be established, the use of the selective alpha-blocker tamsulosin is recommended in this setting.

Orbital metastasis as a first indication of prostate cancer: a case report.

Prostatic carcinoma accounts for only 3.6% of orbital metastases encountered in clinical practice. We report the clinical presentation and response to treatment of a patient with metastatic prostatic carcinoma to the sella turcica. A 73-year-old man presented with a three-months history of progressive right proptosis associated with increasing diplopia in down-gaze and slightly decreased visual acuity. Gadolinium-MRI scans of the head revealed a left osteoblastic intrasellar mass, displacing the pituitary gland. Laboratory testing revealed a serum PSA level of 22 ng/ml. Transrectal ultrasound-guided biopsy revealed prostatic adenocarcinoma (Gleason score 4+3) in both lobes of the prostate. A bone scan was performed showing that the patient had multiple secondary bony lesions. Total androgen blockade was initiated. Moreover, he was referred for radiotherapy of this metastatic lesion to the sella turcica. The visual complaints regressed dramatically within the first month of the treatment. A follow-up MRI scan at 6 months showed almost complete involution of the orbital metastatic process. However the disease subsequently progressed and the patient died 22 months after diagnosis.