Peripheral neuropathy and nerve electrophysiological changes with enfortumab vedotin in patients with advanced urothelial carcinoma: a prospective multicenter cohort study.

BACKGROUND: Enfortumab vedotin is a novel antibody-drug conjugate used as a third-line therapy for the treatment of urothelial cancer. We aimed to elucidate the effect of enfortumab vedotin-related peripheral neuropathy on its efficacy and whether enfortumab vedotin-induced early electrophysiological changes could be associated with peripheral neuropathy onset. METHODS: Our prospective multicenter cohort study enrolled 34 patients with prior platinum-containing chemotherapy and programmed cell death protein 1/ligand 1 inhibitor-resistant advanced urothelial carcinoma and received enfortumab vedotin. The best overall response, progression-free survival, overall survival, and safety were assessed. Nerve conduction studies were also performed in 11 patients. RESULTS: The confirmed overall response rate and disease control rate were 52.9% and 73.5%, respectively. The median overall progression-free survival and overall survival were 6.9 and 13.5 months, respectively, during a median follow-up of 8.6 months. The patients with disease control had significantly longer treatment continuation and overall survival than did those with uncontrolled disease. Peripheral neuropathy occurred in 12.5% of the patients. The overall response and disease control rates were 83.3% and 100%, respectively: higher than those in patients without peripheral neuropathy (p = 0.028 and p = 0.029, respectively). Nerve conduction studies indicated that enfortumab vedotin reduced nerve conduction velocity more markedly in sensory nerves than in motor nerves and the lower limbs than in the upper limbs, with the sural nerve being the most affected in the patients who developed peripheral neuropathy (p = 0.011). CONCLUSION: Our results indicated the importance of focusing on enfortumab vedotin-induced neuropathy of the sural nerve to maximize efficacy and improve safety.

The future of urodynamics: non-invasive ultrasound videourodynamics.

A totally non-invasive transperineal urodynamic technique using Doppler ultrasonography has been developed. Normal urine doesn't have blood cells so urine was thought not to produce Doppler effects. However, basic studies confirmed that the decrease of pressure at high velocity (Bernoulli effects) caused dissolved gas to form microbubbles, which are detected by Doppler ultrasonography. Subjects sat and a probe was advanced via remote control to achieve gentle contact with the perineal skin. The digital uroflow data signals and the color Doppler ultrasound video images were processed on a personal computer. This method was viable to diagnose the degree of bladder outlet obstruction. The advantage of being rapid, effective, and equipped with no special attachments allows it to surpass any other non-invasive urodynamic methods. The difference between the echocardiogram and the ultrasound urodynamic system is only the frequency of obtaining velocity information: more than 50 times per minute vs once every several hours, respectively. Although the ultrasound urodynamic system is more difficult to develop than the echocardiogram, one principle is shared by both methods. The patient can void freely without interruptions, there is no contact between the penis and the equipment and it is specifically directed toward non-invasive diagnosis. The development of non-invasive Doppler ultrasound videourodynamics will dramatically expand understanding of voiding function.

Use of Doppler ultrasound for non-invasive urodynamic diagnosis.

OBJECTIVES: A totally non-invasive transperineal urodynamic technique using Doppler ultrasonography has been developed. METHODS: Since normal urine does not have blood cells, urine was thought not to produce the Doppler effects. However, basic studies confirmed that the decrease of pressure at high velocity (Bernouilli effect) caused dissolved gas to form microbubbles, which are detected by Doppler ultrasonography. Subjects sat and the probe was advanced via remote control to achieve gentle contact with the perineal skin. The digital uroflow data signals and the color Doppler ultrasound video images were processed on a personal computer. The flow-velocity curves from two sites; the distal prostatic urethra just above the external sphincter (V1) and the sphincteric urethra (V2) were plotted against time. The parameters of both the pressure-flow studies and the Doppler ultrasound urodynamic studies were compared in men who had various degrees of obstruction. RESULTS: Functional cross-sectional area at prostatic urethra (A1), calculated by Q(max)/V1, was lower in the group of bladder outlet obstruction (BOO) vs. control group. Velocity ratio (VR), which was calculated by V1/V2, was the parameter having the best correlation with BOO index, though A1 had a similar correlation. This method is viable to diagnose the degree of BOO. CONCLUSIONS: The development of non-invasive Doppler ultrasound videourodynamics (Doppler UDS) will dramatically expand the information on voiding function.

Naftopidil and propiverine hydrochloride for treatment of male lower urinary tract symptoms suggestive of benign prostatic hyperplasia and concomitant overactive bladder: a prospective randomized controlled study.

OBJECTIVE: To assess the efficacy and safety of propiverine hydrochloride (antimuscarinic), naftopidil (alpha(1)-adrenoceptor antagonist) or both in patients with male lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia and concomitant overactive bladder (OAB). MATERIAL AND METHODS: Men aged at least 50 years who had a total International Prostate Symptom Score (IPSS) of 8 or higher and bladder dairy documenting micturition frequency (more than eight micturitions/24 h) and urgency (more than one episode/24 h), with or without urgency urinary incontinence were randomized into three groups: group N, naftopidil (50 mg once daily) only; group P, propiverine hydrochloride (20 mg once daily); and group NP, naftopidil (50 mg once daily) plus propiverine hydrochloride (20 mg once daily) for a 4-week treatment regimen. RESULTS: A total of 66 men, including 20 in group N, 23 in group P and 23 in group NP, were treated and 58 (87.9%) completed the 4 weeks of treatment. IPSS improved significantly in groups N and NP. Urinary frequency improved significantly in groups P and NP. Postvoid residual urine volume increased significantly in groups P and NP. Significant improvements in urgency episodes were noted in each group. One patient in group P required catheterization owing to acute urinary retention and another stopped medication because of difficulty in voiding. CONCLUSION: These results suggest that each treatment showed effectiveness for male LUTS with OAB. However, there are some possibilities of adverse effects with propiverine hydrochloride monotherapy.

[Long-term usefulness and safety of the contemporary balloon catheter].

OBJECTIVE: To evaluate usefulness and safety of an indwelling contemporary balloon catheter, we compared complication rates among five methods of urinary tract management. PATIENTS AND METHODS: History of febrile episode, bladder stones, pyuria and the miscellaneous urinary tract problems of 114 patients were retrospectively reviewed. The rates of complications were compared among five types of urinary tract management as clean intermittent catheterization dry (not incontinent) (CIC-dry: n = 33), clean intermittent catheterization with incontinence (CIC-wet: n = 16), clean intermittent catheterization with a contemporary balloon catheter indwelling at night (Contemporary catheter: n = 20), a suprapubic cystostomy catheter indwelling (Cystostomy: n = 22) and permanent urethral balloon catheter indwelling (Urethral catheter: n = 24). The contemporary balloon catheter used consisted of a reusable balloon catheter and a reservoir to inflate the balloon. The patients in the Contemporary catheter group self-inserted the catheter every night before sleeping, and then removed it in the next morning. After use, the catheter was washed with tap water, and stored in a special purpose case filled with disinfectant. RESULTS: The mean follow up period was 41 months. The incidence of febrile episode in CIC-wet was 3.36 times/100 months, Urethral catheter was 2.96, Cystostomy was 1.26, Contemporary catheter was 0.57, and CIC-dry was 0.42. The incidence of febrile episode in CIC-wet and Urethral catheter were significantly higher than in CIC-dry (p<0.05). The incidence of bladder stone in Urethral catheter was 1.11 times/100 months, Cystostomy was 1.05, Contemporary catheter was 0.96, CIC-wet was 0.61, and CIC-dry was 0.21. The Urethral catheter group had significantly higher incidence of bladder stone than CIC-dry (p<0.05). CONCLUSIONS: The indwelling contemporary balloon catheter is recommended for long-term use in CIC-wet group.

Retroperitoneoscopic pyelolithotomy as initial treatment for upper urinary tract large stone.

We report a case in which retroperitoneoscopic pyelolithotomy was the procedure selected to treat a large stone in the upper urinary tract. A 71-year-old woman who had multiple cerebral infarction and dementia was admitted with a persistent high fever unresponsive to antibiotics. The diagnosis was pyelonephritis and urosepsis associated with ureteral calculus. A large calculus(3.0 x 2.0 cm)was found in the left ureter at the L3 level. She underwent nephrostomy of the left side. After the patient's general condition had improved, surgery was performed successfully with an uneventful recovery. The findings in this case confirm that retroperitoneoscopic surgery allows removal of a large stone in a single, minimally invasive procedures.

Hydronephrosis due to ureteral endometriosis treated by transperitoneal laparoscopic ureterolysis.

Ureteral obstruction secondary to endometriosis is relatively uncommon. We present a 43-year-old multiparous woman who suffered from periodic left loin pain in the terminal period of her menstruation. Excretory urogram demonstrated left hydronephrosis and hydroureter and obstruction of the lower left ureter just inferior to the left sacroiliac joint without urolithiasis. An enhanced computed tomography scan showed soft tissue density mass around the left ureter at the level of the stenosis. She underwent transperitoneal laparoscopic ureterolysis and adhesiotomy of the left ureter under the diagnosis of ureteral endometriosis. Because blueberry spots were clearly observed on the pelvic brim, the fibrous tissue surrounded the ureter was removed with peritoneal bleeding spots. Histological examination of the surrounding tissue confirmed the ectopic endometriosis. Even though retroperitoneoscopy is frequently used for ureteral lesion, transperitoneal laparoscopy has an advantage for resection of ectopic endometriosis surrounding the ureter.