[A Case of Neuropathic Lower Urinary Tract Dysfunction Due to Spina Bifida Occulta Discovered at the Age of 19 Years and Successfully Treated with Multidisciplinary Therapy].

A 19-year-old man had been aware of dysuria and urinary incontinence since childhood but did not seek medical attention. He was diagnosed with acute pyelonephritis due to lower urinary tract dysfunction associated with spina bifida occulta and tethered cord syndrome (TCS) due to spinal cord lipoma. After placement of a urethral catheter and antibacterial chemotherapy, the patient was cured of acute pyelonephritis. He was treated with solifenacin and started clean self-intermittent catheterization (CIC). Shortly after the start of CIC, the acute pyelonephritis flared up again, and he was managed with a reinserted urethral catheter until an untethering operation. Preoperative video urodynamics showed that the bladder morphology was Ogawa classification grade III with vesicoureteral reflux (VUR) at 92 ml infusion. With the combination of an untethering operation and additional mirabegron, the functional bladder capacity was increased to 353 ml and VUR improved, allowing for safe urinary management of the CIC. TCS can be diagnosed at any age and requires appropriate urinary management and therapeutic intervention as early as possible after diagnosis.

Efficacy of cognitive behavioral therapy using self-check sheet for patients with nocturia in real-world clinical practice.

OBJECTIVES: We previously demonstrated the efficacy of cognitive behavioral therapy (CBT) using a self-check sheet for patients with nocturia in a randomized controlled study. Additionally, we investigated the efficacy of the intervention in real-world clinical practice. METHODS: Two hundred forty-three outpatients with complaint of nocturia who practiced CBT for 4 weeks using a self-check sheet were included in this trial, which took place from April 2021 to March 2022 in 20 institutions. RESULTS: Of the 243 patients, 215 who achieved 50% or more of the behavioral therapy tasks were included in the analysis. Their mean age ± SD was 77.1 ± 7.7. A significant decrease was observed in nighttime frequency at 4 weeks after CBT using self-check sheets (pre 3.3 and post 2.8, p < .001). Nighttime frequency was decreased one or more times and was defined as treatment success in 102 patients (47.4%). Pretreatment nighttime frequency in the treatment-success group was significantly higher than that of the failure group (3.5 ± 1.0 vs. 3.2 ± 1.0, p = .013). In multivariate logistic regression analysis, predictive factors of treatment success were pretreatment nocturnal frequency of four or more (odds ratio [OR] 1.82, 95% confidence interval [CI] 1.01-3.30; p = .046) and the absence of diabetes mellitus (OR 3.08, 95% CI 1.34-7.06; p = .008). CONCLUSIONS: CBT using a self-check sheet requiring less time, less labor, less cost, and less medication is very beneficial for both patients and medical staff in real-world clinical practice.

Efficacy and safety of desmopressin orally disintegrating tablets 25 and 50 µg in male patients with nocturia: A Japanese real-world multicenter clinical study.

OBJECTIVES: To clarify Japanese real-world clinical data on the use of desmopressin 25 and 50 µg orally disintegrating tablets (ODT) for male patients with nocturia and evaluate the predictive factors to improve nighttime frequency. METHODS: We retrospectively accumulated real-world clinical data from 27 institutions in Japan. Male patients with two or more episodes of nocturia who received desmopressin ODT for nocturnal polyuria (NP) from 2019 through 2021 were included. The primary endpoint was the change of nighttime frequency until 3 months after desmopressin administration. The secondary endpoints were to clarify the persistence rate, adverse events, and predictive factors of decreasing nighttime frequency. RESULTS: A total of 118 patients were eligible to participate in this study. The persistence rate of desmopressin on the Kaplan-Meier curve at week 12 was 51.3. The reason for discontinuation was mainly the occurrence of adverse events in 67 patients (56.8%), particularly hyponatremia in 7 patients (5.9%). Nighttime frequencies at baseline, - 1 month and 1 - 3 months after desmopressin administration were 4.1 ± 1.3, 2.9 ± 1.4 (P < .01), and 2.6 ± 1.3 (P < .01), respectively. The mean nighttime urine volume voided at baseline was significantly larger in patients whose nighttime frequency decreased by two or more times than in those with a decrease of less than two times. CONCLUSIONS: Desmopressin 25 and 50 µg ODT treatments are feasible for male patients with NP in Japanese real-world clinical practice. Patients with higher voided volumes, particularly in the nighttime, may have great benefit from desmopressin.

Possible role of intravenous administration of mesenchymal stem cells to alleviate interstitial cystitis/bladder pain syndrome in a Toll-like receptor-7 agonist-induced experimental animal model in rat.

BACKGROUND: Interstitial cystitis/bladder pain syndrome (IC/BPS) categorized with and without Hunner lesions is a condition that displays chronic pelvic pain related to the bladder with no efficacious treatment options. There are strong associations suggested between Hunner-type IC and autoimmune diseases. Recently, we established an animal model of Hunner-type IC using a Toll-like receptor-7 (TLR7) agonist. Intravenous infusion of mesenchymal stem cells (MSCs) can be used to treat injury via multimodal and orchestrated therapeutic mechanisms including anti-inflammatory effects. Here, we investigated whether infused MSCs elicit therapeutic efficacy associated with the TLR7-related anti-inflammatory pathway in our Hunner-type IC model. METHODS: Voiding behaviors were monitored 24 h prior to the Loxoribine (LX), which is a TLR7 agonist instillation in order to establish a Hunner-type IC model (from - 24 to 0 h) in female Sprague-Dawley rats. LX was instilled transurethrally into the bladder. At 0 h, the initial freezing behavior test confirmed that no freezing behavior was observed in any of the animals. The LX-instilled animals were randomized. Randomized LX-instilled rats were intravenously infused with MSCs or with vehicle through the right external jugular vein. Sampling tissue for green fluorescent protein (GFP)-positive MSCs were carried out at 48 h. Second voiding behavior tests were monitored from 72 to 96 h. After the final evaluation of the freezing behavior test at 96 h after LX instillation (72 h after MSC or vehicle infusion), histological evaluation with H&E staining and quantitative real-time polymerase chain reaction (RT-PCR) to analyze the mRNA expression levels of inflammatory cytokines were performed. RESULTS: Freezing behavior was reduced in the MSC group, and voiding behavior in the MSC group did not deteriorate. Hematoxylin-eosin staining showed that mucosal edema, leukocyte infiltration, and hemorrhage were suppressed in the MSC group. The relative expression of interferon-ß mRNA in the bladder of the MSC group was inhibited. Numerous GFP-positive MSCs were distributed mainly in the submucosal and mucosal layers of the inflammatory bladder wall. CONCLUSION: Intravenous infusion of MSCs may have therapeutic efficacy in a LX-instilled Hunner-type IC rat model via a TLR7-related anti-inflammatory pathway.

[A Case of Detrusor Hyperactivity with Impaired Contractility (DHIC) after Transverse Myelitis].

A 44-year-old man was carried to the hospital in an ambulance because of dyspnea, paralysis and dysuria after signs of the flu. Acute encephalomyelitis was diagnosed by examination of magnetic resonance imaging. Antimicrobial treatment and respirator management was carried out with indwelling of urethral catheter for urinary retention. After improvement of encephalitis, the urethral catheter was removed. However, he still needed medical care because of persistent lower urinary tract symptoms. He complained of urge incontinence and urination frequency. Decrease of functional bladder capacity was noticed in a frequency volume chart. After consulting with our neurologist, acute transverse myelitis was diagnosed from imaging and neurological findings. Pressure flow study (PFS)demonstrated detrusor overactive during the filling phase and insufficient contractility during the voiding phase. We reached the diagnosis of detrusor hyperactivity with impaired contractility (DHIC). We did not introduce clean intermittent catheterization but used the mirabegron instead. Although storage symptoms did not improve on the mirabegron monotherapy, the symptoms improved by solifenacin added. There is a possibility that combination therapy with mirabegron and solifenacin is effective for DHIC.

Long-term tadalafil administration can prevent functional and structural changes of the urinary bladder in male rats with partial bladder outlet obstruction.

AIMS: There have been few reports on whether long-term oral phosphodiesterase 5 inhibitor administration can ameliorate bladder changes due to bladder outlet obstruction (BOO). Therefore, we clarified the chronological changes of the bladder using male BOO rats and evaluated the effects of tadalafil on these changes. METHODS: Eight-week-old male Sprague-Dawley rats were used. BOO was created by placing a polyethylene catheter around the urethra. Then, the rats were orally treated with a vehicle, or tadalafil 2 or 10 mg/kg until each evaluation period. Cystometric measurements were performed and the degree of fibrosis in the smooth muscle layer was evaluated at 2, 4, and 16 weeks. RESULTS: In BOO rats, a significant increase in the number of non-voiding contractions (NVCs) and a shortened intercontraction interval (ICI) were observed in the earlier phase (2 and 4 weeks) compared to Sham rats. In the chronic phase (16 weeks), markedly increased residual urine volume and an extended ICI were observed accompanied by enhanced smooth muscle fibrosis. These results indicated that the bladder in BOO rats represented the overactive phenotype in the earlier phase and changed into the underactive phenotype in the chronic phase. Even in Sham rats, an increased number of NVCs and enhanced fibrosis were observed with time. Tadalafil administration significantly prevented these bladder changes in both BOO and Sham rats. CONCLUSIONS: Long-term oral administration of tadalafil can prevent functional and histological changes in the BOO rat bladder. This agent is also effective for the bladder functional change even in non-obstructed rats.

Epigenetic silencing of miR-200b is associated with cisplatin resistance in bladder cancer.

In this study, we identified microRNAs (miRNAs) involved in cisplatin (CDDP) resistance in bladder cancer (BCa). After establishing CDDP-resistant BCa cell lines (T24RC and EJ138RC), TaqMan arrays revealed that members of the miR-200 family (miR-200b, miR-200a and miR-429) were downregulated in T24RC as compared to parental T24 cells. miR-200b was associated with CDDP sensitivity in BCa cells, and its downregulation was associated with CpG island hypermethylation. Pharmacological demethylation using 5-aza-2'-deoxycytidine restored miR-200b expression, and the combination of 5-aza-2'-deoxycytidine + CDDP strongly inhibited T24RC cell proliferation. Microarray analysis revealed that miR-200b + CDDP induced genes involved in CDDP sensitivity or cytotoxicity, including IGFBP3, ICAM1 and TNFSF10, in the resistant cells. Expression and DNA methylation of miR-200b were inversely associated in primary BCa, and low expression/high methylation was associated with poor overall survival. These results suggest downregulation of miR-200b is associated with CDDP resistance in BCa. Epigenetic silencing of miR-200b may be a marker of CDDP resistance and a useful therapeutic target for overcoming CDDP resistance in BCa.

Impact of extended prostate biopsy including apical anterior region for cancer detection and prediction of surgical margin status for radical prostatectomy.

OBJECTIVES: We investigated diagnostic yield of initial biopsy and repeated biopsy including apical cores. METHODS: We investigated 573 consecutive men with PSA of ≤20 ng/ml who underwent prostate biopsy between 2004 and 2013. The initial 14-core biopsy consisted of the sextant type, lateral sites at the base and middle, lateral apices (la) at anterior horn sites, and apical anterior sites (aa). The repeated 18-core biopsy consisted of the initial 14-core biopsy with four transition zone (TZ) sites at the base (tzb) and middle (tzm). RESULTS: Prostate cancer was diagnosed in 178 (38.9%) of 458 men with the initial 14-core biopsy, and 44 (38.3%) of 115 men with the repeated 18-core biopsy. In the initial biopsy setting, the unique cancer detection rate was high in apical sites (apex, la, and aa: 6.2%, 6.2% and 5.1%, respectively). In the repeated setting, it was high in the TZ site in addition to the apical site (apex, la, aa, tzm, and tzb: 6.8%, 6.8%, 11.4%, 9.1% and 11.4%, respectively). The positive SM rate at the apex was higher in patients whose cancer was detected only in sites other than the sextant region than for those in the sextant region (36.4% vs. 14.8%, P = 0.037). CONCLUSIONS: The initial 14-core and the repeated 18-core biopsy scheme including apical anterior cores are feasible for prostate cancer detection. We propose that apical biopsy cores can be used to predict not only the existence of cancer but also surgical margin status at the apex.

[Anastomotic stricture following radical retropubic prostatectomy: insights into incidence, management and factors predisposing for occurrence].

PURPOSE: Anastomotic stricture (AS) following radical prostatectomy (RP) decreases patients' quality of life. It occurs in 0.5% to 32% of men after open radical retropubic prostatectomy (RRP), although its etiology is poorly understood. In a series of patients who received RRP, we analyzed the incidence, possible predisposing factors, and management of AS after RP. MATERIALS & METHODS: Between April 1997 and March 2006, 129 consecutive patients underwent RRP in our hospital. Anastomosis between the bladder neck and urethra was performed with interrupted anastomosis using four 2-0 absorbable sutures. AS was diagnosed when a 16Fr. panendoscope could not be passed. We assessed the relationship between the management method for AS and time interval between the surgical procedure and diagnosis of the stricture. The relationships between comorbidities identified preoperatively (hypertension [HT], diabetes mellitus [DM], cardiovascular disease [CVD], cerebral infarction [CI] and smoking history) and the incidence of AS were determined. Risk factors, including age, body mass index [BMI], preoperative PSA, total prostate volume, operative time, blood loss, Foley duration, amount of stress urinary incontinence (SUI) per day, amount of drain output, pathological T stage, Gleason sum and surgical margin status were also assessed. RESULTS: The rate of AS after RRP was 10.9% (14/129). In 10 patients (72%), AS occurred within 3 months of surgery, in 2 (14%) it occurred at 4-12 months after surgery and in 2 (14%) more than 12 months after surgery. In univariate and multivariate analyses, intraoperative bleeding of 1,800 ml or more was independently the strongest predictor of AS. In two patients a urethral bougie was used and 11 underwent internal urethrotomy. Only 1 patient underwent transurethral resection. Of the 8 patients whose strictures were diagnosed within 3 months after surgery and underwent internal urethrotomy, 6 had recurrent anastomotic strictures. CONCLUSIONS: Risk factors for AS are thought to be multifactorial. Intraoperative blood loss was significantly associated with the development of anastomotic stricture. We should understand that anastomotic stricture following radical retropubic prostatectomy is not a rare morbidity and should inform patients about the possibility of postoperative AS.

[A case of Crohn's disease developing bladder rupture 4 months after laparoscopic sigmoidectomy with partial cystectomy for vesicosigmoidal fistula].

A 32-year-old well-nourished man having a vesicosigmoidal fistula due to Crohn's disease received laparoscopic sigmoidectomy with partial cystectomy. The bladder wall was closed with an all-layer running suture and additional interrupted sutures using 2-0 Vicryl. Four months after surgery, the suture site on the bladder showed perforation to the abdominal cavity. Since the same event occurred again 6 months after surgery, open partial cystectomy was performed to repair the perforated site 8 months after the initial surgery. The perforated site showed a thinning bladder wall composed of normal urothelium, scar tissue and thin detrusor muscle. Non-caseating granuloma was not found in the specimen, even though it was slightly observed in the margin of the detrusor muscle resected in the initial surgery. Although it was possible that the persisting activity of Crohn's disease, subclinical impaired nutrition due to Crohn's disease or insufficient suturing of the bladder wall were involved in the bladder rupture, the definitive cause remains unknown.