Koji Ichihara

A Randomized Controlled Study of the Efficacy of Tamsulosin Monotherapy and its Combination with Mirabegron for Overactive Bladder Induced by Benign Prostatic Obstruction

PURPOSE We evaluated the efficacy and safety of add-on treatment with a β3-adrenoceptor agonist (mirabegron) for overactive bladder symptoms remaining after α1-blocker (tamsulosin) treatment in men with benign prostatic obstruction. MATERIALS AND METHODS Patients with benign prostatic obstruction with urinary urgency at least once per week and a total OABSS of 3 or more points after 8 or more weeks of treatment with tamsulosin were enrolled in the study. They were randomly allocated to receive 0.2 mg tamsulosin daily or 0.2 mg tamsulosin and 50 mg mirabegron daily for 8 weeks. The primary end point was change in total OABSS. Safety assessments included change in post-void residual urine volume and adverse events. RESULTS From January 2012 through September 2013 a total of 94 patients were randomized. Of these patients 76 completed the protocol treatment. In the full analysis set the change in total OABSS during the treatment period was significantly greater in the combination group than in the monotherapy group (-2.21 vs -0.87, p=0.012). The changes in scores for urinary urgency, daytime frequency, International Prostate Symptom Score storage symptom subscore and quality of life index at 8 weeks were significantly greater in the combination group. The change in post-void residual urine volume was significantly greater in the combination group. Although 6 patients experienced adverse events in the combination group, urinary retention was observed in only 1 patient. CONCLUSIONS Combined tamsulosin and mirabegron treatment is effective and safe for patients with benign prostatic obstruction who have overactive bladder symptoms after tamsulosin monotherapy.

Transurethral prostate biopsy before radical cystectomy remains clinically relevant for decision-making on urethrectomy in patients with bladder cancer

BackgroundThis study retrospectively evaluated the clinical relevance of transurethral prostate biopsy (TUPB) before radical cystectomy by comparing the pathology of prostatic urethra biopsy specimens with that of cystectomy specimens.MethodsOf 294 patients who underwent cystectomy and urinary diversion, 101 men with preoperative TUPB were included in this study. For these patients, if the result of TUPB was positive for urothelial carcinoma, we performed urethrectomy as a rule. If it was negative, we presented the option of urethral preservation and decided the final type of urinary reconstruction. The sensitivity, specificity, and positive and negative predictive values (PPV and NPV) of TUPB were assessed, and we investigated the number of final urethral recurrences. We also tried to identify which clinical and pathological findings by TUPB most accurately predicted the disease remaining in the prostate of cystectomy specimens.ResultsOf the 25 patients with positive TUPB, 18 had disease in the prostatic urethra or stroma of cystectomy specimens. There were 3 patients with negative TUPB but with involvement of the prostate in cystectomy specimens. Thus, TUPB achieved 86% sensitivity, 91% specificity, 72% PPV, and 96% NPV. Two patients (1.9%) had urethral recurrence in this period. Among the findings for TUPB, non-papillary tumors most accurately predicted the disease in the prostate of cystectomy specimens.ConclusionsTUPB achieved a high NPV and the urethral recurrence rate was acceptable. If TUPB was negative, patients could have chance urethral preservation. Thus, our clinical decision for urethrectomy based on the result of TUPB is still useful.

Clinical Outcomes of Patients with pT0 Bladder Cancer after Radical Cystectomy: A Single-institute Experience

OBJECTIVE To investigate the clinical outcomes of patients who underwent radical cystectomy for bladder cancer at a single institution and compare those who had pT0 specimens with those who had residual cancer. METHODS From January 1990 to December 2006, 186 patients underwent radical cystectomy with or without neoadjuvant chemotherapy for cT2 or higher stage urothelial carcinoma in the bladder in our hospital. We estimated the 5-year disease-free survival, cancer-specific survival and overall survival by the pathological stage. RESULTS The median follow-up of the 186 patients was 38.5 months (0-194). Of these, 51 received neoadjuvant chemotherapy. For all subjects, the 5-year disease-free survival was 54.9%, cancer-specific survival 61.0% and overall survival 57.1%. Of the 186 patients, 24 (12.9%) had no residual cancer in the bladder specimen at radical cystectomy. Of the 24 patients with pT0, only 1 (4.2%) died of bladder cancer. The 5-year disease-free survival, cancer-specific survival and overall survival rates in patients with pT0 were ∼96.0%. We found pT0 histology in 11 of the 51 patients (21.6%) with neoadjuvant chemotherapy and in 13 of the 135 patients (9.6%) with radical cystectomy alone (P = 0.047). CONCLUSIONS We demonstrated that the outcomes of patients who underwent radical cystectomy were similar to those in previous reports. Patients with pT0 showed favorable outcomes for disease-free survival, cancer-specific survival and overall survival in our study. However, they should be periodically followed up because pT0 does not always mean cure.

Toll-like receptor 7 is overexpressed in the bladder of Hunner-type interstitial cystitis, and its activation in the mouse bladder can induce cystitis and bladder pain

Abstract Toll-like receptor 7 (TLR7) is associated with the pathophysiology of systemic lupus erythematosus and Sjögren syndrome, well-known diseases accompanying interstitial cystitis (IC). We studied TLR7 expression in the bladder of patients with Hunner-type IC (HIC) and its functional roles in bladder inflammation and nociception using mice. Bladder biopsy specimens were obtained from patients with HIC. Specimens from the noncancerous portion of the bladder of patients with bladder cancer served as controls. The specimens were examined by immunohistochemistry and real-time polymerase chain reaction of TLR7. Loxoribine (LX), a TLR7 agonist, was instilled in the bladder of C57BL/6N female mice, and TLR7-mRNA expression and histological changes of the bladder, bladder pain–like licking behavior, voiding behavior, cystometry, and bladder afferent nerve activities were investigated. The effects of hydroxychloroquine, a TLR7 antagonist, on the LX-induced changes on cystometry and voiding behavior were studied. The number of TLR7 immuno-reactive cells and the mRNA expression of TLR7 were significantly increased in HIC specimens. Intravesical instillation of LX induced edema, congestion, inflammation, and significantly increased TLR7-mRNA expression in the mouse bladder. Loxoribine-instillation also significantly increased licking behavior, voiding frequency, and afferent nerve activities associated with decreased single-voided volume and intercontraction interval of micturitions. Hydroxychloroquine reversed the LX-induced cystometric and voiding behavioral changes. Toll-like receptor 7 was up-regulated in the bladder mucosa of patients with HIC, and activation of TLR7 in the mouse bladder induced cystitis with sensory hyperactivity of the bladder. Blocking the TLR7 pathway may be an innovative treatment target of HIC.

Incidence and risk factors for acute kidney injury after radical cystectomy

To clarify the incidence, risk factors and clinical impact of acute kidney injury after radical cystectomy.

Clinical Efficacy of a Single Two Gram Dose of Azithromycin Extended Release for Male Patients with Urethritis

To clarify the clinical efficacy of a single oral 2 g dose of azithromycin extended-release for heterosexual male patients with urethritis, and the current antimicrobial sensitivity of Neisseria gonorrhoeae to azithromycin, a prospective clinical trial was conducted from 2011–2013. In patients with gonococcal urethritis, the eradication rate was 90.9% (30 of 33). The susceptibility rates of isolated Neisseria gonorrhoeae strains to ceftriaxone, spectinomycin, cefixime and azithromycin were 100%, 100%, 95.3% (41/43) and 37.2% (16/43), respectively. In the patients with nongonococcal urethritis, the eradication rate was 90.0% (45 of 50). The microbiological eradication rates for the pathogens were 90.9% (30/33) for Neisseria gonorrhoeae, 91.5% (43/47) for Chlamydia trachomatis, 71.4% (5/7) for Mycoplasma genitalium, and 100% (13/13) for Ureaplasma urealyticum. The main adverse event was diarrhea and its manifestation rate was 35.2% (32 of 120). The symptom of diarrhea was mostly temporary and resolved spontaneously. The conclusion was that the treatment regimen with a single oral 2 g dose of azithromycin extended-release would be effective for patients with urethritis. However, the antimicrobial susceptibilities of Neisseria gonorrhoeae and Mycoplasma genitalium should be carefully monitored because of possible treatment failure.

Modified Nephrometry Score With Body Mass Index More Accurately Predicts Ischemic Time in Transabdominal Laparoscopic Partial Nephrectomy for Small Renal Masses

OBJECTIVE To accurately predict the ischemic time (IT) and select candidates for transabdominal laparoscopic partial nephrectomy (LPN). METHODS Transabdominal LPN was performed for 135 Japanese patients with renal masses <7 cm in diameter between 2009 and 2016 by a single surgeon in a single institute. The renal parenchymal sutures were done with a combination of felt, Hem-o-lok and Lapra-Ty. The original R.E.N.A.L. nephreometry score (NS) was modified as follows. In terms of the tumor size (R), 1, 2, and 3 points were given for ≤2.5, 2.5-4, and >4 cm, respectively. For tumor location (A), 1, 2, and 3 points were given for anterior, on the coronal plane, and posterior, respectively. RESULTS The median IT was 24.6 minutes. Using the original NS, 64, 65, and 6 patients were categorized into low (4-6), moderate (7-9), and high (10-12) complexity, respectively. With the modified NS, 42, 75, and 18 patients were categorized into low (5-7), moderate (8-11), and high (12-15) complexity, respectively. Pearsons correlation coefficient (R) between the original NS and IT was 0.297, whereas the R was improved to 0.388 when the modified NS was employed. If the modified NS was low complexity, 95.2% achieved IT <30 minutes. Of them, none showed IT ≥30 minutes if the body mass index was <25 kg/m2. CONCLUSION The modified NS had a better correlation to the IT than the original NS for patients with tumor sizes <7 cm who underwent transabdominal LPN. The modified NS with body mass index is a practical tool to select candidates for transabdominal LPN.

Silodosin as second-line α-blocker monotherapy in patients with benign prostatic hyperplasia: A prospective observational study

To assess the efficacy of silodosin as second‐line α‐blocker monotherapy in patients with lower urinary tract symptoms as a result of benign prostatic hyperplasia.

The efficacy of faropenem for patients with acute cystitis caused by extended spectrum β-lactamase producing Escherichia coli

The number of patients with acute cystitis caused by extended spectrum β lactamase (ESBL)-producing Escherichia coli (E. coli) is increasing gradually. Although it is reported that ESBL-producing E. coli are sensitive to faropenem (FRPM), there are few clinical studies on the efficiency of FRPM against acute cystitis caused by the bacteria. Therefore, we retrospectively reviewed the medical charts of patients with acute cystitis caused by ESBL-producing E. coli who were treated with the oral antimicrobial agent faropenem (FRPM) in our institution from June 2011 to May 2015. Ten patients with acute cystitis caused by ESBL producing E. coli were treated with FRPM. Although clinical cure was achieved in 9 of them, it reoccurred in 3. This study revealed that the treatment regimen with FRPM for patients with acute cystitis caused by ESBL-producing E. coli is promising. However, a non-negligible number of recurrences were caused by ESBL-producing E. coli because of the nature of underlying diseases or pathologies in the urinary tract.

Distribution of Neuroendocrine Cells in the Transition Zone of the Prostate

Objectives. To evaluate the distribution of neuroendocrine (NE) cells which may influence the development of benign prostatic hyperplasia (BPH) in the transition zone (TZ). Methods. We reviewed specimens from 80 patients who underwent radical prostatectomy in our institution and evaluated the density of NE cells in the TZ. They were histologically classified into 3 groups: those with no adenomatous nodule in the TZ (group A), those with small nodules with normal epithelium and stroma around them in the TZ (group B), and those with large nodules occupying the TZ (group C). In the patients of group B, intra-adenoma (adenomatous nodules) and extra-adenoma (normal tissue) NE cells in the TZ were separately counted. Results. There were 22, 23, and 35 patients in groups A, B, and C, respectively. The median density of NE cells in the TZ of group B patients, 2.80/mm2, was significantly higher than that of NE cells in group A, 1.43/mm2, and group C, 0.61/mm2 (p < 0.001). In group B, the median density of extra-adenoma NE cells was significantly higher than that of intra-adenoma. Conclusions. Many NE cells exist around small adenoma in the TZ. NE cells may influence the initial growth of BPH in a paracrine fashion. Trial Registration. This study approved by our institutional review board was retrospectively registered (#272-14).