Improving compliance with guidelines may lead to favorable clinical outcomes for patients with non-muscle-invasive bladder cancer: A retrospective multicenter study.

OBJECTIVES: Clinical guidelines recommend that patients with non-muscle-invasive bladder cancer (NMIBC) should be treated with appropriate adjuvant therapy. However, compliance with guideline recommendations is insufficient, and this may lead to unfavorable outcomes. We aimed to investigate the level of adherence to guideline recommendations in patients with NMIBC and evaluate the outcomes of those who did and did not receive guideline-recommended therapies. METHODS: We performed a retrospective analysis of patients with histologically diagnosed NMIBC. The percentage of patients with intermediate- and high-risk tumors who received adjuvant intravesical therapy or second transurethral resection (TUR) was calculated. Recurrence-free survival was assessed in patients who did and did not receive the therapies. We conducted a propensity score-matched analysis to compare outcomes between patients with intermediate-risk and T1 NMIBC who did and did not undergo guideline-recommended therapies. RESULTS: Overall, 1204 patients from the Tohoku Urological Evidence-Based Medicine Study Group and Kyoto University Hospital were included. Of patients with intermediate- and high-risk tumors, 91.0% and 74.0% did not receive maintenance bacillus Calmette-Guérin (BCG), respectively. In both groups, significantly better recurrence-free survival was found for patients treated with maintenance BCG. Among patients with T1 NMIBC, only 16.7% underwent guideline-recommended therapies, that is, a second TUR and maintenance BCG. Significantly greater recurrence-free survival was observed in patients who received guideline-recommended therapies compared with propensity-matched patients who did not. CONCLUSIONS: Guideline-recommended therapies may contribute to improvements in outcomes for patients with NMIBC, suggesting that improvements in adherence to clinical guidelines may lead to favorable outcomes.

Real-world outcomes of patients with renal cell carcinoma, surgically treated at regional hospitals, based on a prospective long-term survey of the pre-robotic era.

PURPOSE: Renal cancer surgery is frequently performed in small regional hospitals in Japan. This study evaluated the outcomes of renal cancer surgery, comparing results from the pre-robotic surgery era with those obtained with robotic surgery. METHODS: This prospective cohort study was conducted on patients who underwent renal cancer surgery between 2008 and 2013 at 14 hospitals, comprising 13 regional hospitals and a university hospital, registered in the Tohoku Urological Evidence-Based Medicine Study Group. The patients' backgrounds; perioperative data; annual postoperative renal function; and prognostic surveys, performed over a median follow-up period of 10 years were obtained. RESULTS: In 930 surgical cases at the 14 registered hospitals, the 10-year recurrence-free survival rates of cT1a, cT1b, cT2, and cT3 were 0.9326, 0.8501, 0.5786, and 0.5101, respectively. Meanwhile, the 10-year overall survival rates were 0.9612, 0.8662, 0.7505, and 0.7209, respectively. Long-term observation in patients with cT1 showed that vessel involvement and high tumor grade were prognostic factors for recurrence. As a noteworthy fact, radical nephrectomy was performed in 53.3% of patients with cT1a at the regional hospitals. However, even in patients with preoperative chronic kidney disease stage 3, radical nephrectomy was not a prognostic factor of renal function. This indicates that compensatory mechanisms had been working for a long time in many patients who underwent radical nephrectomies without hypertension and preoperative proteinuria, which were predictors of end-stage renal disease. CONCLUSION: Based on a prospective long-term survey of the pre-robotic era, our results suggested no difference of the survival outcomes between the university hospital and regional hospitals. Our study provides baseline data to evaluate the outcomes of renal cancer robotic surgery, performed at regional hospitals.

A massive natural disaster, the Great East Japan Earthquake, and the incidence of dialysis due to end-stage kidney disease.

BACKGROUND: Disaster-related stress can increase blood pressure and the incidence of cardiovascular diseases. However, the role of massive disasters in the development of end-stage kidney disease (ESKD) remains unknown. We investigated the incidence and different causes of dialysis initiation in patients with chronic kidney disease in a city affected by the Great East Japan Earthquake. METHODS: This was a single-center, retrospective observational study. All patients who initiated or were treated with dialysis at Kesennuma City Hospital between 2007 and 2020 were enrolled. The year of dialysis initiation was retrospectively determined based on the initiation date. The causative renal diseases that led to the need for dialysis initiation were divided into four groups: diabetic nephropathy, hypertensive renal disease, glomerulonephritis, and others. RESULTS: Age at dialysis initiation differed significantly among the four groups (p = 0.0262). There was a significant difference in the numbers of the four groups before and after the Great East Japan Earthquake (p = 0.0193). The age of hypertensive renal disease patients was significantly higher than those of patients with diabetic nephropathy (p = 0.0070) and glomerulonephritis (p = 0.0386) after the disaster. The increasing number of dialysis initiations after the Great East Japan Earthquake appeared to be associated with changes in hypertensive renal diseases; the number peaked after 10 years. CONCLUSIONS: There was an increase in the number of dialysis initiations, especially caused by hypertensive renal diseases, for up to 10 years after the Great East Japan Earthquake.

Night-Time Urinary Frequency Is Increased after the Great East Japan Earthquake along with Seasonal Variation: A Five-Year Longitudinal Study in Kesennuma City.

Disasters influence various health conditions; however, little has been reported about urinary symptoms. The objective of this study is to evaluate whether night-time urinary frequency was influenced by the Great East Japan Earthquake (GEJE) in March 2011. We also evaluated seasonal variation of night-time frequency, which may affect the primary objective. A retrospective chart review was conducted on 300 evaluable patients who resided in the impacted area: 263 men with benign prostatic hyperplasia and/or overactive bladder and 37 women with overactive bladder. Data concerning night-time frequency were collected repeatedly every three months from March 2009 until March 2014, then compared yearly and seasonally among same patients. In addition, night-time frequency was analyzed for potential relations to sex, age, comorbidities, and whether residences had been destroyed. There was a significant increase of night-time frequency during 2011-2013 when compared yearly with 2009 and 2010. In seasonal comparisons of the entire period, night-time frequency was greater during autumn and winter compared with summer. In quarterly comparisons, a sudden increase was not observed after the GEJE, but night-time frequency was increased significantly in spring, summer and autumn in 2011 when compared with the corresponding seasons in 2010. While hypertension was related to exacerbation of night-time frequency during winter, we did not find any factors associated with increase after the disaster out of sex, age, comorbidities or residential situations. In conclusion, night-time urinary frequency is increased shortly after the GEJE and remains elevated for the following three years along with seasonal variation.

Efficacy of early ureteral ligation on prevention of intravesical recurrence after radical nephroureterectomy for upper urinary tract urothelial carcinoma: a prospective single-arm multicenter clinical trial.

OBJECTIVE: The rate of intravesical recurrence after radical nephroureterectomy for upper urinary tract urothelial carcinoma is high. Seeding upper urinary tract urothelial carcinoma cells onto the damaged bladder wall is considered to be one of the causes of intravesical recurrence after radical nephroureterectomy. We evaluated the utility of early ureteral ligation in preventing the intravesical recurrence. METHODS: This prospective single-arm clinical trial included patients who underwent radical nephroureterectomy for upper urinary tract urothelial carcinoma in the Tohoku Urological Evidence-Based Medicine Study Group between 2012 and 2013. Early ureteral ligation was defined as ligation of the ureter as quickly as possible after expanding the retroperitoneal space. A historical control was extracted from 454 patients who underwent radical nephroureterectomy in the same group, using propensity score-matched analysis. Intravesical recurrence-free survival rates were analyzed using Kaplan-Meier curves. Factors predicting intravesical recurrence were assessed using multivariate analyses. RESULTS: Seventy-four patients underwent early ureteral ligation. Seventeen (23%) patients had intravesical recurrence with a median follow-up period of 24 months. The 1- and 2-year intravesical recurrence-free survival rates in the early ureteral ligation group were 81% and 76%, and in the control group 75% and 63%, respectively (P = 0.160). In patients with renal pelvic cancer, the 1- and 2-year intravesical recurrence-free survival rates in the early ureteral ligation group were 89% and 86%, but in the control group 74% and 64%, respectively (P = 0.025). However, intravesical recurrence-free survival rates were similar in patients with ureteral cancer. Multivariate analyses of a subset of patients with renal pelvic cancer identified early ureteral ligation as an independent predictor of intravesical recurrence. CONCLUSIONS: Early ureteral ligation decreases the rate of intravesical recurrence after radical nephroureterectomy in patients with renal pelvic cancer. Thus, early ureteral ligation might help in prevention of intravesical recurrence for renal pelvic cancer.

CYP2A13 Genetic Polymorphisms in Relation to the Risk of Bladder Cancer in Japanese Smokers.

Tobacco-specific nitrosamines including 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N-nitrosonornicotine (NNN), which can be activated by the metabolic enzyme CYP2A13, are potent procarcinogens. Smoking plays a role in carcinogenesis in the human bladder, which expresses CYP2A13 at a relatively high level. Numerous genetic polymorphisms of CYP2A13 causing amino acid substitution might reduce CYP2A13 metabolic activity toward NNK and NNN, resulting in decreased susceptibility to bladder cancer. The aim of this study was to reveal any association between bladder cancer development and CYP2A13 genetic polymorphisms in Japanese smokers. The CYP2A13 genotype of each subject (163 bladder cancer patients and 161 controls) was determined by next-generation sequencing (NGS) of the full CYP2A13 gene. All samples were genotyped for five CYP2A13 variant alleles (CYP2A13*2, *3, *4, *6, *7). Based on biological logistic regression, the odds ratio (95% confidence interval) for the CYP2A13*1/*2 genotype was 0.34 (0.17-0.69). Thus, CYP2A13 genetic polymorphisms might play important roles in the development of bladder cancer in Japanese smokers.

A prospective multicenter study of intermittent chemotherapy with docetaxel and prednisolone for castration-resistant prostate cancer.

OBJECTIVE: The optimal schedule of docetaxel chemotherapy for castration-resistant prostate cancer is unknown, although continuous administration is accepted as the standard. We conducted a Phase II trial to evaluate the outcome of intermittent docetaxel and prednisolone therapy in castration-resistant prostate cancer. METHODS: The patients were treated using a 28-day cycle of docetaxel (70 mg/m2 on Day 1) and oral prednisolone (10 mg/day). After three consecutive administrations of docetaxel, a holiday was taken until prostate specific antigen levels returned to the baseline. The therapy was continued intermittently until the disease progressed, drug toxicity occurred, or the patients refused further treatment. The primary endpoint was overall survival. Time to treatment failure, adverse events, the duration of chemotherapy holiday and quality of life were also evaluated. RESULTS: A total of 120 patients were enrolled. The median age and pretreatment prostate specific antigen level were 72 years and 37.5 ng/ml, respectively. Sixty (50.0%) patients resumed chemotherapy after the first holiday, and a maximum of six courses were administered to four patients. The median period of the first, second and third-to-fifth holiday was 18.6, 11.0 and 4.9 weeks, respectively. Toxicity was moderate, except for two fatal adverse events. The median time to treatment failure and overall survival from the initiation of docetaxel and prednisolone therapy in all patients were 17.5 and 35.0 months, respectively. All quality-of-life scores were unchanged statistically from the start of docetaxel and prednisolone therapy to the beginning of the second course. CONCLUSIONS: Intermittent docetaxel and prednisolone therapy might be a feasible treatment option for castration-resistant prostate cancer with comparable outcome and successful chemotherapy holidays.

Genetic Polymorphisms of CYP2A6 in a Case-Control Study on Bladder Cancer in Japanese Smokers.

Several of the procarcinogens inhaled in tobacco smoke, the primary risk factor for bladder cancer, are activated by CYP2A6. The association between the whole-gene deletion of CYP2A6 (CYP2A6*4) and a reduced risk of bladder cancer was suggested in Chinese Han smokers. However, there is no evidence for association between the risk of bladder cancer and CYP2A6 genotypes in the Japanese population. Using genomic DNA from smokers of the Japanese population (163 bladder cancer patients and 116 controls), we conducted a case-control study to assess the association between CYP2A6 polymorphisms and the risk of bladder cancer. Determination of CYP2A6 genotypes was carried out by amplifying each exon of CYP2A6 using polymerase chain reaction (PCR) and Sanger sequencing. The CYP2A6*4 allele was identified by an allele-specific PCR assay. Bladder cancer risk was evaluated using the activity score (AS) system based on CYP2A6 genotypes. The odds ratios (95% confidence interval) for the AS 0, AS 0.5, AS 1.0, and AS 1.5 groups were 0.46 (0.12-1.83), 0.43 (0.15-1.25), 0.86 (0.40-1.86), and 1.36 (0.60-3.06), respectively. In conclusion, although decreased CYP2A6 AS tended to reduce the risk of bladder cancer in Japanese smokers, no significant association was recognized in this population. However, given the relatively small size of the sample, further study is required to conclude the lack of a statistically significant association between CYP2A6 genotypes and the risk of bladder cancer.

Prospective randomized phase II trial of a single early intravesical instillation of pirarubicin (THP) in the prevention of bladder recurrence after nephroureterectomy for upper urinary tract urothelial carcinoma: the THP Monotherapy Study Group Trial.

PURPOSE: We evaluated the efficacy of a single early intravesical instillation of pirarubicin (THP) in the prevention of bladder recurrence after nephroureterectomy for upper urinary tract urothelial carcinoma (UUT-UC). PATIENTS AND METHODS: From December 2005 to November 2008, 77 patients clinically diagnosed with UUT-UC from 11 institutions participating in the Tohoku Urological Evidence-Based Medicine Study Group were preoperatively enrolled in this study. Patients were randomly assigned to receive or not receive a single instillation of THP (30 mg in 30 mL of saline) into the bladder within 48 hours after nephroureterectomy. Cystoscopy and urinary cytology were repeated every 3 months for 2 years or until the occurrence of first bladder recurrence. RESULTS: Seventy-two patients were evaluable for efficacy analysis, 21 of whom had a subsequent bladder recurrence. Significantly fewer patients who received THP had a recurrence compared with the control group (16.9% at 1 year and 16.9% at 2 years in the THP group v 31.8% at 1 year and 42.2% at 2 years in the control group; log-rank P = .025). No remarkable adverse events were observed in the THP-treated group. Based on multivariate analysis, THP instillation (hazard rate [HR], 0.26; 95% CI, 0.07 to 0.91; P = .035) and open surgery (HR, 0.28; 95% CI, 0.09 to 0.84; P = .024) were independently predictive of a reduced incidence of bladder recurrence. CONCLUSION: In this prospective randomized phase II study, a single intravesical instillation of THP seemed to reduce bladder recurrence after nephroureterectomy. A phase III, large-scale, multicenter study is needed to confirm these observations.

A case of villous adenoma of the urinary bladder with tubulovillous architecture: characterization by immunohistochemical analysis.

Villous adenomas of the urinary tract are rare as compared to urothelial carcinoma. We report a case of urinary bladder villous adenoma in a 90-year-old woman. Cystoscopic examination revealed a papillary tumour in the diverticulum at the posterior wall of the urinary bladder. Transurethral resection was performed and histopathological examination revealed predominantly tubulovillous architecture, and showed an identical immunohistochemical profile to villous adenoma associated with cystitis glandularis.

The outcome of prostate cancer screening in a normal Japanese population with PSA of 2-4 ng/ml and the free/total PSA under 12%.

OBJECTIVE: No previous study has reported the numbers of prostate cancer (PC) patients existing among a normal Japanese population with prostate-specific antigen (PSA) < 4 ng/ml. The aim of this study was to elucidate the performance of %free PSA as a screening tool for a normal Japanese population with PSA of 2-4 ng/ml and to examine the characteristics of cancer detected using this criterion. METHODS: We conducted a prospective, multi-center study to evaluate the performance of %free PSA among a normal Japanese population. We decided on a %free PSA cutoff value of 12% according to the preliminary results. A total of 5548 consecutive screening volunteers aged 50-79 years were enrolled in the project. Men with total PSA > 4 ng/ml, or men with total PSA of 2-4 ng/ml and %free PSA of < or =12% were indicated to undergo 12 core biopsies. RESULTS: There were 826 (14.9%) men with PSA of 2-4 ng/ml. Among them, those with %free PSA of < or =12% numbered 100 (12.1%). Forty-nine out of 100 men (49%) received biopsy, and 16 PC patients were detected. Among 10 patients undergoing radical prostatectomy, seven were associated with extra-prostatic extension (pT3) or high-grade cancer (Gleason score > or = 8). CONCLUSIONS: We confirmed the ability of %free PSA and demonstrated that there are considerable numbers of PC patients among the normal Japanese population with PSA of 2-4 ng/ml. We ascertained that cancers detected in this study had a variety of tumor characteristics, including those of an aggressive nature.

Possible relationship between the risk of Japanese bladder cancer cases and the CYP4B1 genotype.

Cytochrome P450 4B1 (CYP4B1) is involved in the metabolism of several xenobiotics, such as 2-aminofluorene, 2-naphthylamine and benzidine. CYP4B1 allelic variants CYP4B1*1-*7 were recently identified. We thus hypothesized that CYP4B1 genotypes may modify bladder cancer risk. We examined the CYP4B1 genotypes in 169 bladder cancer cases and 190 hospital controls using a hybridization probe assay. Among the CYP4B1 genotypes observed, the most frequent genotypes in both the groups were CYP4B1*1/*1, *1/*2, *1/*3 and *2/*2. Logistic regression analysis revealed that the subjects carrying the CYP4B1*1/*2 or *2/*2 genotypes had a 1.75-fold increased risk of bladder cancer (95% CI=1.03-2.95, P = 0.038) compared with the subjects carrying the CYP4B1*1/*1 genotype. We demonstrated the first genetic study regarding the association of CYP4B1 with bladder cancer. Our results suggest that CYP4B1 genotypes might have an effect on the risk of bladder cancer.

Anterior apical biopsy: is it useful for prostate cancer detection?

OBJECTIVES: To evaluate the utility of a 12-core prostate biopsy protocol including apical anterior peripheral zone (AAPZ) cores. METHODS: Between February 2002 and October 2006, 10-core and 12-core initial transrectal prostate biopsies were performed on 164 and 549 men, respectively. Two AAPZ-directed biopsies were included in the 12-core biopsy. During the same period, 12-core repeat biopsies including six AAPZ sites were performed on 118 men. RESULTS: Cancer was found in 66 cases (40.2%) in the 10-core biopsy group and in 252 (45.9%) in the 12-core biopsy group. In this latter group, 13 (5.2%) of the 252 men with positive biopsy had cancer exclusively in the AAPZ cores. When the cancer detection rate at initial biopsy in AAPZ alone was compared according to the digital rectal examination (DRE) findings, it was significantly higher in men with normal rather than abnormal DRE: 12/250 (3.4%) vs 1/185 (0.5%) (P < 0.01). In repeat 12-core biopsies, cancer was detected in 25 (21.2%) men and 9 of them (36.0%) had cancer exclusively in the AAPZ cores. The cancer detection rate from AAPZ sites was significantly higher in repeat biopsy than that in initial biopsy (P < 0.01). CONCLUSIONS: Addition of the AAPZ site-directed biopsy had greater utility in men with normal DRE and particularly in patients with a prior negative biopsy.

Spontaneous rupture of adrenal pheochromocytoma with capsular invasion.

A 67-year-old Japanese man developed a sudden onset of severe right-side upper abdominal pain, nausea and vomiting. On hospitalization, physical examination revealed sweating, tachycardia, hypertension and the appearance of peripheral vasoconstriction. An urgent computed tomography scan with contrast demonstrated a large hematoma in the right retroperitoneal space. A phentolamine test and an 131iodine metaiodobenzylguanidine scan suggested pheochromocytoma. An elective right adrenalectomy was successfully performed after pretreatment for sufficient volume replacement with continuous administration of alpha- and beta-adrenergic blocking agents. Pathological diagnosis was an adrenal pheochromocytoma 9.0 x 6.5 cm in diameter with evidence of capsular invasion, which could be associated with a tear in the capsule.

Acute eosinophilic pneumonia associated with intravesical bacillus Calmette-Guérin therapy of carcinoma in situ of the bladder.

A 71-year-old man with a history of rheumatoid arthritis was treated with intravesical bacillus Calmette-Guérin (BCG) instillation of 80 mg once-a-week for carcinoma in situ. He developed low-grade fever followed by dyspnea and severe hypoxemia. Radiological and laboratory studies revealed bilateral diffuse reticulonodular infiltrates and hypereosinophilia. A lymphocyte stimulation test for BCG was strongly positive. From these findings, a pulmonary hypersensitivity reaction to immunotherapy was suspected, and therefore, methylprednisolone (500 mg per day) was started. After that, the fever and dyspnea disappeared, the hypereosinophilia was normalised and chest radiography results were clear. The present case is the first reported case of eosinophilic pneumonia following intravesical BCG therapy.