Efficacy and safety of axitinib for metastatic renal cell carcinoma: Real-world data on patients with renal impairment.

OBJECTIVES: Limited information is currently available on the efficacy and safety of axitinib for metastatic renal cell carcinoma (mRCC) patients with renal impairment. Therefore, the present study investigated the efficacy and toxicity of axitinib in patients with chronic kidney disease. METHODS: Post-hoc analyses were performed on a Japanese multicenter cohort study of 477 mRCC patients who received axitinib followed by 1 or 2 regimens of systemic antiangiogenic therapy between January 2012 and December 2016. Differences in clinical characteristics and the efficacy and safety of axitinib were assessed based on pretreatment renal function. RESULTS: Patients were categorized into the following 5 renal function groups according to baseline renal function: estimated glomerular filtration rate (eGFR) ≥60 ml/min (n = 133), 45 ml/min ≤eGFR <60 ml/min (n = 153), 30 ml/min ≤eGFR< 45 ml/min (n = 130), eGFR <30 ml/min (n = 45), and dialysis (n = 16). Median progression-free survival (PFS) (95% confidence interval [CI]) in the 5 groups was 11 (8-16), 14 (11-19), 14 (10-19), 12 (8-24), and 6 (3-NR) months, respectively (p = 0.781). After adjustments for treatment-related confounders, the renal function group was not a significant prognostic factor for PFS. Objective response rates in the 5 groups were 22%, 23%, 23%, 18%, 20%, and 38%, respectively (p = 0.468). Regarding adverse events of all grades, hypertension (p = 0.0006) and renal and urinary disorders (p < 0.0001) were more frequently observed in the eGFR <30 ml/min group than in the other groups. CONCLUSIONS: Since renal function at the initiation of treatment with axitinib does not adversely affect the efficacy of VEGF-TKI therapy, clinicians do not need to avoid its administration to mRCC patients with impaired renal function in consideration of the risk of progression to end-stage renal disease.

Impact of the severity of urethrovesical anastomotic leakage on urinary continence following robot-assisted laparoscopic prostatectomy.

We assessed whether the severity of anastomotic urinary leakage detected during routine cystourethrography after robot-assisted laparoscopic prostatectomy (RALP) affects urinary continence recovery. Around 302 patients who underwent RALP between August 2013 and May 2019 were included retrospectively. According to routine cystourethrographic findings obtained on the sixth or eighth postoperative day, which indicated leakage severity, patients were divided into three groups: no-leakage, grade 1 (linear shaped leakage, but not spreading), and grade 2 (spreading strip-shaped leakage). The preoperative factors and intraoperative factors were compared between no-leakage and leakage group (grade 1 and grade 2). Continence recovery was compared between the three groups. Continence recovery was defined as no pad used or one security pad used in a day. Cystourethrography revealed anastomotic urinary leakage in 44 patients (14.5%), of which 20 patients (6.6%) had grade 1 leakage and 24 patients (7.9%) had grade 2 leakage. On multivariate logistic regression analysis, the only significant predictor for urethrovesical anastomotic urinary leakage on cystourethrography following RALP was intraoperative anastomotic leakage (OR 5.306; 95% CI 1.530-18.398, p = 0.009). Continence recovery rates for no-leakage, grade 1 leakage, and grade 2 leakage groups were 11%, 20%, and 25% after 1 month (P = 0.131); 25%, 25%, and 45.8% after 3 months (P = 0.474); 44.6%, 55%, and 60.8% after 6 months (P = 0.184); and 63.1%, 87.5%, and 78.2% after 12 months (P = 0.095), respectively. In conclusion, urinary leakage in urethrovesical anastomosis, even at its severity, had no negative effects on continence recovery after RALP.

Incidental Bladder Cancer Found on Cystoscopy during Prostate Biopsy: Prevalence, Pathological Findings, and Oncological Outcome.

INTRODUCTION: We examined the prevalence, pathological findings, and oncological outcomes of incidental bladder cancer found on cystoscopy among patients eligible for prostate biopsy (PB). METHODS: We retrospectively reviewed 803 patients who underwent cystoscopy prior to PB between January 2010 and September 2020. In cases of bladder tumor-like findings on cystoscopy, biopsy or transurethral resection of the bladder tumor was performed. The primary and secondary outcomes were the prevalence of incidental bladder cancer and pathological and oncological outcomes of incidental bladder cancer, respectively. RESULTS: Incidental findings were observed in 31/803 patients (3.9%). Bladder tumor-like findings were found in 24/803 patients (3%), while 9/803 patients (1.1%) were pathologically diagnosed with urothelial carcinoma. The stage and grade of incidental bladder cancer were pTa in 8/9 patients and pT1 in 1/9 and low grade in 8/9 and high in 1/9, respectively. The median tumor size of the papillary pedunculated type was 0.5 cm. At 26-month median follow-up, no recurrence was observed. CONCLUSION: Cystoscopy during PB may yield incidental bladder cancer findings, although the prevalence is very low. Incidental bladder cancer was of low stage and grade, which seemed unrelated to survival. Moreover, performing routine cystoscopy in conjunction with PB is not recommended as it may lead to overdiagnosis of low-risk bladder cancer.

A case of pyelocalyceal diverticulum urothelial carcinoma that was difficult to distinguish from cystic renal cell carcinoma preoperatively.

INTRODUCTION: Pyelocalyceal diverticulum is a rare disease sometimes difficult to distinguish from cysts. We report a case of urothelial carcinoma originating from a pyelocalyceal diverticulum, difficult to distinguish from cystic renal cell carcinoma preoperatively. CASE PRESENTATION: A 51-year-old Japanese man complained of gross hematuria. Computed tomography revealed a solid mass in one of the many cystic lesions in the left kidney. He was diagnosed with left cystic renal cell carcinoma and underwent retroperitoneal laparoscopic nephrectomy. Pathological examination revealed high-grade invasive urothelial carcinoma arising within the renal pyelocalyceal diverticulum. The definitive diagnosis was high-grade invasive urothelial carcinoma (pT3). In retrospect, the retrograde pyelography findings indicated the cyst and urinary tract connection. Residual ureterectomy and adjuvant chemotherapy were later performed. The patient has since been recurrence-free. CONCLUSION: Whether cystic renal cell carcinoma is suspected on imaging, pyelocalyceal diverticulum should be considered a differential diagnosis, though unlikely to be encountered in daily practice.

Myocarditis as an immune-related adverse event following treatment with ipilimumab and nivolumab combination therapy for metastatic renal cell carcinoma: a case report.

BACKGROUND: Immune checkpoint inhibitors are new immunotherapy drugs globally used for many malignancies, including renal cell carcinoma. Myocarditis as an immune-related adverse event is rare but highly fatal, suggesting that its frequency may be higher than reported. This paper describes a case of myocarditis that developed asymptomatically following ipilimumab and nivolumab combination therapy for renal cell carcinoma. CASE PRESENTATION: A 71-year-old Asian man who presented to hospital with fever, fatigue, and weight loss of approximately 10 kg within 2 months was diagnosed with Xp.11.2 translocation renal cell carcinoma. Computed tomography revealed multiple lung masses, mediastinal lymph node enlargement, and a level II tumor thrombus reaching the inferior vena cava (cT3bN0M1; International Metastatic Renal Cell Carcinoma Database Consortium, poor risk). Ipilimumab/nivolumab combination therapy was started as induction therapy. The patient experienced acute interstitial nephritis as an immune-related adverse event after treatment initiation; however, a good response to steroid therapy was observed. The antitumor effect of the immunotherapy was notable. Although he experienced pulmonary embolism, it seemed asymptomatic and harmless; thus, a second infusion was introduced. From the eighth day, he demonstrated rapidly worsening cardiogenic shock with asymptomatic electrocardiographic changes and drastic drop in cardiac biomarkers, and a diagnosis of myocarditis as an immune-related adverse event was made. Although immediate methylprednisolone mini-pulse therapy followed by tapered prednisolone prevented mortality, extensive myocardial fibrosis with marked ejection fraction decline persisted as a sequela. Consequently, follow-up without treatment was instituted; however, much of the tumor response initially observed was maintained over several months. CONCLUSION: Physicians treating patients with immune checkpoint inhibitors should be aware of their potentially life-threatening cardiotoxic effects. This study emphasized the importance of a high index of suspicion, prompt diagnosis, and early intervention in patients who present with cardiac abnormalities and possible myocarditis after receiving immunotherapy.

Positive Culture Prior to Transperineal Prostate Biopsy Was Not Associated with Post-Biopsy Febrile Urinary Tract Infection Development.

PURPOSE: To investigate the association between urine culture before transperineal prostate biopsy and post-biopsy febrile urinary tract infection (fUTI). PATIENTS AND METHODS: We retrospectively reviewed 307 patients who underwent urine culture before transperineal prostate biopsy between April 2017 and September 2020. Patients with indwelling urinary catheters (n=7) were excluded. Urine culture was performed 1-3 days before the biopsy, and all patients received prophylactic cefazolin regardless of culture results. A urine culture was defined as positive if cell density was more than 1×105 colony-forming units per mL. Baseline characteristics and the incidence of post-biopsy fUTI were compared between patients showing positive pre-biopsy culture results and those showing negative findings. RESULTS: Out of 300, seven patients (2.3%) had positive urine culture results before the biopsy. Age (p=0.077); prostate-specific antigen at diagnosis (p=0.267); prostate volume (p=0.78); number of biopsy cores (p=0.277); percentage of patients testing positive for cancer on biopsy (p=0.71); and percentages of patients with a history of biopsy (p>0.999), diabetes mellitus (p=0.604), and immunosuppressive medication use (p>0.999) were similar between the two groups. No patient in the positive urine culture group had post-biopsy fUTI. However, 1.7% (five patients) of the negative urine culture group had the disease (p>0.999) (four patients with prostatitis and one with pyelonephritis). Among them, two patients were diagnosed by urine culture at the time of post-biopsy fUTI. CONCLUSION: In asymptomatic patients, positive pre-biopsy cultures were not associated with the development of post-biopsy fUTI.

Efficacy and toxicity of intravesical Bacillus Calmette-Guérin therapy in elderly patients with non-muscle-invasive bladder cancer.

OBJECTIVES: This study aimed to compare the efficacy and toxicity of intravesical Bacillus Calmette-Guérin (BCG) therapy between elderly and younger patients with non-muscle-invasive bladder cancer (NMIBC). MATERIAL AND METHODS: This retrospective study included 87 NMIBC patients who received intravesical BCG between January 2011 and December 2018. We compared the treatment outcomes of patients ≥75 and <75 years old. Our primary endpoint was intravesical recurrence-free survival after treatment. The secondary endpoint was the toxicity caused by intravesical BCG. RESULTS: The elderly and younger patients included 38 and 49 patients with mean ages of 80.6 and 66.3 years (p < 0.01), respectively. Their baseline parameters were similar, aside from age. The elderly and younger patients' 5-year recurrence-free survival rates were 59.4% and 51.6%, respectively, and were not significantly different (log-rank test, p = 0.72). Moderate to severe pain on micturition requiring prescription medications was observed more frequently in the elderly patients than in the younger patients (p < 0.01). No elderly patients required hospitalization for any adverse events. However, 3 (6.1%) younger patients were treated for urinary tract infection in the hospital. CONCLUSIONS: The efficacy and toxicity of intravesical BCG therapy for NMIBC patients are not associated with age. Therefore, elderly patients with high-risk NMIBC should be treated in the same manner as younger patients in clinical practice.

Use of surgical checklist during transurethral resection increases detrusor muscle collection rate and improves recurrence-free survival in patients with non-muscle-invasive bladder cancer.

OBJECTIVE: To elucidate the therapeutic benefits of using a surgical checklist during transurethral resection for non-muscle-invasive bladder cancer. METHODS: A nine-item surgical checklist was established in January 2016 to assess disease risk and resection adequacy, and it was prospectively implemented into clinical practice. Patients diagnosed with non-muscle-invasive bladder cancer who underwent complete resection from January 2009 to August 2019 were included in this study. The presence of detrusor muscle in the transurethral resection specimen and the intravesical recurrence-free survival were compared between patients who underwent transurethral resection before and after surgical checklist implementation. RESULTS: A total of 125 patients who underwent transurethral resection after surgical checklist implementation were reviewed and compared with 125 patients who underwent transurethral resection before surgical checklist implementation. The use of the surgical checklist led to an increase in the proportion of transurethral resection specimens containing detrusor muscle (92% vs 69.6%, P < 0.01) and a decrease in the recurrence rate (19.2% vs 49.6%, P < 0.01). Multivariate analysis showed that transurethral resection without a surgical checklist was an independent predictive factor influencing the absence of detrusor muscle in the transurethral resection specimen (odds ratio 4.78, P < 0.01) and intravesical recurrence (hazard ratio 1.92, 95% confidence interval 1.14-3.23; P = 0.01). Kaplan-Meier plots showed that the recurrence-free survival rate was significantly lower when the surgical checklist was not used (log-rank test result P < 0.01). CONCLUSIONS: This study shows the therapeutic benefits of surgical checklist in improving the quality of resection during transurethral resection and reducing the recurrence rate in patients with non-muscle-invasive bladder cancer.

The predictive factor for pathological downgrading after prostatectomy in patients with biopsy Gleason score 4+3 or 4+4 prostate cancer.

The proportion of Gleason pattern (GP) 4 prostate cancers at prostate biopsy has a clinically significant impact on risk stratification for patients with prostate cancer. In pathological diagnosis including GP 4, a biopsy Gleason score (GS) of 3+4 has a more favorable prognosis than a GS of 4+3 and 4+4. However, the discrepancy between biopsy and prostatectomy specimens is well known. The current study investigated the clinical parameters and biopsy specimens associated with pathological downgrading after prostatectomy in biopsies with a GS of 4+3 or 4+4 prostate cancer. A total of 302 patients with prostate cancer who underwent robot-assisted radical prostatectomy between August 2013 and May 2019 were retrospectively reviewed. A total of 103 patients had biopsies with GSs of 4+3 and GS 4+4 (unfavorable pathology). The proportion of patients who were downgraded from unfavorable disease to GS ≤3+4 (favorable pathology) in prostatectomy specimens was investigated. Logistic regression analysis was used to explore the association between clinical parameters and downgrading in prostatectomy specimens. A total of 43 patients (41.7%) were downgraded from biopsy GS to prostatectomy GS. The proportions of downgrade in biopsy GS 4+4 and 4+3 were 14.6 and 27.1%, respectively. The percentage of highest GS out of positive biopsy cores and the maximum percentage of cancer involvement within a positive core with the highest GS were lower in the downgrade group than in the no downgrade group (45 vs. 66.7%, P=0.025; 20 vs. 30%, P=0.048, respectively). When performing multivariate logistic regression analysis, the only significant predictor for downgrade was lower percentage of highest GS cores out of positive biopsy cores (odds ratio, 2.469; 95% confidence interval, 1.029-5.925 P=0.043). In conclusion, patients with biopsy GS 4+4 and 4+3 often exhibit a downgrade to GS 3+4 or less in prostatectomy specimens. The lower percentage of highest GS cores out of positive biopsy cores was associated with downgrade.

The Impact of Histopathological Features of Prostate Cancerous Lesions on Multiparametric Magnetic Resonance Imaging Findings using PI-RADS Version 2.

OBJECTIVES: To determine the square measure threshold of prostate cancer lesions in pathological specimens showing PI-RADS categories 3 to 5, and to identify the pathological characteristics of cancerous lesions over the threshold. METHODS: Cancer foci detected in horizontal sections of specimens were defined as pathological cancerous lesions, in which square measure, lesion location (peripheral or transition zone), Gleason pattern (GP), GP4-5 component percentages, and GP 4 subtypes were assessed. A receiver operating characteristic curve was used to determine the threshold of the square measure of pathological specimens that distinguishes between lesions of PI-RADS categories 1 and 2 and those of 3 to 5. Univariable and multivariable analyses were performed to determine the histopathological features associated with PI-RADS categories 3 to 5. RESULTS: A total of 100 consecutive patients underwent multiparametric magnetic resonance imaging before robotic-assisted laparoscopic prostatectomy. A total of 1366 pathological cancerous lesions were detected, 217 of which were classified as PI-RADS categories 3 to 5. A square measure of 40 mm2 on pathological specimens was the threshold for PI-RADS categories 3 to 5. Of the 415 lesions that were over 40 mm2, 211 lesions exhibited PI-RADS categories 1, 2 and 204 lesions exhibited PI-RADS categories 3 to 5. Multiple logistic regression analysis showed that square measure, fused glands, and cribriform glands were independently associated with PI-RADS categories 3 to 5. CONCLUSION: Cancerous lesions over 40 mm2 showing PI-RADS categories 3 to 5 are associated with square measure, fused glands, and cribriform glands.

Ureteroiliac artery fistula caused by full-length metallic ureteral stenting in a malignant ureteral obstruction: a case report.

BACKGROUND: The metallic stent is a new device for relieving the urinary tract in patients with malignant ureteral obstruction with short life expectancy and has been used frequently worldwide for its efficacy and safety. A ureteroarterial fistula with indwelling ureteral stent is rare but highly fatal, and there are several reports of ureteroarterial fistula treated by conventional polymer stents, although there are no reports on metallic stents. To our knowledge, this paper describes the first case of a ureteroiliac artery fistula caused by a full-length metallic ureteral stent in malignant ureteral obstruction. CASE PRESENTATION: Our patient was a 57-year-old Asian woman with a history of locally advanced cervical cancer who underwent abdominal total hysterectomy and chemoradiotherapy. She was diagnosed with right hydronephrosis and hydroureter secondary to upper ureteral obstruction because of retroperitoneal lymph node metastasis. A urinary tract obstruction after placement of 12 months of polymer stent followed by 18 months of metallic stent was relieved, consequently resulting in intermittent gross hematuria with bladder tamponade and anemia. Contrast-enhanced computed tomography could not reveal a ureteroarterial fistula; however, retrograde pyelography emphasized the existence of a ureteroiliac artery fistula. The patient underwent successful endovascular heparin-bonded stent graft placement, and her gross hematuria disappeared thereafter. CONCLUSION: The metallic stent is a useful device for patients with malignant ureteral obstruction with a short life expectancy, although it may impose a higher pressure on the extraureteral tissue than conventional polymer stents due to its properties and may cause a ureteroarterial fistula. The narrowing of the external iliac artery diameter visualized by computed tomography may be helpful for predicting ureteroarterial fistulas.

Impact of second transurethral resection on recurrence in patients with high-grade Ta bladder cancer.

OBJECTIVES: To clarify the potential therapeutic benefit of a second transurethral resection for high-grade Ta bladder cancer. METHODS: From January 2009 to August 2019, 521 patients with bladder tumors underwent initial transurethral resection procedures at Kagawa University Hospital. Patients diagnosed with high-grade Ta bladder cancer considered to have been resected completely were included in this study. Recurrence and progression rates were compared between patients who received a second transurethral resection and those who did not. RESULTS: We identified 97 eligible patients, including 22 patients who received a second transurethral resection. In terms of clinical characteristics, the proportion of patients with bladder cancer and upper urinary tract tumor history was lower in the second transurethral resection group than in the no second transurethral resection group (P < 0.01 and P = 0.03, respectively). The histopathological findings of 22 transurethral resection procedures were no cancer in 13 (59.2%), Ta in six (27.2%) and carcinoma in situ in three patients (13.6%). After the second transurethral resection, one patient (4.6%) had recurrent high-grade T1 bladder cancer. The no second transurethral resection group showed a 44% recurrence rate (33 patients), including five patients (6.7%) with progression, and consequently, had a higher rate of recurrence than in the second transurethral resection group (P < 0.01). Multivariate analysis showed that no second transurethral resection was the independent predictive factor influencing recurrence (hazard ratio 8.662, P = 0.04). The Kaplan-Meier curve showed that a second transurethral resection significantly decreased the recurrence rate than that of patients without a second transurethral resection (P < 0.01). CONCLUSIONS: A second transurethral resection can reduce the recurrence rate in high-grade Ta bladder cancer, showing a possible therapeutic benefit of this procedure.

Obstructive Sleep Apnea Syndrome as a Potential Cause of Nocturia in Younger Adults.

OBJECTIVES: To investigate the impact of age on the relationship between obstructive sleep apnea syndrome (OSAS), nocturia, and other lower urinary tract symptoms (LUTSs). METHODS: This was a secondary analysis study based on data derived from a previously conducted prospective observational cohort study on OSAS and nocturia. We analyzed 90 subjects who were suspected of having OSAS. Prior to polysomnography, we assessed International Prostate Symptom Score-Quality of Life scores, Overactive Bladder Symptom Scores, and International Consultation on Incontinence Modular Questionnaire-Nocturia Quality of Life scores to evaluate LUTSs. Nocturnal urine volume, night-time frequency, and night-time urine electrolyte content were measured during polysomnography. Patients were divided into groups according to age and OSAS severity determined using apnea-hypopnea index (AHI) scores. Young patients were those aged <65 years and elderly patients, ≥65 years. A multiple linear regression with multiple imputations was performed to examine the association of night-time frequency with demographic, polysomnographic, and clinical characteristics. RESULTS: In young patients, night-time frequency was significantly associated with nocturnal urine volume, AHI score, and total IPSS. However, night-time frequency in elderly subjects was not associated with demographic and polysomnographic characteristics. In order to compare the severity of OSAS, night-time frequency and urinary sodium content significantly increased only in young patients (P = .007 and .004, respectively). CONCLUSION: OSAS is a strong candidate of causative factor for nocturia in younger individuals. When a younger patient complains nocturia without any urological disorders, OSAS should be kept in mind as a potential cause of nocturia.

Oncological outcomes of a multicenter cohort treated with axitinib for metastatic renal cell carcinoma.

The present study aimed to evaluate the efficacy of the real-world use of axitinib and to develop a prognostic model for stratifying patients who could derive long-term benefit from axitinib. This was a retrospective, descriptive study evaluating the efficacy of axitinib in patients with metastatic renal cell carcinoma that had been treated with 1 or 2 systemic antiangiogenic therapy regimens at 1 of 36 hospitals belonging to the Japan Urologic Oncology Group between January 2012 and February 2019. The primary outcome was overall survival (OS). Using a split-sample method, candidate variables that exhibited significant relationships with OS were chosen to create a model. The new model was validated using the rest of the cohort. In total, 485 patients were enrolled. The median OS was 34 months in the entire study population, whereas it was not reached, 27 months, and 14 months in the favorable, intermediate, and poor risk groups, respectively, according to the new risk classification model. The following 4 variables were included in the final risk model: the disease stage at diagnosis, number of metastatic sites at the start of axitinib therapy, serum albumin level, and neutrophil : lymphocyte ratio. The adjusted area under the curve values of the new model at 12, 36, and 60 months were 0.77, 0.82, and 0.82, respectively. The efficacy of axitinib in routine practice is comparable or even superior to that reported previously. The patients in the new model's favorable risk group might derive a long-term survival benefit from axitinib treatment.

Body Fat Area as a Predictive Marker of New-Onset Diabetes Mellitus After Kidney Transplantation.

BACKGROUND: New-onset diabetes after kidney transplantation (NODAT) adversely affects patient survival. Excessive fat accumulation is generally considered a risk factor of NODAT. Body mass index (BMI) and abdominal circumference (AC) are frequently used to assess fat accumulation but cannot directly measure it. This study measured body fat area (BFA) via computed tomography and aimed to clarify whether preoperative BFA can predict the development of NODAT more accurately than BMI and AC. METHODS: This retrospective study included 62 patients without diabetes mellitus who received living-donor kidney transplantation at our institute between July 2005 and April 2016. We investigated the association between preoperative BMI, AC, and BFA and the development of NODAT. RESULTS: Eight patients (12.9%) developed NODAT during a mean follow-up period of 78.1 months. The preoperative BMI, AC, and BFA were markedly higher in NODAT patients than in patients without NODAT (P = .05, P = .02, P < .01, respectively). Correlation analyses revealed that BFA had a strong relationship with BMI (r = 0.68, P < .01) and AC (r = 0.77, P < .01). Receiver operating characteristic curve analyses demonstrated that BFA, compared to BMI and AC, had considerable predictive accuracy for the development of NODAT, with an area under the curve of 0.803 (sensitivity 75%, specificity 87%). CONCLUSIONS: Preoperative BFA could be a predictive marker of NODAT in renal graft recipients. Our findings underline the importance of routine preoperative BFA measurements in clinical practice.

A phosphodiesterase 5 inhibitor, tadalafil, suppresses stromal predominance and inflammation in a rat model of nonbacterial prostatitis.

BACKGROUND: Chronic inflammation is thought to be a major causative factor for the development of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). Tadalafil, a phosphodiesterase type 5 inhibitor (PDE5-I), which has been used for the treatment of BPH-LUTS in daily practice, is known to act at several urinary organs. In this study, focused on the prostate, we examined the effect of tadalafil on the pathological changes and inflammatory factors in a rat nonbacterial prostatitis (NBP) model. METHODS: Forty ten-month-old male Wistar rats were divided into nonbacterial prostatitis (NBP), NBP with tadalafil treatment (NBP-tadalafil), control, and control treated with tadalafil (control-tadalafil) groups (n = 10 per group). The NBP and NBP-tadalafil groups were castrated and then received daily subcutaneous 17ß-estradiol for 30 days. The control-tadalafil and NBP-tadalafil groups were administered daily oral tadalafil for 30 days. All rats were then sacrificed and pathological changes and inflammatory factors were assessed in the prostatic tissues. RESULTS: In the NBP group, the stroma-to-epithelium (S/E) ratio in the ventral prostate was significantly higher than in the control group (P < 0.001). In the NBP-tadalafil group, the S/E ratio was significantly lower than in the NBP group (P < 0.001). The macrophage levels and the extent of T-cell infiltration in the NBP-tadalafil group were significantly lower than in the NBP group (P < 0.005; P < 0.001, respectively). Compared with the NBP group, tissue concentrations of inflammatory cytokines, such as tumor necrosis factor-α, interleukin-8, and interleukin-1ß, were significantly downregulated in the NBP-tadalafil group (P < 0.01; P < 0.05; P < 0.005, respectively). CONCLUSIONS: Tadalafil suppressed stromal predominance and showed anti-inflammatory effects in a rat NBP model in association with downregulation of inflammatory cytokines.

Retroperitoneal liposarcoma excreting insulin-like growth factor 2 that induced severe hypoglycemia.

Insulin-like growth factor 2 is overexpressed in various cancers, and is associated with a poor prognosis. Also, it is known that insulin-like growth factor 2 is an etiology of non-islet cell tumor hypoglycemia. In this report, we describe a case of unexpected hypoglycemia caused by a dedifferentiated liposarcoma producing insulin-like growth factor 2. A large mass in the retroperitoneum was detected in a 61-year-old man who complained of appetite loss. Despite having no history of diabetes mellitus, hypoglycemia suddenly occurred after admission, but oral glucose therapy was ineffective. After total parenteral nutrition, tumor resection was attempted, but failed as a result of rigid adhesion to the surrounding organs. The patient died of the disease 21 days after surgery. Pathological diagnosis at autopsy revealed dedifferentiated liposarcoma, and immunohistochemical staining showed that the tumor excreted insulin-like growth factor 2. The possibility of an insulin-like growth factor 2-producing tumor should be taken into consideration when we encounter a patient with spontaneous hypoglycemia resistant to glucose substitution therapy.

Effect of the continuous positive airway pressure on the nocturnal urine volume or night-time frequency in patients with obstructive sleep apnea syndrome.

OBJECTIVE: To evaluate the effect of continuous positive airway pressure (CPAP) treatment on nocturnal urine volume, night-time urine frequency, and quality of life (QOL) in patients with obstructive sleep apnea syndrome (OSAS). METHODS: Ninety-eight participants with suspicious diagnosis of OSAS were prospectively enrolled in this study. Before polysomnography, measurement of the International Prostate Symptom Score-QOL score, the Overactive Bladder Symptom score (OABSS), the International Consultation on Incontinence Modular Questionnaire-Nocturia QOL were carried out to evaluate the lower urinary tract symptoms. During polysomnography, nocturnal urine volume and night-time urine frequency were recorded, and the concentrations of electrolytes in urine were determined. OSAS was confirmed in 92 patients, and 63 patients started to undergo CPAP treatment. Change in lower urinary tract symptoms-related QOL was assessed 1 month after CPAP treatment in 51 patients. Additionally, urine was collected at the time of CPAP titration in 25 patients. RESULTS: CPAP treatment significantly improved night-time frequency, which resulted in the improvement of total IPSS and QOL score. The night-time frequency questionnaire in OABSS similarly decreased, although total OABSS scores were not significantly improved. The International Consultation on Incontinence Modular Questionnaire-Nocturia QOL showed no significant changes after CPAP treatment. In addition to the night-time frequency, nocturnal urine volume and urine electrolyte contents significantly decreased after CPAP treatment. CONCLUSION: CPAP treatment decreases night-time urine frequency by reducing nocturnal urine volume and improves QOL in OSAS patients.

[A case with hepatitis and interstitial pneumonitis caused by intravesical bacillus Calmette-Guérin (BCG) instillation].

A 49-year man, with past history of right total nephroureterectomy due to urothelial carcinoma of the right renal pelvis in September 2006 and left partial ureterectomy due to contralateral ureteral recurrence in October 2007, underwent TUR-BT due to superficial high-grade recurrent bladder cancer. After TUR-Bt, he was treated with intravesical Bacillus Calmette-Guérin (BCG) instillation at weekly intervals. Just after 5th instillation, he suffered a continuous high fever up to 38 degrees C and complained of general fatigue. Chest CT showed diffuse micronodular shadows in both lungs, and serum liver enzyme was markedly elevated. All cultures from his sputum and urine were negative for mycobacterium tuberculosis. TB-PCR test and quantiferon were also negative. These findings together with no improvement of the symptoms with anti-tuberculous treatment finally made us to judge that this was due to a hypersensitivity reaction to BCG. Soon after pulse steroid therapy, body temperature was normalized and the abnormal findings of the lung and liver disappeared.