Bacillus Calmette-Guerin intravesical instillation therapy-induced urothelial necrosis of the bladder and upper urinary tract.

Bacillus Calmette-Guerin (BCG) intravesical instillation therapy is the most effective adjuvant therapy for bladder cancer after transurethral resection of bladder tumor (TURBT). We present the first case to our knowledge with bladder and ureteral necrosis as a severe local side effect of it.

Intravesical mitomycin C (MMC) and MMC + cytosine arabinoside for non-muscle-invasive bladder cancer: a randomised clinical trial.

OBJECTIVES: To compare the urinary pH, recurrence-free survival (RFS), and safety of adjuvant intravesical therapy in patients with non-muscle-invasive bladder cancer (NMIBC) receiving mitomycin C (MMC) therapy and MMC + cytosine arabinoside (Ara-C) therapy. PATIENTS AND METHODS: A total of 165 patients with NMIBC from six hospitals were randomly allocated to two groups: weekly instillation of MMC + Ara-C (30 mg/30 mL + 200 mg/10 mL) for 6 weeks and the same instillation schedule of MMC (30 mg/40 mL). The primary outcome was RFS, and secondary outcomes were urinary pH and toxicity in the two groups. RESULTS: A total of 81 and 87 patients were randomised into the MMC and MMC + Ara-C groups, respectively. Overall, the RFS in the MMC + Ara-C group was significantly longer (P = 0.018) than that in the MMC group. A similar significant difference was detected in patients with intermediate-risk NMIBC, but not in those with high-risk NMIBC. The mean (SD) urinary pH was significantly higher in the MMC + Ara-C group than in the MMC group, at 6.56 (0.61) vs 5.78 (0.64) (P < 0.001), and the frequency of a urinary pH of >7.0 in the MMC and MMC + Ara-C groups was 6.3% and 26.7%, respectively (P < 0.001). Multivariate analysis models including clinicopathological features and second transurethral resection demonstrated that increased urinary pH was associated with better outcomes (hazard ratio 0.18, 95% confidential interval 0.18-0.038; P < 0.001). In all, there were 14 and 10 adverse events in the MMC and MMC + Ara-C groups, respectively, without a significant difference (P = 0.113). CONCLUSIONS: Our randomised clinical trial suggested that intravesical therapy with MMC and Ara-C is useful and safe for patients with intermediate-risk NMIBC. Increase in urinary pH with Ara-C is speculated as a mechanism for increased anti-cancer effects.

[A Case of Glans Penile Necrosis Due to Hyaluronic Acid into the Penis for Male Genital Augmentation].

A 65-year-old man visited us with a painful penis after receiving an injection of hyaluronic acid into the penis for male genital augmentation. On admission, physical examination revealed black necrotic lesions and ulcerations on his glans penis. We performed partial penectomy to remove the necrotic tissues. Histopathological examination showed necrosis with severe inflammatory infiltration in the dermis and subcutis. Glans penile necrosis due to hyaluronic acid injected into the glans penis for male genital augmentation is exceedingly rare. This case is reported herein along with a review of the Japanese literature.

Preliminary Study of a Single Instillation of Low-Concentration High-Volume Silver Nitrate Solution for Chyluria: Is >10 mL Instillation an Absolute Contraindication in the Real World?

Silver nitrate instillation (SNI) is one form of treatment for chyluria. However, there is the opinion that a high volume of SNI (>10 mL) should be avoided because life-threatening complications have been reported. However, we have noticed that most severe complications occur in high-concentration treatments (≥1%), even with a small volume. In addition, a small volume (≤10 mL) of low-concentration (<1%) SNI occasionally causes recurrence. Based on these facts, we aimed to evaluate a preliminary study of a novel single-injection regimen of low-concentration high-volume SNI. In this preliminary study, nine patients who underwent SNI were retrospectively examined. Patient characteristics, anesthesia, procedure, efficacy, complications, and duration of hospital stay were investigated. The volume of silver nitrate solution was decided based on symptoms, findings of pyelography, and vital signs, and it was given as a single instillation. This study was approved by the Institutional Review Board. The ranges of silver nitrate concentration and volume were 0.1%-0.5% and 15-30 mL, respectively. In all patients, proteinuria and cloudy urine disappeared immediately. However, two patients had recurrence after the initial SNI. These two patients were subsequently treated with increasing concentrations of silver nitrate (0.2% and 0.5%) from 0.1%, and they had complete symptomatic relief without recurrence for more than 6 years. None of the patients experienced severe complications. In conclusion, our preliminary study showed that a single instillation of low-concentration (0.1%-0.5%) and high-volume (15-30 mL) SNI is safe and useful. It is worth considering as a treatment option for chyluria.

[Indwelling of Full-Length Metallic Ureteral Stents as an Initial Treatment for Patients with Untreated Malignant Ureteral Obstruction].

To examine the efficacy and safety of a full-length metallic ureteral stent (MS), Resonance®, we retrospectively evaluated 16 cases (22 ureteral units) with indwelling MS as the initial treatment for patients with untreated malignant ureteral obstruction (MUO). All patients had undergone MS insertion by the retrograde approach without cystoscopy, with indirect stent placement under fluoroscopy, as a new method that can be performed even if the number of medical staff is one less than that required. Both serum creatinine and estimated glomerular filtration rate values in all cases improved significantly (p<0. 001). Moreover, MS failure occurred in only one patient and the stent patency rate was 93.8%. Stent-related complications were observed in four patients. Two patients experienced stent dislodgement, and one each had fever and acute pyelonephritis, although none of the complications were life-threatening. After the introduction of MS in our hospital, the rate of percutaneous nephrostomy in MUO patients excluding those not suited for indwelling MS, clearly decreased from 80% to 20%. This is the first report on the clinical evaluation of indwelling MS as the initial treatment of MUO in Japan, and this report indicates that MS is a very useful choice in terms of effectiveness, safety, medical cost, and reduction in the workload of medical staff. We believe that the indwelling MS will become a standard initial treatment for patients with untreated MUO in the future.

Influence of prior oral ethinylestradiol use on the efficacy of enzalutamide for the treatment of castration-resistant prostate cancer in men.

OBJECTIVE: To elucidate the effect of prior use of ethinylestradiol on enzalutamide treatment for men with castration-resistant prostate cancer. METHODS: We retrospectively analyzed data from 99 consecutive patients (median age 72 years, range 50-88 years) treated with enzalutamide for castration-resistant prostate cancer between May 2014 and November 2015 after receiving several lines of hormonal therapy. RESULTS: A total of 45 patients were given ethinylestradiol before enzalutamide. The prostate-specific antigen response rate (decline in prostate-specific antigen >50% from baseline) of patients receiving ethinylestradiol and enzalutamide were 51.1% and 41.4%, respectively. Cross-resistance between ethinylestradiol and enzalutamide was clearly observed in the setting of pre-docetaxel. In multivariate analysis, the T stage and number of therapies before enzalutamide were the only significant predictors of prostate-specific antigen response to enzalutamide. However, in patients treated pre-docetaxel use, prior use of ethinylestradiol was a significant predictor of prostate-specific antigen response to enzalutamide, whereas ethinylestradiol did not affect the overall survival of these patients. CONCLUSIONS: Cross-resistance between ethinylestradiol and enzalutamide in the setting of pre-docetaxel therapy seems to be evident. Therefore, ethinylestradiol should be used prudently before enzalutamide in this setting.

Oncological outcomes of hormonal therapy with a gonadotropin-releasing hormone agonist combined with a steroidal or non-steroidal antiandrogen in patients with prostate cancer.

AIM: To determine the treatment outcome of combined androgen blockade (CAB) therapy using the non-steroidal antiandrogen bicalutamide or the steroidal antiandrogen chlormadinone in patients with prostate cancer. PATIENTS AND METHODS: In total, 124 patients with prostate cancer enrolled in the present study were randomized to receive CAB therapy using a gonadotropin-releasing hormone (GnRH) agonist, combined with bicalutamide or chlormadinone. The survival of patients was analyzed. RESULTS: The 5-year cancer-specific survival for the bicalutamide- and chlormadinone-treated groups were 91.7% and 86.6%, respectively, with no significant difference (p=0.39). Five-year overall survival was significantly (p=0.029) better in the bicalutamide-treated group. Moreover, M1 patients in the chlormadinone group had significantly lower cancer-specific and overall survival compared to those in the bicalutamide-treated group. However, in the case of M0 patients, no significant difference in cancer-specific nor in overall survival was observed. CONCLUSION: CAB therapy using chlormadinone led to a significantly poorer survival outcome versus the use of bicalutamide. However, because this survival trend was not observed in M0 cases, chlormadinone may still be an option for CAB therapy, depending on clinical stage and the severity of adverse effects, such as hot flashes.

[Outcome after radical prostatectomy with extended pelvic lymphadenectomy for untreated high-risk clinically localized prostate cancer].

PURPOSE: We assessed the outcome after radical prostatectomy and extended pelvic lymphadenectomy in patients with untreated high-risk clinically localized prostate cancer, retrospectively. MATERIALS AND METHODS: Between 2001 and 2010, 89 patients for untreated high-risk clinically localized prostate cancer on the risk classification as defined by D'Amico, underwent retropubic radical prostatectomy and extended pelvic lymphadenectomy. Boundaries of the pelvic lymph node dissection field divided into external iliac vessels, obturator fossa, and internal iliac vessels. We investigated mainly the postoperative outcome of 84 patients without any adjuvant therapies. PSA recurrence-free survival among the pretreatment variables was estimated using Kaplan-Meier plots, and the statistical significance was determined by log rank test. RESULTS: In 89 high-risk patients, 32.7% had pT3-pT4 tumors, 16.9% positive surgical margin, 6.7% positive lymph node metastases and 30.3% Gleason score 8-10 at the pathological examination. A median of 13 nodes (mean 14.0, range 9-25 nodes) were removed per patient. In 96.6% cases, postoperative PSA values decreased less than 0.2 ng/ml. The median observation period after operation was 1,819 days. Median PSA recurrence-free survival rates, overall survival and cancer cause-specific survival rates at 5 year, in 84 high-risk patients without any adjuvant therapies, were 73.8%, 100% and 100%, respectively. Median PSA recurrence-free survival rates according to pathological T stage and surgical margin status were statistically significant, but that according to preoperative 3 factors (clinical T stage, Gleason score at biopsy, preoperative PSA values) were statistically insignificant. Moreover, that according to both the number of positive preoperative 3 factors (1 vs. 2 positive factors) and the number of removed lymph nodes (< or =13 vs. > or = 14), were statistically insignificant. The median PSA recurrence-free survival rates at 5 year for positive margin cases were 0%. CONCLUSION: Radical prostatectomy and extended pelvic lymphadenectomy is feasible in patients with high-risk clinically localized prostate cancer. We suggest that both wide resection and extended pelvic lymphadenectomy may improve the postoperative outcome for high-risk clinically localized prostate cancer.

[Efficacy of naftopidil in patients with overactive bladder associated with benign prostatic hyperplasia: prospective randomized controlled study to compare differences in efficacy between morning and evening medication].

A total of 100 patients with benign prostatic hyperplasia (BPH) and overactive bladder (OAB) symptoms (BPH/OAB), enrolled between June 2006 to March 2008, were randomly divided into 2 groups of morning medication (M) and evening medication (E) groups, then 50 mg of naftopidil was given once a day after breakfast or supper for 8 weeks. Data were available for efficacy analysis on 80 patients (M group ; 43, E group ; 37). Naftopidil significantly improved the overall international prostatic symptom score ; from 19.2±7.9 to 11.7±5.8 in the M group and from 19.4±6.4 to 12.3±6.8 in the E group (p<0.0001), QOL score from 4.9±0.8 to 3.2±1.4 in the M group and from 5.0±0.8 to 3.6±1.3 in the E group (p<0.0001), and OAB symptom score from 7.8±2.6 to 5.0±2.5 in the M group (p<0.0001) and from 8.6±2.9 to 5.8± 3.3 in the E group (p<0.0001). There was no significant difference in the incidence of adverse effects between the M group (6.1%) and E group (2.2%). These results suggest that naftopidil improves storage symptoms as well as voiding symptoms regardless of timing of administration.

[Case of persistent false elevation of prostate-specific antigen after radical prostatectomy].

We report a rare case of persistent false elevation of prostate-specific antigen (PSA) after radical prostatectomy (RP). Preoperative total PSA was 25.4 ng/ml and final pathology was Gleason score 3+5=8, pT3aN0M0. His first postoperative total PSA was 3.85 ng/ml. He received adjuvant hormone therapy for 10 months. Since PSA gradually elevated despite adjuvant hormone therapy, he underwent imaging for metastasis, confirming no evidence of prostate cancer recurrence. Moreover, total PSA was unmeasurable level in three other PSA assays.

Hot flashes during androgen deprivation therapy with luteinizing hormone-releasing hormone agonist combined with steroidal or nonsteroidal antiandrogen for prostate cancer.

OBJECTIVES: To investigate hot flashes and quality of life during combined androgen blockade (CAB) therapy using steroidal or nonsteroidal antiandrogens. METHODS: A total of 151 patients with prostate cancer, who were enrolled into this study from May 2001 to June 2003, were randomized to receive CAB therapy using a luteinizing hormone-releasing hormone agonist (leuprorelin) combined with a steroidal antiandrogen (chlormadinone) or a nonsteroidal antiandrogen (bicalutamide). The incidence of, frequency of, and distress due to hot flashes were evaluated with a self-administered questionnaire during a 2-year period. The general and disease-specific quality-of-life outcomes were also measured using the Functional Assessment of Cancer Therapy-Prostate questionnaire. RESULTS: Data were available for analysis from 124 patients. Although the incidence of hot flashes largely tended to be greater in the bicalutamide group than in the chlormadinone group, no significant difference was noted in the cumulative incidence of hot flashes at 2 years. The median frequency of hot flashes daily was 1.3 and 2.2 for warmth/flushing (P = .16) and 1.0 and 3.6 for sweating (P = .021) in the chlormadinone and bicalutamide groups, respectively. Patients in the chlormadinone group were significantly less likely to be distressed by warmth/flushing (odds ratio 0.47, P < .001) and sweating (odds ratio 0.61, P = .01) than were those in the bicalutamide group. The Functional Assessment of Cancer Therapy-Prostate scores over time showed no intergroup differences. CONCLUSIONS: Our results suggest that CAB using a steroidal antiandrogen such as chlormadinone might induce fewer and less-distressing hot flashes than CAB with bicalutamide.

[Extraperitoneal bilateral tubeless cutaneous ureterostomy with umbilical stoma].

In some patients with intractable symptoms from incurable pelvic cancer, for example, urgency, severe hematuria, fistula formation and hydronephrosis, palliative urinary diversion with intestinal segments may not be available. Percutaneous nephrostomy or indwelling of double-J ureteral stents were usually performed. However, they suffered catheter trouble and their quality of life considerably worsened. Therefore, we developed a new technique of bilateral extraperitoneal tubeless cutaneous ureterostomy with single umbilical stoma. It resulted in symptom relief in 3 patients. The advantage of this method was as follows. The dissection was entirely extraperitoneal. The operative time was short and the procedure could be performed easily. The left ureter need not be led behind the mesosigmoid. Finally, ostomy care was easy with only one bag.

Unicentric Castleman's disease with leiomyosarcoma: a rare association.

A 54-year-old asymptomatic woman was first diagnosed with unicentric Castleman's disease at 51 years of age. The disease was identified incidentally behind the inferior vena cava after a computed tomography (CT) scan. She was followed conservatively and no enlargement of the mass was observed. However, a follow-up CT scan revealed another solid mass in the left retroperitoneal area. Both tumors were surgically removed in the same session. The retrocaval mass was histologically confirmed to be Castleman's disease of the hyaline vascular type. Histological examination of the left peritoneal mass revealed low-grade leiomyosarcoma. We present here a case of leiomyosarcoma associated with unicentric Castleman's disease, both of which were localized in the retroperitoneum.

Zone-dependent expression of estrogen receptors alpha and beta in human benign prostatic hyperplasia.

Estrogen, which acts through estrogen receptors (ERs) alpha and beta, has been implicated in the pathogenesis of benign and malignant human prostatic tumors, i.e. benign prostatic hyperplasia and prostate cancer, thought to originate from different zones of the prostate [the transition zone (TZ) and peripheral zone (PZ), respectively]. Here, we examined the cellular distribution of ERalpha and ERbeta in human normal and hyperplastic prostate tissues, using in situ hybridization and immunohistochemistry. ERalpha expression was restricted to stromal cells of PZ. In contrast, ERbeta was expressed in the stromal cells of PZ as well as TZ. ERbeta-positive epithelial cells were evenly distributed in PZ and TZ of the prostate. Our results suggest that estrogen may play a crucial role in the pathogenesis of benign prostatic hyperplasia through ERbeta.