[A Crossover Comparison Study on Lower Urinary Tract Symptoms with Overactive Bladder Secondary to Benign Prostatic Hyperplasia: Naftopidil versus Tamsulosin with Solifenacin].

We compared the efficacy of naftopidil monotherapy with combination therapy using tamsulosin hydrochloride and solifenacin succinate in the treatment of lower urinary tract symptoms (LUTS) with overactive bladder (OAB) secondary to benign prostatic hyperplasia (BPH). Thirty one patients were enrolled in a randomized crossover study. Fourteen patients were initially prescribed naftopidil 75 mg (N) for 8 weeks, followed by tamsulosin 0.2 mg and solifenacin 5 mg (TS) for 8 weeks (group N) ; another 17 were initially prescribed TS, followed by N (group TS). The efficacy variables were the changes in international prostate symptom score (I-PSS), quality of life (QOL) score, overative bladder symptom score (OABSS), and post-void residual (PVR) urine volume. After the study, a questionnaire survey was carried out about the choice of treatment. After treatment with each agent, total I-PSS, storage symptom score, QOL score and OABSS except for the daytime frequency were significantly improved from baseline. PVR was significantly increased after TS treatment. There were no significant differences between the two treatments except for PVR. As a result of the questionnaire survey, 13 patients chose N and 17 chose TS. In conclusion, N monotherapy can be expected to have an equal effect in the treatment of LUTS with OAB secondary to BPH in comparison with TS combination therapy.

CLINICAL OUTCOMES OF EXTERNAL-BEAM RADIOTHERAPY COMBINED WITH NEOADJUVANT ANDROGEN DEPRIVATION THERAPY FOR HIGH-RISK PROSTATE CANCER.

(Purpose) We investigated the outcome of external-beam radiotherapy (EBRT) with neoadjuvant androgen deprivation therapy (NeoADT) for high-risk prostate cancer defined by National Comprehensive Cancer Network (NCCN) guideline. (Patients and method) From 2002 to 2013, 70 patients with high-risk prostate cancer (PSA ≥20 ng/ml or clinical T stage ≥T3a, Gleason score ≥8) were treated with NeoADT and EBRT. EBRT consisted of three-dimensional conformal or intensity modulated radiotherapy with or without whole-pelvic radiation. Biochemical failure was defined according to the Phoenix definition. Biochemical progression-free survival (bPFS) and overall survival (OS) were calculated by Kaplan-Meier method, and prognostic factors for bPFS were analyzed by using the Cox proportional hazard model. (Result) The median age and initial prostate-specific antigen (PSA) level were 72 years old and 25.2 ng/ml, respectively. 43 patients had PSA level ≥20 ng/ml, 51 patients had clinical stage ≥T3a, 27 patients had Gleason score ≥8. The number of risk factors patients possessed was 1 (RiskN-1) in 31 patients, 2 (RiskN-2) in 27 patients and 3 (RiskN-3) in 12 patients. Median EBRT dose and duration of Neo ADT were 74 Gy and13.0 months, respectively. Whole-pelvic radiation was administered in 7 patients. After median follow-up of 4.8 years, biochemical and clinical failure occurred in 23 and 2 patients, respectively. No patients died of cancer. Five-year/8-year bPFS and OS were 63%/54% and 100%/91%, respectively. In multivariate analysis, three high-risk factor of NCCN guideline (PSA, clinical stage, Gleason score) did not predict outcome after EBRT independently, but RiskN (-1 vs -2, 3, HR 35.35, 95%CI 2.51-498.05, p<0.01) and pre-EBRT PSA (continuous, hazard ratio 1.31, 95%CI 1.01-1.71, p<0.05) were the significant predictors of bPFS. Five-year/8-year bPFS in RiskN-1 group and RiskN-2 or -3 group were 89%/79% and 47%/39%, respectively. Grade 3/4 adverse events (CTCAE ver4.0-JCOG) occurred in 2 patients. (Conclusion) Median dose of 74 Gy EBRT with intermediate-term NeoADT was safe and beneficial for high-risk prostate cancer. The number of risk factors and pre-EBRT PSA level were the independent prognostic factors for biochemical progression-free survival.

[THE IMPACT OF LOWER URINARY TRACT SYMPTOMS ON GENERIC HEALTH-RELATED QUALITY OF LIFE IN MALE PATIENTS WITHOUT CO-MORBIDITY].

PURPOSE: We investigated the impact of lower urinary tract symptoms (LUTS) on generic health-related quality of life (HRQOL) in male patients without co-morbidity. PATIENTS AND METHOD: From 2003 to 2011, a total 567 men who presented out urological department completed the questionnaires including International Prostate Symptom Score (IPSS), incontinence-frequency score (IFS) from the UCLA prostate cancer index, MOS 36-Item Short-Form Health Survey (SF-36). Among 230 patients with no coexisting morbidity, the relations between each LUTS score of IPSS indices and IFS and 8 domain scores of SF-36 were analyzed by Pearson's product-moment correlation and stepwise multiple regression analysis. RESULT: Univariate analysis showed that the IFS had a significant correlation with all of 8 domain scores of SF-36, and also the IPSS item scores of urgency, nocturia and straining correlated significantly with multiple domain scores of SF-36. In multiple regression analysis, the proportionate contributions of LUTS to each SF-36 domain scores were low (R2 was 10% or less). Incontinence was considered as the most influential factor that had a negative impact on HRQOL in 7 SF-36 domains of physical functioning, role-physical, bodily pain, general health perception, vitality, social functioning and mental health. Additionally, nocturia, straining and urgency were significantly associated with deficit of HRQOL in 4 SF-36 domains (role-physical, general health perception, role-emotional, mental health), 2 domains (bodily pain, social functioning) and 1 domain (role-emotional) of SF-36, respectively. CONCLUSION; Among LUTS, incontinence, nocturia and straining were the most important symptoms in association with the negative impact on generic HRQOL measured by SF-36.

[Observational study on urinary status following HoLEP].

We assessed the safety, and postoperative urinary status of holmium laser enucleation of the prostate (HoLEP) for the treatment of benign prostatic hyperplasia (BPH). Of the initial 117 patients who underwent HoLEP from November 2004 to March 2011, 49 were followed up for two yearsor longer. These 49 patients were evaluated once preoperatively, and at the 3rd, 6th, 12th, 24th, 48th, and 60th month postoperatively using International Prostate Symptom Scores (I-PSS) total and sub-score, quality of life score (QOL), maximum flow rate (Qmax), and post-voiding residual urine volume (PVR). The median estimated transition zone and enucleated volume were 45. 1 and 47. 9 g, respectively. Evaluation scores showed significant improvementsthroughout the follow-up. I-PSS total scoresimproved from 21 points(before surgery) to 6 points(12 monthsafter surgery), QOL scoresimproved from 5 pointsto 2 points, Qmax improved from 6.8 ml/s to 17.4 ml/s, and PVR improved from 101 ml to 26 ml, respectively. Transient urinary incontinence was noted in 14 patients (28.5%). One case showed a Clavien grade 3 complication of postoperative bleeding. No blood transfusion or re-surgery for BPH was required. In conclusion, HoLEP proved to be a safe and effective therapy, with potential to become a new gold standard for treating BPH.

[Risk factors for recurrence in pT3aN0M0 renal cell carcinoma according to 2009 TNM classification].

The TNM classification of renal cell carcinoma was updated in 2009. In this new classification system, T3a consists of tumors with renal vein involvement and tumors with fat invasion. To assess risk factors for recurrence, we retrospectively reviewed 89 patients with pT3aN0M0 renal cell carcinoma who underwent radical or partial nephrectomy between 1992 and 2011. Analyzed risk factors for recurrence were age, gender, tumor size, grade, v factor, infiltrative growth (INF), adjuvant interferon, surgical technic (radical or partial), clinical T classification, renal vein thrombus, and pathological fat invasion. The median follow-up was 52.2 months. Five-year recurrence-free survival rate was 69.0%. Within the pT3a subcategory, the five-year recurrence-free survival was 76.7% in patients with fat invasion only, 42.9% in patients with renal vein thrombus only, and 28.6% in patients with the two concomitant features. On univariate analysis, tumor size, grade, INF, clinical T classification, and renal vein thrombus were significantly associated with recurrence. On multivariate analysis, INF (p = 0.023, HR 3.927) was an independent risk factor for recurrence. In pT3aN0M0 renal cell carcinoma, INF significantly affects recurrence, and patients with both fat invasion and renal vein thrombus have worst prognosis.

[Rechallenge of everolimus for metastatic renal cell carcinoma after recovery from grade 3 interstitial lung disease: a case report].

We report a case of the rechallenge of everolimus for metastatic renal cell carcinoma (RCC) after successful recovery from grade 3 interstitial lung disease (ILD). A 76-year-old man with metastatic RCC developed grade 3 ILD one month after the initiation of everolimus therapy (10 mg/day). ILD subsided in 4 months after the withdrawal of everolimus and treatment with corticosteroids. Half dose (5 mg/day) of everolimus was rechallenged for 9 months until another grade 3 ILD developed. Everolimus kept the disease under control for 13 months including the discontinuation period.

[Gemcitabine and cisplatin (GC) or gemcitabine and carboplatin (GCarbo) in patients with metastatic urothelial cancer].

Twenty-four patients with metastatic urothelial carcinoma of bladder (11) and upper urinary tract (13) received gemcitabine 1,000 mg/m2 on days 1, 8, and 15, and cisplatin 70 mg/m2 (GC) or carboplatin area under the serum concentration-time curve (AUC) 5 (GCarbo) on day 2, every 28 days. One to 13 chemotherapy cycles (median number, 4) per patient were administered. Three patients (12.5%) achieved a complete response (CR) and 9 (37.5%) a partial response (PR). Six patients (25%) experienced no change (NC) and six patients (25%) progressive disease (PD). The overall response rate (CR＋PR) of GC (57.9%) was greater than that of GCarbo (20%), but the difference was not statistically significant (p＝0.13). At a median follow-up of 14.7 months, the median time to progression was 4.6 months (range, 0.9-34.7), and the median overall survival 12.3 months (range, 2.1-46.4). Grade 3 and 4 leukocytopenia occurred in 15 patients (53.6%) and grade 3 and 4 thrombocytopenia in 16 (57.1%). Gemcitabine could be administrated on both day 8 and day 15 only in 43 (34.7%) of the total 114 courses because of hematological toxicity. Gemcitabine chemotherapy combined with cisplatin or carboplatin is effective in the management of metastatic urothelial cancer. High hematological toxicity was observed and caused high omission rates of gemcitabine on day 8 and/or day 15.

[A case of Bellini collecting duct carcinoma with hypercalcemia in a young adult].

A 25-year-old man presented to a local clinic with right flank pain and gross hematuria. Computed tomography revealed the right renal tumor and he was referred to our hospital. Laparoscopic radical nephrectomy was performed and diagnosis of Bellini collecting duct carcinoma was made pathologically. Adjuvant therapy with interferon-α, followed by a gemcitabine and cisplatin-based regimen of chemotherapy was performed, but the disease progressed. Sunitinib was started 14 months after the operation. After one course of sunitinib, mental status was altered due to hypercalcemia (serum calcium level was 18.6 mg/dl and PTH-rP was 3.7 pmol/l). Level of consciousness recovered along with decreasing serum calcium level, but he died of multiple organ dysfunction 17 months after the operation. Autopsy showed liver, bone, lymph node, mediastinum and left adrenal tumor metastases.

[Granulocyte-colony-stimulating factor (G-CSF)-producing carcinoma of collecting ducts of Bellini: a case report].

We report a case of granulocyte-colony-stimulating factor (G-CSF)-producing carcinoma of collecting ducts of Bellini. A 62-year-old male was admitted to our hospital with the chief complaint of high grade fever,right flank pain and general malaise. The white blood cell count and serum G-CSF concentration were elevated to 20,100/ µ l and 140 pg/ml,respectively. Enhanced thoracoabdominal computed tomography (CT) showed a right renal malignant tumor without capsule,para-aortic lymph node metastases and lung metastases. CT-guided right renal biopsy was performed. The histological diagnosis was GCSF- producing carcinoma of collecting ducts of Bellini. The chemotherapy (gemcitabine and cisplatin) and the molecular target therapy (sunitinib) were administerd but the primary lesion and metastases was progressive and serum G-CSF concentration was elevated to 229 pg/ml. He died 3 months after diagnosis.

[Compartment syndrome in bilateral lower legs after total cystectomy: a case report].

We report a case of compartment syndrome in bilateral lower legs after total cystectomy with urethrectomy and ileal conduit diversion. A 64-year-old man who had diabetes mellitus for 20 years underwent an operation for invasive bladder cancer. He was placed in the lithotomy position and both lower legs were protected with an elastic stocking and intermittent pneumatic compression for prevention of deep vein thrombosis during the operation. Seven hours postoperatively, he complained of bilateral calf pain. Eleven hours postoperatively, skin redness, swelling, movement and sensory disorder of bilateral lower legs were found. Contrasting computed tomography (CT) of lower legs showed the swelling of bilateral soleus muscles and gastrocnemius muscles without any contrasting effect. Creatinine phosphokinase (CPK) increased to 46, 740 IU/l and the intramuscular pressure was 50 mmHg. He was diagnosed with compartment syndrome, in bilateral lower legs and emergent fasciotomy was performed. Bilateral calf pain was improved immediately after fasciotomy and could walk on his own after rehabilitation. Lower leg compartment syndrome is an uncommon disease but may require lower leg amputation or result in death if the treatment is delayed. Urologists should recognize this disease as a complication after prolonged operation in the lithotomy position.

[A case of Candida parapsilosis fungal balls in the urinary tract associated with a retrocaval ureter].

A 70-year-old man with a medical history of diabetes mellitus presented to a local clinic with seven days history of right flank pain and fever. Because there was no symptomatic improvement after one-week antibiotic administration, abdominal ultrasonography and computed tomographic scans were performed to show mass lesions in the right hydropelvis, and he was transferred to our hospital. Retrograde pyelography revealed a retrocaval ureter and a ureteral stent was indwelt. After the symptoms improved, the lesions were removed by percutaneous nephrostomy and fungal balls were diagnosed as Candida parapsilosis after culture. After intermittent one-week irrigation of the renal pelvis with normal saline, the nephrostomy tube was removed. In six-month follow-up, mild hydronephrosis remains without fungal ball recurrence. To the best our knowledge, there has been no case report of Candida parapsilosis fungal balls in the urinary tract.

[Acquired male hypogonadotropic hypogonadism (MHH) in a patient with empty sella: a case report].

A 40-year-old unmarried male was referred to our hospital with anejaculation. His secondary sex characteristics, sexual function and ejaculation were previously normal but for the last 5 years he found it impossible to ejaculate even though he could achieve an erection. His genital stage was Tanner V, and pubic hair stage was Tanner III. There were no varicoceles or chromosomal aberrations. His testis volume was 10 ml on the right side and 12 ml on the left. His hormonal data were luleinizing hormone (LH) 0.3 mIU/ml (normal: 2.2-8.4 mIU/ml), fillicle stimulating hormone (FSH) 1.5 mIU/ ml (1.8-12 mIU/ml), testosterone 0.05 ng/ml (2.01-7.5 ng/ml). A gonadtropin releasing hormone (GnRH) test and human chorionic gonadotropin (hCG) stimulation test revealed low responses of LH, FSH and a normal response of testosterone. Magnetic resonance imaging of the head revealed slight depression of the diaphragma sellae, indicating an "empty sella". We diagnosed acquired hypogonadtropic-hypogonadism related empty sella. An hCG replacement therapy was introduced and after 3 months the patient's capacity to ejaculate was restored and testis volume was 14 ml on both sides. Six months after hormone replacement therapy, semen analysis revealed azoospermia. Then we added r-hFSH to his treatment and expect his sperm to reappear.

Retroperitoneoscopic pyeloplasty: using reconstructive methods based on intraoperative findings.

AIM: Reconstructive laparoscopic procedures have been recognized as a less invasive treatment than conventional open procedures. However, although the laparoscopic pyeloplasty has also been accepted as useful, few findings have been reported relevant to the retroperitoneal approach. To elucidate its effectiveness and safety, laparoscopic surgery via the retroperitoneal approach was examined in our institution. Furthermore, the importance of laparoscopic observation for ureteropelvic junction and urine passage ureteropelvic junction without indwelling ureteral stent. METHODS: Between July 1998 and December 2004, 13 men and 15 women underwent laparoscopic retroperitoneal surgery for ureteropelvic junction obstruction. The mean patient age was 33.6 years (range: 13-70 years). Methods of repair were determined by intraoperative findings for the relationship between the ureteropelvic junction and surrounding vessels. An indwelling ureteral stent was removed before initiating laparoscopic operation to observe the relationship between ureteropelvic junction and aberrant vessels more precisely. RESULTS: An aberrant renal vessel was found in 13 patients (46%). Dismembered pyeloplasty was carried out in 21 patients, Y-V plasty in five patients and Hellstrom technique in two patients. Ureteral transposition was not required in dismembered pyeloplasty cases. All patients achieved retroperitoneoscopic pyeloplasty without open conversion. The mean operative time was 272 min (range: 155-490 min). The mean estimated blood loss was 44 mL (range: 10-200 mL). No major complications were observed during the intraoperative period, but urinary tract infection occurred in two patients in the postoperative period. In all patients except one, obstruction was improved or resolved. CONCLUSIONS: Laparoscopic retroperitoneal surgery is not only able to repair ureteropelvic junction obstruction, but can also be done safety and less invasively. We believe that laparoscopic observation without indwelling stent will contribute to a more appropriate choice of pyeloplasty.

[Experience of laparoscopic nerve-sparing radical cystectomy and construction of ileal neobladder at Kansai Medical University].

Laparoscopic nerve-sparing radical cystectomy and construction of ileal neobladder was performed on a 76-year-old man with atrophic bladder after the intravesical instillation therapy for bladder cancer. Ileal neobladder was constructed by the combined extracorporeal technique through the camera port dilated to 45 mm. Operation time was 8 hours, with 3.5 hours for the nerve-sparing cystoprostatectomy, 2.5 hours for the extracorporeal neo-bladder construction and 2 hours for the laparoscopic urethra neo-bladder anastomosis and wound closing. The post-operative course was uneventful with minimum use of analgesia. This operation was minimally invasive therapy and from the functional aspect the potency was preserved. Although this method was technically challenging, various advantages can be promising for the patients compared to the standard open technique. Indication of this operation should be carefully expanded. Various methods, such as the complete intracorporeal technique and minimally invasive laparoscopic neobladder (MILaN) technique, have been reported for urinary diversion. In this report, we compared our method with other techniques.

[Diagnosis and treatment of obstructive azoospermia].

There are two types of azoospermia, namely, obstructive and nonobstructive azoospermia. Urologists play a more important role in the former, because many patients of the former can expect spontaneous pregnancy after surgical reconstruction of the seminal tract. In this review, we discuss about the causes, diagnosis, and treatment of obstructive azoospermia. The treatment includes vasovasostomy, epididymovasostomy, and transurethral resection of the ejaculatory duct. Surgical outcomes in our series are also described. The urologist must take care that the obstructive-azoospermic patients do not undergo unnecessary assisted reproduction procedures.

Retroperitoneoscopic partial nephrectomy with transient occlusion of renal artery for treatment of small renal tumors.

OBJECTIVES: To evaluate the results of retroperitoneoscopic partial nephrectomy with transient occlusion of the renal artery for treatment of patients with small renal tumors. METHODS: From May 2002 to March 2003, 12 consecutive patients with T1N0M0 renal tumors with a median diameter of 3.0 cm underwent retroperitoneoscopic partial nephrectomy. The renal artery was clamped transiently without occlusion of the renal vein and the tumor was excised with scissors. Intracorporeal renal cooling was achieved by cold saline perfusion of the renal pelvis through a single-J ureteral catheter. Hemostasis was achieved by approximating the renal parenchyma over the perirenal fatty tissue using a retroperitoneoscopic suturing technique. RESULTS: Of the 12 patients, 11 successfully underwent partial nephrectomy retroperitoneoscopically. The median operative time, renal ischemic time, and amount of blood loss in the successful procedures was 220 minutes (range 132 to 340), 50 minutes (range 16 to 115), and 150 mL (range 50 to 800), respectively. The renal calix was opened and repaired in 10 patients. The surgical margin was negative in all patients. The postoperative course was uneventful in all patients, and the return to work was achieved in a median of 18 days (range 9 to 39). The renal function of the affected kidney was well preserved postoperatively, when examined by renal scintigraphy. Neither local recurrence nor distant metastasis was found during the median follow-up period of 10 months (range 1 to 18). CONCLUSIONS: Retroperitoneoscopic partial nephrectomy with transient occlusion of the renal artery is a useful and less-invasive method for resection of small renal tumors. Additional technologic developments to reduce ischemic times and to cool the kidneys laparoscopically are required.

[A clinical analysis of patients with early-stage prostate cancer managed without initial treatment].

To search for a more suitable qualification indicating watchful waiting, we performed a retrospective study against early-stage prostate cancer patients managed without initial treatment. Thirty-three patients who had not been treated for more than 6 months after diagnosed as T1c or T2 prostate cancer were studied. The median values of total observation period, age at diagnosis, and initial PSA were 27.0 months, 69.0 years old, and 7.0 ng/ml, respectively. Among 28 patients who had had measurement of serum PSA at least three times, seven patients showed a significant PSA elevation when transition of PSA level was analyzed using linear regression analysis. The other patients had been stable or PSA level declined. Between these two groups, there was no significant difference regarding age, initial PSA, PSA density, Gleason score, number of cancer-positive core, and cancer-occupying rate in biopsy specimen. The median PSA doubling time in patients showing PSA elevation was 36.3 months. There were no patients showing PSA elevation among those with a cancer-occupying rate of less than 5%. Clinical disease progression was obviously observed in two cases although one did not show PSA elevation. During the observation period, treatment was eventually started in seven patients. The 5-year rate of no treatment was 53.8%. Although a significant independent factor predicting the future treatment was not identified, univariate analysis revealed that the initial PSA value in patients undergoing treatment was significantly higher than that of those without treatment (p = 0.032). We concluded that early-stage prostate cancer has clinical variability, and regular clinical evaluations as digital rectal examination should be performed when the patient was managed with watchful waiting.