[Repair of Vaginal Cuff Dehiscence after Laparoscopic Radical Cystectomy with Gracilis Myocutaneous Flap].

Vaginal cuff dehiscence after total hysterectomy or total cystectomy had been increasing since laparoscopic or robotic surgery became a common surgery among gynecologists and urologists. A 52-yearold woman underwent laparoscopic radical total cystectomy for muscle invasive bladder carcinoma at Rakuwakai Otowa Hospital. She was emergently admitted with a fist-sized lump protruding from her vagina four months after surgery. Physical examination and her past history on admission disclosed vaginal cuff dehiscence after cystectomy. Computed tomographic scan and magnetic resonance imaging showed no bowel evisceration in the lump. We confirmed that the content of lump was peritoneal tissue and removed it by laparoscopic surgery. Simultaneously, we repaired the vaginal cuff dehiscence with a gracilis myocutaneous flap. There was no subsequent recurrence of vaginal dehiscence or bladder carcinoma in one-year follow-up.

[Male Refractory Urethral Diverticular Abscess Requiring Transurethral Fenestration : A Case Report].

An 85 year-old man was referred to our hospital because of a relapse of abscess after open surgical drainage of the right scrotum. Computed tomography (CT) showed fluid accumulation in the right scrotum and around the membranous urethra. The abscess was controlled by an open surgical drainage of the right scrotum, CT guided percutaneous drainage of the periurethral abscess and administration of antibiotics. However, the scrotal abscess recurred after 4 weeks. CT showed an enlarged abscess, and retrograde urethrography showed an urethral diverticulum extending into the scrotum associated with a scrotal abscess. Endoscopic urethral diverticulum unroofing and cautery were performed. The urinary catheter was removed 2 days after the operation. The abscess has been resolved without recurrence.

Trp53 Mutation in Keratin 5 (Krt5)-Expressing Basal Cells Facilitates the Development of Basal Squamous-Like Invasive Bladder Cancer in the Chemical Carcinogenesis of Mouse Bladder.

The biological processes of urothelial carcinogenesis are not fully understood, particularly regarding the relationship between specific genetic events, cell of origin, and molecular subtypes of subsequent tumors. N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced mouse bladder cancer is widely accepted as a useful model that recapitulates the pathway of human bladder tumorigenesis from dysplasia to invasive cancer via carcinoma in situ. However, the long and variable time of tumorigenesis often hinders efficient preclinical or translational research. We hypothesized that Trp53 mutation in specific types of urothelial cells facilitates efficient development of clinically relevant bladder cancer. Using lineage tracing, we showed that Trp53 mutation in Krt5-expressing cells resulted in more efficient tumorigenesis of mouse muscle-invasive bladder cancer (MIBC) with squamous differentiation compared with Trp53 mutation in Upk2-expressing cells, or wild-type or hemizygous Trp53 in the entire urothelium. Mouse MIBC that developed at 24 weeks of BBN treatment showed morphologic and genetic similarities to the basal squamous subtypes of human MIBC, irrespective of pre-induction of Trp53 mutation or whether the cell of origin was Krt5- or Upk2-expressing cells. Our findings suggest that intermediate cells as well as basal cells also can give rise to basal-like MIBC, with pre-induction of Trp53 mutation accelerating MIBC. Thus, in BBN chemical carcinogenesis, pre-induction of Trp53 mutation in basal cells facilitates efficient modeling of the basal squamous subtype of human MIBC.

[A Case of Metastatic Clear Cell Renal Cell Carcinoma Showing Long-Term Complete Response after the Discontinuation of Tyrosine Kinase Inhibitor].

Randomized phase III trials demonstrated superiority of targeted therapy with tyrosine kinase inhibitors over cytokine-based therapy as first-line therapy for metastatic renal cell carcinoma. However, the rate of complete response (CR) with targeted therapy is smaller than that with cytokine-based therapy. A 47-year-old man was referred to our hospital with a 12 cm left renal tumor and polycythemia. He was diagnosed with renal cancer, cT3aN0M1, with multiple lung metastases. He underwent cytoreductive nephrectomy, with the histopathological diagnosis of clear cell renal cell carcinoma, Fuhrman nuclear grade 2, INFb, pT2b. Three months postoperatively, spontaneous regression of lung metastases was observed. Seventeen months postoperatively, a 17×13 mm retroperitoneal tumor facing the pancreas recurred. CR of the recurrent tumor was achieved by targeted therapy with sunitinib for 12 months. This CR was maintained for 32 months after the discontinuation of targeted therapy with sunitinib.

[Prostate Cancer Diagnosed during Androgen Replacement Therapy for Late-Onset Hypogonadism Treatment: A Case Report].

We report a 60-year-old man with prostate cancer diagnosed during androgen replacement therapy (ART) for late onset hypogonadism after surgery for pituitary adenoma. He was refered to the department of urology since prostate specific antigen values were elevated after 6 months of ART. After the diagnosis of prostate cancer, ART was discontinued, and robot-asssited laparoscopic radical prostatectomy with pelvic lymphadenoctomy was performed. Pathological examination revealed Gleason score 4 + 5 prostate adenocarcinoma with seminal vesicle invasion and lymph node metastasis(pT3bN1). He has stayed biochemically and radiologically disease-free 33 months postoperatively.

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.

[Efficacy of prophylactic intravesical mitomycin C in patients with non-muscle-invasive bladder cancer].

Intravesical chemotherapy is beneficial for patients with non-muscle-invasive bladder cancer (NMIBC), but optimal drug and regimen selection can be controversial. Mitomycin C (MMC) is commonly used as adjuvant treatment for NMIBC. We retrospectively evaluated the outcomes of 73 patients with NMIBC who were treated with weekly doses of low-dose MMC (20 mg ; n=28 ; 38.4%) or high-dose MMC (40 mg ; n=45 ; 61.6%) for 6 weeks each, at our hospital between 2001 and 2010. Treatment outcomes were examined by Kaplan‒Meier analysis with log-rank tests. Patients in the high-dose group showed greater recurrent-free survival (61.3%) at 2 years than did patients in the low-dose group (32.6%) (P<0.05). We also found that a single early dose of pirarubicin following transurethral resection of bladder tumor improved MMC efficacy in the high-dose group. The high-dose group had a somewhat higher incidence of dysuria, urinary frequency and drug eruption, but the difference was not significant.

[Effect of change to flutamide for prostate cancer patient who developed breast pain during bicalutamide treatment (BIP-F study)].

In Japan, prostate cancer is treated with non-steroidal anti-androgen (flutamide and bicalutamide). Development of breast pain during bicalutamide treatment, in prostate cancer patients reduces their quality of life (QOL) and treatment compliance. We studied the safety and effectiveness of switching from bicalutamide to flutamide in 13 prostate cancer patients who developed breast pain during bicalutamide treatment. We estimated the change in breast pain using a face scale and the Expanded Prostate Cancer Index Composite (EPIC) and EPIC-hormone domain (HD) score. The switch to flutamide relieved breast pain in nine patients, had no effect in one patient, and increased breast pain in two patients. One patient dropped out. Furthermore, summary score and hormone function were improved with a significant difference in the EPIC-HD score. Switching to flutamide in prostate cancer patients who develop breast pain during bicalutamide is safe and effective.

[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.

[The role of dynamic contrast-enhanced magnetic resonance imaging in diagnosis of torsion of the testicular appendix : a case report].

A 7-year-old male presented to our hospital with pain and swelling in the right scrotum for 9 days. On physical examination a swollen right scrotum was noted and right side cremasteric reflex disappeared. Ultrasound examination showed enlarged right testis and epididymis. Subsequent dynamic contrast enhanced magnetic resonance imaging (MRI) showed a 7 mm area of high signal intensity anterior to the right testis on coronal imaging of T2-weighted. Subtraction MRI revealed testicular perfusion and a nonenhanced mass was also identified anterior to the right testis. These findings indicated a diagnosis of torsion of the testicular appendix. We performed excision of the torsed appendage.

[Experience of transobturator sling for iatrogenic male stress urinary incontinence].

We performed transobturator sling (TOS) surgery for iatrogenic stress urinary incontinence (SUI) in 7 men. Assessment with the International Consultation Society Incontinence Questionnaire Short Form revealed that complete continence, significant improvement, and no change of incontinent status were observed in two, three, and two patients, respectively, at one year after surgery. Of the three patients with significant improvement, two patients obtained a pad-free status. Both of the two patients without improvement had a past history of salvage radiation therapy for biochemical recurrence after radical prostatectomy before TOS surgery. The severity of SUI seems not to be associated with the outcome of TOS surgery. TOS surgery can be one of the surgical options for iatrogenic male SUI.

First report of idiopathic segmental ureteritis successfully treated by steroid therapy.

We report a case of bilateral idiopathic segmental ureteritis in a 52-year-old woman. The diagnosis was established by imaging studies (magnetic resonance imaging/computed tomography scan), ureteroscopy and biopsies. The left side improved spontaneously, but the right ureteral stricture persisted after 3 months of ureteral stenting. Administration of prednisolone effectively relieved obstruction on the right side after 4 months. This is the first report of idiopathic segmental ureteritis successfully treated by steroid therapy, without invasive open procedures.

[A case report of Cowper's syringocele in an adult treated with transurethral unroofing].

We present an adult case of Cowper's syringocele. A 19-year-old male presented with the chief complaint of persistent post-voiding dribbling 5 months after onset. Urethroscopy demonstrated a thin membrane with a small orifice on the ventral aspect distal to the external sphincter. Magnetic resonance imaging showed a restiform shadow on the left side of the corpus spongiosum. Retrograde urethrogram showed filling of diverticulum-like structure in the region of urethral bulb terminating in the urogenital diaphragm. Considering the results mentioned above, we diagnosed the patient with Cowper's syringocele. Transurethral unroofing of the Cowper's syringocele was performed with a cold knife, and the excessive tissue on the edge of syringocele was electroresected to avoid recurrence. His post-voiding dribbling resolved completely after the procedure and has not recurred in 13 months postoperatively. Cowper's syringocele is typically diagnosed presenting with hematuria, urinary tract infection, and disuria in male infants and children. Adult cases of Cowper's syringocele are rare, and only 32 cases including the present case have been reported. Proper awareness of this entity and careful evaluation are important if patients present with persistent adult-onset voiding dysfunction.

[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.

[Usefulness of MRI prior to prostate needle biopsy in PSA gray zone].

To evaluate the diagnostic accuracy of prostate magnetic resonance imaging (MRI), we compared MRI findings with the results of biopsy as well as findings from specimens following total prostatectomy. The subjects consisted of 260 males who showed a prostate specific antigen (PSA) level in the gray zone (4 ng/ml ≤PSA <10 ng/ml) and also underwent digital rectal examination (DRE), transrectal ultrasound (TRUS), and MRI prior to prostate biopsy between April 2005 and December 2009. In Evaluation 1, the results of DRE/TRUS/MRI were compared with those of prostate biopsy. The biopsy-positive rate was higher in males positive in each examination. However, 24.8% of males negative in all examinations were biopsypositive. Thus, these examinations were considered to be inappropriate for secondary screening. In evaluation 2, the prostate was divided into 4 regions, and the findings from specimens following total prostatectomy were compared with MRI findings in each region. For the region containing prostate cancer, MRI showed a sensitivity of 26.0%, specificity of 98.3%, positive predictive value of 96.2%, and negative predictive value of 44. 4%. In patients with a Gleason score ≥7, cancer foci were more frequently detectable using MRI. MRI prior to prostate biopsy in patients in the PSA gray zone is inappropriate for secondary screening due to its low sensitivity. However, by virtue of its high positive predictive value, MRI is useful for determining patients indicated for biopsy, as well as DRE and TRUS. Accurate evaluation of the localization of all cancer lesions is difficult using MRI. However, when MRI findings are present, they frequently indicate the cancer lesion, which may be useful information for treatment.

[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.

[A case report of renal cell carcinoma with metastatic intraductal tumor thrombus of the common bile duct].

We present a case of liver metastasis of renal cell carcinoma (RCC) presenting as an intraductal tumor thrombus of the common bile duct. A 62-year-old man was admitted with jaundice. He had undergone right nephrectomy for RCC 8 years previously, and had been administered interferon alfa for lung, bone, and liver metastases for these 3 years. Abdominal enhanced computerized tomography (CT) disclosed the progression of liver metastasis to the common bile duct and the dilated bilateral bile ducts. Endoscopic retrograde cholangiopancreatography (ERCP) revealed a smooth filling defect in an upper portion of the common bile duct, suggesting an intraductal RCC tumor thrombus of the common bile duct. He died 4 months later despite the percutaneous biliary drainage. Liver metastasis of RCC proceeding to the common bile duct is extremely rare, and this is the 8th case. We should be aware of the fact that metastatic intraductal tumor thrombus of the common bile duct can cause obstructive jaundice.

Meta-analysis of a 10-plex urine-based biomarker assay for the detection of bladder cancer.

A 10-plex urine-based bladder cancer (BCa) diagnostic signature has the potential to non-invasively predict the presence of BCa in at-risk patients, as reported in various case-control studies. The present meta-analysis was performed to re-evaluate and demonstrate the robustness and consistency of the diagnostic utility of the 10-plex urine-based diagnostic assay. We re-analyzed primary data collected in five previously published case-control studies on the 10-plex diagnostic assay. Studies reported the sensitivity and specificity of ten urinary protein biomarkers for the detection of BCa, including interleukin 8, matrix metalloproteinases 9 and 10, angiogenin, apolipoprotein E, syndecan 1, alpha-1 antitrypsin, plasminogen activator inhibitor-1, carbonic anhydrase 9, and vascular endothelial growth factor A. Data were extracted and reviewed independently by two investigators. Log odds ratios (ORs) were calculated to determine how strongly the 10-plex biomarker panel and individual biomarkers are associated with the presence of BCa. Data pooled from 1,173 patients were analyzed. The log OR for each biomarker was improved by 1.5 or greater with smaller 95% CI in our meta-analysis of the overall cohort compared with each analysis of an individual cohort. The combination of the ten biomarkers showed a higher log OR (log OR: 3.46, 95% CI: 2.60-4.31) than did any single biomarker irrespective of histological grade or disease stage of tumors. We concluded that the 10-plex BCa-associated diagnostic signature demonstrated a higher potential to identify BCa when compared to any single biomarker. Our results justify further advancement of the 10-plex protein-based diagnostic signature toward clinical application.