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

Introduction Mucinous urethral adenocarcinoma is a rare and progressive cancer of the prostatic urethra. Reports on palliative systemic treatment for mucinous urethral adenocarcinoma are few. We present a case of coexisting mucinous urethral and prostate adenocarcinomas managed with systemic treatment. Case presentation A 66-year-old man presented with gross hematuria and urinary retention. Prostate-specific antigen level was elevated, at 99 ng/mL, and prostate biopsy revealed moderately to poorly differentiated adenocarcinoma. Hormone therapy and standard chemotherapy for prostate adenocarcinoma were ineffective. Prostate re-biopsy revealed coexisting mucinous urethral and prostate adenocarcinomas. Gemcitabine + cisplatin chemotherapy and folinic acid + 5-fluorouracil + irinotecan chemotherapy temporarily suppressed the cancer, but 14 months after presentation, he developed liver metastasis and died. Autopsy revealed metastasis of both mucinous urethral adenocarcinoma and carcinosarcoma. Conclusion Mucinous urethral adenocarcinoma is difficult to diagnose in coexistence with prostate adenocarcinoma. This was an extremely rare case showing chemoresistance due to epithelial-mesenchymal transition.

Introduction Atypical femoral fractures are atraumatic or minimally traumatic fractures and rare side effects of bone resorption inhibitors. Bone resorption inhibitors are frequently used in the treatment of prostate cancer. Case presentation A 62-year-old man complained of difficulty in walking and left lower limb pain. Androgen deprivation and denosumab therapy for prostate cancer-induced bone metastasis was initiated 27 months ago. Even though the prostate-specific antigen level did not increase, imaging studies indicated the possibility of bone metastasis. The patient underwent bone biopsy; however, no malignancy was detected. Afterward, he had a fall, causing a complete fracture in his left femur. Conclusion Atypical femoral fractures occasionally mimic typical imaging findings and outcomes of bone metastasis. This case is important for recognizing such cases.

Background A spontaneous iliopsoas muscle hematoma is relatively rare and often associated with abnormal coagulation. Nafamostat mesilate is an anticoagulant agent that is sometimes used to treat hemodialysis patients at high risk of bleeding. Although severe drug allergy caused by nafamostat mesilate was previously reported, spontaneous iliopsoas muscle hematoma secondary to disseminated intravascular coagulation caused by nafamostat mesilate allergy has not yet been reported. Case presentation Severe nafamostat mesilate allergy occurred in a 78-year-old male patient with a 2-year history of hemodialysis. During hospitalization, disseminated intravascular coagulation occurred followed by a progressive iliopsoas muscle hematoma a few days later. Emergent transarterial lumbar artery embolization was successfully performed. Conclusion For dialysis patients, a detailed medical history including repeated nafamostat mesilate use and considering an allergy to nafamostat mesilate in differential diagnosis are critical. In addition to early diagnosis, when an iliopsoas hematoma occurs, early intravascular treatment is important.

Purpose: To evaluate renal function 1 year after radical nephrectomy (RN) for renal cell carcinoma, the preoperative predictors of postnephrectomy renal function were investigated by sex, and equations to predict the estimated glomerular filtration rate (eGFR) 1 year after RN were developed. Materials and Methods: A total of 525 patients who underwent RN between May 2007 and August 2011 at Tohoku University Hospital and its affiliated hospitals were prospectively evaluated. Overall, 422 patients were analyzed in this study. Results: Independent preoperative factors associated with postnephrectomy renal function were different in males and females. Preoperative eGFR, age, tumor size, and body mass index (BMI) were independent factors in males, while tumor size and BMI were not independent factors in females. The equations developed to predict eGFR 1 year after RN were: Predicted eGFR in males (mL/min/1.73 m2 )=27.99-(0.196×age)+(0.497×eGFR)+(0.744×tumor size)-(0.339×BMI); and predicted eGFR in females=44.57- (0.275×age)+(0.298×eGFR). The equations were validated in the validation dataset (R2 =0.63, p

A combination therapy of nivolumab and ipilimumab is effective for advanced renal cell carcinoma, but there are concerns about immune-related adverse events. A 46-year-old man was hospitalized for metastatic renal cell carcinoma. On day 9, he received nivolumab and ipilimumab. On days 16 and 49, he presented with fever, skin rash, and hypotension after contrast-enhanced computed tomography. A 70-year-old man was hospitalized for metastatic renal cell carcinoma. On day 9, he received nivolumab and ipilimumab. On day 44, he presented with fever, skin rash, and hypotension after contrast-enhanced computed tomography. Both patients were diagnosed with anaphylaxis due to the contrast agent.

Objectives To determine whether penile blood pressure (PBP) can be used to identify patients who can benefit from tadalafil treatment, the correlation between PBP at baseline and changes in lower urinary tract symptoms (LUTS) induced by tadalafil treatment was studied prospectively. Patients and methods Patients with BPH who were poor responders to α1 -blockers and took tadalafil instead of an α1 -blocker were registered between 2014 and 2016. The patients were divided into two groups (low- and high-PBP groups) using the median baseline PBP of 110 mmHg as the threshold. The changes in the International Prostate Symptom Score (IPSS) between before and at 4 and 12 weeks after tadalafil treatment were compared between the low- and high-PBP groups. Multivariate analysis was performed to identify parameters associated with IPSS improvement with tadalafil treatment. Results In all, 51 patients were investigated. The IPSS in the low-PBP group decreased immediately after the start of treatment, and there was significant improvement in the IPSS from baseline at 4 and 12 weeks after the start of treatment, whilst the IPSS in the high-PBP group did not show significant changes. On multivariate analysis, PBP at baseline, anticholinergic drug use, and IPSS at baseline were significant predictors of a good IPSS response to tadalafil treatment. Conclusions This study demonstrated that PBP could reliably identify patients with BPH who could benefit from tadalafil treatment. Patients with low PBP could be better responders to tadalafil.

Objective: The Pirarubicin Monotherapy Study Group trial was a randomized Phase II study that evaluated the efficacy of intravesical instillation of pirarubicin in the prevention of bladder recurrence after nephroureterectomy for upper urinary tract urothelial carcinoma. This study conducted further analysis of the Pirarubicin Monotherapy Study Group cohort, focusing on intravesical seeding of cancer cells. Methods: Using the data from the Pirarubicin Monotherapy Study Group trial, bladder recurrence-free survival rates and factors associated with bladder recurrence in the control group were analyzed. Results: Of 36 patients in the control group, 14 with positive urine cytology had more frequent recurrence when compared with the 22 patients with negative cytology (P ¼ 0.004). Based on the multivariate analysis in the control group, voided urine cytology was an independent predictive factor of bladder recurrence (hazard ratio, 5.54; 95% confidence interval 1.12‐27.5; P ¼ 0.036). Of 72 patients in the Pirarubicin Monotherapy Study Group trial, 31 had positive urine cytology. Among the 31 patients, 17 patients who received pirarubicin instillation had fewer recurrences when compared with 14 patients who received control treatment (P ¼ 0.0001). On multivariate analysis, pirarubicin instillation was an independent predictor of better recurrence-free survival rates in the patients with positive urine cytology (hazard ratio, 0.02; 95% confidence interval, 0.00‐0.53; P ¼ 0.018). Of 21 patients with bladder recurrence, 17 had recurrent tumor around cystotomy or in the bladder neck compromised by the urethral catheter, supporting the notion that tumor cells seeded in the injured urothelium. Conclusions: Intravesical instillation of pirarubicin immediately after nephroureterectomy significantly reduced the bladder recurrence rate in patients with positive voided urine cytology. The results suggest that intravesical seeding of upper urinary tract urothelial carcinoma occurs during nephroureterectomy.

2012. Half the patients had localized disease and were referred for curative intended radiation, whereas the remaining patients had disseminated disease. ADT was given as LHRH agonists, LHRH antagonists, or orchiectomy. We collected blood samples, questionnaire, performed DXA scan and bone scintigraphy prior to initiating ADT and during the following two years of ADT. The study was approved by the local ethical committee. None of the patients had received prior androgen deprivation nor osteoporosis treatment. RESULTS: A total of 105 individuals were included. The mean age of the participants was 70 (range 53-91, SD 6.3) years. The median PSA level was 30.5 (range 1-5714) mg/L. The median Gleason score was 7 (range 5-10, SD 1.1). A total of 50 patients had localized prostate cancer; the remaining 55 patients had disseminated disease. The prevalence of osteoporosis was 10% and the prevalence of osteopenia was 58% prior to initiating ADT, and after two years of ADT it rose to 22% and 57%, respectively. In multivariate analysis smoking and presence of disseminated disease were significantly associated with an increased risk of osteoporosis, whereas a high body mass index was significantly associated with a decreased risk of osteoporosis. CONCLUSIONS: Osteoporosis was present among patients with prostate cancer and evolved rapidly during two years of ADT. Further awareness regarding osteoporosis and bone health in prostate cancer patients is needed and we recommend that patients with prostate cancer are DXA scanned prior to and during ADT.

We prospectively examined influence of androgen deprivation therapy (ADT) on lipid and glucose metabolisms in Japanese patients with prostate cancer.Patients with prostate cancer who were hormone-naive and scheduled to receive long-term ADT were recruited between 2011 and 2013. Body weight, abdominal circumference and blood testing associated with lipid and glucose metabolism were recorded every 3 months during 1 year of ADT. Computed tomography (CT) was performed to measure areas of subcutaneous and visceral fat before and after 1 year of ADT. ADT was limited to a luteinizing hormone-releasing hormone (LHRH) agonist with or without bicalutamide.Of 218 patients registered, data were available from 177 patients who completed 1 year of ADT. Of these, CT was performed before and after 1 year of ADT in 88 patients. Median age was 75 years (range, 49-85 years). Median PSA before ADT was 16.7 ng ml(-1) (range, 0.3-3316). Clinical stage was B (54.2%), C (23.2%) and D (20.9%). Mean increases in body weight and abdominal circumference after 1 year of ADT were 2.9 and 3.0%, respectively. Mean increases in total, low-density lipoprotein and high-density lipoprotein cholesterol and triglycerides were 10.6, 14.3, 7.8 and 16.2%, respectively. Mean increases in fasting blood sugar and hemoglobin A1c (HbA1c) were 3.9 and 2.7%, respectively. Lipid alterations were noted in patients without comorbidities, whereas changes in HbA1c were noted in patients with diabetes mellitus at baseline. These lipid and glucose alterations were prominent in the early ADT period. Both visceral and subcutaneous fat, as measured by CT, increased by20%. The increase in subcutaneous fat was significantly greater than that in visceral fat (P=0.028).One year of ADT significantly changed lipid and glucose metabolism in Japanese patients with prostate cancer. Patient characteristics or comorbidities at baseline may be associated with ADT-induced metabolic changes.

INTRODUCTION AND OBJECTIVES: Weight gain derived from androgen deprivation therapy (ADT) should be based on the balance between fat accumulation and decreased lean mass (sarcopenic obesity). We used computed tomography (CT) to evaluate the association between weight gain and decreased lean mass in patients with prostate cancer treated using ADT. METHODS: Patients with newly diagnosed prostate cancer were recruited between 2011 and 2013. The method for ADT was limited to luteinizing hormone-releasing hormone agonist with or without bicalutamide. Body weight, abdominal circumference, and blood test results were recorded every 3 months, and cross-sectional areas of subcutaneous and visceral fat and psoas muscle were measured on CT before and after 1 year of ADT. Patients were divided into two subgroups according to weight gain to analyze the association with CT findings. Patients who presented with progression of disease during the study period were excluded from this study. RESULTS: Eighty patients completed CT examinations before and after 1 year of ADT as of September 2014. Median age was 74 years (range, 46-83 years), and median prostate-specific antigen level was 17 ng/ml (range, 3-3316 ng/ml). Mean increases in body weight and abdominal circumference after 1 year were 2.8% and 3.2%, respectively. Mean increases in total cholesterol, triglyceride, fasting blood sugar and hemoglobin A1c levels were 10.6%, 13.0%, 1.0% and 0.5%, respectively. Mean decrease in hemoglobin was 7.6%. Mean increases in areas of subcutaneous and visceral fat were 32.3% and 18.6%, while mean decreases in area and Hounsfield Unit of psoas muscle were 9.0% and 7.1%, respectively. Mean increases in areas of subcutaneous and visceral fat were more prominent in patients who gained 3.0% weight (subcutaneous, 43.0%; visceral, 29.0%) than in patients who gained

of postoperative renal dysfunction, and NACT was recommended for those patients. In selecting eligible NACT patients, this algorithm has a prediction ability with 76% (25/33) sensitivity and 77% (358/467) specificity. CONCLUSIONS: We developed a preoperative selection algorithm for the eligible NACT patients in UTUC. This algorithm might contribute to effective decision making in regard to providing NACT.

Purpose: N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes β1-6 branching of N-acetylglucosamine on asparagine (N)-linked oligosaccharides (N-glycan) of cell proteins. We examined the relationship between GnT-V expression and clinicopathologic features of the patients with bladder cancer. Experimental Design: We immunohistochemically examined GnT-V expression in paraffin-embedded bladder cancer specimen using anti-GnT-V monoclonal antibody. We compared GnT-V expression with cause-specific survival of the patients with bladder cancer treated by radical cystectomy. Kaplan-Meier survival curves were generated to show the cause-specific survival. Univariate and multivariate analyses were carried out to compare GnT-V expression with other clinical and pathologic variables. We also evaluated mRNA expression of GnT-V and N-linked oligosaccharide structure in bladder cancer specimens. Results: Immunohistochemistry revealed that GnT-V expression inversely correlated with tumor grade and stage. The incidence of positive GnT-V expression in bladder cancer was significantly higher in low-grade/superficial cancer than in high-grade/invasive cancer. The patients whose tumor was positive for GnT-V survived significantly longer than those whose tumor was negative for GnT-V. Univariate and multivariate analyses revealed that GnT-V expression was an independent predictor of prognosis of the patient. The expression of GnT-V mRNA determined by reverse transcription-PCR was consistent with the results with immunohistochemistry for tumor samples. Carbohydrate structural analysis revealed that superficial bladder cancer is rich in branched N-linked oligosaccharides, for which biosynthesis GnT-V is responsible. Conclusions: GnT-V and its resultant β1-6 branching N-linked oligosaccharides are closely related to low malignant potential and good prognosis of the patients with bladder cancer.

Background : The incidence and clinical features of bilateral germ cell testicular tumor (GCTT) in the Japanese population are not fully characterized. We examined the incidence, clinical features, management and outcome, sexual status, hormonal environment, implication of androgen replacement, and human leukocyte antigen (HLA) typing of bilateral GCTT. Methods: We treated nine consecutive patients with bilateral GCTT from 1980 through to 1999, and reviewed their hospital and clinic charts. Testosterone, luteinizing hormone, follicle stimulating hormone, dehydroepiandrosterone, and dehydroepiandrosterone-sulfate were measured in bilateral orchiectomized patients. Human leukocyte antigen typing was assessed with peripheral lymphocyte. Results: The incidence of bilateral GCTT against the total number of patients with GCTT was 9/274 (3.3%). The median age of the first tumor was 29 (range 21–75) years. Three cases were synchronous and the remaining six cases were metachronous. In the case of metachronous tumor, the median interval between first and contralateral tumor was 8 (range 2–25) years. Standard treatment was defined as surveillance policy in stage I, chemotherapy for higher stages of non-seminoma, and radiotherapy for stage II seminoma. Human leukocyte antigen typing was examined for seven cases. Five cases were positive for HLA-A24. The incidence of HLA-A24 in bilateral GCTT was identical to that of the Japanese population. The relapsing incidence of stage I disease with surveillance policy was almost identical to unilateral GCTT. A 74-year-old patient with stage II seminoma died of the disease at 1.3 years. The other eight patients remained well without any evidence of recurrence at a median follow-up period of 78 (range 12–204) months. Four patients with bilateral orchiectomy did not require androgen replacement without easy fatigability. Sexual status was conserved using androgen replacement. Conclusions: Long-term follow-up, as long as 25 years, is recommended for contralatelral relapse. Some patients with bilateral orchiectomy do not require androgen replacement. The significance of HLA-A24 for bilateral testicular tumor is equivocal in the Japanese population.

Shinichi Yamashita*, Akihiro Ito, Sendai, Japan; Ichiro Shintaku, Higashimatsushima, Japan; Masataka Aizawa, Sendai, Japan; Tatsuo Tochigi, Natori, Japan; Fumihiko Soma, Hachinohe, Japan; Shozo Ota, Takashige Namima, Sendai, Japan; Kazuhiko Orikasa, Kesennuma, Japan; Atsushi Kyan, Shirakawa, Japan; Kenji Numahata, Yamagata, Japan; Atsushi Takeda, Ichinoseki, Japan; Shinnosuke Katoh, Yuzawa, Japan; Yasuhiro Kaiho, Haruo Nakagawa, Naomasa Ioritani, Yoichi Arai, Sendai, Japan

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

From 1991 to 1994, we experienced 5 patients with Fournier's gangrene. Their age, associated diseases, etiology, area of the disease, microbiologic findings, treatment and prognosis were reviewed. Patient age ranged from 25 to 72 years, with a mean age of 47 years. An associated disease process could be identified in all patients. Two patients had diabetes mellitus, 1 systemic lupus erythematosus, 1 chronic alcoholism and 1 multiple myeloma. The etiology of the infectious process was presumed to be wound infection in 2 patients and indwelling urethral catheter in 2 patients. All patients were treated with broad-spectrum antibiotics. Extensive debridement with later skin graft was done in 2 patients. Multiple Penrose-drains were placed subcutaneously after limited removal of necrotic tissue in 3 patients. In these 3 patients, redness and swelling reduced quickly, the wound was cured without defects of skin except 1 patient who had multiple myeloma and was in a very serious condition. Although inflammation reduced after the placement of drains, the patient with multiple myeloma died of sepsis and DIC. The majority of patients with Fournier's gangrene are immunocompromised. Although extensive debridement is commonly performed as the surgical treatment, defects of the skin seem to have some disadvantages, such as the need for the skin graft and the chance of secondary wound infection. In the narrow excision of necrotic tissue and drainage of involved areas by multiple Penrose-drains, skin defects are minimum, and the effectiveness of the surgical management seems to be competitive with the wide debridement.(ABSTRACT TRUNCATED AT 250 WORDS)

We studied orchiectomy specimens from 130 patients immuhistochemically with testicular germ cell tumor (TGCT) using anti-core 2 N-acetylglucosaminyltransferase-1 (C2GnT-1) antibody. The incidence of C2GnT-1 positivity in stage I disease (29.5%, 21/71) was significantly lower than that in higher stages (84.7%, 50/59) (P < 0.001, chi(2) test). This significant difference was also found when the cases were divided into seminoma and NSGCT according to histopathological classification. Kaplan-Meier plots and the log rank test showed that in the patients with stage I seminoma, C2GnT-1-positive cases had a higher risk for recurrence (P < 0.001). This was also the case with the patients with stage I NSGCT (P < 0.001). To determine whether C2GnT-1 promotes aggressive behavior of cancer cells, a C2GnT-1-negative human TGCT cell line, JKT-1, was stably transfected with a mammalian expression vector containing C2GnT-1 cDNA. In vitro assays revealed that JKT-1-C2 cells are more invasive than mock transfectants, although there are no differences in proliferation activity. When orthotopically inoculated into athymic nude mice, JKT-1-C2 cells produced larger testicular tumors extending to the retroperitoneum with mesenteric metastasis, while mock transfectants produced small tumors without metastasis (P < 0.01, Mann-Whitney's U-test). When injected via the tail vein, JKT-1-C2 cells produced a number of metastatic lung foci. In contrast, mock transfectants produced a small number of nodules (p < 0.01, Mann-Whitney's U-test). These results strongly suggest that C2GnT-1 enhances the metastatic potential of TGCT and may be a reliable biomarker for aggressive potential of TGCT.

N-acetylglucosaminyltransferase-V (GnT-V) is an enzyme that catalyzes beta1-6 branching of N-acetylglucosamine on asparagines (N)-linked oligosaccharides of cell proteins. We examined the implication of GnT-V and beta1-6 branching N-linked oligosaccharide expression in human testicular germ cells during malignant transformation and cancer progression. We analyzed immuhistochemically orchiectomy specimens of 130 patients with testicular germ cell tumors (TGCT) using anti-GnT-V monoclonal antibody, and compared GnT-V expression with clinicopathological features. N-linked oligosaccharide structural analysis was also performed to confirm the oligosaccharide profile produced by GnT-V. GnT-V was positive in all normal testis samples. This positive incidence declined in TGCT according to clinical stage; 16/71 (22.5%) in stage I, and 3/59 (5.1%) in stage II/III (p=0.015, chi(2) test). When divided into pathological subtypes, GnT-V positive incidences in stage I seminoma, stage II/III seminoma, stage I non-seminomatous germ cell tumor (NSGCT), and stage II/III NSGCT were 3/43 (7%), 0/22 (0%), 13/28 (46.4%), and 3/37 (8.1%), respectively. In stage I NSGCT, patients with GnT-V-negative tumor samples were at a significantly higher risk of recurrence than those with GnT-V-positive tumors (p=0.015, log-rank test). N-linked oligosaccharide structural analysis revealed that a normal testis has three kinds of beta1-6 branching N-linked oligosaccharides, all of which are downregulated in TGCT tissues. These results suggest that GnT-V and beta1-6 branching N-linked oligosaccharide expressions are downregulated during carcinogenesis and progression of human TGCT. GnT-V may be a promising recurrence predictor for stage I NSGCT.

323 Background: While the adverse effects of androgen deprivation therapy (ADT) in patients with prostate cancer are generally well-known among physicians, it is not clear whether ADT affects renal function. Therefore, the goal of the present study was to assess changes in renal function in response to ADT for 1 year. Methods: Patients with prostate cancer who were hormone-naïve and scheduled to receive long-term ADT were recruited between 2011 and 2013. Body weight and blood testing, including lipid and glucose metabolism and renal function, were recorded every 3 months during 1 year of ADT. Estimated glomerular filtration rate (eGFR) was calculated based on baseline age throughout ADT. Computed tomography (CT) was performed to measure psoas muscle area before and after 1 year of ADT to evaluate the influence of a decrease in lean mass on renal function. ADT was limited to a luteinizing hormone-releasing hormone agonist with or without bicalutamide. Patients who had severe renal dysfunction (eGFR < 30 mL/min/m2) or who had disease progression during 1 year of ADT were excluded from analyses. Results: Of 217 registered patients, renal function data were available from 170 patients who completed 1 year of ADT. Mean changes in serum creatinine and eGFR were 1.3% and 0.2%, respectively. Prostate specific antigen, clinical stage, body mass index, total testosterone, hemoglobin A1c, creatinine, eGFR, and comorbidities (e.g., hypertension, dyslipidemia, diabetes mellitus, cardiovascular disease) at baseline were not associated with a change in renal function. Age < 70 years at baseline was associated with an increase in eGFR in univariate and multivariate analyses (univariate: P = 0.01, multivariate: 95% confidence interval 1.13-4.87, P = 0.03). CT was performed in 72 patients before and after 1 year of ADT. The mean decrease in psoas muscle area was -8.4%. Decrease in psoas muscle area and increase of eGFR were more frequent in patients of age < 70 years than in those of age ≥ 70 years (psoas muscle: -10.2% vs. -7.5%, P = 0.05; eGFR: 6.4% vs. 0.2%, P = 0.03). Conclusions: ADT did not impair renal function in patients with prostate cancer. eGFR was more likely to increase in younger patients, but this increase may be due to a decrease in lean mass. Clinical trial information: UMIN000004709.

189 Background: Weight gain in response to androgen deprivation therapy (ADT) can be a marker for adverse effects of ADT. However, a concomitant decrease in lean mass in response to ADT may decrease the utility of weight gain in terms of sarcopenia. Therefore, the goal of the present study was to analyze the relationship among weight gain, obesity, and sarcopenia in patients undergoing ADT. Methods: Patients with prostate cancer who were hormone-naïve and scheduled to receive long-term ADT were recruited between 2011 and 2013. Body weight and results from blood tests of lipid and glucose metabolism were recorded every 3 months during 1 year of ADT. Computed tomography (CT) was performed to measure areas of subcutaneous and visceral fat and the psoas muscle before and after 1-year of ADT. ADT was limited to a luteinizing hormone-releasing hormone agonist with or without bicalutamide. Results: CT was performed in 72 patients before and after 1 year of ADT. Median age was 74 years (49-83). Median prostate-specific antigen before ADT was 21.9 ng/ml (0.3-3316). Clinical stage was B (43.1%), C (26.4%), and D (29.2%). Mean increase in weight was 2.7% after 1 year of ADT. Mean increase in the area of subcutaneous and visceral fat was 31.3% and 20.7%, respectively. Mean change in the area of the psoas muscle was -8.4%. When patients were divided into two groups according to weight change during 1 year of ADT (Group A (n = 34): weight gain < 3.0%, Group B (n = 38): weight gain ≥ 3.0%), an increase in subcutaneous and visceral fat was significantly more frequent in Group B, whereas the frequency of a decrease in psoas muscle area was not significantly different between the two groups (Group A: -9.5%, Group B: -7.5%, P = 0.11). Pearson correlation coefficients showed a moderate relationship between weight gain and fat accumulation (r = 0.44-0.52), but little relationship between weight gain and a decrease in psoas muscle area (r = 0.18). Conclusions: Fat accumulation tended to increase in patients who gained weight during ADT, whereas a decrease in psoas muscle area was not related to weight change. Sarcopenia could occur despite weight change during ADT. Clinical trial information: UMIN000018478.

426 Background: Most upper urinary tract urothelial carcinomas (UTUC) are invasive and advanced with a poor prognosis. Patients often relapse after treatment with radical nephroureterectomy (RNU). However, little is known about an association between sites of recurrence after RNU and oncological outcomes. The present study retrospectively evaluated the impact of a first recurrence site on survival. Methods: A total of 650 patients with UTUC treated by RNU at 12 institutions that participated in the Tohoku Urological Evidence-Based Medicine Study Group between 2000 and 2011 were initially enrolled. Patients who experienced relapse other than intravesical recurrence after RNU were included in this study. Those who had metastasis at the time of UTUC diagnosis or missing data regarding the time and location of relapse were excluded. Finally, 173 patients were eligible to participate in this study. Survival rates were analyzed using Kaplan-Meier curves and the log-rank test, and factors predicting survival were assessed using multivariate analyses. Results: The median follow-up after relapse was nine months. The cancer-specific survival rates at one and two years after relapse were 49% and 22%, respectively. Cancer in 59 (34%), 32 (18%), 23 (13%), and 94 (53%) patients recurred in the lung, liver, bone and lymph nodes, and 23 (13%) had local recurrence. The one-year cancer-specific survival rates were 44%, 27%, 22% and 52% among patients with metastasis of the lungs, liver, bone and lymph nodes respectively, and 41% among those with local recurrence. The survival rate was worse among 48 patients with metastasis at multiple sites, than in those with metastasis at a single site. Fourteen (8%) patients with a single lymph, lung or local recurrence survived for over three years after a first relapse. Multivariate analyses selected the liver, bone and local recurrence as critical factors for cancer-specific survival. Conclusions: Liver or bone metastasis was a negative prognostic factor for UTUC with relapse after RNU. Information about recurrence sites might be helpful for patient counseling.

N-acetylglucosaminyltransferase-V (GnT-V) is an enzyme that catalyzes beta1-6 branching of N-acetylglucosamine on asparagines (N)-linked oligosaccharides of cell proteins. We examined the implication of GnT-V and beta1-6 branching N-linked oligosaccharide expression in human testicular germ cells during malignant transformation and cancer progression. We analyzed immuhistochemically orchiectomy specimens of 130 patients with testicular germ cell tumors (TGCT) using anti-GnT-V monoclonal antibody, and compared GnT-V expression with clinicopathological features. N-linked oligosaccharide structural analysis was also performed to confirm the oligosaccharide profile produced by GnT-V. GnT-V was positive in all normal testis samples. This positive incidence declined in TGCT according to clinical stage; 16/71 (22.5%) in stage I, and 3/59 (5.1%) in stage II/III (p=0.015, chi(2) test). When divided into pathological subtypes, GnT-V positive incidences in stage I seminoma, stage II/III seminoma, stage I non-seminomatous germ cell tumor (NSGCT), and stage II/III NSGCT were 3/43 (7%), 0/22 (0%), 13/28 (46.4%), and 3/37 (8.1%), respectively. In stage I NSGCT, patients with GnT-V-negative tumor samples were at a significantly higher risk of recurrence than those with GnT-V-positive tumors (p=0.015, log-rank test). N-linked oligosaccharide structural analysis revealed that a normal testis has three kinds of beta1-6 branching N-linked oligosaccharides, all of which are downregulated in TGCT tissues. These results suggest that GnT-V and beta1-6 branching N-linked oligosaccharide expressions are downregulated during carcinogenesis and progression of human TGCT. GnT-V may be a promising recurrence predictor for stage I NSGCT.

A 66-year-old male patient underwent left radical nephrectomy for stage III renal cell carcinoma (RCC) two years and eight months previously. He complained of discomfort at his pharynx. An otolaryngeal examination revealed a tumor about 1.3 cm in size at the base of tongue, and the tumor was resected. It was pathologically diagnosed as clear cell carcinoma and as tongue metastasis of RCC. The subsequent appearance of a minute pulmonary metastasis caused the administration of interferon-alpha and interleukin-II. At present, two years after the treatment, neither growth of lung metastasis nor recurrence of tongue tumor are noticed. Tongue metastasis of RCC is rare and its prognosis is poor. This is the 17th case reported in Japan.

Trophinin is a membrane protein that is potentially involved in human embryo implantation by mediating homophillic cell adhesion between trophoblastic cells and endometrial cells. Trophinin expression by maternal cells may be induced by the embryo that secretes human chorionic gonadotropin (hCG). Because the process of tumor metastasis resembles that of trophoblast invasion and proliferation during embryo implantation, we hypothesized that testicular cancers that synthesize hCG express trophinin thus becoming aggressive trophoblast-like cells. We screened paraffin-embedded orchiectomy specimens of 158 patients with testicular germ cell tumor by immunohistochemistry using antitrophinin antibody. This screening identified trophinin-positive specimens with the frequencies 39 of 91 (43%) in stage I, 14 of 24 (58%) in stage II, and 41 of 43 (95%) in stage III (P < 0.001). Thus, trophinin expression positively correlates with clinical stage. Remarkably, trophinin was found in all of the cases (33 of 33) with lung metastasis. The levels of serum hCG-β were significantly higher in the patients with trophinin-positive tumors than those with trophinin-negative tumors (P = 0.004). To determine whether trophinin promotes aggressiveness of the cell, trophinin-negative human seminona cell line JKT-1 was stably transfected with a mammalian expression vector containing trophinin cDNA. In vitro assays revealed that trophinin-expressing JKT-1-Tro cells are more invasive than JKT-1-mock cells, whereas there are no differences between JKT-1-Tro and JKT-1-mock in their proliferation activity. Upon orthotopic inoculation to athymic nude mice, JKT-1-Tro cells exhibited i.p. metastases in all of the mice (n = 5), whereas JKT-1-mock produced no metastases (n = 5). These results suggest strongly that trophinin enhances invasiveness of the cells and promotes metastasis of testicular germ cell tumor.

87 Background: The adverse events of androgen deprivation therapy (ADT) are widely recognized, but ADT-induced alterations in lipid and glucose metabolism may be race-dependent. We prospectively recruited Japanese patients with newly diagnosed prostate cancer who underwent at least one year of ADT and examined changes in lipid and glucose metabolism in these patients. Methods: Patients with newly diagnosed prostate cancer were recruited between January 2011 and August 2012. Body weight, abdominal circumference, and blood testing results were recorded every three months, and visceral and subcutaneous fat were measured by computed tomography before and after one year of ADT. Results: One hundred three patients completed a one year course of ADT. Median age was 74 (range, 50 to 85). Thirty nine patients underwent ADT with luteinizing hormone-releasing hormone (LHRH) agonist monotherapy, while 64 patients underwent ADT with LH-RH agonist plus bicalutamide. Median prostate-specific antigen (PSA) before ADT was 16.7 ng/ml (range, 3.6-3316 ng/ml). Clinical stage was B (46.6%), C (28.2%), and D (25.2%). Mean increase in body weight, abdominal circumference and body mass index after one year of ADT was 3.8%, 4.1%, and 3.8%, respectively. Mean decrease of hemoglobin was 5.5%. Mean increase of total, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides was 9.0%, 10.8%, 5.0%, and 21.0%, respectively. Mean increase in fasting blood sugar and HbA1c was 4.6% and 1.7%, respectively. Changes in each variable from baseline to 0, 3, 6, 9, and 12 months was as follows: body weight, 0, 0.9, 2.7, 3.3, and 3.8%; hemoglobin, 0, 4.5, 3.7, 5.5, and 5.5%; total cholesterol, 0, 12.9, 11.4, 9.7, and 9.0%; triglycerides, 18, 26, 25, 21%; and HbA1c, 0, 2.1, 1.2, 1.2, and 1.7%. Increase of visceral and subcutaneous fat measured by computed tomography before and after one year of ADT was 32.4% and 35.4%, respectively. Conclusions: One year of ADT caused significant changes, especially in lipid metabolism, in Japanese patients with prostate cancer. Visceral and subcutaneous fat increased more than 30%. These changes were noticeable in the first half of the one year course of ADT. Appropriate monitoring and management of these patients is needed, because these changes might cause critical cardiovascular events. Clinical trial information: UMIN000004709.

Space radiation dosimetry measurements have been made onboard the Space Shuttle STS-65 in the Second International Microgravity Laboratory (IML-2: 28.5 degrees x 300 km: 14.68 days) and the STS-79 in the 4th Shuttle MIR mission (S/MM#4: 51.6 degrees x 300-400km: 10.2 days). In these measurements, three kinds of detectors were used; one is a newly developed active detector telescope called "Real-time Radiation Monitoring Device (RRMD-I for IML-2 and RRMD-II with improved triggering system for S/MM#4)" utilizing silicon semi-conductor detectors and the other detectors are conventional passive detectors of thermoluminescence dosimeters (TLDs) and CR-39 plastic track detectors. The main contribution to dose equivalent for particles with LET5.0 keV/micrometer (IML-2) and LET3.5 keV/micrometer (S/MM#4) is seen to be due to galactic cosmic rays (GCRs) and the contribution of the South Atlantic Anomaly (SAA) is less than 5% (IML-2: 28.5 degrees x 300 km) and 15% (S/MM#4: 51.6 degrees x 400 km) in the above RRMD LET detection conditions. For the whole LET range (0.2 kev/micrometer) obtained by TLDs and CR-39 in these two typical orbits (a small inclination x low altitude and a large inclination x high altitude), absorbed dose rates range from 94 to 114 microGy/day, dose equivalent rates from 186 to 207 microSv/day and average quality factors from 1.82 to 2.00 depending on the locations and directions of detectors inside the Spacelab at the highly protected IML-2 orbit (28.5 degrees x 300 km), and also, absorbed dose rates range from 290 to 367 microGy/day, dose equivalent rates from 582 to 651 microSv/day and average quality factors from 1.78 to 2.01 depending on the dosimeter packages around the RRMD-II "Detector Unit" at the S/MM#4 orbit (5l.6 degrees x 400km). In general, it is seen that absorbed doses depend on the orbit altitude (SAA trapped particles contribution dominant) and dose equivalents on the orbit inclination (GCR contribution dominant). The LET distributions obtained by two different types of active and passive detectors, RRMDs and CR-39, are in good agreement for LET of 15 - 200 kev/micrometer and difference of these distributions in the regions of LET15 kev/micrometer and LET200 kev/micrometer can be explained by considering characteristics of CR-39 etched track formation especially for the low LET tracks and chemical etching conditions.