Circulating free testosterone and risk of aggressive prostate cancer: Prospective and Mendelian randomisation analyses in international consortia.

Previous studies had limited power to assess the associations of testosterone with aggressive disease as a primary endpoint. Further, the association of genetically predicted testosterone with aggressive disease is not known. We investigated the associations of calculated free and measured total testosterone and sex hormone-binding globulin (SHBG) with aggressive, overall and early-onset prostate cancer. In blood-based analyses, odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression from prospective analysis of biomarker concentrations in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group (up to 25 studies, 14 944 cases and 36 752 controls, including 1870 aggressive prostate cancers). In Mendelian randomisation (MR) analyses, using instruments identified using UK Biobank (up to 194 453 men) and outcome data from PRACTICAL (up to 79 148 cases and 61 106 controls, including 15 167 aggressive cancers), ORs were estimated using the inverse-variance weighted method. Free testosterone was associated with aggressive disease in MR analyses (OR per 1 SD = 1.23, 95% CI = 1.08-1.40). In blood-based analyses there was no association with aggressive disease overall, but there was heterogeneity by age at blood collection (OR for men aged <60 years 1.14, CI = 1.02-1.28; Phet  = .0003: inverse association for older ages). Associations for free testosterone were positive for overall prostate cancer (MR: 1.20, 1.08-1.34; blood-based: 1.03, 1.01-1.05) and early-onset prostate cancer (MR: 1.37, 1.09-1.73; blood-based: 1.08, 0.98-1.19). SHBG and total testosterone were inversely associated with overall prostate cancer in blood-based analyses, with null associations in MR analysis. Our results support free testosterone, rather than total testosterone, in the development of prostate cancer, including aggressive subgroups.

The associations of anthropometric, behavioural and sociodemographic factors with circulating concentrations of IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 in a pooled analysis of 16,024 men from 22 studies.

Insulin-like growth factors (IGFs) and insulin-like growth factor binding proteins (IGFBPs) have been implicated in the aetiology of several cancers. To better understand whether anthropometric, behavioural and sociodemographic factors may play a role in cancer risk via IGF signalling, we examined the cross-sectional associations of these exposures with circulating concentrations of IGFs (IGF-I and IGF-II) and IGFBPs (IGFBP-1, IGFBP-2 and IGFBP-3). The Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset includes individual participant data from 16,024 male controls (i.e. without prostate cancer) aged 22-89 years from 22 prospective studies. Geometric means of protein concentrations were estimated using analysis of variance, adjusted for relevant covariates. Older age was associated with higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGF-I, IGF-II and IGFBP-3. Higher body mass index was associated with lower concentrations of IGFBP-1 and IGFBP-2. Taller height was associated with higher concentrations of IGF-I and IGFBP-3 and lower concentrations of IGFBP-1. Smokers had higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGFBP-3 than nonsmokers. Higher alcohol consumption was associated with higher concentrations of IGF-II and lower concentrations of IGF-I and IGFBP-2. African Americans had lower concentrations of IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 and Hispanics had lower IGF-I, IGF-II and IGFBP-3 than non-Hispanic whites. These findings indicate that a range of anthropometric, behavioural and sociodemographic factors are associated with circulating concentrations of IGFs and IGFBPs in men, which will lead to a greater understanding of the mechanisms through which these factors influence cancer risk.

RBM10-TFE3 renal cell carcinoma characterised by paracentric inversion with consistent closely split signals in break-apart fluorescence in-situ hybridisation: study of 10 cases and a literature review.

AIMS: Xp11 rearrangement in renal cell carcinoma (RCC) typically involves gene fusion to the gene encoding transcription factor E3 (TFE3), a member of the microphthalmia-associated transcription factor family on chromosome Xp11.2. Dual-colour break-apart fluorescence in-situ hybridisation (FISH) is recommended to confirm histological diagnoses. Recently, RNA-binding motif protein 10 (RBM10), encoded by a gene on chromosome Xp11.3, was identified as a chimeric partner of TFE3; thus, RBM10-TFE3 fusion results from paracentric inversion. RBM10-TFE3 RCC may yield a false-negative result in FISH analysis of TFE3 expression. The aim of the present study was to investigate the clinicopathological features of RBM10-TFE3 RCC. METHODS AND RESULTS: Ten patients with RBM10-TFE3 RCC aged 31-71 years were investigated. Histological analysis, immunostaining, dual-colour break-apart FISH for TFE3, reverse transcription polymerase chain reaction and sequencing analysis were performed. No patient had a history of exposure to chemotherapy. Two of these patients died of RCC, and three were alive but developed metastases. Microscopically, the tumours were composed of a mixed architecture of tubulocystic and papillary patterns with scattered psammoma bodies. The tumours showed strong nuclear immunoreactivity for TFE3. FISH showed consistent closely spaced split signals in the RCCs of four patients, and polysomic signals with occasional closely spaced split signals in the RCCs of six patients. Of the latter six patients, five had renal failure, and four developed tumours in kidneys subjected to haemodialysis. CONCLUSIONS: The present study suggests that the carcinogenesis of RBM10-TFE3 RCC in some, but not all, patients may be associated with chronic kidney disease. The aggressive nature of RBM10-TFE3 RCC should be considered, as five patients experienced metastases.

Circulating isoflavone and lignan concentrations and prostate cancer risk: a meta-analysis of individual participant data from seven prospective studies including 2,828 cases and 5,593 controls.

Phytoestrogens may influence prostate cancer development. This study aimed to examine the association between prediagnostic circulating concentrations of isoflavones (genistein, daidzein, equol) and lignans (enterolactone and enterodiol) and the risk of prostate cancer. Individual participant data were available from seven prospective studies (two studies from Japan with 241 cases and 503 controls and five studies from Europe with 2,828 cases and 5,593 controls). Because of the large difference in circulating isoflavone concentrations between Japan and Europe, analyses of the associations of isoflavone concentrations and prostate cancer risk were evaluated separately. Prostate cancer risk by study-specific fourths of circulating concentrations of each phytoestrogen was estimated using multivariable-adjusted conditional logistic regression. In men from Japan, those with high compared to low circulating equol concentrations had a lower risk of prostate cancer (multivariable-adjusted OR for upper quartile [Q4] vs. Q1 = 0.61, 95% confidence interval [CI] = 0.39-0.97), although there was no significant trend (OR per 75 percentile increase = 0.69, 95 CI = 0.46-1.05, ptrend = 0.085); Genistein and daidzein concentrations were not significantly associated with risk (ORs for Q4 vs. Q1 = 0.70, 0.45-1.10 and 0.71, 0.45-1.12, respectively). In men from Europe, circulating concentrations of genistein, daidzein and equol were not associated with risk. Circulating lignan concentrations were not associated with the risk of prostate cancer, overall or by disease aggressiveness or time to diagnosis. There was no strong evidence that prediagnostic circulating concentrations of isoflavones or lignans are associated with prostate cancer risk, although further research is warranted in populations where isoflavone intakes are high.

Fifteen-second skin icing using a frozen gel pack is effective for reducing goserelin injection pain.

OBJECTIVE: The efficacy of skin icing to reduce the pain of goserelin injection has been reported. We investigated the optimal icing time with a frozen gel pack and its effectiveness. METHODS: Abdominal skin temperatures of 49 healthy volunteers were measured after application of the frozen gel pack for 10, 15 and 30 s, and it was decided that a 15-second icing was adequate. For 55 consecutive patients who received goserelin (10.8 mg) injection, pain was evaluated employing a visual analog scale (VAS). The first injection was administered routinely. A second injection was administered after skin icing in 27 of 55 patients who wanted to try icing. At the time of the third injection, all patient decided whether they were to receive icing or the routine method. RESULTS: After icing, VAS scores decreased in 20 of 27 patients. At the third injection, 18 patients requested icing. CONCLUSION: When a patient complains of injection pain, the icing method should be considered for pain reduction.

Clinical characteristics and oncological outcomes of testicular cancer patients registered in 2005 and 2008: the first large-scale study from the Cancer Registration Committee of the Japanese Urological Association.

OBJECTIVES: To describe the clinical and pathological characteristics and oncological outcomes of testicular cancer diagnosed in Japan, we report the results of the testicular cancer registration carried out by the Japanese Urological Association. METHODS: Testicular cancer survey was conducted by the Japanese Urological Association in 2011 to register newly diagnosed testicular cancers in 2005 and 2008. The survey included details such as age, presenting symptoms, physical examination findings, tumor markers, histopathology, clinical stage, initial treatment and clinical outcomes. RESULTS: We analyzed 1121 cases of testicular primary germ cell tumor among 1157 registered patients. The median age was 37.0 years. Seminomas and non-seminomatous germ cell tumors accounted for 61.9% and 38.1%, respectively. Measurements of tumor markers were documented in 98.6% of the patients; however, there was an unsatisfactory uniform measurement of human chorionic gonadotropin, which made it difficult to evaluate the International Germ Cell Consensus Classification in all patients. The 1- and 3-year overall survival rates from the entire cohort were 98.3% and 96.8%, respectively. According to the International Germ Cell Consensus Classification, 3-year overall survival rates in the good, intermediate, and poor prognosis group were 99.1%, 100% and 79.9%, respectively. CONCLUSIONS: The present report is the first large-scale study of the characteristics and survival of testicular cancer patients in Japan based on multi-institutional registry data, and showed a good prognosis even in an advanced stage. The improved survival attributed substantially to accurate diagnosis and effective multimodal treatment.

Assessment of screenees' knowledge on prostate cancer: results of a questionnaire using the fact sheet.

PURPOSE: The aim of this study was to assess the screenees' knowledge on prostate cancer and attitude to PSA screening using the Fact Sheet from one district, Kyoto, Japan. METHODS: A PSA screening program is offered to people aged more than 54 years since 1995. The Fact Sheet consists of several chapters, as follows: (1) possibility of diagnosing prostate cancer in terms of the PSA threshold, and future morbid risk, (2) benefit and harm of biopsy, (3) necessary examinations after the diagnosis of prostate cancer and risk for overdiagnosis and overtreatment, and (4) comorbidity of main treatments such as surgery and radiation therapy. Each screenee was asked how well the Fact Sheet was understood. RESULTS: Of the 330 men, 288 read the Fact Sheet for the first time. Of those, 59 and 75% did not know that biopsy indication was determined based on the PSA value and the concept of overdiagnosis, respectively. Furthermore, 68% did not know that active surveillance is established as one option for prostate cancer treatment. However, the screenee's knowledge in the 42 men who read the Fact Sheet previously improved substantially. CONCLUSIONS: The degree of comprehension of examinees is currently insufficient, and repeated enlightenment is required.

Circulating insulin-like growth factors and risks of overall, aggressive and early-onset prostate cancer: a collaborative analysis of 20 prospective studies and Mendelian randomization analysis.

BACKGROUND: Previous studies had limited power to assess the associations of circulating insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) with clinically relevant prostate cancer as a primary endpoint, and the association of genetically predicted IGF-I with aggressive prostate cancer is not known. We aimed to investigate the associations of IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 concentrations with overall, aggressive and early-onset prostate cancer. METHODS: Prospective analysis of biomarkers using the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset (up to 20 studies, 17 009 prostate cancer cases, including 2332 aggressive cases). Odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression. For IGF-I, two-sample Mendelian randomization (MR) analysis was undertaken using instruments identified using UK Biobank (158 444 men) and outcome data from PRACTICAL (up to 85 554 cases, including 15 167 aggressive cases). Additionally, we used colocalization to rule out confounding by linkage disequilibrium. RESULTS: In observational analyses, IGF-I was positively associated with risks of overall (OR per 1 SD = 1.09: 95% CI 1.07, 1.11), aggressive (1.09: 1.03, 1.16) and possibly early-onset disease (1.11: 1.00, 1.24); associations were similar in MR analyses (OR per 1 SD = 1.07: 1.00, 1.15; 1.10: 1.01, 1.20; and 1.13; 0.98, 1.30, respectively). Colocalization also indicated a shared signal for IGF-I and prostate cancer (PP4: 99%). Men with higher IGF-II (1.06: 1.02, 1.11) and IGFBP-3 (1.08: 1.04, 1.11) had higher risks of overall prostate cancer, whereas higher IGFBP-1 was associated with a lower risk (0.95: 0.91, 0.99); these associations were attenuated following adjustment for IGF-I. CONCLUSIONS: These findings support the role of IGF-I in the development of prostate cancer, including for aggressive disease.

High mobility group protein AT-hook 1 (HMGA1) is associated with the development of androgen independence in prostate cancer cells.

BACKGROUND: We previously reported that the level of high mobility group protein AT-hook 1 (HMGA1) is low in androgen-dependent prostate cancer (PCa) cells (LNCaP), but is high in androgen-independent PCa cells (DU145 and PC-3) and that HMGA1 is a strong candidate gene playing a potential role in the progression of PCa. These findings have prompted us to evaluate the effect of HMGA1 on developing androgen independency, which is associated with the progression of PCa. METHODS: Expression of HMGA1 in PCa cells and mouse tissues was examined by Western blot. In order to examine the effect of HMGA1 on cell growth under androgen-deprived condition, we transfected HMGA1 into LNCaP cells, and siRNA into both DU145 and PC-3 cells, respectively. RESULTS: Androgen-deprivation induced an increase in the level of HMGA1 in LNCaP cells in vitro and in vivo, but did not in normal prostate tissue. Overexpression of HMGA1 maintained the cell growth of LNCaP under androgen-deprived condition. Furthermore, knockdown of HMGA1 suppressed the cell growth of DU145 and PC-3. CONCLUSIONS: These data suggest that elevated expression of HMGA1 is associated with the transition of PCa cells from androgen-sensitive to androgen-independent growth and plays a role in the cell growth of androgen-independent PCa cells.

[Management of side effects of everolimus treatment for metastatic renal cell carcinoma].

Treatment with everolimus is known to prolong progression-free survival in patients with renal cell carcinoma resistant against tyrosine-kinase inhibitor therapy. The side effects must be known for more effective use of this drug. Information of side effects was collected from a randomized controlled study, the early post-marketing phase vigilance and from our own experience. Interstitial lung disease (ILD) was a potentially severe side effect. Incidence of ILD was relatively large compared with that of other target therapy agents. Infections, thrombocytopenia, stomatitis and others were experienced as other side effects. However, there were few uncontrollable side effects. Management of side effects of everolimus can be improved by obtaining sufficient knowledge.

Oncological outcomes of the prostate cancer patients registered in 2004: report from the Cancer Registration Committee of the JUA.

OBJECTIVES: In 2001, the Cancer Registration Committee of the Japanese Urological Association initiated a data collection of prostate cancer patients into a computer-based database. The aim of the present study is to report the clinical and pathological characteristics and outcomes of prostate cancer patients diagnosed in 2004 in Japan. METHODS: Overall, 11,385 patients from 239 institutions were registered into the database. After excluding 1105 patients because of insufficient data, duplication or insufficient follow up, 10,280 patients were eligible for the analysis. Most of them (10,198, 99.2%) were Japanese and 1195 (11.6%) had metastatic disease at the time of diagnosis. The mean and median follow up was 53.2 months and 61.5 months, respectively. RESULTS: The 5-year overall and prostate cancer-specific survival rate was 89.7% and 94.8%, respectively. The 5-year prostate cancer-specific survival rate of M0 and M1 disease was 98.4% and 61.1%, respectively. For 8424 cases of organ-confined or regional disease, Japanese urologists used as the initial treatment hormone ablation therapy alone (3360, 39.9%), radical prostatectomy (3140, 38.1%), radiation therapy (1530, 18.2%) and watchful waiting (394, 4.7%) including active surveillance or palliative observation. CONCLUSIONS: This is the first large population report of survival data in Japanese prostate cancer patients. In Japan, the disease population, survival period with metastatic disease and ratio of patients having hormone ablation therapy differ from those in Western countries.

Dairy products and the risk of developing prostate cancer: A large-scale cohort study (JACC Study) in Japan.

Dairy products have been indicated as a risk factor for prostate cancer. However, only a few epidemiological studies have reported dairy products as being a risk factor for prostate cancer in Japan, reporting contradictory results. We therefore investigated the association between the intake of dairy products and the occurrence of prostate cancer through a large-scale cohort study. The Japan Collaborative Cohort study analyzed approximately 110,000 residents from various Japanese districts who participated in our questionnaire survey during 1988-1990. The subjects of the present study were 26,464 men (age range: 40-79 years) from 24 districts wherein cancer incidence was reported. Their clinical course was followed up until 2009. Hazard ratios (HRs) were calculated using Cox's proportional hazards model, adjusted for age, survey area, family history of prostate cancer, body mass index, and total energy intake. For diet, we calculated the HRs associated with intermediate and high consumption of dairy products and compared them with those associated with low consumption. There were 412 cases of prostate cancer in the survey population. As dairy products, milk, yogurt, cheese, and butter were evaluated. Among them, milk consumption was associated with a significant risk (HR = 1.37, p = 0.009) and a dose-dependent response (p for trend = 0.009) adjusted for age and family history of prostate cancer, stratified by area. Milk and yogurt consumption showed a significantly positive risk and a dose-response relationship adjusted for age, family history of prostate cancer, body mass index, and total energy intake, stratified by area. In summary, a high intake of dairy products such as milk increased the risk of developing prostate cancer in Japanese men.

Community-based prostate cancer screening in Japan: predicting factors for positive repeat biopsy.

OBJECTIVES: To assess possible predictors in determining criteria for repeat biopsy in a prostate cancer screening population. METHODS: A total of 50 207 men over 55 years-of-age have participated in a prostate cancer screening program in Otokuni, Kyoto, Japan for 12 years. Transperineal systematic biopsy was carried out in case of positive digital rectal examination (DRE) or positive transrectal ultrasonography (TRUS) or a prostate-specific antigen (PSA) value greater than 10.0 ng/mL. For those with a PSA level from 4.1 to 10.0 ng/mL, and negative DRE and TRUS findings, biopsy was indicated only when PSA density (PSAD) was greater than 0.15. The same indication was applied for the repeat biopsy. RESULTS: A repeat biopsy after an interval of more than 2 years was carried out in 140 patients and was positive in 50 (36%) patients. The PSA value at the diagnosis of cancer declined from the initial value in six (12%) patients. On multivariate logistic regression analysis, PSA velocity (PSAV) as well as PSAD and DRE findings at latest screening were independent predictors for positive repeat-biopsy outcome. The odds ratio (95% confidence intervals) of PSAV >0.48, latest PSAD >0.33 and positive latest DRE were 4.17 (1.05-18.5), 4.15 (1.31-14.0), and 3.62 (1.06-13.2), respectively. A combination of three variables defined as positive if any of these were positive, reduced 31% of unnecessary biopsies while missing 8% of low volume, low grade cancers. CONCLUSIONS: A combination of latest PSAD, PSAV and positive DRE at latest screening might help to reduce unnecessary repeat biopsies in high-risk patients with an initial negative biopsy.

Remitting seronegative symmetrical synovitis with pitting edema syndrome in maintenance hemodialysis.

INTRODUCTION: The remitting seronegative symmetrical synovitis with pitting edema syndrome primarily occurs in elderly individuals to represent symptoms of edema, pain, and joint swelling. It could be misdiagnosed in elderly maintenance hemodialysis patients, as hemodialysis patients often present with pain and joint swelling induced by hypervolemia, inflammation, amyloidosis, and/or chronic kidney disease. Here, we describe a maintenance hemodialysis patient with remitting seronegative symmetrical synovitis with pitting edema syndrome. CASE PRESENTATION: A 71-year-old man on maintenance hemodialysis who complained of continuous pain and swelling of joints was diagnosed with remitting seronegative symmetrical synovitis with pitting edema syndrome on his clinical findings that revealed tenosynovitis at the joint without joint erosions and no elevation of anti-cyclic citrullinated peptide antibody and rheumatoid factor. After administration of prednisolone, systemic edema, and pain improved in 2 days. CONCLUSION: Remitting seronegative symmetrical synovitis with pitting edema syndrome should be considered as a differential diagnosis in hemodialysis patients with edema and/or arthralgia.

Salvage chemotherapy with paclitaxel and gemcitabine plus nedaplatin (TGN) as part of multidisciplinary therapy in patients with heavily pretreated cisplatin-refractory germ cell tumors.

BACKGROUND: We investigated the efficacy and toxicity of a regimen consisting of paclitaxel and gemcitabine plus nedaplatin, a derivative of cisplatin (TGN) in patients with heavily pretreated cisplatin-refractory germ cell tumors (GCTs). METHODS: Fifteen patients with advanced GCTs were treated with the TGN regimen. The combination chemotherapy consisted of paclitaxel (210 mg/m(2)) on day 1 and gemcitabine (1000 mg/m(2)) on days 1 and 8 in combination with nedaplatin (100 mg/m(2)) on day 2 every 3 weeks. RESULTS: Patients enrolled in this study had been heavily pretreated with a median of 12 platinum-containing cycles (range, 7 to 26 cycles). Most of the regimens had included paclitaxel and ifosfamide plus cisplatin or nedaplatin (TIP/TIN) chemotherapy. The median follow-up period of the present study was 15 months. Patients received 2-11 cycles of the TGN combination chemotherapy. Six patients received the treatment combined with other therapeutic modalities; 2 patients received radiation therapy for retroperitoneal lymph node metastasis, 1 patient had cyber-knife radiosurgery for brain metastasis and 3 patients had radiofrequency ablation for liver and lung metastasis. Seven (46.7%) of the 15 patients achieved an objective response; 6 had marker-negative partial responses (PRs) and 1 had a marker-positive PR. Two (13%) of the 7 patients with PRs achieved a disease-free status after chemotherapy combined with RT and followed by surgical resection. However, 10 patients died of the disease and 3 patients are still alive with the disease. CONCLUSION: The TGN regimen alone had limited efficacy in this patient population, with severe but manageable toxicities. However, TGN chemotherapy may offer a chance of cure for some heavily pretreated cisplatin-refractory (TIP/TIN-refractory) patients as part of multidisciplinary therapy.

Radiofrequency ablation for renal tumors: our experience.

OBJECTIVES: To report our results of percutaneous radiofrequency ablation (RFA) for renal tumors and to assess predictors of therapeutic efficacy. METHODS: Forty patients (median age 73 years) with renal tumors were treated with RFA under local or epidural anesthesia. All of them had high surgical risk or refused radical surgery. Tumors were punctured percutaneously using the Radionics Cool-tip RF System under computed tomography or ultrasonographic guidance. Median tumor diameter was 24 mm. After RFA, contrast-enhanced computed tomography or magnetic resonance imaging was performed within 1 month. Complete response (CR) was defined as no enhancement inside the tumor. Factors related to the outcome and to renal function were assessed. RESULTS: Median follow up was 16 months. CR was observed in 34 cases (85.0%). A significant difference in CR rate was observed between tumors < or =30 mm and those >30 mm. Outcomes tended to be better for tumors in the mid to lower kidney, and those away from the renal hilum. Recurrence was observed in one case (2.9%), but a CR was obtained again by additional RFA. Out of a total of 77 RFA procedures, complications occurred in only three cases (3.9%), and conservative treatment was possible in all cases. Serum creatinine levels 3 months after RFA did not differ from those before RFA. CONCLUSIONS: Percutaneous RFA is a safe and effective treatment for small renal tumors in patients with high surgical risk or who refuse radical surgery.

[Radio-frequency ablation (RFA) for post-chemotherapeutic metastatic germ cell tumors as minimally invasive salvage therapy].

Radio-frequency ablation (RFA) has been successfully applied for local control of metastatic tumor. The aim of this study was to assess the effectiveness and safety of RFA to post-chemotherapeutic metastatic germ cell tumors (GCTs). As combined modality therapy, RFA was performed to 42 tumors in 19 patients of GCTs at our institution between November 2000 and December 2008. RFA was performed for 10 liver metastatic tumors (in 6 cases), 32 lung metastatic tumors (in 13 cases), and median age was 36 years old (range 20-53) and the median tumor size was 12 mm (range 2-40). We used Cool-tip RF system (straight electrode needle of the internal cooling type, Radionics, Palm Coast, USA) for RFA with ultrasound or CT fluorosent guidance under intravenous or local anesthesia. The therapeutic effect was assessed by the contrast-enhanced CT or MRI. When contrast enhancement was remained in the tumor, the treatment was repeated. The 28 evaluable lesions followed were with median 25 months in the term of the surveillance, and 9 tumors were treated by an additional session of RFA repeatedly. complete response (CR) was achieved in 12 out of 12 tumors (100%) with tumor maker normalization. On the other hand, 12 out of 16 tumors (75%) without marker normalization showed CR. All of the 24 tumors with tumor diameter of 30 mm or less achieved CR, and the tumor greater than 30 mm achieved no CR. Major complications included pneumothorax (n=9) and hemato-thoraxes (n=2), but no complications in surrounding organs. The chest drainage tube was required in 4 cases (36%). RFA might be an alternative therapeutic option of combined modality therapy as salvage therapy for post-chemotherapeutic metastatic germ cell tumors.

Ten year trend in prostate cancer screening with high prostate-specific antigen exposure rate in Japan.

BACKGROUND: The tendency of the results and quality control of prostate cancer screening serially performed for 10 years in an area of Japan were evaluated. METHODS: A total of 39 213 men over 55 years of age have participated in the mass screening of prostate cancer in the Otokuni District, since 1995. Men whose prostate-specific antigen (PSA) levels were more than 4.1 ng/mL were indicated for the second screening. In the second screening, prostate-specific antigen density (PSAD) was calculated in men whose PSA levels ranged from 4.1 to 10.0 ng/mL. RESULTS: Secondary screening was indicated in a total of 2428 subjects, of whom 1633 underwent it. Prostate cancer was diagnosed in 267 men. As a result of the evaluation of the indication of prostate biopsy according to the PSAD in 894 who underwent secondary screening for the first time, the procedure was judged to be unnecessary in 269 (35%) of 765 cases. Of these 269 subjects, 23 (8.5%) were found to have cancer. Clinically localized prostate cancer increased by 17%, and locally advanced and metastatic cancers decreased by 12% in the second compared with the first five years of the ten-year period. The exposure rate of PSA screening in the Otokuni District was 65% with the application for the rate of screenees whose PSA level was 4.1 ng/mL or above. CONCLUSIONS: The Japanese basic health screening system allows the determination of high-PSA exposure areas. Serial prostate cancer screening showed a tendency of stage migration in the screened cancer patients. The use of PSAD in secondary screening substantially reduces the necessity of prostate biopsy; however, the encouragement of PSA-positive individuals to periodically receive prostate cancer screening is essential to maintain the quality of the screening system.

[Squamous cell carcinoma of the renal pelvis with elevation of G-CSF in the serum: a case report].

A 67-year-old man was admitted with left renal pelvic tumor. He had a leukocytosis of 26,500/mm3 (neutrophils: 81.7%) in the peripheral blood, but with no obvious focus of infection. Moreover, the serum granulocyte-colony stimulating factor (G-CSF) and squamous cell carcinoma antigen (SCC) were elevated. Abdominal enhanced computed tomography (CT) and left retrograde pyelography showed left renal pelvic cancer T4N0M0. He received neoadjuvant chemotherapy (M-VAC: cisplatin + methotrexate + vinblastin + doxorubicin, TN: paclitaxel + nedaplatin). After neoadjuvant chemotherapy, left nephroureterectomy was performed because of normalization of the serum SCC and G-CSF. Histological examination revealed squamous cell carcinoma of the renal pelvis. He is alive with no evidence of disease for 4 years.

Randomized study of intravesical pirarubicin chemotherapy with low and intermediate-risk nonmuscle-invasive bladder cancer in Japan: Comparison of a single immediate postoperative intravesical instillation with short-term adjuvant intravesical instillations after transurethral resection.

PURPOSE: The objective of this study was to evaluate the efficacy, defined by the 3-year tumor recurrence-free survival rate, of intravesical chemotherapy using pirarubicin (THP) in patients with low or intermediate-risk nonmuscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: Between October 2010 and January 2015, 206 patients were enrolled, and finally 113 were randomized to receive either a single immediate postoperative intravesical instillation of THP (30 mg) (Group A), or 8 additional weekly intravesical instillations of THP (30 mg) after a single postoperative instillation (Group B). The patients were examined by performing cystoscopy and urine cytology every 3 months after transurethral resection to determine bladder tumor recurrence. The primary endpoint was 3-year-recurrence-free survival rate. RESULTS: All 113 patients were bacillus Calmette-Guérin (BCG)-naïve. The 3-year recurrence free survival rate was 63.7% for Group A and 85.3% for Group B (log-rank test, P = .0070). In patients with intermediate recurrence risk, the 3-year recurrence-free survival rate was 63.4% in Group A and 86.1% in Group B (log-rank test, P = .0036). Cox regression analysis revealed that only additional instillation of THP was a significant independent factor for recurrence-free rate in patients with intermediate risk. No patient with progression was noted during this period. Frequent adverse effects (AEs) were frequent urination and micturition pain, and no severe AEs (Grade 3 or more) occurred. CONCLUSION: Additional instillation of THP (30 mg) weekly for 8 weeks reduced the risk of tumor recurrence without severe AEs in BCG-naïve NMIBC patients with intermediate risk.