[Adult Prepubertal-Type Teratoma Diagnosed Using Fish Analysis : A Case Report].

A 34-year-old man visited our hospital complaining of a small painless left scrotal mass. His serum alpha-fetoprotein and human chorionic gonadotropin-beta levels were normal. Ultrasonography revealed a solitary 14 mm mass. Magnetic resonance imaging revealed a mass with high intensity on T2-weighted imaging. Computed tomography revealed a heterogeneous tumor in the left scrotum. Left high orchiectomy was performed. The histopathological diagnosis was a teratoma without germ cell neoplasia in situ (GCNIS). Fluorescence in situ hybridization analysis showed no appearance of i(12p). The patient was clinically diagnosed as having a prepubertal-type testicular teratoma. Adult teratomas contain GCNIS and are aggressively treated as malignant germ cell tumors. However, a prepubertal-type teratoma is benign and does not relapse. It is essential to validate the appearance of i(12p) to differentiate prepubertal and postpubertal-type teratoma.

Clinical outcomes of second transurethral resection in non-muscle invasive high-grade bladder cancer: a retrospective, multi-institutional, collaborative study.

BACKGROUND: A retrospective, multi-institutional collaborative study was conducted to evaluate the impact of second transurethral resection (TUR) on the clinical outcome of non-muscle invasive high-grade bladder cancer and to identify predictors of invasion to the lamina propria (pT1) or deeper and residual tumor at the second TUR. METHODS: The clinical and pathological features of 198 patients with non-muscle invasive high-grade bladder cancer treated in five medical institutions from April 1990 to March 2013 were reviewed retrospectively. All patients underwent a second TUR within a mean of 1.5 months after the first resection. Clinicopathological findings of the first and second TURs were compared. Cancer-specific survival and recurrence-free survival were evaluated. Univariate and multivariate analyses for predictors of residual cancer at the second TUR were performed using a logistic regression model. RESULTS: At the second TUR, no tumor was found in 111 (56 %) patients, and 87 (44 %) had residual cancer. At the first TUR, five pT1 patients (3 %) were upstaged to pT2, one pTa patient (1 %) was upstaged to pT1, and 12 G2 patients (6 %) had their tumor upgraded to G3. Patients the group with less than stage pT1 cancer at the second TUR had significantly better survival than those in the group with stage pT1 or deeper cancer. Tumor multiplicity at the first resection was an independent risk factor for pT1 or deeper tumor at the second TUR. CONCLUSION: A second TUR is a valuable diagnostic procedure for accurate staging of non-muscle invasive high-grade bladder cancer. Tumor multiplicity at the first TUR was a significant independent predictor of pT1 or deeper tumor at the second TUR.

Distinctive expression patterns of glycoprotein non-metastatic B and folliculin in renal tumors in patients with Birt-Hogg-Dubé syndrome.

Birt-Hogg-Dubé syndrome (BHD) is an inherited disorder associated with a germline mutation of the folliculin gene (FLCN). The affected families have a high risk for developing multiple renal cell carcinomas (RCC). Diagnostic markers that distinguish between FLCN-related RCC and sporadic RCC have not been investigated, and many patients with undiagnosed BHD fail to receive proper medical care. We investigated the histopathology of 27 RCCs obtained from 18 BHD patients who were diagnosed by genetic testing. Possible somatic mutations of RCC lesions were investigated by DNA sequencing. Western blotting and immunohistochemical staining were used to compare the expression levels of FLCN and glycoprotein non-metastatic B (GPNMB) between FLCN-related RCCs and sporadic renal tumors (n = 62). The expression of GPNMB was also evaluated by quantitative RT-PCR. Histopathological analysis revealed that the most frequent histological type was chromophobe RCC (n = 12), followed by hybrid oncocytic/chromophobe tumor (n = 6). Somatic mutation analysis revealed small intragenic mutations in six cases and loss of heterozygosity in two cases. Western blot and immunostaining analyses revealed that FLCN-related RCCs showed overexpression of GPNMB and underexpression of FLCN, whereas sporadic tumors showed inverted patterns. GPNMB mRNA in FLCN-related RCCs was 23-fold more abundant than in sporadic tumors. The distinctive expression patterns of GPNMB and FLCN might identify patients with RCCs who need further work-up for BHD.

The association of CXCR3 and renal cell carcinoma metastasis.

PURPOSE: Renal cell carcinoma expresses CXCR3 but the function of CXCR3 in renal cell carcinoma has not been clarified. We explored the function of CXCR3 in renal cell carcinoma and investigated CXCR3 regulating factors. MATERIALS AND METHODS: We obtained 56 clinical samples of clear cell renal cell carcinoma and corresponding normal renal tissue samples from the surgical specimens of Japanese patients who underwent radical nephrectomy at Chiba University Hospital between 2000 and 2011. As renal cell carcinoma cell lines, we used 786-O, ACHN and Caki-1. The expression profiles of CXCR3 and its splice variants were examined. For functional analyses 786-O and interferon-γ inducible 10 kDa protein or IP-10 (CXCL10) were selected as representatives. RESULTS: CXCR3 and its ligands were abundant in renal cell carcinoma samples compared to corresponding normal kidney samples. The CXCR3-A-to-CXCR3-B ratio was 1.5 times higher in renal cell carcinoma samples than in normal kidney samples. CXCL10 treatment induced 786-O cell migration and invasion, and these effects were inhibited by neutralizing antibody. Phosphorylated RhoA and pro/active matrix metalloproteinase-9 expression was up-regulated by CXCL10 treatment. In clinical samples CXCR3 and CXCR3-A expression was significantly higher in metastatic than in nonmetastatic carcinoma samples. Finally, the expression of CXCR3-A and HIF-1α correlated significantly in clinical samples. In 786-O treatment with CoCl2 up-regulated CXCR3 and HIF-1α expression 4.5 and 2.2-fold, respectively. CONCLUSIONS: We determined the association of CXCR3 and renal cell carcinoma metastasis. CXCR3 expression may be regulated by hypoxia.

[Treatment outcome of intrarenal Bacillus Calmette-Guerin therapy for carcinoma in situ of the upper urinary tract].

We investigated the long-term efficacy and safety of intrarenal bacillus Calmette-Guerin (BCG) therapy for carcinoma in situ (CIS) of the upper urinary tract. We retrospectively reviewed the medical records of 9 patients who underwent BCG perfusion therapy for CIS of the upper urinary tract from January 2005 to December 2011 at our institute. All patients were treated by retrograde catheterization using a 6 Fr double- J ureteric stent. BCG at half the dose (40.5 mg or 40 mg) in 40ml saline was instilled into the bladder weekly for 6 or 8 weeks as one course. The mean follow-up period was 32.7 months (range 4-75 months). In all patients (100%), cytology became negative after one course of BCG perfusion and 8 patients (88. 9%) remained disease-free for a median follow-up of 35.1 months. Among these 9 patients, 1 patient showed recurrence after 6 months of the first BCG therapy. The patient received a second course of BCG therapy, but the patient developed invasive tumor and distant metastases. Two patients could not continue the treatment due to pyelonephritis. In conclusion, although longer follow up and further experience with treatment for CIS of the upper urinary tract are required, this treatment is considered to be effective and safe.

[Neoadjuvant hormonal therapy versus surgery alone for radical prostatectomy in high-risk prostate cancer patients].

We examined the effect of neoadjuvant hormonal therapy (NHT) on biochemical failure. We retrospectively analyzed 146 high-risk prostate cancer patients (clinically (c), T1c-3N0M0) who underwent radical prostatectomy between June 2002 and March 2008. Thirty-eight patients were treated with NHT for ≥2 months (NHT group), and 108, with surgery alone (SA group). The study population comprised 89 cT1c-2N0M0 patients and 57 cT3N0M0 patients, and pathologically (p), 66 pT0-2N0M0 patients and 76 pT3N0M0 patients. Downstaging was noted in 36.4 and 0% of cT1c-2N0M0 patients and in 74.1 and 20.0% of cT3N0M0 patients in the NHT and SA groups, respectively. For both cT1c-2N0M0 and cT3N0M0 patients, the downstaging rate was significantly higher in the NHT group than in the SA group (p＜0.01). Positive resection margin rates were significantly lower in the NHT group (34.2%) than in the SA group (65.7%) (p＜0.01). The overall prostate-specific antigen (PSA) progression-free rate did not differ significantly between the 2 groups in both pT0-2N0M0 and pT3N0M0 patients. However, in pT0-2N0M0 patients with negative resection margins, the 5-year PSA progression-free rate was significantly lower in the NHT group than in the SA group (p＜0.01), whereas this rate did not differ significantly between the groups in both pT0-2N0M0 and pT3N0M0 patients with positive resection margins. Although NHT seemed to have some effect on downstaging, its pathological effects could be underestimated. Thus, NHT was considered to have no significant effect on biochemical failure.

Laparoscopic redo pyeloplasty with a buccal mucosal graft.

Introduction: Redo pyeloplasty can be difficult due to scar tissue or fibrosis. Ureteral reconstruction with a buccal mucosal graft is performed safely and successfully, but most reports of ureteral reconstruction using a buccal mucosal graft are of robot-assisted surgery, with few reports of laparoscopic-assisted surgery. A case of laparoscopic-assisted redo pyeloplasty using a buccal mucosal graft is presented. Case presentation: A 53-year-old woman was diagnosed with ureteropelvic junction obstruction, and a double-J stent was placed to relieve backache. She visited our hospital 6 months after double-J stent placement. Three months later, laparoscopic pyeloplasty was performed. At 2 months postoperatively, anatomic stenosis occurred. Holmium laser endoureterotomy and balloon dilation were performed; however, the anatomic stenosis recurred, and laparoscopic redo pyeloplasty with a buccal mucosal graft was performed. After redo pyeloplasty, obstruction was improved, and her symptoms disappeared. Conclusion: This is the first case of using a buccal mucosal graft for laparoscopic pyeloplasty in Japan.

Efficacy and Safety of Tolvaptan for Patients With Autosomal Dominant Polycystic Kidney Disease in Real-world Practice: A Single Institution Retrospective Study.

BACKGROUND/AIM: We evaluated the efficacy and safety of tolvaptan for autosomal dominant polycystic kidney disease (ADPKD) in real-world practice. PATIENTS AND METHODS: We retrospectively reviewed the cases of 27 patients who had been diagnosed with ADPKD between January 2014 and December 2022. Among them, 14 patients received tolvaptan (60 mg/day; morning: 45 mg, night: 15 mg) after being admitted for 2 days. In the outpatient clinic, blood and urine samples were taken monthly. RESULTS: The mean age, pretreatment estimated glomerular filtration rate (eGFR), treatment duration, and total kidney volume were 60 years, 45.6 ml/min/1.73 m2, 2.8 years, and 2,390 ml, respectively. One month later, the patients' renal dysfunction had worsened slightly, and their serum sodium concentrations had significantly increased. After one year, the mean reduction in the eGFR was -5.5 ml/min/1.73 m2 Moreover, at 3 years the patients' renal function was stable. No hepatic dysfunction or electrolyte abnormalities were noted, although discontinuation occurred in two cases. Tolvaptan treatment is considered to be safe. CONCLUSION: Tolvaptan was effective against ADPKD in a real-world setting. Moreover, the safety of tolvaptan was confirmed.

Outcomes of dutasteride discontinuation in patients with benign prostatic hypertrophy.

To the Editor, Benign prostatic hyperplasia (BPH) is a common cause of lower urinary tract symptoms (LUTS) in elderly males. The current guidelines recommend the use of a 5-alpha reductase inhibitor (5ARI) to treat males with moderate-to-severe LUTS and an enlarged prostate. Combination therapy with an alpha blocker and a 5ARI has proven effective at ameliorating LUTS and reducing the total prostate volume (TPV) and the risk of the disease progression.

The choice of therapeutic agent in female overactive bladder patients in real-world practice.

OBJECTIVE: The reasons why anticholinergic drugs or ß3 adrenergic agonists are selected as treatments for overactive bladder (OAB) are unclear. The aim of this study was to investigate the background data of female OAB patients that were prescribed anticholinergic drugs or ß3 adrenergic agonists in a real-world setting. MATERIALS AND METHODS: Between January 2013 and December 2014, 75 patients who had been diagnosed with OAB were included in this study. Administered medications, age, the persistence on treatment rate at one-year, medical history, pretreatment total Overactive Bladder Symptom Score (OABSS), pretreatment score for each OABSS factor, body mass index (BMI), and various comorbidities were evaluated retrospectively. Since there were many types of anticholinergic drugs and few patients, we grouped the patients into those that were prescribed anticholinergic drugs (group A) and those that were prescribed ß3 adrenergic agonists (group B). RESULTS: 75 patients (29 in group A and 46 in group B) were included in this study. There were no significant differences in age, BMI, obesity, medical history, pretreatment total OABSS, or pretreatment score for each OABSS factor. There was a significant difference in the post-voiding residual urine volume (PVR) between the groups (group A: 22 ml, group B: 9 ml; p = 0.0252). The 1-year persistence on treatment rate was 28% in both groups. CONCLUSIONS: There were no significant differences in clinical characteristics of patients who were prescribed anticholinergics and ß3 adrenergic agonists for OAB treatment, but a marginal difference of PVR value before treatment. The 1-year persistence rates of anticholinergic drugs and ß3 adrenergic agonists were considered to be almost equivalent.

Cancer/Testis Antigens as potential predictors of biochemical recurrence of prostate cancer following radical prostatectomy.

BACKGROUND: The Cancer/Testis Antigens (CTAs) are an important group of proteins that are typically restricted to the testis in the normal adult but are aberrantly expressed in several types of cancers. As a result of their restricted expression patterns, the CTAs could serve as unique biomarkers for cancer diagnosis/prognosis. The aim of this study was to identify promising CTAs that are associated with prostate cancer (PCa) recurrence following radical prostatectomy (RP). METHODS: The expression of 5 CTAs was measured by quantitative multiplex real-time PCR using prostate tissue samples obtained from 72 patients with apparently clinically localized PCa with a median of two years follow-up (range, 1 to 14 years). RESULTS: The expression of CTAs namely, CEP55, NUF2, PBK and TTK were significantly higher while PAGE4 was significantly lower in patients with recurrent disease. All CTAs with the exception of TTK were significantly correlated with the prostatectomy Gleason score, but none were correlated with age, stage, or preoperative PSA levels. In univariate proportional hazards models, CEP55 (HR = 3.59, 95% CI: 1.50-8.60), p = 0.004; NUF2 (HR = 2.28, 95% CI: 1.11-4.67), p = 0.024; and PAGE4 (HR = 0.44, 95% CI: 0.21-0.93), p = 0.031 were significantly associated with the risk of PCa recurrence. However, the results were no longer significant after adjustment for prostatectomy Gleason score. CONCLUSIONS: To our knowledge, this is the first study to identify CTAs as biomarkers that can differentiate patients with recurrent and non-recurrent disease following RP and underscores its potential impact on PCa prognosis and treatment.

External validation of a pre-operative prognostic nomogram for renal cell carcinoma in two patient populations: a retrospective cohort study.

The aim of this study was to establish the discriminating accuracy of Kanao's pre-operative nomogram for renal cell carcinoma in predicting cause-specific survival among representative patients who underwent nephrectomy. Patients originated from two centers: Chiba University Hospital (n= 151) and Chiba Cancer Center (n = 91). We validated the predictive accuracy, which was assessed using Harrell's concordance-index. The concordance-index values were 0.692 and 0.834 for Chiba University Hospital and Chiba Cancer Center, respectively, although it was 0.822 for the combined data sets. Results of external validation were different at each cohort. We constructed calibration plots of Kanao's nomogram and confirmed the tendency at each institution. Inconsistency of results among two centers makes it difficult to reach a valid conclusion. Therefore, the predictive accuracy of Kanao's nomogram was not settled. Clinicians need to confirm the predictive accuracy of Kanao's nomogram and construct calibration plots when applying this nomogram to different patient populations.

High Serum Alkaline Phosphatase Flare after First-Line Androgen Deprivation Therapy Predicts Poor Prognosis in Metastatic Prostate Cancer Patients Treated with Second-Generation Androgen Receptor Targeted Therapy.

OBJECTIVES: To determine whether an alkaline phosphatase (ALP) flare after androgen deprivation therapy (ADT) is associated with the treatment response in castration-resistant prostate cancer (CRPC) and predicts the prognosis of metastatic prostate cancer (PCa) patients. METHODS: One hundred and nineteen patients diagnosed with metastatic PCa between 2008 and 2017 were retrospectively studied. The ALP flare ratio was calculated as the ratio of ALP levels 1 month after beginning ADT to ALP levels at diagnosis. The association of the ALP flare ratio with the prostate-specific antigen (PSA) response to CRPC treatment (second-generation androgen receptor targeted therapy (ART) or docetaxel), time to CRPC, and overall survival (OS) were investigated. RESULTS: The time to CRPC and OS was significantly longer in patients with an ALP flare ratio less than 1.33 compared to a ratio more than 1.33. No difference in PSA response was seen regarding the ALP flare ratio in both ART and docetaxel treatment. Second-generation ART-treated patients with a low ALP flare ratio showed longer OS than those with a higher ALP flare ratio (p=0.0367). However, no difference was seen between a high and low ALP flare ratio (p=0.8054) in docetaxel-treated patients. The ALP flare ratio was the most significant prognostic factor for OS (p < 0.0001). CONCLUSIONS: A higher ALP flare ratio after first-line ADT was a significant prognostic factor in metastatic PCa, especially in patients treated with second-generation ART for CRPC. Chemotherapy for patients with a higher ALP flare ratio 1 month after induction of ADT may be a clinically relevant decision.

False-positive 123I-metaiodobenzylguanidine scan in a patient with renal cell carcinoma: A case of chromophobe renal cell carcinoma oncocytic variant with a complicated clinical course.

INTRODUCTION: 123I-metaiodobenzylguanidine scanning has high sensitivity and specificity for the diagnosis of tumors derived from sympathetic nerves or the adrenal medulla. We report the rare case of a 123I-metaiodobenzylguanidine false-positive renal cell carcinoma. CASE PRESENTATION: The patient was referred to our hospital with an incidental left renal mass during evaluation for hypertension. An ovarian tumor and prominent ascites were also observed. Serum and urine catecholamine levels were high to suspect a catecholamine-producing tumor of the kidney. 123I-metaiodobenzylguanidine scintigraphy showed increased 123I-metaiodobenzylguanidine intake in the tumor. Laparoscopic radical left nephrectomy was performed. The pathologic diagnosis was an oncocytic variant of chromophobe renal cell carcinoma. No pheochromocytoma features were found. CONCLUSION: We report the first case of a 123I-metaiodobenzylguanidine false-positive renal cell carcinoma. This case was diagnosed with primary aldosteronism and Meigs' syndrome, which made the clinical course more complicated.

The Association Between Hot Flashes and Renal Dysfunction After Androgen Deprivation Therapy With Radiotherapy in Japanese Patients With High-risk Prostate Cancer.

BACKGROUND/AIM: We investigated the changes in and characteristics of renal function in Japanese patients with high-risk prostate cancer (PCa) who underwent radiotherapy and long-term androgen deprivation therapy (ADT), including those seen after the ADT was discontinued. PATIENTS AND METHODS: Among 60 patients who were pathologically diagnosed with PCa and received ADT for 24 months and radiotherapy, 36 patients who underwent treatment for stage B or C PCa were eligible. We assessed renal function using the estimated glomerular filtration rate (eGFR) and investigated the rate of change in the eGFR (ΔeGFR) during and after ADT. Univariate and multivariate logistic analyses were carried out to identify clinical factors that were significantly associated with renal dysfunction at 36 months. RESULTS: The incidence of renal dysfunction at 36 months was 75% (27/36). Multivariate analysis showed that the presence/absence of HF was an independent predictor of renal dysfunction at 36 months. CONCLUSION: Renal function tended to recover after ADT was received for 24 months and subsequently discontinued. The presence/absence of HF represents new and meaningful information for patients receiving ADT, and high-risk PCa patients prior to ADT.

Renal Function Improves After the Discontinuation of Androgen Deprivation Therapy in Japanese Patients With Prostate Cancer.

BACKGROUND: Androgen deprivation therapy (ADT) is one of the most effective treatments for advanced prostate cancer (PCa). However, it has been reported that the use of ADT is significantly associated with an increased risk of acute kidney injury (AKI) among patients with newly diagnosed non-metastatic PCa. We investigated changes in renal function that occurred in Japanese patients with PCa after ADT was discontinued. PATIENTS AND METHODS: Among 121 patients who underwent prostate biopsies, were pathologically diagnosed with PCa, and received ADT for ≥6 months at our Institution between 2009 and 2014, 60 patients who underwent radiotherapy for stage B or C PCa were eligible for inclusion in this retrospective study. Renal function was assessed using the estimated glomerular filtration rate (eGFR) before treatment and at 1, 3, 6, 9, and 12 months after the initiation of ADT and the rate of change in the eGFR (ΔeGFR) during ADT and after the discontinuation of ADT was investigated. We divided patients into two groups: Group 1 received ADT for 6 months, and group 2 received ADT for 12 months. Age; ΔeGFR; prostate-specific antigen, testosterone and hemoglobin levels; clinical stage; Gleason score; comorbidities; body mass index; heart rate; and the cardiothoracic ratio were analyzed. RESULTS: A total of 60 patients (group 1: n=23, group 2: n=37) were analyzed. The Gleason score of group 2 was higher than that of group 1 (p=0.0011). Regarding clinical stage, group 1 had more patients with stage B disease, and group 2 had more with stage C (p<0.0001). The eGFR decreased with the duration of ADT treatment. At 12 months, renal function had started to recover in group 1, while it had continued to decrease in group 2. CONCLUSION: Discontinuation of ADT tended to result in improvements in renal function. Furthermore, this study indicated that renal dysfunction caused by 6 months of ADT is transient. Normalization of the serum testosterone level seen after the discontinuation of ADT may be associated with improvements in renal function. Thus, intermittent ADT may be a useful treatment for PCa, as it would help to preserve renal function.

Successful Response to Nivolumab Plus Ipilimumab Therapy in a Hemodialysis Patient With Metastatic Renal Cell Carcinoma.

Background/Aim: There are few reports about the administration of nivolumab plus ipilimumab to hemodialysis patients and their efficacy and safety have not been established yet. Case Report: A 74-year-old male, who was receiving hemodialysis, was presented with metastatic renal cell carcinoma (mRCC). Two years later, more metastases were found, hence, immunotherapy involving nivolumab plus ipilimumab was initiated. After two doses of immunotherapy, interstitial pneumonia was observed. Thus, steroid pulse therapy was administered immediately. Subsequently, computed tomography (CT) findings and symptoms improved markedly. One month later, a CT scan showed a nodular shadow and an air cavity. A fungal infection was strongly suspected, so an antifungal drug was administered. Conclusion: Combination immunotherapy with nivolumab plus ipilimumab was demonstrated to be effective in a hemodialysis patient with mRCC.

Validation of the Effectiveness of Neutrophil-to-lymphocyte Ratio (NLR) as a Predictive Factor in Patients Undergoing Prostate Biopsy With Prostate Specific Antigen (PSA) Between 4.0 and 10.0 ng/ml.

BACKGROUND/AIM: This study aimed to access the effectiveness of serum neutrophil-to-lymphocyte ratio (NLR) in patients undergoing prostate needle biopsy with a prostate specific antigen (PSA) between 4.0 and 10.0 ng/ml. PATIENTS AND METHODS: A total of 633 cases were eligible. We evaluated several factors including age, PSA, PSA-density (PSAD), platelet-to-lymphocyte ratio (PLR) and NLR in the presence or absence of prostate cancer (PCa), retrospectively. We evaluated statistically the associations between each factor and pathological findings or Gleason score. RESULTS: A total of 201 were evaluated in this study. Regarding the presence or absence of prostate cancer, there were statistically significant differences in age, PSA levels, PSAD, the PLR and NLR. The mean NLR value of the patients with PCa was significantly lower compared to the entire cohort. Multivariate analysis showed that age, PSAD, and NLR were independent risk factors predicting PCa. CONCLUSION: For patients having a PSA between 4.0 and 10.0 ng/ml, NLR was a predicting factor of PCa prior to prostate needle biopsy and an effective biomarker and useful tool for avoiding unnecessary biopsies.

Expression of cancer/testis antigens in prostate cancer is associated with disease progression.

BACKGROUND: The cancer/testis antigens (CTAs) are a unique group of proteins normally expressed in germ cells but aberrantly expressed in several types of cancers including prostate cancer (PCa). However, their role in PCa has not been fully explored. METHODS: CTA expression profiling in PCa samples and cell lines was done utilizing a custom microarray that contained probes for two-thirds of all CTAs. The data were validated by quantitative PCR (Q-PCR). Functional studies were carried out by silencing gene expression with siRNA. DNA methylation was determined by methylation-specific PCR. RESULTS: A majority of CTAs expressed in PCa are located on the X chromosome (CT-X antigens). Several CT-X antigens from the MAGEA/CSAG subfamilies are coordinately upregulated in castrate-resistant prostate cancer (CRPC) but not in primary PCa. In contrast, PAGE4 is highly upregulated in primary PCa but is virtually silent in CRPC. Further, there was good correlation between the extent of promoter DNA methylation and CTA expression. Finally, silencing the expression of MAGEA2 the most highly upregulated member, significantly impaired proliferation of prostate cancer cells while increasing their chemosensitivity. CONCLUSIONS: Considered together, the remarkable stage-specific expression patterns of the CT-X antigens strongly suggests that these CTAs may serve as unique biomarkers that could potentially be used to distinguish men with aggressive disease who need treatment from men with indolent disease not requiring immediate intervention. The data also suggest that the CT-X antigens may be novel therapeutic targets for CRPC for which there are currently no effective therapeutics.

Treatment outcomes of sorafenib for first line or cytokinerefractory advanced renal cell carcinoma in Japanese patients.

The objective of the present study was to document the treatment efficacy and safety of sorafenib in Japanese patients with advanced renal cell carcinoma (RCC). A retrospective analysis of 50 consecutive patients with metastatic RCC between January 2005 and December 2009 was carried out. Patients received sorafenib after failed cytokine therapy or first-line sorafenib treatment. All received 400 mg of sorafenib orally twice daily. Five of 14 patients with bone metastases were also given bisphosphonates. Tumor response was evaluated every 1-2 months according to the Response Evaluation Criteria in Solid Tumors. Adverse events (AE) were evaluated at each visit during and after treatment, and were recorded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 3.0. Dose modification of sorafenib was permitted if grade 3 or 4 AE occurred. Treatment continued until disease progression or treatment intolerance occurred. Partial response, and stable disease as best objective responses were observed in 11 (22%) and 23 (46%) patients, respectively. Median progression-free survival was 7.3 months and median overall survival was 11.9 months. All patients experienced AE and one or more grade 3/4 AE occurred in 43 of 50 (86%) patients. Although it requires close monitoring, sorafenib treatment seemed to be effective in the present study population.