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Background Docetaxel is first-line chemotherapy for castration-resistant prostate cancer (CRPC), but most patients acquire docetaxel resistance. CD44 has been shown to be involved in drug resistance of cancers including prostate cancer. We hypothesized that CD44 in serum exosomes could be a diagnostic marker for docetaxel resistance in CRPC patients. In this study, we examined CD44 protein and mRNA expression in cell lysates and exosomes isolated from prostate cancer cells, evaluated the effect of CD44v8-10 knockdown on docetaxel sensitivity and measured CD44 mRNA copy numbers contained in serum exosomes in prostate cancer patients. Materials and methods Docetaxel-sensitive PC-3 prostate cancer cells and docetaxel-resistant PC-3R cells established previously from parental PC-3 cells were used. CD44v8-10 knockdown was performed by siRNA transfection. Blood was collected from 50 docetaxel-naïve and 10 docetaxel-resistant patients and 15 control males. CD44 protein expression was evaluated by Western blotting. CD44 mRNA expression was measured by RT-digital PCR. Results The levels of CD44v8-10 protein and mRNA in cell lysates and exosomes were higher in PC-3R cells than in PC-3 cells. CD44v8-10 knockdown significantly increased docetaxel sensitivity of PC-3R cells. The CD44v8-10 mRNA copy numbers in serum exosomes were higher in docetaxel-resistant patients than in docetaxel-naïve patients and control males (median 46, 12 and 17 copies/mL serum, respectively, P = 0.032). In contrast, the serum exosomal mRNA copy numbers of CD44 standard isoform (CD44s) were not different among 3 groups (median 25, 14 and 13 copies/mL serum, respectively, P = 0.150). Conclusions CD44v8-10 may be involved in docetaxel resistance in prostate cancer and serum exosomal CD44v8-10 mRNA could be a diagnostic marker for docetaxel-resistant CRPC., Cell biology; Molecular biology; Cancer research; Chemotherapy; Urology; Castration-resistant prostate cancer, CD44, Docetaxel resistance, Exosomes, Diagnostic marker

Castration-refractory prostate cancer (CRPC) is treated with taxane-based chemotherapy, but eventually becomes drug resistant. It is thus essential to identify novel therapeutic targets for taxane resistance in CRPC patients. We investigated the role of the chemokine (C-C motif) receptor 1 (CCR1) and its ligand, chemokine (C-C motif) ligand 5 (CCL5), in taxane-resistant CRPC using paclitaxel-resistant prostate cancer cells (PC3PR) established from PC3 cells. We found that the expression levels of CCR1 mRNA and protein were up-regulated in PC3PR cells compared to PC3 cells. In order to investigate the role of increased CCR1 in PC3PR cells, we stimulated cells with CCL5, one of the chemokine ligands of CCR1. In CCL5-stimulated PC3PR cells, siRNA-mediated knockdown of CCR1 expression reduced phosphorylation of ERK1/2 and Rac1/cdc42. Furthermore, CCR1 knockdown and MEK1/2 inhibition decreased CCL5-stimulated secretion of MMPs 2 and 9, which play important roles in cancer cell invasion and metastasis. In the Matrigel invasion assay, knockdown of CCR1 and inhibition of the ERK and Rac signaling pathways significantly decreased the number of invading cells. Finally, the serum CCL5 protein level as measured by ELISA was not different among the three groups of patients: those with negative prostate biopsy, those at initial diagnosis of prostate cancer, and those with taxane-resistant prostate cancer. These results demonstrated for the first time that the interaction of CCR1 with CCL5 caused by increased expression of CCR1 promotes invasion of PC3PR cells by increasing secretion of MMPs 2 and 9 and by activating ERK and Rac signaling. Our findings suggest that CCR1 could be a novel therapeutic target for taxane-resistant CRPC.

Our aim was to provide nomograms that allow urologists to easily calculate a nonmuscle invasive bladder cancer patient’s risk of recurrence and progression. We retrospectively analyzed 800 nonmuscle invasive bladder cancer patients newly diagnosed between 1991 and 2001 from the Gifu urothelial cancer registry program. We developed the nomogram using the original 500 patients and validated it using the remaining 300 patients. The prognostic factors of recurrence and progression were identified by multivariate analysis in 500 patients. In the multivariate analysis, tumor number, shape, grade, and intravesical instillation were associated with recurrence-free survival. Tumor shape and grade were associated with progression-free survival. Six factors for recurrence and three factors for progression were used to make the nomogram. Using the original 500 patients who were modeled for the nomogram, the areas under the receiver operating characteristic curves (AUCs) were calculated to be 0.61 for recurrence and 0.71 for progression. To validate nomogram performance, we applied an additional 300 patients to the nomograms. The AUCs were 0.57 for recurrence and 0.67 for progression. The nomograms that have been developed can be used to predict the probability of recurrence and progression of nonmuscle invasive bladder cancer.

To identify predictive markers for biochemical failure after radical prostatectomy in patients with clinically confined prostate cancer.Immunohistochemistry of bcl-2, p53, Ki-67, and caveolin-1 was performed in samples of paraffin-embedded prostate cancer from 119 Japanese patients. The clinicopathologic significance of staining with these markers was analyzed in relation to biochemical failure (prostate-specific antigen [PSA]0.2 ng/mL).Univariate analysis showed the pretreatment PSA level (P = 0.03), postoperative Gleason score (P = 0.04), pathologic stage (P0.001), seminal vesicle invasion (P0.001), p53 staining (P0.001), Ki-67 staining (P = 0.04), and caveolin-1 staining (P0.0001) to be associated with biochemical failure. Multivariate Cox proportional hazards modeling showed that pretreatment PSA in group A (clinicopathologic parameters), caveolin-1 staining in group B, biomarkers, and the combination (group C) were independently associated with prediction of biochemical failure. The accuracy rate of each group was 76.2% (group A), 75.1% (group B), and 83.1% (group C), respectively.The combination of clinicopathologic parameters and biomarkers (group C) showed the highest accuracy rate. Caveolin-1 staining is an independent predictor of biochemical failure after radical prostatectomy.

Aim: Two-thirds of patients with a gray-zone prostate-specific antigen (PSA) level undergo unnecessary biopsy. Sensitivity is not yet sufficient to permit the use of modified PSA parameters or magnetic resonance (MR) imaging alone for prostate cancer screening. Thus, we evaluated the combination of MR imaging and PSA density (PSAD) for specificity and sensitivity. Methods: During the period April 2004 through March 2006, 185 patients with a PSA level of 4.0–10.0 ng/mL underwent MR imaging and transrectal ultrasonography-guided 8-core biopsy (systemic sextant biopsy of the peripheral zone plus two cores of transition zone). All MR images were interpreted prospectively by two radiologists. An image was considered positive for prostate cancer if any feature indicated a cancerous lesion. Receiver operating characteristic (ROC) curves were used to compare the usefulness of the PSA level, PSAD and PSA transitional zone density (PSATZ) for the detection of prostate cancer. Results: Of the 185 patients, 62 had prostate cancer. Sensitivity and specificity of the axial T2-weighted MR imaging findings for cancer detection were 79.0% and 59.4%, respectively. The area under the ROC curve was 0.590 for the PSA level, 0.718 for PSAD and 0.695 for PSATZ. MR imaging findings and PSAD were shown by multivariate analysis to be statistically significant independent predictors of prostate cancer (P

背景：二次性副甲状腺機能亢進症（SHPT）に対するマキサカルシトール（OCT）長期使用に関する報告は稀である．対象と方法：副甲状腺ホルモン（iPTH）が200pg/mLより高く，補正Ca（cCa）が11.5mg/dL未満の血液透析患者70例を対象とした．OCTは週3回，24週間投与された．OCT投与量は1週置きの最初の投与日のiPTHとcCaの値で調整された．24週での評価後，患者はSHPTに対するOCTまたはインターベンション治療が続けられた．約5年後，主治医へのアンケートにより患者の状態が評価された．結果：最初の24週間投与後に，31例（44.3％）でiPTHが200pg/mL以下になり，27例（38.6％）でiPTHが試験前の50％以下に減少した．11例に高Ca血症を認め，それは治療開始前のcCaと相関した（p＝0.0003）．予後調査では，27例が死亡，2例が腎移植を受け，2例が転院後不明であった．5例で副甲状腺摘除術が実施されていた．2006年12月末で，24週投与終了時と比較して，iPTHは有意に低下，cCaは有意に上昇，血清Pは変化を認めなかった．調査の直近6か月では，21例でOCT療法が維持されていたが，8例では中止されていた．この2群を比較した場合，2006年12月末の検査値ではiPTHのみに有意差を認めた．結語：これらの所見はある一部の症例においてはOCTの長期使用がSHPTの治療に有用であることを示唆している．

Vinexinbeta is an adaptor protein supposed to play pivotal roles in cell adhesion, cytoskeletal organization and signaling. Vinexinbeta is reported to be phosphorylated by extracelluler signal-regulated kinase (ERK) and the phosphorylation has been shown to be involved in cell adhesion, migration and growth. However, physiological function as well as pathophysiological relevance of vinexinbeta in cancer cells is almost unknown.By use of biochemical and cell biological techniques, we analyzed the effects of overexpression or RNAi-mediated silencing of vinexinbeta on the growth and paclitaxel sensitivity in a prostate cancer cell line PC-3.Vinexinbeta was highly expressed in androgen-independent prostate cancer cell lines, PC-3 and DU145, but not in androgen-dependent LNCaP cells. We established two PC-3 cell lines, PC-3/Vinbeta#1 and #2, overexpressing GFP-tagged vinexinbeta and found that growth rate of these lines was significantly increased compared to a mock-transfected cell line. In addition, we found that PC-3/Vinbeta#1 and #2 became resistant to the treatment with 100 nM paclitaxel for 48 h. On the other hand, when siRNA-mediated vinexinbeta gene silencing was performed, PC-3 cell growth was suppressed. In addition, by vinexinbeta silencing, PC-3 cells became significantly sensitized to 10 nM paclitaxel treatment for 48 h.Vinexinbeta plays an important role in PC-3 cell growth, and abrogation of vinexinbeta may be effective for therapeutic cell death and enhanced chemotherapy sensitization in androgen-independent prostate cancer cells.

Background. There are few studies on coinfection with genital mycoplasmas and ureaplasmas in men with gonococcal urethritis (GU). The role of these species in postgonococcal urethritis (PGU) is poorly understood. Thus, we conducted a study to determine the prevalence of coinfection with genital mycoplasmas and ureaplasmas among men with GU and to assess the role of these pathogens in PGU. Methods. Three hundred ninety men infected with culture-confirmed Neisseria gonorrhoeae participated in the study. Chlamydia trachomatis, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma parvum biovar 1, and Ureaplasma urealyticum biovar 2 in first-voided urine samples were detected by polymerase chain reaction-based assay at the patients' initial visits. PGU was judged to be present if the urethral smear was positive for polymorphonuclear leucocytes 7-14 days after treatment for gonorrhea. The association between each microorganism and PGU, measured by the odds ratio, was estimated by multivariate logistic regression analysis. Results. C. trachomatis, M. genitalium, M. hominis, U. parvum biovar 1, and U. urealytiucm biovar 2 were detected in 85 (21.8%), 16 (4.1%), 8 (2.1%), and 33 men (8.5%), respectively. In patients with chlamydia-negative GU, coinfection with M. genitalium was associated with a 14.54-fold greater risk of PGU (95% confidence interval, 2.91-72.74), and coinfection with U. urealyticum biovar 2 was associated with a 3.64-fold greater risk of PGU (95% confidence interval, 1.24-10.63). Conclusions. Coinfection with M. genitalium or U. ureaplasma biovar 2 in men with GU was significantly associated with PGU, independent of C. trachoamtis. Men with GU should be treated presumptively with antibiotics that are active against C. trachomatis, M. genitalium, and U. urealyticum biovar 2.

OBJECTIVES To simultaneously analyze multiple biologic markers to identify strong prognostic markers for disease-specific survival of patients with clear cell renal cell carcinoma (ccRCC). METHODS The expression of Ki-67, p53, bcl-2, cyclin-D1, caveolin-1, vascular endothelial growth factor, and HER-2 was evaluated in 119 paraffin-embedded ccRCC specimens using immunohistochemistry. The clinical significance of these markers in relation to disease-specific survival was analyzed. RESULTS On univariate analysis, high-level staining for Ki-67 (P

Data from the Japanese Urological Society showed that, in Japan, almost half of patients with localized prostate cancer are treated with hormone therapy (HT), regardless of disease stage, and that radiation therapy (RT) is also widely used to treat high-risk patients. A retrospective study was undertaken in Japan to evaluate the potential benefits of using primary HT in locally advanced prostate cancer. Of 628 patients in the study, 63.5% were treated with combined androgen blockade (CAB; luteinizing hormone-releasing hormone agonists plus an antiandrogen) and 36.5% with medical or surgical castration. CAB treatment was significantly better than hormone monotherapy for disease-specific survival. The results also showed that, even if a patient is classified as 'high-risk', a good prognosis could normally be predicted based on certain variables: if their initial prostate-specific antigen (PSA) level was < or = 20 ng/mL, their Gleason score was < or = 6, and their nadir PSA decreased to < or = 0.2 ng/mL within 6 months of HT. In this subgroup of 'good responders', any treatment, be it prostatectomy, RT or CAB, is likely to be effective. However, in 'poor responders', combined therapies with CAB and high-dose rate brachytherapy are likely to be needed for a clinical response. While HT is effective, it might be associated with a reduction in the patient's quality of life (QoL) due to adverse effects, e.g. a reduction in sexual function. Results from the analysis of QoL questionnaires completed by men of different ages with prostate cancer found that only sexual function, and not other QoL variables, in men aged 50-59 years appeared to be reduced in men who had HT, compared to age-matched controls.

Objectives Docetaxel is used as the first-line chemotherapy for castration-resistant prostate cancer (CRPC), but docetaxel resistance occurs in part owing to induction of P-glycoprotein (P-gp) encoded by multidrug resistance protein 1 (MDR1) gene. A recently developed taxane—cabazitaxel—has poor affinity for P-gp and is thereby effective in docetaxel-resistant CRPC. It has been recently demonstrated that exosomes in the body fluids could serve as a diagnostic marker because they contain proteins and RNAs specific to the cells from which they are derived. In this study, we aimed to investigate if P-gp in blood exosomes could be a marker to diagnose docetaxel resistance and select a taxoid for patients with CRPC. Methods and materials Exosomes were isolated by differential centrifugation from docetaxel-resistant prostate cancer (PC-3) cells (PC-3R) and their parental PC-3 cells and from the serum of patients. Silencing of P-gp was performed by small interfering RNA transfection. Protein expression was examined by Western blot analysis. Viability of cells treated with docetaxel or cabazitaxel was determined by water soluble tetrazolium salt (WST) assay. Results The level of P-gp was higher in exosomes as well as cell lysates from PC-3R cells than in those from PC-3 cells. Cabazitaxel effectively killed PC-3R cells, and MDR1 knockdown improved the sensitivity of PC-3R cells to docetaxel but not to cabazitaxel. The P-gp level in blood exosomes was relatively higher in clinically docetaxel-resistant patients than in therapy-naive patients. Conclusions Our results suggest that detection of P-gp in blood exosomes, which is involved in resistance to docetaxel but not to cabazitaxel, could be useful to diagnose docetaxel resistance and select an appropriate taxoid for patients with CRPC—docetaxel or cabazitaxel.

A 62-year-old Japanese man had been suffering from dysuria since January 2011. Since symptoms persisted regardless of antibiotics therapy at a urological clinic, he consulted our clinic in February 2011. Digital rectal examination revealed a large irregular and stony hard prostatic mass, with the serum prostated specific antigen (PSA) of 2.76 ng/ml. T2-weighted magnetic reasonance imaging showed diffuse hypointensity and sharp margin in prostatic peripheral zone. Transperineal biopsy of the prostate was performed in March 2011. Considering histopathological findings of tumor cells in all specimens combined with positive immunoreactivity of neoplastic cells to chromogranin A but negative immunoreactivity to PSA, we diagnosed him with small cell carcinoma. The whole body computed tomography showed no metastatic lesion, he was diagnosed with small cell carcinoma of the prostate at clinical stage T2cN0M0. He received 4 cycles of chemotherapy (cisplatinum and etoposide) and underwent external beam radiotherapy to the pelvis and prostate, up to a total dose of 64 Gy. The urologic and radiologic outcomes including the serum levels of neuron-specific enolase and pro-gastrin releasing peptide have been satisfactory after more than 3 years of follow-up.

Aim: A retrospective review of patients with localized and locally advanced prostate cancer was performed to evaluate the efficacy of primary hormonal therapy and predict long-term prognosis in these patients. Methods: A total of 628 patients who were diagnosed with stage T1c to T3 prostate cancer were treated with primary hormonal therapy at participating institutions. The patients were classified based on pretreatment prostate-specific antigen (PSA) level, Gleason score, and time to nadir PSA level. Disease-specific and progression-free survival rates were investigated, and compared among the subgroups. Results: The mean age of patients was 74.5 years, and median pretreatment PSA level was 14.0 ng/mL. A total of 399 patients (63.5%) were treated with combined androgen blockade (CAB), and 229 patients (36.5%) were treated with castration monotherapy. The disease-specific survival rate of all 628 patients was 89.1% at 8 years. The group that showed a good response to primary hormonal therapy (Group G, pretreatment PSA level ≤20 ng/mL, Gleason score ≤7, and time to nadir PSA ≤6 months) accounted for approximately one-third of the total number of T1c–T3 patients. Disease-specific and progression-free survival rates at 8 years in Group G were 98.9% and 82.0%, respectively. These rates increased to 100% and 87.3%, respectively, in patients receiving CAB treatment in Group G. Conclusions: The results indicate the usefulness of primary hormonal therapy, especially CAB treatment, for patients showing a good response to hormonal therapy in long-term control of localized and locally advanced prostate cancer.

PURPOSE The purpose of the present paper was to evaluate clinical factors responsible for recurrence and prognosis of superficial bladder cancer. SUBJECTS AND METHOD We reviewed date from 800 patients who were initially treated between 1991 and 2000. Recurrent and prognostic factors were examined with univariate and multivariate analysis. Kaplan-Meier Method and log rank test were used for comparing the significance of recurrence free curve and survival curve. Cox's proportional hazard model was used for univariate and multivariate analysis. A 5% level of significance was used for all statistical testing. RESULTS Of 800 cases 282 patients (35.2%) had recurrence and 27 patients (3.4%) were died in during follow up. Progression was defined as the development of muscle invasion or metastasis, progression were noted on 10 metastasis cases and 16 muscle invasion cases. Univariate analysis revealed that tumor numbers, shape, size, stage and grade were significant recurrent and prognostic factors. Multivariate analysis revealed that tumor numbers (P

Exosomes have been demonstrated to be useful non-invasive biomarkers for several cancers including prostate cancer. Since normal cells also secrete exosomes, isolation of cancer-derived exosomes from blood is a prerequisite for their better understanding. The aim of this study is to establish the method for isolation of prostate cancer-related exosomes from blood.Exosomes were collected from prostate cancer LNCaP and PC-3 cell lines by ultracentrifugation and by using magnetic beads conjugated with anti-CD9 antibody and anti-prostate-specific membrane antigen (PSMA) antibody. Prostate cancer-related exosomes were also isolated from the plasma of prostate cancer patients by anti-PSMA beads. Isolated exosomes were analyzed by western blotting.Exosomes were isolated from LNCaP cells by ultracentrifugation, contained PSMA and androgen receptor (AR). AR was also detected in exosomes isolated from LNCaP cells by anti-PSMA and anti-CD9 beads, showing that AR is present in prostate cancer-related exosomes. The amount of CD9 in isolated exosomes was much higher in advanced and chemo-resistant prostate cancer patients than in prostate cancer patients without metastasis and healthy volunteers, indicating that patients with aggressive prostate cancer exhibit higher levels of prostate cancer-related exosomes in blood.The immunoaffinity-based method we developed is capable of isolating prostate cancer-related exosomes from blood, the use of which will enhance investigation processes on exosomes in prostate cancer.

We report two cases of left ureteral carcinoma that may have been related to prior radiotherapy and anticancer chemotherapy for stage II testicular seminoma. Both patients had undergone radiotherapy (60 Gy) and cisplatin-based chemotherapy, one 17 years before the present presentation and the other 24 years earlier. They underwent retroperitoneoscopy-assisted left nephroureterectomy under a diagnosis of left upper ureteral cancer, established by means of ureteroscopy and brush biopsy. The urologic and radiologic outcomes have been satisfactory after more than 2 years of follow-up. Recently, some investigators have reported that testicular cancer survivors are at significantly increased risk of solid tumors for at least 35 years after treatment. Young patients may have a high risk of cancer when they reach an advanced age.

Thirty-five patients with prostate cancer were examined for micrometastases to the bone marrow using reverse transcription-polymerase chain reaction (RT-PCR) with primers specific for the prostate-specific antigen (PSA) gene. Of nine patients with bone metastases detectable by bone scan imaging, five patients had PSA mRNA expression in the bone marrow detectable by RT-PCR. Of 26 patients with negative bone scan findings, seven patients had PSA mRNA expression detectable in the bone marrow. RT-PCR could detect micrometastatic prostate cancer cells in the bone marrow that were not detectable by bone scan imaging. Of 16 patients with a serum PSA concentration of 25 ng ml(-1) or greater, only nine (56.3%) had bone metastases detected by bone scans. Of the remaining seven patients, five had micrometastases to the bone marrow detected by RT-PCR. Overall, 14 of 16 patients (87.5%) with a serum PSA concentration of 25 ng ml(-1) or greater had metastatic bone diseases including bone marrow micrometastases. Of 19 patients with a serum PSA concentration of less than 25 ng ml(-1), two (10.5%) had only micrometastatic disease detected by RT-PCR. A significant correlation was observed between the incidence of bone involvement and the serum PSA concentration. This study suggests that RT-PCR will potentially develop into a relevant tool to assess bone involvement including bone marrow micrometastases and establish a precise correlation between serum PSA concentration and metastatic bone disease in patients with prostate cancer. Images Figure 1

Blood accessの血栓除去に対し, new type Fogarty器質化血栓除去 (Adherent Clot) カテーテルを使用し, 本カテーテルの有用性を基礎的, 臨床的に検討した. balloon catheterもAdherent Clot catheterのどちらも, 兎大動脈に対する血管内膜への傷害は, 肉眼的にも組織学的にも認められなかった. また, 臨床における摘出血栓の剥離面には, 血管成分は含まれていなかった. 臨床におけるAdherent Clot catheterは, 器質化血栓除去において有用であった. 動物実験, 臨床例とも術中, 血管損傷およびカテーテルトラブルは認められなかった.Adherent Clot catheterは透析症例におけるシャント血栓除去において有用であり, balloon catheterと併用することにより, より確実な血栓除去が可能である.

Although information on the states of androgen receptor (AR) expression at the individual cell level is essential in understanding the human diseased prostate, histological approaches are often hampered by the artifactual loss of AR or AR antigenicity. Here we examined the effects of various antigen retrieval methods, including microwave irradiation and autoclave treatment, for immunohistochemical detection of AR in cultured LNCaP cells and paraffin embedded sections of human prostate, and found beneficial effects of autoclave treatment over microwave treatment. Staining results were consistent with that of AR messenger RNA expression assessed by the reverse transcriptase-polymerase chain reaction method. The procedures described in this article provided intense and reproducible immunostaining for AR, estrogen receptor and progesterone receptor in paraffin sections of the human diseased prostate. Finally, 0.01M EDTA (pH7.4) gave us the most intense nuclear signal for the steroid hormone receptors, though the best soaking solution was 0.01M citrate buffer (pH6.0) considering the lost of tissue morphology., Acta Histochemica et Cytochemica, 29(4), pp.311-318; 1996

To understand the role of estrogen in the pathogenesis of benign prostatic hyperplasia, expressions of estrogen receptor (ER) mRNA and ER protein by in situ hybridization and by immunohistochemistry, respectively, were investigated in human prostatic tissues. In non-malignant region, ER mRNA and ER protein were found in cytoplasm and nucleus, respectively, of stromal cells, but not in glandular epithelial and basal cells. In benign regions, ER mRNA/ER protein positive cells were found in fibromyoadenomatous and myoadenomatous hyperplasia, but not in adenomatous hyperplasia. A striking feature was periacinar arrangement of ER mRNA/ER protein positive stromal cells in all prostate carcinoma treated with androgen withdrawal. The ER mRNA/ER protein positive cells were immunohistochemically identified as fibroblasts, myoblasts, and smooth muscle cells. These results indicate that stromal cells are the primary target of estrogen in prostate, and that androgen withdrawal upregulates the expression of ER gene.

We report an unusual case of a 14-year old boy who presented with proteinuria and pyuria detected in a medical checkup at school. After denial of kidney disease, computed tomography of the pelvis showed a bladder stone with an internal low density and urethroscopy showed an odd stick at the prostatic urethra. Because of the failure of removal by the transurethral technique, he underwent suprapubic cystostomy against the foreign body stuck into the prostatic urethra. After surgery, he admitted that he had self-introduced a sewing instrument into the bladder for the purpose of masturbation one year three months previously.

Prostatic stromal tumor of uncertain malignant potential (STUMP) is a rare neoplasm characterized by an atypical, unique stromal proliferation of the prostate. Two patients consulted our hospital with the complaint of urinary retardation. We performed holmium laser enucleation of the prostate since by digital rectal examination, magnetic resonance imaging and needle biopsy suggested benign prostatic hyperplasia. The pathologic examination of the surgical specimens revealed prostatic STUMP. Urologic and radiologic examinations have revealed no abnormalities after more than 2 years of follow-up.

We studied a relationship between in vitro sensitivity of the tumors to anti-cancerous drugs and histopathological effectiveness of an intra-arterial infusion chemotherapy in 15 patients with bladder cancers. The in vitro sensitivity test was performed by measuring intra-cellular ATP contents (ATP assay). The intra-arterial chemotherapy were performed by injecting methotrexate (MTX), adriamycin (ADM) and eisplatin (CDDP) from the internal iliac artery. When the intra-cellular ATP contents of the tumor cells treated with an anti-cancerous drug decreased to less than 50% of the untreated tumor cells, the tumor was evaluated as sensitive to the drug. The effectiveness of the chemotherapy were histopathologically evaluated by a pathologist according to the response criteria for bladder cancer treatment. When the histopathological responses of higher than grade 2 were observed in the tumor, the chemotherapy was evaluated as effective. In 8 of 9 tumors sensitive to ADM, chemotherapy were effective histopathologically and in all 6 tumors resistant to ADM, histopathological response of the chemotherapies were poor. The overall coincidence ratio between sensitivity to ADM and the histopathological effectiveness of the chemotherapy was 93%, showing statistically significant correlation. In 7 of 12 tumors sensitive to CDDP, the chemotherapies were effective and in 2 of 3 tumors resistant to CDDP, the chemotherapies were ineffective. Although the overall coincidence ratio between the sensitivities to CDDP and chemotherapeutic effectiveness was 60%, there was no significant correlation between them. In 7 of 8 tumors sensitive to both of ADM and CDDP, the chemotherapies were effective and in 6 of 7 tumors resistant to at least one of them, the chemotherapies were ineffective. (ABSTRACT TRUNCATED AT 250 WORDS)

We retrospectively reviewed the records of 35 patients with penile cancer, who had been treated at Gifu University Hospital and its affiliated hospitals between July 1994 and January 2009. The mean values of follow-up periods, ages, serum squamous cell carcinoma levels and maximum diameters of the tumor were 23.7±28.0 months, 72.3±10.5 year-old, 4.5±4.3 ng/ml, and 4.0±2.6 cm, respectively. Systemic chemotherapy and local radiotherapy were performed in six, and three cases, respectively. Ten patients died of penile cancer. By univariate analyses, maximum tumor diameter (＜- 4.3 cmvs ＞4.3 cm), T factor (＜T3 vs ＞- T3) and N factor (＜N2 vs ＞- N2) were significantly associated with cancer-specific survival. The five-year survival of stage N2 cases (28.6%) were significantly lower than that of stage N0 and N1 cases (68.4%) (p＝0.0003). By multivariate analyses N factor (＜N2 vs ＞- N2) was significantly associated with cancer specific survival (p＝0.020). We concluded that the development of effective systemic chemotherapy might be crucial to improve the prognosis of patients with metastatic diseases.

Xp11.2/TFE3 translocation renal cell carcinoma (RCC), a recently classified distinct subtype, is a rare tumor that usually affects children and adolescents. The morphology and biological behavior are not widely recognized, Xp11.2 translocation RCC is suggestive of early metastases despite the small tumor size. The definitive diagnosis requires the evidence of several different reciprocal translocations involving the TFE3 gene located on chromosome Xp11.2. Here, we present a case of Xp11.2 translocation RCC in an 18-yearold male. He was referred to our hospital because of a right renal tumor with macroscopic hematuria and right flank colic. The radiographic evaluation including magnetic resonance imaging (MRI) suggested it to be a typical papillary renal cell carcinoma or benign renal tumor. He underwent laparoscopic nephrectomy against the repeat symptom in spite of small tumor (3.5 cm in diameter). The immunohistochemical study revealed nuclear staining for TFE3 protein in the cancer cells. The urologic and radiologic outcomes were satisfactory after more than 1 year of follow-up.

In order to improve the efficacy of chemotherapy against urogenital cancers, we developed a chemosensitivity test by measuring intracellular ATP in cancer cells. In the fundamental experiments using HeLa cells, a significant correlation was observed between intracellular ATP levels and numbers of viable cells. We employed 8 drugs, ADM, VCR, VLB, MTX, 5-FU, PEP, MMC, and CDDP for the assay Thirty-four renal tumors, 68 urothelial tumors and 19 testicular tumors were tested, and evaluable results were obtained in 25 specimens of renal tumors (76%) 55 specimens of urothelial tumors (80%) and 17 specimens of testicular tumors (98%). According to the ATP assay, renal tumors were sensitive to ADM and MMC, urothelial tumors to ADM, MMC and CDDP and testicular tumors to ADM and MMC. The ATP assay to determine the chemosensitivity to clinical specimens was sensitive and efficient. Thus the ATP assay could be applied for selection of anticancer drugs in the chemotherapy of urogenital cancers.

The present report describes a 31-year-old Japanese woman with a retroperitoneal cystic mass adjoining below the left kidney. No disseminated tumors were observed, and resection of the tumor only was performed laparoscopically. The surgical specimen showed a well-differentiated papillary mucinous cystadenocarcinoma of the ovarian type. Additional gynecological examination, including positron emission tomography-computed tomography, showed no malignancy at other sites. Recurrence or metastasis has not been observed after more than 1 year of follow-up. Primary retroperitoneal mucinous cystadenocarcinoma is a very rare tumor. Thirty-six and 55 cases have been reported previously in the English and Japanese literature, respectively. The pathogenesis of the disease remains unclear and controversial. A standard treatment has not been established in the literature, and a consistent prognosis has not been reported. Therefore, close post-operative follow-up is strongly recommended.

We prospectively studied the usefulness of chlormadinone acetate (CMA) as an alternative therapy for prostate cancer relapse after combined androgen blockade (CAB) therapy. Sixteen patients with relapsed prostate cancer after treatment with CAB, including surgical or medical castration and nonsteroidal antiandrogens, 80 mg bicalutamide daily or 375 mg flutamide daily, were enrolled. After discontinuing the antiandrogen for evaluating the patient for the antiandrogen withdrawal syndrome, we administered 100 mg CMA daily as alternative antiandrogen and estimated its effect. Four patients showed aor = 50% decline in prostate-specific antigen (PSA) levels and another 4 patients showed a50% decline in PSA levels but residual 8 patients showed no decline in PSA levels. In 8 patients with a decline in PSA levels, the median duration of alternative CMA therapy was 11.4 months. Patients with a PSA level of1 ng/ml at the start of CMA therapy showed the tendency of decline in PSA levels. In contrast, patients with a nadir PSA level ofor = 0.2 ng/ml during pretreatment showed no effectiveness of the alternative CMA therapy. The alternative CMA therapy may be useful in a part of patients with prostate cancer relapse after CAB therapy.

症例は透析歴12年の53歳男性. 眼サルコイドーシスの既往がある. 1990年10月四肢末梢の脱力としびれが出現し, 原因不明のままステロイドパルス療法が奏効した. 1991年4月, 胃部不快感, 微熱を, さらに両肩痛を訴えるようになり, やがてせん妄が出現し, 意識混濁に至った. 意識障害の原因として高カルシウム血症が疑われ, プレドニゾロンとエルカトニンの投与により意識障害と高カルシウム血症がともに急速に改善した. 高カルシウム血症の原因としてサルコイドーシスが疑われ, 前斜角筋リンパ節生検の病理組織診断で証明された.本邦ではサルコイドーシスによる高カルシウム血症は稀であり, 血液透析患者に高カルシウム血症, 意識障害をきたしたサルコイドーシスの報告例は我々が調べた限り文献上認めなかった.

We report a case of prostate cancer that presented initially as an intracranial tumor. Biopsy specimens of the prostate before endocrine treatment were nearly negative immunohistochemically for prostate-specific antigen and the androgen receptors. All metastases including those in the brain expressed neither androgen receptor nor prostate-specific antigen at the protein and mRNA levels. The tumor, which did not respond to the anti-androgen therapy, had an aggressive course. In this case, the androgen-independent growth and rapid progression might be associated with the initial loss of the antigen and androgen characteristics of the prostate.

We retrospectively reviewed the discrepancy in Gleason score between needle biopsy and radical prostatectomy specimens. Specimens from 153 patients who underwent radical retropubic prostatectomy at Gifu University Hospital and 9 community-based institutions between January 2001 and December 2005, were studied. Gleason score was determined by the general pathologist at each institution. The coincidence rate of Gleason score between biopsy and prostatectomy specimens was 49.7%. In contrast, 37.4% of biopsy specimens were undergraded. In biopsy specimens given a Gleason score of 5 or less, the Gleason score was coincident or undergraded compared with prostatectomy specimens. In biopsy specimens given a Gleason score of 6, the coincidence rate was 39.6%. In 56% in biopsy specimens of cancers with a Gleason score of 6 the Gleason score was undergraded compared with the prostatectomy specimen. In this group, extra-prostatic extention was found significantly more often than in other groups (p = 0.04). In patients, who underwent extended biopsy, or had a more positive biopsy core (or = 25%), the coincidence rate was significantly greater (p = 0.03). We should be aware of the limitations of Gleason scores based on biopsy specimens, and give treatment opinions careful consideration.

Fourteen cases of a "floating balls" appearance on imaging studies in a mature ovarian cystic teratoma have been reported in published studies since 1991. Past investigators could not provide an explanation for the true mechanism of the formation of the balls. However, the floating balls occurred in rather large cysts. Because of self-examination, patients with testicular teratoma are usually referred to the hospital when the tumor is of a smaller size than that seen in patients with ovarian teratoma. We report the first case of a floating balls appearance in a testicular teratoma.

A 52-year-old woman was referred to our hospital for treatment of urachal cancer. She complained of supurapubic dull pain and gross hematuria. Computed tomography and magnetic resonance imaging showed a non-papillary sessile tumor, which was located on the dome of the bladder and invaded the small intestine. The tumor was diagnosed as Sheldon's stage IIIC urachal cancer. After three courses of neoadjuvant chemotherapy with FOLFOX4 (oxaliplatin, 5-FU and leukovolin), the tumor was reduced from 7 x 6 cm to 5.5 x 5 cm in size. Consequently, the patient underwent an en-bloc resection of the urachal tumor with the dome of the bladder and the parts of the ileum invaded by the tumor. One course of adjuvant chemotherapy (FOLFOX4) was performed. Surgical specimen revealed histologically well differentiated squamous carcinoma and invasion to the propria of the ileum. The surgical margins were negative for the cancer. For 1.5 years after the surgery, no local recurrence or distant metastasis has been observed.

This study aimed to investigate whether the expression of carbonic anhydrase IX (CAIX) is associated with the expression of vascular endothelial growth factor (VEGF) and whether the co-expression of the two correlates with survival outcome in clear cell renal cell carcinoma (ccRCC). The expression of CAIX and VEGF was evaluated immunohistochemically in 122 paraffin-embedded ccRCC specimens. The clinical significance of these markers in relation to disease-specific survival (DSS) was analyzed. Patients with a low expression of CAIX had a significantly worse prognoses than those with a high expression (p=0.0005). Inversely, patients with a high expression of VEGF had a significantly worse prognoses than the patients with a low expression (p=0.0030). Furthermore, CAIX expression significantly stratified the DSS of patients with high-stage (p=0.0001), high-grade (p=0.0392), low-grade (p=0.0273), metastasis (p=0.0034), no metastasis (p=0.0303) and ECOG-PS=0 (p=0.0003). VEGF expression significantly predicted the survival of patients with low-grade (p=0.0003), high-stage (p=0.0401) and ECOG-PS=0 (p=0.0063). A multivariate Cox regression analysis showed that tumor stage (p=0.0054), metastasis (p=0.0193), ECOG-PS (p=0.0065) and CAIX expression (p=0.0001) were independent prognostic factors of DSS. Since CAIX and VEGF expression correlated inversely (p=0.0032), the prognostic value of the co-expression of CAIX-VEGF was evaluated. Multivariate analysis revealed that the co-expression was an independent prognostic factor of DSS (p=0.0002). In addition, the co-expression was able to stratify DSS into three risk groups: high-risk, intermediate-risk and low-risk (p

An anterior urethral valve is uncommon compared to a posterior urethral valve as a cause of lower obstructive uropathy. Furthermore, an anterior urethral valve in the fossa navicularis is extremely rare. We describe the case in a 6-year-old boy who presented with a split urinary stream. Endoscopy revealed an anterior urethral valve in the fossa navicularis, and we successfully incised the valve with a hook knife. We should consider the possibility of an anterior urethral valve in any child with an abnormal urinary stream.

慢性腎不全による続発性上皮小体機能亢進症13例に対して, 上皮小体全摘術と自家移植術を施行した. 113例は維持血液透析患者10例, CAPD患者3例で, 平均年齢は50.2歳, 平均透析期間は101.8か月であった. 原疾患は慢性糸球体腎炎11例, 多発性嚢胞腎1例, 糖尿病性腎症1例であった. 自覚症状としては骨関節痛を8例に, 掻痒感を5例に認めた. 骨X線検査では全例に上皮小体機能亢進症による骨変化を認めた. 術前に骨型isozyme優位の高ALP血症を12例に, 高C-PTH血症を全例に認めた. 術前に全例に施行した画像診断の部位診断率は頸部CTは48.1%, 超音波検査は61.5%, 201Tl99mTc subtraction scintigramは50%であった. 手術術式は, 上皮小体全摘術および前腕筋膜下へ, 摘出した上皮小体の約30mgを5-6個の細片にして移植した. 全例supernumerary glandsを考慮して両側胸腺舌区の摘除および気管ならびに甲状腺周囲の脂肪織摘除, リンパ節郭清を施行した. 4腺摘出が9例, 5腺摘出が3例, 7腺摘出が1例であった. 測定した12例における摘出総重量は, 平均2,082.5mgであった. 上皮小体の摘出総重量と術前のC-PTH, 血清ALP値との間にそれぞれ相関係数0.807, 0.769の正の相関を認めた. 上皮小体の組織型では, diffuse typeは23腺で平均重量156mgに対し, nodular typeは26腺で平均重量768mgと有意に重かった. 術後自覚症状の改善を10例に認めたが, 3例では不十分であった. 画像診断による術前に腫大した上皮小体の確認と, 術中の迅速標本による確認ならびに胸腺摘除と周囲組織の郭清により, 上皮小体の取り残しを防げた.

We report a case of huge renal arteriovenous malformation treated with superselective endovascular embolization in two treatments using N-butyl-2-cyanoacrylate (Hystoacryl).

A 56-year-old Japanese man consulted a urologist because of urethral bleeding. He had been undergoing hemodialysis for the past 15 years due to polycystic kidney disease. Computed tomography revealed an irregular cyst wall in the left kidney. Since a neoplasm could not be ruled out, we removed the left kidney, by laparoscopic radical nephrectomy after obtaining the patient's consent. Histopathologic diagnosis was renal cell carcinoma. Fourteen months after the operation, urethral bleeding recurred. Further examination of the bladder and the urethra revealed no significant abnormalities. The patient insisted on right nephrectomy. Therefore, laparoscopic radical nephrectomy was performed. Histopathologic diagnosis was also renal cell carcinoma. Renal cell carcinoma in patients with end-stage renal disease is fairly common and is associated with acquired cystic kidney disease. However, renal cell carcinoma associated with polycystic kidney disease is extremely rare.

OBJECTIVES We compared the cancer detection rate of extended 14-core biopsy with that of sextant biopsy to assess whether additional biopsy cores are useful for detection of prostate cancer and to clarify the indications for obtaining additional cores. METHODS Study subjects were 313 patients who underwent transrectal ultrasound-guided 14-core biopsy because of a prostate-specific antigen (PSA) level greater than 4.0 ng/mL and/or abnormalities found on digital rectal examination (DRE). In addition to the standard 6 biopsy cores, 6 lateral cores were obtained as well as 2 transition zone cores. PSA density (PSAD) was determined as the total PSA level divided by the prostate volume as estimated by transrectal ultrasound. RESULTS Prostate cancer was diagnosed in 127 patients (40.6%). In 28 (22%) patients, the cancer would not have been detected by the sextant method alone. Among 211 patients with normal DRE findings, the cancer detection rate with 14-core biopsy was statistically higher than that with 6-core biopsy in the 141 patients with a PSA level of 4.01 ng/mL to 10.0 ng/mL, and 14 (38.9%) of 36 cancers were diagnosed in additional cores only, not in the standard sextant biopsy cores. Among the 141 patients with a gray-zone PSA level, the cancer detection rate with extended biopsy was statistically higher in those with PSAD greater than 0.13 ng/mL. CONCLUSIONS Lateral biopsy should be used in conjunction with sextant biopsy in patients with a PSA level of 4.01 ng/mL to 10.0 ng/mL with normal DRE findings, especially in those with PSAD greater than 0.13 ng/mL.

A retrospective review of patients with localized and locally advanced prostate cancer was performed to evaluate the efficacy of primary hormonal therapy and predict long-term prognosis in these patients.A total of 628 patients who were diagnosed with stage T1c to T3 prostate cancer were treated with primary hormonal therapy at participating institutions. The patients were classified based on pretreatment prostate-specific antigen (PSA) level, Gleason score, and time to nadir PSA level. Disease-specific and progression-free survival rates were investigated, and compared among the subgroups.The mean age of patients was 74.5 years, and median pretreatment PSA level was 14.0 ng/mL. A total of 399 patients (63.5%) were treated with combined androgen blockade (CAB), and 229 patients (36.5%) were treated with castration monotherapy. The disease-specific survival rate of all 628 patients was 89.1% at 8 years. The group that showed a good response to primary hormonal therapy (Group G, pretreatment PSA levelor =20 ng/mL, Gleason scoreor =7, and time to nadir PSAor =6 months) accounted for approximately one-third of the total number of T1c-T3 patients. Disease-specific and progression-free survival rates at 8 years in Group G were 98.9% and 82.0%, respectively. These rates increased to 100% and 87.3%, respectively, in patients receiving CAB treatment in Group G.The results indicate the usefulness of primary hormonal therapy, especially CAB treatment, for patients showing a good response to hormonal therapy in long-term control of localized and locally advanced prostate cancer.

Acute vascular access (VA) obstruction is one of the most common complications for hemodialysis patients and medical professions. We performed early vascular access intervention therapy (VAIVT) to reduce the incidence of acute VA obstruction, VAIVT and fistula reconstruction. During a 2-year period, we performed 125 procedures of VAIVT in 145 cases in 50 patients who underwent arterio-venous fistula angiography. We performed early VAIVT within two weeks since we clinically found VA stenosis. The 125 procedures of VAIVT (95 non-thrombosed cases, 30 thrombosed cases) involved 86 native fistulas (74 non-thrombosed, 12 thrombosed) and 39 graft fistulas (21 non-thrombosed, 18 thrombosed). Prevalence of thrombosed cases was significantly higher in graft fistula than in native fistula (P0.001). The primary patency rate in 50 patients at 6, 12 and 24 months was 62.1, 46.9 and 41.7%, respectively, while the secondary patency rate was 93.7, 90.7 and 86.6%, respectively. The highest primary patency rate was found in the non-thrombosed group with native fistula and the lowest secondary patency rate was found in the thrombosed group with graft fistula. By comparing the results of this study with the events for the previous 2 years, the total VAIVT number was almost the same. The number of non-thrombosed cases increased significantly from 54 to 95, and those of thrombosed cases decreased from 68 to 30 (P0.001). The number of fistula reconstructions significantly decreased from 59 to 22 (P0.001). Early VAIVT for VA stenosis could decrease acute VA obstruction and fistula reconstruction without increasing the total number of VAIVT.

OBJECTIVES To explore the significance of an E-cadherin gene promoter polymorphism for risk and disease severity of prostate cancer in a Japanese population. METHODS We enrolled 200 patients with sporadic prostate cancer and 159 control patients with benign prostatic hyperplasia in this case-control study. The -160C/A polymorphism in the E-cadherin gene promoter was genotyped by polymerase chain reaction-restriction fragment length analysis. RESULTS The C/C, C/A, and A/A genotypes were observed in 58%, 39%, and 3% of patients, respectively, whereas the C/C, C/A, and A/A genotypes were observed in 75%, 25%, and 0.63% of control subjects, respectively. Japanese men carrying the A allele and A/A genotype had 1.88-fold (95% confidence interval [CI], 1.25 to 2.84) and 9.03-fold (95% CI, 1.50 to 172.36) higher risks, respectively, for prostate cancer than did carriers of the C allele and C/C genotype. There was no significant association between the polymorphism and clinical stage or pathologic grade. CONCLUSIONS The presence of the A allele of the -160C/A polymorphism in the E-cadherin gene may be a risk factor for prostate cancer in the Japanese population.

We retrospectively studied patients with clinical stage C-D1 prostate cancer in Gifu University and affiliated hospitals. The overall survival rate of patients treated with hormonal therapy after radical prostatectomy was superior to that of patients treated with hormonal therapy alone. This result was remarkable in the patients under 76 years old with clinical stage C. A PubMed search of the literature on various randomized controlled trials revealed that the overall survival rate of patients treated with hormonal therapy alone was inferior to that treated with adjuvant hormonal therapy. We recommend prospective evaluation of combined therapy including prostatectomy, radiotherapy and hormonal therapy for the patient with a risk factor such as high Gleason score.

Previously, renal arterial aneurysms were thought to be extremely uncommon. However, these lesions are now being detected more frequently as incidental findings on computed tomography (CT) and magnetic resonance imaging (MRI). The incidence of ruptured renal artery aneurysms is very low. A 58-year-old man presented to a physician complaining of left flank pain and was diagnosed as having a left kidney stone. Abdominal CT scan demonstrated a mass in the left renal pelvis. The mass measured 40mm in diameter and showed calcification. The patient was referred to our hospital 5 days after the first attack. Left renal mass was diagnosed as renal aneurysm based on clinical signs and perirenal findings on CT. Emergent endvascular embolization was performed. The postoperative course was uneventful. Hypertension improved after embolization.

The purpose of the present paper was to evaluate clinical factors responsible for recurrence and prognosis of superficial bladder cancer.We reviewed date from 800 patients who were initially treated between 1991 and 2000. Recurrent and prognostic factors were examined with univariate and multivariate analysis. Kaplan-Meier Method and log rank test were used for comparing the significance of recurrence free curve and survival curve. Cox's proportional hazard model was used for univariate and multivariate analysis. A 5% level of significance was used for all statistical testing.Of 800 cases 282 patients (35.2%) had recurrence and 27 patients (3.4%) were died in during follow up. Progression was defined as the development of muscle invasion or metastasis, progression were noted on 10 metastasis cases and 16 muscle invasion cases. Univariate analysis revealed that tumor numbers, shape, size, stage and grade were significant recurrent and prognostic factors. Multivariate analysis revealed that tumor numbers (P0.0001), shape (P = 0.066) and size (P = 0.0178) were significant recurrent factors, and tumor shape (P = 0.0422), size (P = 0.0140) and stage (P = 0.0330) were significant prognostic factors. Of 272 recurrent cases, univariate analysis revealed that tumor shape, stage and grade were significant prognostic factors, and multivariate analysis revealed that tumor shape (P = 0.0164) and stage (P = 0.0017) were significant prognostic factors.We conclude that tumor numbers, shape and size are predictive value in recurrence and tumor shape, size and stage are predictive value in prognosis, and when recurrent case, tumor shape and stage are predictive value.