市川 智彦

BACKGROUND: A novel risk assessment method, Japan Cancer of the Prostate Risk Assessment, has been developed based on database of patients receiving primary androgen deprivation therapy. To investigate the usefulness of Japan Cancer of the Prostate Risk Assessment for non-metastatic, high-risk prostate cancer patients treated with carbon ion radiotherapy plus androgen deprivation therapy. METHODS: Patients with non-metastatic, high-risk prostate cancer (T3, initial prostate specific antigen level ≥20 ng/ml, and/or Gleason score ≥8) were included. The patients were treated with carbon ion radiotherapy (the total dose from 57.6 Gy (relative biological effectiveness)/16 fractions to 66.0 Gy(relative biological effectiveness)/20 fractions), and neoadjuvant as well as adjuvant androgen deprivation therapy for at least 24 months. RESULTS: Four hundred and twenty-six patients were included with the median follow-up of 68.1 months. Of 426, 210 (49.3%), 270 (63.4%) and 251 (58.9%) had Gleason 8-10, prostate specific antigen ≥20 ng/ml and T3, respectively. The 10-year progression-free and cause-specific survival rates in Japan Cancer of the Prostate Risk Assessment 1-2 group (76.5 and 98.9%) were significantly better than those in Japan Cancer of the Prostate Risk Assessment 3-6 group (52.6 and 93.1%), (P < 0.001 and P = 0.044, respectively). The median progression-free survivals in the Japan Cancer of the Prostate Risk Assessment 1-2 and 3-6 groups were 158.9 months and 125.9 months (95% confidence interval: 108.6-143.2 months), respectively. CONCLUSIONS: For non-metastatic, high-risk prostate cancer patients treated with carbon ion radiotherapy plus androgen deprivation therapy, Japan Cancer of the Prostate Risk Assessment score was useful for predicting the progression-free and cause-specific survivals.

OBJECTIVES: To clarify clinical predictors for a prostate-specific antigen decrease ≥50% in response to alternative non-steroidal antiandrogen therapy and to develop a nomogram to predict the prostate-specific antigen decrease ≥50% in response to alternative non-steroidal antiandrogen therapy in patients with advanced prostate cancer that relapsed after initial combined androgen blockade. We previously reported that combined androgen blockade with an alternative non-steroidal antiandrogen is effective for advanced prostate cancer that has relapsed after initial combined androgen blockade. METHODS: We enrolled 161 patients from 14 medical institutions with histologically confirmed prostate cancer who had been treated with combination therapy and in whom cancer progressed after first-line combined androgen blockade therapy. A nomogram for the prostate-specific antigen decrease ≥50% from baseline prostate-specific antigen in response to alternative non-steroidal antiandrogen therapy was developed based on the final logistic regression model. RESULTS: Overall prostate-specific antigen decreased ≥50% in 75 of 161 patients (46.6%) in response to alternative non-steroidal antiandrogen therapy. Using five independent risk factors (initial serum level of prostate-specific antigen, hemoglobin, C-reactive protein, prostate-specific antigen nadir to second hormone therapy and Gleason sum), a nomogram was developed for the prediction of prostate-specific antigen decrease ≥50% in response to alternative non-steroidal antiandrogen therapy. The receiver operating characteristic curve showed that the accuracy of the predicted probability was 72.5% for the model. CONCLUSIONS: This predictive nomogram could predict the prostate-specific antigen decrease ≥50% in response to alternative non-steroidal antiandrogen therapy and might be of benefit to determine the sequential treatment strategy in patients with relapse after first combined androgen blockade.

BACKGROUND: The aim of this study was to retrospectively investigate clinical outcomes by relative dose and dose intensity of docetaxel (DOC) as chemotherapy for Japanese patients with castration-resistant prostate cancer (CRPC). METHODS: A total of 145 CRPC patients who received more than 4 courses of DOC chemotherapy at 14 hospitals between 2005 and 2011 were enrolled. Patients were divided into two groups--those receiving a higher or lower dose (mg/m(2)) or dose intensity (mg/m(2)/week). Differences between the groups regarding treatment outcomes and adverse events (AEs) were determined. Additionally, prognostic factors predictive of cancer-specific survival (CSS) in these patients were identified by both univariate and multivariate analysis. RESULTS: The total patient group underwent a mean of 11.2 ± 7.4 DOC cycles, and the mean CSS after therapy was 15.6 ± 10.1 months. The higher-dose group had a better prostate-specific antigen (PSA) response than the lower-dose group. However, there was no significant difference between the groups in prognosis after DOC chemotherapy. Leukopenia and neutropenia were observed more frequently in the higher-dose group. Serum biomarkers (including PSA, lactate dehydrogenase and alkaline phosphatase), hemoglobin levels and presence of pain at initiation of chemotherapy, as well as the PSA nadir level on first-line hormone therapy, all were significant predictors of CSS. CONCLUSIONS: In the Japanese population, relatively low-dose DOC chemotherapy had no deleterious effect on the CSS of CRPC patients, and a lower incidence of AEs occurred, in spite of a diminished PSA response compared with those receiving a higher dose.

原発性アルドステロン症（primary aldosteronism：PA）は外科的に治癒が期待できる二次性高血圧であり，患側の副腎腫瘍に対する腹腔鏡下副腎摘除術が標準術式である。PAは適切な診断・治療が遅れると高血圧の重症化だけではなく，高アルドステロン血症による心・脳血管障害の発生や腎機能障害の進行など不可逆的な臓器障害に至る可能性がある。スクリーニング検査の発展・普及に伴い早期発見が可能となり，現在では高血圧患者の３～10％程度を占めると報告されている。推定患者数は非常に多くcommon diseaseとも考えられるが，PA診断に必要な検査を行う内分泌内科医や放射線科医が必ずしも各施設に在籍しているとは限らない。本稿ではPA診療ガイドラインに沿いつつ，手術療法の対象となるPA患者の診断・治療および術後のフォローアップに関して，われわれ外科医が診療可能な範囲を意識して述べる。

原発性アルドステロン症は，疾患特有のglomerular hyperfiltrationのため腎機能障害がマスクされており，アルドステロン拮抗薬（MRA）導入後や術後に腎機能障害が顕在化する．今回，術前にMRAを用いてHyperfiltrationを解除した後に腹腔鏡下副腎摘除術を受けた症例98例で， 術前の腎機能障害をeGFR別（eGFR≧90 ml/min/1.73m²：19例，60-89：49例， ＜60：30例） に分け，術後6ヶ月の時点での降圧薬内服中止に関する統計学的検討を行った． 降圧薬内服中止は， 術前eGFR≧90ml/min/1.73m²（14例）：73.7 ％， 術前eGFR60-89（22例）：44.9％，術前eGFR＜60（7例）：23.3％の症例で可能だった．多変量解析で高血圧罹患年数8年未満及び2種類以下の術前降圧薬内服が降圧薬内服中止の予測因子となった．術前eGFRは独立した予測因子になりえなかったが，これは腎機能障害と高血圧との間に強い相関があることが結果に影響していると考えられた．<br> 外科的治療可能な疾患であっても，長期間高アルドステロン血症に暴露されている症例では高血圧の完治は困難であり，高血圧症例のスクリーニングにてPAを早期発見・早期治療することは非常に重要であると考えられた．

Background: We investigated how urinary, sexual, and testicular functions and generic health-related quality of life (HR-QOL) affect each other in aged men. Methods: Ninety patients who were negative for cancer on prostate biopsies were enrolled in this study. The mean patient age was 66 +/- 7 years (mean +/- s.d.). The mean prostate volume was 44.3-21.9 mL, and the mean serum total testosterone (TT) level was 3.63-1.18 ng/mL. Before conducting the prostate biopsies, the patients were asked to complete questionnaires, including the International Prostate Symptom Score (I-PSS), UCLA Prostate Cancer Index (UCLA-PCI), and the Rand Medical Outcome Study 36-Item Short Form (SF-36), to evaluate urinary symptoms, sexual function, and generic HR-QOL. The relationships between these parameters were analyzed. Other objective variables, such as the prostate volume, maximal urinary flow (Q(max)), postvoid residual urine volume, and age, were also evaluated. Results: The TT level was found to be related to the I-PSS Q6 (r= -0.23108, p = 0.03230) and Q(max) (r = 0.44210, p = 0.00073). The mental component summary (MCS) score exhibited a significant negative relationship with the presence of urinary symptoms (sum of I-PSS Q1-7). When each I-PSS question was analyzed separately, nocturia (Q7) was found to have the most significant impact on SF-36; the physical component summary (PCS) and MCS were also worsened by nocturia. The UCLA-PCI sexual function was positively related to the SF-36 MCS, SF-36 PCS, and TT level and negatively related to the I-PSS Q3, Q5, Q6, and Q7. Aging also showed a negative impact on nocturia, sexual function, and the SF-36 PCS. Conclusions: TT levels are correlated with the parameters of urination. Urinary symptoms, sexual function, and generic HR-QOL were found to have close relationships. In the management of the health of aged men, physicians should consider urinary function together with testicular and sexual functions as well as overall QOL.

Purpose: Adrenal vein (AV) sampling (AVS) is the diagnostic gold standard for primary aldosteronism (PA), but right-sided AVS is difficult. We compared detection of AVs by selective retrograde CT adrenal venography (SRCTAV) with digital subtraction angiography (DSA). Materials and methods: Data on 29 subjects (11 males, mean age 55 y) with increased serum aldosterone concentrations (SAC) and a diagnosed right or left aldosterone-producing tumor (APT) by AVS who underwent laparoscopic adrenalectomy were retrospectively analyzed. Before AVS, visualizing AVs was attempted by DSA and SRCTAV (Aquilion). If after the adrenocorticotropic hormone loading test serum cortisol concentration (SCC) from either AV was &gt; 200 mu g/dl, AVS was considered successful. If the SAC/SCC ratio for one side was &gt;= 4 times higher than the other side, we diagnosed a one-sided APT. Results: Left and right AV, respectively, were visualized in 29 (100%) and 22 subjects (76%) by DSA and 29 (100%) and 28 subjects (97%) by SRCTAV, with right-AV detection significantly higher by SRCTAV (p &lt; 0.05). Cannulations were regarded successful in 28 subjects having both AVs observed on SRCTAV but not in the remaining subject whose adrenocortical scintigram was positive, however. Adrenalectomy was performed with a diagnosis of adenoma. Among 28 subjects with successful AVS, histopathological diagnoses included adenoma (25), nodular hyperplasia (2) and normal (1). After adrenalectomy, antihypertensive drug usage in 28 patients was reduced or stopped with decreases in SAC (97%). Conclusions: Detection of AV was significantly higher by SRCTAV than DSA, especially on the right side, in 29 subjects diagnosed with one-sided APT. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

前立腺癌におけるFOXA1の機能解析を行った。FOXA1はARの機能を活性化し、IGFBP-3を介して細胞増殖を制御していることが明らかとなった。また前立腺癌摘出標本においてFOXA1の発現は癌部で有意に高く、PSA値、Gleason score、ARの発現と相関が認められた。さらに、FOXA1の発現が高い症例は有意にPSA再発を認めた。FOXA1は将来、病理学的診断マーカー、および、治療分子標的としての可能性が示唆された。(著者抄録)

OBJECTIVE: Correct interpretation of renal function in patients with primary aldosteronism is difficult before adrenalectomy, because subtle kidney impairment is often masked by glomerular hyperfiltration peculiar to primary aldosteronism. The aim of this study was to investigate postoperative changes in renal function for patients with primary aldosteronism and to identify clinical predictors of chronic kidney disease manifested postoperatively in the patients without pre-existing chronic kidney disease. METHODS: Records of 78 Japanese patients who underwent unilateral adrenalectomy for primary aldosteronism were retrospectively surveyed. Patients who had been followed up for <6 months were excluded. Preoperative and postoperative estimated glomerular filtration rate were compared. Furthermore, uni- and multivariate analyses were carried out to identify clinical predictors for chronic kidney disease manifested postoperatively. RESULTS: Patients with preoperative estimated glomerular filtration rate ≥60 mL/min/1.73 m(2) showed a significant decrease after surgery. Of the 66 patients without pre-existing chronic kidney disease, 24 developed chronic kidney disease postoperatively. Multivariate logistic regression analysis identified a medical history of dyslipidemia as an independent predictor for chronic kidney disease manifested postoperatively. According to univariate analyses, additional factors associated with postoperative manifestation of chronic kidney disease included older age, lower diastolic blood pressure and lower estimated glomerular filtration rate. CONCLUSIONS: The interpretation of normal or abnormal renal functions by examining estimated glomerular filtration rate heightened by hyperfiltration alone can mislead clinicians before adrenalectomy. Clinicians should pay attention to patients at greater risk of a significant decline in postoperative renal function.

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.

OBJECTIVES: To develop and to internally validate a novel nomogram for predicting the stone-free rate after transurethral ureterolithotripsy. METHODS: A total of 412 patients with 534 ureteral stones were treated with transurethral ureterolithotripsy using semi-rigid ureteroscopes. Treatment efficacy was evaluated 3 months after the procedure. Multivariate stepwise logistic regression analysis was used to identify independent predictors of being stone-free in the model-building set. A total of 427 stones (80% of 534) were randomly allocated for identification and statistical analysis to build the model, and the remaining 107 (20%) were used for cross-validation. A nomogram for the stone-free rate was developed based on the final logistic regression model. RESULTS: Stone length, number of stones, stone location and the presence of pyuria were independent factors related to the stone-free rate after transurethral ureterolithotripsy treatment, and these were used to develop a nomogram. In this nomogram, the area under the receiver operating characteristic curve was 0.7432 for the nomogram, 0.5641 for stone size, 0.5908 for the number of stones, 0.6594 for stone location and 0.6076 for pyuria. Validation using 20% of the data also achieved a reasonable predictive accuracy (area under the receiver operating characteristic curve = 0.682). CONCLUSIONS: The first nomogram for predicting the stone-free rate after transurethral ureterolithotripsy was developed. It has a reasonable predictive accuracy, and in combination with extracorporeal shock wave lithotripsy nomograms, it might be useful for deciding treatment methods.

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.

Great advances in tissue androgen analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) have made it possible to evaluate the tissue androgen content from a single needle prostate biopsy specimen. In this study, we investigated if pre-treatment androgen content in prostate biopsy specimens could predict their response to primary androgen deprivation therapy (ADT) and future castration-resistant prostate cancer (CRPC). One-hundred and sixty-five prostate cancer patients who received primary ADT were enrolled. They had received multiple core prostate needle biopsy at diagnosis, and an additional one needle biopsy specimen was obtained for tissue androgen determination using LC-MS/MS. The patients&#039; prostate specific antigen (PSA) values were periodically followed during the treatment and patients were determined to have CRPC when their PSA value increased continuously to 25% above the nadir and a 2.0 ng/mL increase. A significant correlation was found between PSA value decline velocity (PSA half-time) after ADT and pre-ADT tissue androgen content. Twenty-three patients were determined to have CRPC. These CRPC patients had a significantly high concentration of tissue T (p &lt; 0.01) and low concentration of tissue 5α-dihydrotestosterone (DHT) (p &lt; 0.01), resulting in a higher tissue T/DHT ratio (p &lt; 0.001). A multivariate Cox proportional hazard model revealed the pre-ADT tissue T/DHT ratio and Gleason score as independent predictors for CRPC development. By using the two statistically significant variables, the relative risk of CRPC development could be calculated. The results of this study suggest that the evaluation of prostate androgen content in a single needle biopsy specimen may be useful to predict future CRPC development after primary ADT. Further studies are required for the clinical application of T/DHT ratio evaluation. © 2013 American Society of Andrology and European Academy of Andrology.

原発性アルドステロン症（PA）は外科的に治癒が可能な二次性高血圧であるが，全症例で術後降圧薬内服を全て中止することができる訳ではない．今回，当院でPAに対し片側の腹腔鏡下副腎摘除術を受けた102例を対象に術後降圧薬内服に関して統計学的検討を行った．43.1%の症例で術後降圧薬内服を全て中止できた．多変量解析の結果，術前降圧薬内服におけるアルドステロン拮抗薬の割合が0.5以上（オッズ比［OR］10.6；p＜0.01）及び6年以下の高血圧罹患歴（OR5.0；p＜0.01），女性（OR4.0；p＜0.01）が，術後降圧薬内服の中止に関する予測因子となった．多くの文献で，術前降圧薬の種類の少なさ（2種類以下）が予測因子として報告されているが，内服の数だけでなくその内容も検討するとアルドステロン拮抗薬を用いた術前血圧コントロールの重要性が示唆された．

【目的】ロボット支援腹腔鏡下前立腺全摘除術（RALP）の初期治療成績につき検討を行った．<br>  【対象】2011年9月より2012年12月までにRALPを行った120例を対象として検討した．<br>  【結果】平均出血量は85ml，輸血は自己血のみが2例，術中に開腹手術への移行は認めなかった．平均手術時間は273分，平均コンソール時間は204分，術者のラーニングカーブは良好であり20例ほどの経験で安定した手術を行えるようになった．pT2の断端陽性率はdorsal vein complexの無結紮法導入前は40.9％に認めたが，導入後は8.7％と改善を認めた．全体の95.2％がクリティカルパス通りに退院可能であった．尿の禁制率もsafety pad（0-1枚/日）の確率が術後3月，6月で82.1％，100％と良好であった．<br>  【結論】腹腔鏡下前立腺全摘除術の経験はなくともスムーズにRALPの導入，移行ができると考えられた．合併症も少なく，患者にとっても利益の大きい治療であると考えられた．

Angiomyolipomas （AMLs） located in the adrenal region are exceptionally rare. The preoperative diagnosis of AMLs is difficult. <br>  We report our experience with a 68-year-old woman who presented with right-sided back pain. A computed tomography scan showed a 66×45 mm fatty adrenal mass. Hormonal function was within normal limit. Laparoscopic adrenalectomy was performed. Because bleeding occurred from the tumor surface, we decided on an open conversion and removed the tumor together with a part of the normal adrenal gland. The histopathological features confirmed the diagnosis of AML in the adrenal region. The patient made an uneventful recovery and was discharged one week following the operation. <br>  When we perform laparoscopic adrenalectomy for a fatty adrenal tumor, we must handle the tumor considering the possibility of an AML. Additionally, to reduce excessive bleeding, we must use an open conversion in cases of uncontrollable bleeding.

原発性アルドステロン症（PA）は外科的に治療可能な二次性高血圧の一つであり，術後に血圧の低下や降圧薬内服の減量が可能となるが，術後降圧薬内服を中止できる症例は42％程度と報告されている．多くの文献では，片側のPAに対する腹腔鏡下副腎摘除術の高血圧治療成績を考えるとき，治療アウトカムに「術後降圧薬内服の中止」を設定し予測因子を検討している．文献で共通して報告されることが多い予測因子には，短い高血圧罹患年数や少ない術前降圧薬内服がある．また，術後降圧薬内服の中止に関する予測モデルとしてZarnegarらが作成したAldosteronoma Resolution Scoreが存在し，日本人患者においても外部検証で有用性が確認された．術後降圧薬内服の中止は，腹腔鏡下副腎摘除術を受けるPA患者が最も期待し実感できる治療効果であり，この治療成績を予測し説明することは患者本位の診療において重要であると考えられた．

OBJECTIVES: We evaluated the effectiveness of antimuscarinic treatment on disease-specific and generic quality of life (QoL) in females with clinically diagnosed overactive bladder (OAB) by prospectively analyzing improvements in the overactive bladder symptom score (OABSS) and the Rand Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). METHODS: We prospectively recruited newly diagnosed female patients with OAB. Pretreatment disease-specific symptoms were documented, and generic QoL questionnaires were administered. All subjects received solifenacin 5 mg/day for >8 weeks. Symptoms and general health-related QoL (HRQoL) were assessed using the OABSS and SF-36, respectively. Other objective variables, such as maximum urinary flow rate and postvoid residual urine volume, were also evaluated. RESULTS: Seventy-eight subjects met all inclusion criteria and no exclusion criteria. After 8 weeks, the mean OABSS decreased by approximately 50% compared with baseline (from 9.1 ± 2.8 to 4.5 ± 3.6). All individual scores in OABSS improved after administration of solifenacin. Before treatment, the scores of the study subjects in all SF-36 domains were significantly worse than the age- and gender-adjusted Japanese national norms (P < 0.01), except the vitality (VT) scale. Intra-group comparisons between age groups showed worse mental health (MH) scores in all age groups. In the OAB group, three mean SF-36 scales (physical function [PF], VT, and MH) significantly improved after treatment. CONCLUSION: Treatment of OAB with solifenacin is associated with significant improvement in generic HRQoL and disease-specific symptoms at 8 weeks after drug administration. Particularly for generic HRQoL as measured by the SF-36, solifenacin treatment effectively improves three SF-36 scores: PF, VT, and MH.

Background. The aim of this study was to determine concordance rates for prostatectomy specimens and transrectal needle biopsy samples in various areas of the prostate in order to assess diagnostic accuracy of the transrectal biopsy approach, especially for presurgical detection of cancer in the prostatic apex. Materials and Methods. From 2006 to 2011, 158 patients whose radical prostatectomy specimens had been evaluated were retrospectively enrolled in this study. Concordance rates for histopathology results of prostatectomy specimens and needle biopsy samples were evaluated in 8 prostatic sections (apex, middle, base, and transitional zones bilaterally) from 73 patients diagnosed at this institution, besides factors for detecting apex cancer in total 118 true positive and false negative apex cancers. Results. Prostate cancer was found most frequently (85%) in the apex of all patients. Of 584 histopathology sections, 153 (49%) from all areas were false negatives, as were 45% of apex biopsy samples. No readily available preoperative factors for detecting apex cancer were identified. Conclusions. In Japanese patients, the most frequent location of prostate cancer is in the apex. There is a high false negative rate for transrectal biopsy samples. To improve the detection rate, transperitoneal biopsy or more accurate imaging technology is needed.

microRNAs (miRNAs) have key roles in human tumorigenesis, tumor progression and metastasis. miRNAs are aberrantly expressed in many human cancers and can function as tumor suppressors or oncogenes that target many cancer-related genes. This study seeks to identify novel miRNA-regulated molecular pathways in prostate cancer (PCa). The miRNA expression signature in clinical specimens of PCa showed that 56 miRNAs were significantly downregulated in PCa compared with non-PCa tissues. We focused on the top four downregulated miRNAs (miR-187, miR-205, miR-222 and miR-31) to investigate their functional significance in PCa cells. Expression levels of these four miRNAs were validated in PCa specimens (15 PCa tissues and 17 non-PCa tissues) to confirm that they were significantly reduced in these PCa tissues. Gain-of-function analysis demonstrated that miR-222 and miR-31 inhibited cell proliferation, invasion and migration in PCa cell lines (PC3 and DU145), suggesting that miR-222 and miR-31 may act as tumor suppressors in PCa. Genome-wide gene expression analysis using miR-222 or miR-31 transfectants to identify the pathways they affect showed that many cancer-related genes are regulated by these miRNAs in PC3 cells. Identification and categorization of the molecular pathways regulated by tumor suppressive miRNAs could provide new information about the molecular mechanisms of PCa tumorigenesis.

Bone metastases occur in approximately 70% of patients with advanced prostate cancer. Skeletal-related events have been correlated with reduced survival and quality of life of patients with prostate cancer. Biochemical markers of bone metabolism (e.g. bone formation, bone resorption, osteoclastogenesis) might meet an unmet need for useful, non-invasive and sensitive surrogate information for following patients' skeletal health. Recently, zoledronic acid and denosumab have been proven to have the potential for preventing skeletal-related events among prostate cancer patients with bone metastasis. An improved understanding of the mechanisms underlying bone metastasis has also led to the recognition of multiple molecular targets and advances in therapy. However, estimating the efficacy of these agents is difficult. A clinical trial for castration-resistant prostate cancer is currently underway based on the definition of The Prostate Cancer Clinical Trials Working Group, and bone turnover markers are being used as conventional end-points for the clinical trial. Bone turnover markers are useful surrogate markers reflecting the effect of new therapeutic drugs and prognosis, as well as assessment of bone metastases. In particular, N-terminal cross-linked telopeptide of type 1 collagen and bone-specific alkaline phosphatase are widely used bone metabolism markers, and offer reliable surrogate markers to detect bone metastatic spread and to predict prognosis for prostate cancer patients with bone metastases.

PURPOSE: To examine the efficacy of an alpha-1 blocker and its correlation to structural alteration of the prostatic urethra and the loss of energy in the urine flow using a virtual urethra processed from an endoscopic video image. MATERIALS AND METHODS: Video images of the prostatic urethra were recorded during cystourethroscopy in 11 patients with benign prostatic hyperplasia (BPH) before and after treatment with an alpha-1 blocker, naftopidil. The three-dimensional (3D) structure of the prostatic urethra was reproduced from video files. Fluid dynamic analysis and hydraulic energy calculations were performed using the "virtual" 3D urethral images. RESULTS: In 9 of 11 patients studied, an 11% improvement in the loss of energy (range, 1%-82%) was seen. Alpha-1 blocker treatment mediated the disappearance or decrease of the bulky vortex formation in seven patients, which led to an improved urinary stream. A positive correlation was found between improved energy loss and residual urine volume (P=0.0312). CONCLUSION: Alpha-1 blocker therapy led to a decreased energy loss in the urine flow in the prostatic urethra in relation to the improvement of clinical symptoms. The cystourethroscopy could be a tool to assess the urethral resistance in patients with BPH using image processing methodology.

局所限局前立腺癌に対し密封小線源永久刺入療法を施行した39例をretrospectiveに臨床的検討を行った。D'Amicoのリスク分類ではlow risk group 18例、intermediate risk group 21例であった。小線源刺入後の観察期間は中央値33ヵ月であった。生化学的再発症例は現在まで認めていない。全例に術後塩酸タムスロシンを投与した。平均離脱期間は15ヵ月であった。術後の排尿状況の評価はIPSS、QOLともに術後1年で術前と同程度に回復した。長期的な観察ではないが、適格な症例選択と良好な治療成績であり、今後もさらに症例を蓄積していく予定である。(著者抄録)