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前立腺針生検施行654例.1回目で癌が検出されたのは239例で, 陰性例のうち104例に2回目を行い, 16例に検出された.更に3回目が39例中4例, 4回目は10例中3例の検出であった.再検査で最終的に癌が検出された23例(A群)とされなかった81例(B群)において, 年齢, PSA, PSA density, PSA velocityに有意差はなかった.再検査時の所見で, MRIのT2強調像でlow intensityのあるものを陽性とすると, p=0.118, 感度79%, 特異度42%, 経直腸エコーでlow echoic areaのあるものを陽性とした場合はp=0.134, 感度74%, 特異度48%, 直腸診はp=0.027, 感度65%, 特異度59%で, 直腸診にのみ有意差を認めた.生検でatypical findings(AF)とされ再検査を施行した症例では, 9例中6例に癌が検出された.AFの内訳は「高分化腺癌を疑うが検体量少なく判別困難」3例, 「核異型があるが癌とは言い切れない」5例, 「ハイグレードprostatic intraepithelial neoplasia」1例であった, We retrospectively analyzed the results of 104 patients who underwent a second prostate needle biopsy. Between January 1993 and September 2000, 654 needle biopsies were performed and cancer was found in 239 patients. Among the other 415 patients, 104 patients underwent a second biopsy. The average prostate specific antigen (PSA) value was 9.6 ng/ml (2.0-30.9) (Tandem R conversion value). Cancer was detected in 16 out of 104 cases (15%) at the second biopsy, 4 out of 39 (10%) at the third biopsy, and 3 out of 10 (30%) at the fourth biopsy. The age, PSA value, digital examination, echography, and magnetic resonance imaging (MRI) were not helpful in distinguishing the patients with prostate cancer and atypical histological findings at the previous biopsy were the most important information. Among the 9 patients who showed atypical findings at the previous biopsy, 6 (67%) had cancer.

72歳男.主訴は夜間頻尿.経腹的前立腺超音波検査では前立腺に多房性嚢胞を認め, 嚢胞は一部充実性であった.尿道膀胱造影では, 前立腺部尿道は著明に延長, 扁平化し, 左側へ強く圧排されていた.胸腹部造影CTスキャンでは壁肥厚を伴う多房性前立腺嚢胞と右水腎症と右内腸骨リンパ節腫大を認めた.経直腸的超音波ガイド下に嚢胞内容液採取及び前立腺針生検を施行した.病理組織学的所見から, 膀胱と直腸へ浸潤し, 多房性嚢胞形成を伴った前立腺癌T4N1M0と診断し, Bicalutamide(Casodex)による内分泌療法を開始した.治療開始からPSAは緩徐に低下し, 治療開始5ヵ月にPSAは正常化し, MRIでも前立腺は著明に縮小し, 多房性嚢胞と右水腎症は消失した, A 72-year-old man was admitted to our department with the complaint of nocturia. PSA was elevated to 18.2 ng/ml. Transrectal ultrasonography, CT scan and MRI showed multilocular cystic lesions at the posterior site of the prostate, with rectal and bladder invasion and lymph node metastasis. Transrectal needle biopsy of the prostate and fluid aspiration of the prostatic cyst were performed. The aspirated fluid was bloody, but the result of cytology was negative. Histopathological examination of the needle biopsy specimen revealed ductal carcinoma of the prostate. We diagnosed this case as a T4N1M0 prostatic cancer, and started endocrine therapy. Thirty-nine cases of adenocarcinoma of the prostate with cystic formation in the Japanese literature are reviewed.

72歳男.無症候性肉眼的血尿を自覚したため受診し, 直腸診で鶏卵大, 弾性硬の前立腺を触知し, 表面平滑で圧痛, 硬結は認めず, 表在リンパ節も触知しなかった.腫瘍マーカーのうちPSAのみが高値で, 尿沈渣で極度の血尿と軽度の膿尿を認めた.膀胱鏡で膀胱三角部後方に有茎性, 乳頭状の腫瘍と凝血塊突出を認めた.DIPでは左中下腎杯の圧排と陰影欠損を, ダイナミックCTで左腎中部から下極に腫瘤を認めた.左腎腫瘍, 膀胱腫瘍と診断し, 前立腺癌を疑った.全身麻酔下, 左腎尿管摘出術, 腎門部リンパ節郭清, 経尿道的膀胱腫瘍切除術, 経会陰的前立腺針生検を施行した.病理組織学的所見より泌尿器同時性三重複癌(腎細胞癌・膀胱移行上皮癌・前立腺癌)と診断した, A case of synchronous triple urogenital cancer, which was comprised of renal cell carcinoma of the left kidney, transitional cell carcinoma of the urinary bladder, and adenocarcinoma of the prostate, is reported. A 72-year-old Japanese male patient was referred to our outpatient clinic with the complaint of asymptomatic hematuria. At that time, his serum of level of PSA was elevated to 20 ng/ml. Cystourethroscopy showed a papillary bladder tumor and coagula through the left urinary orifice. Ultrasonography, computed tomography and magnetic resonance imaging showed a mass lesion measuring about 6 cm by 5 cm in the left kidney. Angiography showed a hypervascular lesion measuring about 6 cm by 5 cm at the same site. Double cancer, consisting of renal cell carcinoma and transitional cell carcinoma of the urinary bladder, was suspected and we performed left total nephroureterectomy, hilar lymphadenectomy, and transurethral rection of the bladder tumor, one month later. At the same time, we performed a biopsy of the prostate. Histological diagnosis was renal cell carcinoma, clear cell carcinoma and transitional cell carcinoma of urinary bladder. Histological diagnosis of the prostate biopsy was moderately differentiated adenocarcinoma. Since this case fulfilled the criteria of Warren and Gates, it was classified as synchronous triple urogenital cancer. A review of the literature revealed 17 authentic cases of triple urogenital cancer, of which 14 and 10 cases were reported as a combination of renal cancer, bladder cancer and prostatic cancer, in the world and in Japan, respectively. Furthermore, he had been exposed to the atomic bomb explosion in Hiroshima in 1945. This carcinogenic precursor may be related to the development of the triple cancer.

When prostate needle biopsies are involved discontinuously by tumor, no consensus remains on the optimal method of tumor quantification. We investigated whether discontinuous biopsy involvement usually results from a large tumor focus or multiple small foci. Prostate needle biopsies with discontinuous tumor and corresponding whole-mounted radical prostatectomies from 2008 to 2013 were analyzed. Linear length and percentage of biopsy involvement were measured both including and subtracting the benign intervening tissue. The corresponding region of the prostatectomy specimen was evaluated for tumor size and multifocality. From over 800 biopsy sets and 400 prostatectomies performed annually, 40 patients met inclusion criteria. Excluding benign tissue, length and percentage of biopsy involvement ranged from 1 to 7 mm and 5% to 66% (median 2.5 mm, 20%), whereas including intervening tissue yielded 4 to 15.5 mm and 25% to 100%, (median 7 mm, 70%), respectively. Benign intervening tissue measured from 2 to 10.5 mm (median 3.5 mm). In 31 patients (78%), a single tumor focus was present in the corresponding region of the prostate (the dominant tumor in 25/31). In 9 patients, multiple small foci were present. Eleven patients could have been excluded from active surveillance eligibility by measuring tumor from end to end (>50% involvement), of whom only 1 met criteria for clinically insignificant cancer at prostatectomy. Discontinuous tumor in a prostate biopsy often results from a single tumor focus in the corresponding region of the prostate (78%). Therefore, we recommend that an end-to-end measurement be provided, with accompanying diagnostic comment that this often correlates with the size of a single tumor focus.

Primary signet ring cell adenocarcinoma (SRCC) of the prostate is a rare malignancy. Only 42 cases have have been repeorted in the literature. Here we report a case of 76-year-old man with signet ring cell carcinoma and adenocarcinoma of the prostate. Tumor cells were stained positive for prostate spesific antigen immunohistochemically and histochemically negative for alcian blue and mucin. Turkish Başlık: Prostatın Primer Taşlı Yüzük Hücreli Karsinomu Anahtar Kelimeler: Taşlı yüzük hücreli karsinom; prostat tümörleri/ patoloji Prostatın primer taşlı yüzük hücreli karsinomları çok nadirdir. Bu güne kadar literatürde bildirilmiş 42 olgu vardır. Burada 76 yaşında bir hastanın prostatında görülen adenokarsinom ve taşlı yüzük hücreli prostat kanseri olgusu sunulmuştur. İmmünohistokimyasal olarak tümör hücreleri prostat spesifik antijen pozitif, histokimyasal olarak alsien blue ve müsin negatif boyanmıştır.

This article is based on a systematic literature search and meta-analyses of clinical data regarding effects of bisphosphonates (BP) and denosumab (DS) on preventing skeletal related events (SRE) in patients with bone metastases from solid tumours. Although there are pharmacological differences between the different types of BP no major differences were observed between BP in preventing SRE or in adverse events. Treatment with DS has in three randomised trials showed a greater effect than BP in preventing SRE. The optimal choice of bone-anti-resorptive agent should depend on the patient's general condition, renal function and treatment logistics.

Background: According to the TNM staging system, patients with prostate cancer (PCa) with lymph node invasion (LNI) are considered a single-risk group. However, not all LNI patients share the same cancer control outcomes. Objective: To develop and internally validate novel nomograms predicting cancerspecific mortality (CSM)-free rate in pN1 patients. Design, setting, and participants: We evaluated 1107 patients with pN1 PCa treated with radical prostatectomy, pelvic lymph node dissection, and adjuvant therapy at two tertiary care centers between 1988 and 2010. Outcome measurements and statistical analysis: Univariable and multivariable Cox regression models tested the relationship between CSM and patient clinical and pathologic characteristics, which consisted of prostate-specific antigen (PSA) value, pathologic Gleason score, pathologic tumor stage, status of surgical margins, number of positive lymph nodes, and status of adjuvant therapy. A Cox regression coefficient-based nomogram was developed and internally validated. Results and limitations: All 1107 patients received adjuvant hormonal therapy (aHT). Additionally, 35% of patients received adjuvant radiotherapy (aRT). The 10-yr CSM-free rate was 84% in the entire cohort and 87% in patients treated with aRT plus aHT versus 82% in patients treated with aHT alone (p = 0.08). At multivariable analyses, PSA value, pathologic Gleason score, pathologic tumor stage, surgical margin status, number of positive lymph nodes, and aRT status were statistically significant predictors of CSM (all p

Silva, Fernando Calais da Silva, Fernando Manuel Calais da Goncalves, Frederico Santos, Americo Kliment, Jan Whelan, Peter Oliver, Tim Antoniou, Nicos Pastidis, Spiro Marques Queimadelos, Anton Robertson, Chris ENG 2013/04/16 06:00 Eur Urol. 2013 Apr 4. pii: S0302-2838(13)00342-4. doi: 10.1016/j.eururo.2013.03.055.; International audience; BACKGROUND: Few randomised studies have compared antiandrogen intermittent hormonal therapy (IHT) with continuous maximal androgen blockade (MAB) therapy for advanced prostate cancer (PCa). OBJECTIVE: To determine whether overall survival (OS) on IHT (cyproterone acetate; CPA) is noninferior to OS on continuous MAB. DESIGN, SETTING, AND PARTICIPANTS: This phase 3 randomised trial compared IHT and continuous MAB in patients with locally advanced or metastatic PCa. INTERVENTION: During induction, patients received CPA 200mg/d for 2 wk and then monthly depot injections of a luteinising hormone-releasing hormone (LHRH; triptoreline 11.25mg) analogue plus CPA 200mg/d. Patients whose prostate-specific antigen (PSA) was /=20 ng/ml or they were symptomatic) or the continuous arm (CPA 200mg/d plus monthly LHRH analogue). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcome measurement was OS. Secondary outcomes included cause-specific survival, time to subjective or objective progression, and quality of life. Time off therapy in the intermittent arm was recorded. RESULTS AND LIMITATIONS: We recruited 1045 patients, of which 918 responded to induction therapy and were randomised (462 to IHT and 456 to continuous MAB). OS was similar between groups (p=0.25), and noninferiority of IHT was demonstrated (hazard ratio [HR]: 0.90; 95% confidence interval [CI], 0.76-1.07). There was a trend for an interaction between PSA and treatment (p=0.05), favouring IHT over continuous therapy in patients with PSA /=2.5 yr or >5 yr, respectively, after randomisation. The main limitation is that the length of time for the trial to mature means that other therapies are now available. A second limitation is that T3 patients may now profit from watchful waiting instead of androgen-deprivation therapy. CONCLUSIONS: Noninferiority of IHT in terms of survival and its association with better sexual activity than continuous therapy suggest that IHT should be considered for use in routine clinical practice.

Objectives To describe survival and cause of death in a nationwide cohort of Danish patients with prostate cancer undergoing radical prostatectomy (RP). To describe risk factors associated with prostate cancer mortality. Patients and Methods Observational study of 6489 men with localised prostate cancer treated with RP at six different hospitals in Denmark between 1995 and 2011. Survival was described using Kaplan-Meier estimates. Causes of death were obtained from the national registry and cross-checked with patient files. Cumulative incidence of death, any cause and prostate cancer-specific, was described using Nelson-Aalen estimates. Risk for prostate cancer death was analysed in a Cox multivariate regression model using the covariates: age, cT-category, PSA level and biopsy Gleason score. Results The median follow-up was 4 years. During follow-up, 328 patients died, 109 (33.2%) from prostate cancer and 219 (66.8%) from other causes. Six patients (0.09%) died ≤30 days of RP. In multivariate analysis, cT-category was a predictor of prostate cancer death (P < 0.001). Compared with T1 disease, both cT2c (hazard ratio [HR] 2.2) and cT3 (HR 7.2) significantly increased the risk of prostate cancer death. For every doubling of PSA level the risk of prostate cancer death was increased by 34.8% (P < 0.001). Biopsy Gleason score 4 + 3 and ≥8 were associated with an increased risk of prostate cancer death compared with biopsy Gleason score ≤ 6 of 2.3 and 2.7 (P = 0.003), respectively. The cumulative hazard of all-cause and prostate cancer-specific mortality after 10 years was 15.4% (95% confide3nce interval [CI] 13.2-17.7) and 6.6% (95% CI 4.9-8.2) respectively. Conclusions We present the first survival analysis of a complete, nationwide cohort of men undergoing RP for localised prostate cancer. The main limitation of the study was the relatively short follow-up. Interestingly, our national results are comparable to high-volume, single institution, single surgeon series.

Human cancers nearly ubiquitously harbor epigenetic alterations. While such alterations in epigenetic marks, including DNA methylation, are potentially heritable, they can also be dynamically altered. Given this potential for plasticity, the degree to which epigenetic changes can be subject to selection and act as drivers of neoplasia has been questioned. Here, we carried out genome-scale analyses of DNA methylation alterations in lethal metastatic prostate cancer and created DNA methylation “cityscape” plots to visualize these complex data. We show that somatic DNA methylation alterations, despite showing marked inter-individual heterogeneity among men with lethal metastatic prostate cancer, were maintained across all metastases within the same individual. The overall extent of maintenance in DNA methylation changes was comparable to that of genetic copy number alterations. Regions that were frequently hypermethylated across individuals were markedly enriched for cancer and development/differentiation related genes. Additionally, regions exhibiting high consistency of hypermethylation across metastases within individuals, even if variably hypermethylated across individuals, showed enrichment of cancer-related genes. Interestingly, whereas some regions showed intra-individual metastatic tumor heterogeneity in promoter methylation, such methylation alterations were generally not correlated with gene expression. This was despite a general tendency for promoter methylation patterns to be strongly correlated with gene expression, particularly at regions that were variably methylated across individuals. These findings suggest that DNA methylation alterations have the potential for producing selectable driver events in carcinogenesis and disease progression and highlight the possibility of targeting such epigenome alterations for development of longitudinal markers and therapeutic strategies.

類似臨床を呈したBCG誘発肉芽腫性前立腺炎と膀胱上皮内癌(CIS)前立腺浸潤の各1例を経験した.症例1は77歳男性.膀胱CISと再発CISにBCG膀胱内注入療法を2度施行したが, 尿細胞診でclass 5を認め, 3度目のBCG注入で強い頻尿と排尿時痛を認めて中断, 直腸診で前立腺に硬結を触知し, TRUSで左葉にhypoechoic lesionを認めた.抗結核薬でも改善せず, TUR-Pを施行した.病理所見ではBCGによる肉芽腫性前立腺炎であった.症例2は71歳男性.膀胱CISにBCG膀胱内注入療法を開始し, 4回注入後に膀胱刺激症状, 排尿困難を認めたが, 治療を継続して6回の注入を終了した.その後も尿細胞診でclass 3～5が継続し, 排尿症状増悪で抗結核薬を使用したが改善せず, 直腸診で前立腺に硬結を触れ, TRUSでhypoechoic lesionを認め, TRU-Pを施行した.病理所見では前立腺癌細胞は認めず, 移行上皮癌であった, Intravesical instillation of bacillus Calmette-Guerin (BCG) is the first-line therapeutic option for flat carcinoma in situ (CIS) of the bladder. Intravesical BCG instillation has been demonstrated to cause granulomatous prostatitis. Bladder CIS often also is known to show prostatic stromal invasion. We report a case of BCG-induced granulomatous prostatitis and a case of prostatic stromal invasion of bladder CIS accompanied by locally advanced prostate cancer, which showed similar clinical findings after the intravesical BCG therapy. In these 2 patients, urinary symptoms such as dysuria were prolonged regardless of anti-tuberculous medication, hard nodules were palpable at the prostate, and hypoechoic lesions were visualized by transrectal ultrasound. Both patients were treated by transurethral resection of the prostate, and the diagnoses were made by histopathological examination. Urinary symptoms were resolved in both patients after surgery, but the prostatic stromal tumor showed recurrence of growth. We report the usefulness of transurethral resection of the prostate for medication-resistant BCG-induced granulomatous prostatitis, and the importance of the correct diagnosis of prostatic stromal invasion of bladder CIS especially in the cases with concurrent prostate cancer.

Background: The role of adjuvant radiotherapy (ART) after radical prostatectomy (RP) on survival of patients with prostate cancer (PCa) is still controversial. Objective: We tested the impact of ART on cancer-specific mortality (CSM) and overall mortality (OM) in PCa patients according to pathologic PCa features. Design, setting, and participants: We evaluated 1049 PCa patients treated with RP and extended pelvic lymph node dissection alone or in combination with adjuvant treatments between 1998 and 2008. All patients had positive surgical margins and/or pT3/pT4 disease with or without positive lymph nodes. Outcome measurements and statistical analysis: Cox regression analyses tested the relationship between pathologic characteristics and CSM rates. Independent predictors of survival were used to develop a novel risk score based on the number of risk factors. Finally, Cox regression models tested the relationship between ART and survival according to the number of risk factors. Results and limitations: On multivariable analyses, only pathologic Gleason score >= 8, pT3b/T4 stage, and presence of positive lymph nodes represented independent predictors of CSM (all p = 0.4). Conversely, in patients with a risk score >= 2, ART was associated with lower CSM and OM rates (all p = 0.006). The observational nature of the cohort represents a limitation of the study. Conclusions: ART significantly improved survival only in patients with at least two of the following pathologic features at RP: Gleason score >= 8, pT3/pT4 disease, and positive lymph nodes. These patients represent the ideal candidates for ART after RP. (c) 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Objective: Prostate carcinoma (PCa) is one of the most frequent neoplasms, with more than 110.000 new cases/year in Europe. As PCa is not clearly demonstrable at transrectal ultrasound (TRUS), guidelines on TRUS guided biopsy suggest to perform a random tissue sampling (at least 8-12 “cores” depending on gland volume). Although accuracy grows with core number, patient discomfort and adverse event probability grow as well. Thus it would be worth to aim to reduce the number of prostate biopsy cores without loss of diagnostic accuracy. Materials and Methods: A retrospective study was performed to evaluate the feasibility of an improved version of a rtCAB tool developed at DEIS (University of Bologna) for the reduction of prostate biopsy cores. rtCAB is an innovative processing technique which enhances TRUS video stream by a live false color overlay image that helps the physician to perform the biopsy by guiding the sampling into target zones. In order to train rtCAB, a monocentric, single operator prostate gland adenocarcinoma database has been built. The database enlists 81 patients, for a total of 743 prostate byoptic (PBx) cores and 14860 ROI. For each patient we collected age, PSA levels, digital rectal examination (DRE) findings, presence or absence of focal lesions, and prostate volume. During TRUS, raw ultrasound data were acquired and associated to each PBx core. For each core we collected both the radio frequency (RF) signal and the histological outcome. Results: The whole system was optimized for reducing the number of false positives while preserving an acceptable number of false negatives. Comparing to a classical PBx approach (8-12 cores), the estimated positive predictive value ( PPV) of our method increased from 25% to 40%, with an overall sensitivity of 85%. Conclusions: Preliminary results show that the proposed tool can provide real-time feedback to the operator during TRUS. Sensitivity and PPV values suggest that a reduction of almost 50% the number of biopsy cores without losing in diagnostic accuracy is feasible. A prospective study is needed to further confirm these preliminary retrospective results.

Objective Several studies showed that high serum levels of insulin-like growth factor-I (IGF-I) correlate with an increased risk for prostate cancer, although the causal role of IGF-I remains to be established. In this study, we addressed the role of IGF-I as a serum factor on the growth of two androgen-independent cell lines (Du145 and PC3) and one androgen-dependent cell line (LNCaP). Design We investigated the effects of a blocking antibody against the IGF-I receptor (αIR3) on DNA synthesis in prostate cancer cells cultured in the presence of recombinant human IGF-I or normal human serum (NHS). Results We show that in all three prostate cancer cell lines, NHS exerts a markedly stronger stimulating effect on DNA synthesis than IGF-I, and that the effect of NHS can be completely abrogated by an antibody against the IGF-I receptor (αIR3). Using pharmacological inhibitors of the two canonical IGF-I receptor signaling pathways, we show that the phosphatidylinositol-3′-kinase (PI3K) and the Mek–Erk pathways are not required for the stimulating effect of NHS. Conclusion Our observations indicate that the stimulating effect of NHS is completely dependent on IGF-I receptor signaling transduction and that IGF-I stimulates DNA synthesis in prostate cancer cells in strong synergy with other serum factors. We speculate that the role of other serum factors could explain the discrepancy between the results observed in different animal models to study the function of IGF-I in prostate cancer.

The translationally controlled tumor protein (TCTP) is an abundantly expressed protein found in a wide range of organisms from both the animal and plant kingdom. Initially described as a growth-related protein, knowledge of the biological actions of TCTP has been recently extended to include calcium binding, regulation of apoptosis, and microtubules stabilization. This report describes expression, distribution, and characterization of TCTP in human prostatic tissues and cell lines.Samples were analyzed by Western blot, RT-PCR, immunohistochemistry, and confocal microscopy. Calcium binding activity of the recombinant human prostatic protein was evaluated on a calcium overlay assay. A public SAGE database was analyzed to determine TCTP expression levels in normal and cancer tissues.TCTP protein and mRNA were detected in all the specimens and cell lines analyzed. The protein was mainly expressed by the secretory luminal epithelial and basal layer cells. A significant amount of protein was present in the prostatic fluids. Subcellular distribution studies in prostate epithelial cells detected the protein in the cytoplasm in interphase and colocalized with tubulin during mitosis. The calcium binding capacity of prostatic TCTP was shown in vitro. Finally, SAGE data indicated TCTP as the calcium binding protein with the highest expression levels among those examined.The results of the present study demonstrate, for the first time, the expression of TCTP in the human prostate and in prostate cancer cells, and suggest the involvement of the protein in key-processes such as apoptosis, cellular differentiation, and in the control of sperm functions.

A 29-year-old male with bladder cancer was referred to our hospital. Histological examination of transurethral biopsy showed transitional cell carcinoma with invasion into prostate (T4aN0M0, grade 3). Nerve-sparing radical cystectomy with ileal neobladder reconstruction was performed after 3 courses of neoadjuvant chemotherapy with Methotrexate, Epirubicin and Cisplatin. Continence and erectile function were preserved and no recurrence has been observed for 18 months after the operation. This is the sixth case of an invasive bladder cancer in Japanese patients under 30 years old.

A 79-year-old male presented in December. In January, 2001, with complaints of black nodules and bleeding from the glans of the penis to the foreskin. Inguinal lymph nodes were palpable bilaterally. Clinical diagnosis was penile malignant melanoma. Cystoscopy and urethrography revealed urethral invasion of malignant melanoma, and magnetic resonance imaging (MRI) of the penis revealed invasion to prostate, and pelvic lymph node metastases in abdominal compuled tomography (CT) but no organ metastases. Total cystectomy, total penectomy, bilateral inguinal and pelvic lymph node dissection and bilateral ureterocutaneostomy were performed in February, 2002. The pathological findings were nodular malignant melanoma, pT4bN2bM1a, and the surgical margin was positive. After these therapies, chemotherapy was performed. Five months later, CT revealed multiple lung and brain metastases, and radiation therapy and chemotherapy were performed. Twelve months after the operation, he died of cancer. Review of the literature revealed that our patient is the thirtieth reported case of penile malignant melanoma in Japan since 1924. In 30 cases, stage III, IV were 20 cases and 16 cases performed operation.

Intravesical instillation of bacillus Calmette-Guerin (BCG) is the first-line therapeutic option for flat carcinoma in situ (CIS) of the bladder. Intravesical BCG instillation has been demonstrated to cause granulomatous prostatitis. Bladder CIS often also is known to show prostatic stromal invasion. We report a case of BCG-induced granulomatous prostatitis and a case of prostatic stromal invasion of bladder CIS accompanied by locally advanced prostate cancer, which showed similar clinical findings after the intravesical BCG therapy. In these 2 patients, urinary symptoms such as dysuria were prolonged regardless of anti-tuberculous medication, hard nodules were palpable at the prostate, and hypoechoic lesions were visualized by transrectal ultrasound. Both patients were treated by transurethral resection of the prostate, and the diagnoses were made by histopathological examination. Urinary symptoms were resolved in both patients after surgery, but the prostatic stromal tumor showed recurrence of growth. We report the usefulness of transurethral resection of the prostate for medication-resistant BCG-induced granulomatous prostatitis, and the importance of the correct diagnosis of prostatic stromal invasion of bladder CIS especially in the cases with concurrent prostate cancer.

We retrospectively analyzed the results of 104 patients who underwent a second prostate needle biopsy. Between January 1993 and September 2000, 654 needle biopsies were performed and cancer was found in 239 patients. Among the other 415 patients, 104 patients underwent a second biopsy. The average prostate specific antigen (PSA) value was 9.6 ng/ml (2.0-30.9) (Tandem R conversion value). Cancer was detected in 16 out of 104 cases (15%) at the second biopsy, 4 out of 39 (10%) at the third biopsy, and 3 out of 10 (30%) at the fourth biopsy. The age, PSA value, digital examination, echography, and magnetic resonance imaging (MRI) were not helpful in distinguishing the patients with prostate cancer and atypical histological findings at the previous biopsy were the most important information. Among the 9 patients who showed atypical findings at the previous biopsy, 6 (67%) had cancer.

A 72-year-old man was admitted to our department with the complaint of nocturia. PSA was elevated to 18.2 ng/ml. Transrectal ultrasonography, CT scan and MRI showed multilocular cystic lesions at the posterior site of the prostate, with rectal and bladder invasion and lymph node metastasis. Transrectal needle biopsy of the prostate and fluid aspiration of the prostatic cyst were performed. The aspirated fluid was bloody, but the result of cytology was negative. Histopathological examination of the needle biopsy specimen revealed ductal carcinoma of the prostate. We diagnosed this case as a T4N1M0 prostatic cancer, and started endocrine therapy. Thirty-nine cases of adenocarcinoma of the prostate with cystic formation in the Japanese literature are reviewed.

A case of synchronous triple urogenital cancer, which was comprised of renal cell carcinoma of the left kidney, transitional cell carcinoma of the urinary bladder, and adenocarcinoma of the prostate, is reported. A 72-year-old Japanese male patient was referred to our outpatient clinic with the complaint of asymptomatic hematuria. At that time, his serum of level of PSA was elevated to 20 ng/ml. Cystourethroscopy showed a papillary bladder tumor and coagula through the left urinary orifice. Ultrasonography, computed tomography and magnetic resonance imaging showed a mass lesion measuring about 6 cm by 5 cm in the left kidney. Angiography showed a hypervascular lesion measuring about 6 cm by 5 cm at the same site. Double cancer, consisting of renal cell carcinoma and transitional cell carcinoma of the urinary bladder, was suspected and we performed left total nephroureterectomy, hilar lymphadenectomy, and transurethral rection of the bladder tumor, one month later. At the same time, we performed a biopsy of the prostate. Histological diagnosis was renal cell carcinoma, clear cell carcinoma and transitional cell carcinoma of urinary bladder. Histological diagnosis of the prostate biopsy was moderately differentiated adenocarcinoma. Since this case fulfilled the criteria of Warren and Gates, it was classified as synchronous triple urogenital cancer. A review of the literature revealed 17 authentic cases of triple urogenital cancer, of which 14 and 10 cases were reported as a combination of renal cancer, bladder cancer and prostatic cancer, in the world and in Japan, respectively. Furthermore, he had been exposed to the atomic bomb explosion in Hiroshima in 1945. This carcinogenic precursor may be related to the development of the triple cancer.

Paraffin embedded and formalin fixed needle biopsies of prostate cancer (PC) were used to immunocytochemically detect the p120 nucleolar protein in relation to the Gleason histological gradings (GHG), the labelling indices of proliferating nuclear immunocytochemical markers (PCNA/Cyclin, Ki-67/MIB1) and the argyrophilic nucleolar region (AgNOR) rate. The twenty-six cases of PC (6 from large histological samples and 20 from needle biopsies) were equally distributed into low (or = 6) or high (or = 7) GHG groups. The p120 nucleolar protein immunocytochemical reaction was randomly expressed in large histological sections but uniformly distributed without gaps in needle biopsy sections. Only on the latter were quantitative values of PCNA/Cyclin (23.2 in low and 45.3 in high GHG), Ki-67/MIB1 (13.8 in low and 43.3 in high GHG) and AgNOR (5.0 in low and 7.5 in high GHG) related to those of p120 nucleolar protein (0.8 in low and 3.8 in high GHG). The values of all these cell cycle markers increased from low to high GHG of PC, all four reaching high statistical significance between the two groups (ANOVA-two tailed p0.0001). The PCNA/Cyclin index showed a higher positivity than the Ki-67/MIB1 index in PC with low GHG but not in PC with high GHG. In conclusion, paraffin embedded and formalin fixed PC needle biopsies exhibit a higher diagnostic PCNA/Cyclin than Ki-67/MIB1 index for cases presenting differentiated features, whereas p120 nucleolar protein detection seems to be a suitable marker of poorer outcome of PC.

Stem cell assay法を用いてヒト前立腺癌細胞の二層軟寒天培養を検討し, 14例中9例にコロニー形成を認めた.とくにリンパ節より得られた組織で高いコロニー形成率が認められ, 各種ホルモン添加の影響を検討できた.testosterone添加の検体の中にはコロニー形成の増大を示すものがあり, 臨床的に抗アンドロジェン療法に対する反応と相関を示すと考えられるものがあった, Soft agar cultures of human prostatic carcinoma cells obtained from prostates with needle biopsy and metastatic lymph nodes were examined. Colony formation were observed in 2 of the 4 needle biopsy specimens and in 7 of the 10 lymphatic nodes specimens. The plating efficiency was 0.04 to 0.43%. The effect of testosterone on the clonal growth of these cells in soft agar culture was studied. In half of the cases, colony formation was increased by the addition of testosterone. Whereas in the other cases, colony formation was not influenced by the testosterone. Clinically, most of the former cases responded well to the anti-androgen therapy. Neither EGF nor hydrocortisone showed any effect on the colony formation of the prostatic cancer cells in soft agar. These results suggest that primary culture of human prostatic cancer is possible in soft agar medium, and that androgen dependency of these cells can be examined in vitro.

膀胱癌を含む高次重複癌の4例.第1例は70歳男性で, 膀胱移行上皮癌, 前立腺小腺房性高分化型腺癌, 膵高分化型腺癌の3重複癌で, 悪液質で死亡した.第2例は69歳男性であり, 膀胱移行上皮癌, 陰茎扁平上皮癌, 喉頭扁平上皮癌の3重複癌で, 発症後6年経過したが, 再発を認めていない.第3例は78歳の男性で, 膀胱移行上皮癌, 胃中分化型腺癌, 前立腺小腺房性高分化型腺癌, 肺微小扁平上皮癌の4重複癌で, 胃癌の広汎転移により閉塞性黄疸・腎不全を併発し死亡した.第4例は76歳男性で, 膀胱移行上皮癌, 頸部鰓性癌, 頬部扁平上皮癌, 直腸高分化型腺癌の4重複癌であり, 第1癌発症後17年を経過したが, 再発なく生存している, Two cases of triple primary neoplasm and two cases of quadruple primary neoplasm including transitional cell carcinoma (TCC) of bladder are reported. The first case was a 70-year-old male who had bladder cancer, occult cancer of prostate (adenocarcinoma) and highly differentiated adenocarcinoma of pancreas. He died of cachexy. The second case was a 69-year-old male. This case was also triple primary neoplasm including bladder cancer, squamous cell carcinoma (SCC) of penis and SCC of larynx. The third case was a 78-year-old male who had bladder cancer, adenocarcinoma of prostate similar to that of the first case, adenocarcinoma of stomach, and SCC of lung. He died of obstructive jaundice and renal failure owing to massive metastases of gastric cancer. The fourth case was a 78-year-old male who had four primary neoplasms such as bladder cancer, branchiogenic epithelial carcinoma, SCC of buccal mucosa and adenocarcinoma of rectum.

泌尿性器腫瘍の21例に経皮的後腹膜リンパ節吸引生検をおこない, 20例に充分な生検材料を得た.リンパ管造影で転移を診断できたのは1例のみであったが, リンパ節吸引生検により, 先の例を含め6例にリンパ節転移を証明しえた.後腹膜リンパ節吸引生検法は前立腺癌のstaging lymph node dissectionにかわりうる検査法であり, また, 膀胱癌に対する手術方法の決定に重要な検査法となる, Percutaneous fine needle aspiration of retroperitoneal pelvic and abdominal lymph nodes was done in 21 patients with clinically localized bladder, prostate, or penile cancers. A diagnosis of metastases to regional lymph nodes was detected by this method in 6 patients, but only one case could be diagnosed by bipedal lymphography. Positive aspiration results may spare the patient with prostatic or bladder cancer an unnecessary radical operation. This method also enables the detection of micrometastasis of lymph node which can not be detected by lymphography. No complications were seen in this series.

A case of a 65-year-old man with prostatic cancer associated with von Recklinghausen's disease ( VRD ) is reported. The coexistence of neural crest malignancies with VRD is well known. Recently, it has been reported that non-neural crest malignancies appear to occur with increased frequency in patients with VRD . The non-neural crest malignancies now known to be associated with VRD are Wilms' tumor, non-lymphocytic leukemia, rhabdomyosarcoma, and others. The relationship between VRD and non-neural crest malignancy (including carcinoma) is reviewed and briefly discussed.

A 29-year-old man had been keeping bed under the diagnosis of pulmonary tuberculosis and bladder stone. Urological examinations revealed tumor invading into the bladder but no calculi. The patient died of pulmonary insufficiency. Autopsy disclosed tumor of the prostate extending into the left half of the intrapelvic space including the bladder. Metastases of disseminating type were found in the lungs. There was also metastasis to the liver. Histologically the tumor was pleomorphic cell sarcoma.

Percutaneous fine needle aspiration of retroperitoneal pelvic and abdominal lymph nodes was done in 21 patients with clinically localized bladder, prostate, or penile cancers. A diagnosis of metastases to regional lymph nodes was detected by this method in 6 patients, but only one case could be diagnosed by bipedal lymphography. Positive aspiration results may spare the patient with prostatic or bladder cancer an unnecessary radical operation. This method also enables the detection of micrometastasis of lymph node which can not be detected by lymphography. No complications were seen in this series.

A case of a 65-year-old man with prostatic cancer associated with von Recklinghausen's disease ( VRD ) is reported. The coexistence of neural crest malignancies with VRD is well known. Recently, it has been reported that non-neural crest malignancies appear to occur with increased frequency in patients with VRD . The non-neural crest malignancies now known to be associated with VRD are Wilms' tumor, non-lymphocytic leukemia, rhabdomyosarcoma, and others. The relationship between VRD and non-neural crest malignancy (including carcinoma) is reviewed and briefly discussed.

Soft agar cultures of human prostatic carcinoma cells obtained from prostates with needle biopsy and metastatic lymph nodes were examined. Colony formation were observed in 2 of the 4 needle biopsy specimens and in 7 of the 10 lymphatic nodes specimens. The plating efficiency was 0.04 to 0.43%. The effect of testosterone on the clonal growth of these cells in soft agar culture was studied. In half of the cases, colony formation was increased by the addition of testosterone. Whereas in the other cases, colony formation was not influenced by the testosterone. Clinically, most of the former cases responded well to the anti-androgen therapy. Neither EGF nor hydrocortisone showed any effect on the colony formation of the prostatic cancer cells in soft agar. These results suggest that primary culture of human prostatic cancer is possible in soft agar medium, and that androgen dependency of these cells can be examined in vitro.

Two cases of triple primary neoplasm and two cases of quadruple primary neoplasm including transitional cell carcinoma (TCC) of bladder are reported. The first case was a 70-year-old male who had bladder cancer, occult cancer of prostate (adenocarcinoma) and highly differentiated adenocarcinoma of pancreas. He died of cachexy. The second case was a 69-year-old male. This case was also triple primary neoplasm including bladder cancer, squamous cell carcinoma (SCC) of penis and SCC of larynx. The third case was a 78-year-old male who had bladder cancer, adenocarcinoma of prostate similar to that of the first case, adenocarcinoma of stomach, and SCC of lung. He died of obstructive jaundice and renal failure owing to massive metastases of gastric cancer. The fourth case was a 78-year-old male who had four primary neoplasms such as bladder cancer, branchiogenic epithelial carcinoma, SCC of buccal mucosa and adenocarcinoma of rectum.

A 29-year-old man had been keeping bed under the diagnosis of pulmonary tuberculosis and bladder stone. Urological examinations revealed tumor invading into the bladder but no calculi. The patient died of pulmonary insufficiency. Autopsy disclosed tumor of the prostate extending into the left half of the intrapelvic space including the bladder. Metastases of disseminating type were found in the lungs. There was also metastasis to the liver. Histologically the tumor was pleomorphic cell sarcoma.

Actas Urol Esp

TNFα exerts apoptosis throughout an intracellular transduction pathway that involves the kinase proteins TRAF-2 (integration point of apoptotic and survival signals), ASK1 (pro-apoptotic protein), MEK-4 (p38 activator and metastasis suppressor gene), JNK (stress mitogen activated protein kinase) and the transcription factor AP-1. TNFα also exerts proliferation by p38 activation, or when TRAF-2 simultaneously induces the transcription factor NF-κB by NIK. NIK and p38 may also be activated by IL-1. P38 activated several transcription factors such as Elk-1, ATF-2 and NF-κB. NIK also may activate NF-κB. The aim of the present article was to evaluate the different components of this TNFα/IL-1 transduction pathway in human prostate carcinoma (PC) in comparison with normal human prostate. In prostate cancer, pro-apoptotic TNFα/AP-1 pathway is probably inactivated by different factors such as p21 (at ASK-1 level) and bcl-2 (at JNK level), or diverted towards p38 or NIK activation. IL-1α enhances proliferation through IL-1RI that activates either NIK or p38 transduction pathway. P38 and NIK activate different transcription factors related with cell proliferation and survival such as ATF-2, Elk-1 or NF-κB. In order to search a possible target to cancer prostate treatment we proposed that inhibition of several proinflamatory cytokines such as IL-1 and TNFα might be a possible target for PC treatment, because decrease the activity of all transduction pathway members that activate transcription factors as NF-κB, Elk-1 or ATF-2., Ministerio de Educación y Ciencia