BACKGROUND & AIMS: PURPOSE:The aim of this study was to compare the dosimetric consequences of 4 treatment delivery techniques for prostate cancer patients treated with intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS:During an 8-week course of radiotherapy, 10 patients underwent computed tomography (CT) scans 3 times per week (243 total) before daily treatment with a CT-linear accelerator. Treatment delivery was simulated by realigning a fixed-margin treatment plan on each CT scan and calculating doses. The alignment methods were those based on the following: skin marks, bony registration, ultrasonography (US), and in-room CT. For the last two methods, prostate was the alignment target. The dosimetric effects of these alignment methods on the prostate, seminal vesicles, rectum, and bladder were compared. The average daily minimum dose to 0.1 cm3 was used as the metric for target coverage. RESULTS:Skin and bone alignments provided acceptable prostate coverage for only 70% of patients, US alignment for 90%, and CT alignment for 100%. CT-based alignment of the prostate provided seminal vesicle (SV) coverage of > or = 69 Gy for all patients; US and bone alignments provided SV coverage of > or = 60 Gy. This SV coverage may be acceptable for early-stage cancer (equivalent SV dose = 55.8 Gy at 1.8 Gy per fraction), but unacceptable for late-stage cancer (SV dose = 75.6 Gy). At 75.6 Gy, the acceptable rate for SV coverage was 40% for skin and bone alignments, 70% for US, and 80% for CT. CONCLUSIONS:Direct target alignment methods (US and CT) provided better target coverage. CT-guided alignment provided the best and most consistent dosimetric coverage. A larger planning target volume margin is needed for SV coverage when the alignment target is the prostate.

背景与目标：

BACKGROUND & AIMS: Prostate-specific antigen (PSA), a glycoprotein initially thought to be produced only by the epithelial cells of the prostate, has recently been found in 30% of female breast tumours using immunofluorometry. Our aim was to localize PSA immunohistochemically in a selected group of 27 paraffin-embedded breast tissues. A scoring system was developed for the histological assessment of PSA positivity within the breast tissue. One pathologist (DH) scored, classified and graded all tumours. Site-specific PSA staining was noted in the histology slides. Intense staining was identified in apocrine metaplasia and within the lining ductal epithelium of cystically dilated ducts. The epithelium in lesions of sclerosing adenosis was also frequently positive for PSA staining. Hyperplastic ductal epithelium (especially of mild degree) occasionally stained positive, as did normal breast ducts. Better differentiated tumours showed PSA staining [e.g. mucinous carcinoma (colloid)]. If an infiltrating duct carcinoma showed staining for PSA, adjacent intraductal carcinoma was also noted to stain positively, if present.

背景与目标： 前列腺特异性抗原 (PSA) 是一种最初认为仅由前列腺的上皮细胞产生的糖蛋白，最近已在使用免疫荧光法的女性乳腺肿瘤30% 中发现。我们的目标是通过免疫组织化学方法将PSA定位在27个石蜡包埋的乳腺组织的选定组中。开发了一种评分系统，用于对乳腺组织内的PSA阳性进行组织学评估。一位病理学家 (DH) 对所有肿瘤进行评分，分类和分级。在组织学载玻片中发现了位点特异性PSA染色。在顶汗腺化生和膀胱扩张的导管上皮内发现了强烈的染色。硬化性腺病病变中的上皮也经常出现PSA染色阳性。增生的导管上皮 (尤其是轻度) 偶尔呈阳性，正常的乳腺导管也是如此。分化更好的肿瘤显示PSA染色 [例如粘液癌 (胶体)]。如果浸润性导管癌显示PSA染色，则邻近的导管内癌 (如果存在) 也被阳性染色。

BACKGROUND & AIMS: :The course of untreated localized prostate cancer after 10 years of follow-up is at large unknown. As curative treatment is usually only offered patients with a life expectancy exceeding 10 Years, the expected course of the disease if left untreated is of the utmost interest. This paper aims to describe the outcome for patients who survive for more than 10 years when treated without curative intent. The results indicate that cancer specific mortality in patients with localized prostate cancer increases steadily over time and is approximately 50% after 15 years. This is a much higher figure than in reported series on radical prostatectomy. Even if many deaths occur at an old age, prostate cancer death is shown to be associated with a significant morbidity, need for palliative treatment, hospital care and cost. Preventing prostate cancer death is therefore not only a matter of saving year of life but also to prevent suffering caused by the disease. Modern diagnostic tools, such as prostate specific antigen, seem to detect clinically significant cancers in the vast majority of patients. Over diagnosis seems to be uncommon if diagnostic procedures are restricted to patients with a long life expectancy. Localized prostate cancer is a slow-growing but progressive neoplastic disease. When diagnosed in a man with a longer life expectancy it should be handled as such.

背景与目标： : 经过10年的随访，未经治疗的局部前列腺癌的病程尚不清楚。由于通常只为预期寿命超过10年的患者提供治愈性治疗，因此，如果不及时治疗，该疾病的预期病程是最大的利益。本文旨在描述无治疗意图治疗后存活10年以上的患者的结果。结果表明，局部前列腺癌患者的癌症特异性死亡率随着时间的推移而稳定增加，并且在15年后约为50%。这比报道的根治性前列腺切除术系列要高得多。即使许多死亡发生在老年，前列腺癌的死亡也被证明与显着的发病率，姑息治疗的需求，医院护理和费用有关。因此，预防前列腺癌死亡不仅是挽救生命的问题，而且还可以防止疾病造成的痛苦。现代诊断工具 (例如前列腺特异性抗原) 似乎可以在绝大多数患者中检测到临床上重要的癌症。如果诊断程序仅限于预期寿命长的患者，则过度诊断似乎并不常见。局限性前列腺癌是一种生长缓慢但进行性的肿瘤性疾病。当被诊断为预期寿命较长的男性时，应该这样处理。

BACKGROUND & AIMS: A 66-year-old man, admitted to the hospital for prostatic carcinoma, presented with a nodular lesion located on the presternal region and a small nodule (0.5 cm in diameter) simulating a scalp sebaceous cyst located on the scalp. Moreover, an irregular darkbrown lesion was observed on the left side of the abdomen, and a brownish macula was also present on the presternal region. Histologic examination of the two nodular lesions revealed cutaneous metastases from prostatic carcinoma. The pigmented lesion, localized on the abdomen, proved to be a superficial spreading melanoma with a maximal depth of 1.36 mm. Histologic examination of the brownish lesion on the presternal region revealed nevus cell nests within the epidermis and in the dermis. We discuss the propensity of developing a secondary cancer in a patient with a primary malignancy.

背景与目标： 一名66岁的男子因前列腺癌入院，表现为位于胸骨前区的结节状病变和位于头皮上的小结节 (直径0.5厘米)，模拟头皮皮脂腺囊肿。此外，在腹部左侧观察到不规则的深褐色病变，胸骨前区域也出现褐色黄斑。对两个结节性病变的组织学检查显示前列腺癌的皮肤转移。位于腹部的色素性病变被证明是表面扩散的黑色素瘤，最大深度为1.36毫米。对胸骨前区域的褐色病变进行组织学检查，发现表皮和真皮内有痣细胞巢。我们讨论了原发性恶性肿瘤患者发生继发性癌症的倾向。

BACKGROUND & AIMS: Low intensity ultrasound signals, similar to that employed in clinical therapy, are found to mediate differential gene transfer and expression of the Green Fluorescence Protein (GFP) reporter in two human prostate cancer cell lines, LnCap and PC-3. Cell suspensions in the presence or in the absence of GFP (44.5nM) were treated at 37 degrees C under a standing wave condition. Cells were exposed to either continuous wave, 932.7kHz ultrasound, or to several independent bursts, each burst comprising a 20% duty cycle (932.7kHz) sine wave. The burst "repetition" frequency was varied from 10Hz to 10kHz in several different experiments and each treatment received a net identical ultrasound energy exposure. Transient GFP expression levels in viable cells were monitored by flow cytometry. The findings revealed a strong ultrasound tone-burst frequency dependence on the transfection efficiencies. Interestingly, the ultrasound signal parameters which are routinely employed in clinical therapy did not yield any statistically significant enhancement in transfection efficiency relative to their sham counterparts.

背景与目标： 发现与临床治疗中使用的低强度超声信号相似，可介导两种人前列腺癌细胞系LnCap和PC-3中的差异基因转移和绿色荧光蛋白 (GFP) 报告基因的表达。在驻波条件下，在37 ℃ 下处理存在或不存在GFP (44.5nm) 的细胞悬浮液。将细胞暴露于连续波、932.7khz超声波或几个独立的突发，每个突发包括20% 占空比 (932.7khz) 正弦波。在几个不同的实验中，突发 “重复” 频率从10Hz到10kHz不等，并且每种处理均获得净相同的超声能量暴露。通过流式细胞术监测活细胞中的瞬时GFP表达水平。研究结果表明，超声音调爆发频率对转染效率有很强的依赖性。有趣的是，与假手术相比，临床治疗中常规使用的超声信号参数在转染效率上没有任何统计学上的显着提高。

BACKGROUND & AIMS: OBJECTIVE:To compare prostate carcinoma, with and with no lymph node metastasis, to benign prostatic hyperplasia (BPH) tissue for lymphatic vessel density (LVD) and the expression of the lymph-endothelial specific growth factor, vascular endothelial growth factor C (VEGF-C), to determine their role in lymphogenic metastasis. PATIENTS, MATERIALS AND METHODS:Lymphatic vessels were stained using lymphatic vessel endothelial hyaluronan receptor 1 and assessed in standard areas. The expression of VEGF-C was assessed by the number of positive epithelial cells. The data were compared with the clinical staging. RESULTS:The lowest LVD was found in tumorous areas as opposed to periphery and nontumorous tissue (P = 0.007; P < 0.001). The highest LVD was in BPH tissue (P < 0.001). There was no correlation with clinical staging. There was more VEGF-C staining in pN1 than in pN0 and in BPH specimens (P = 0.002). CONCLUSION:LVD is not a prognostic variable for the process of lymphogenic metastasis in prostate cancer. VEGF-C is up-regulated in prostate cancer and its correlation with lymph node status suggests a role for the development of lymph node metastasis, e.g. via an increased permeability of lymphatic vessels.

背景与目标：

BACKGROUND & AIMS: :The Authors report their personal experience relating to diagnostic screening for prostatic carcinoma using serum assays for specific markers of this tumour: prostatic acid phosphatase (PAP) and prostatic specific antigen (PSA). They underline the importance of high serum values of these substances, especially in tumors in an advanced state, and point out that these markers can play a role both in the diagnosis and in the follow-up of prostatic carcinoma.

背景与目标： : 作者报告了他们的个人经验，他们使用血清检测该肿瘤的特定标志物 (前列腺酸性磷酸酶 (PAP) 和前列腺特异性抗原 (PSA)) 进行前列腺癌诊断筛查。他们强调了这些物质的高血清值的重要性，尤其是在晚期肿瘤中，并指出这些标志物可以在前列腺癌的诊断和随访中发挥作用。

BACKGROUND & AIMS: :In recent years, there has been a marked increase in the number of approved therapies that increase survival of patients with castration-resistant prostate cancer. Current treatment guidelines provide therapeutic management recommendations, but these are primarily based on clinical factors such as performance status or site of metastasis (bone vs. visceral), and not on underlying molecular or cellular features of disease that may predict response. The ability to tailor treatment based on molecular or cellular features of disease could potentially reduce the occurrence of unnecessary side effects and ineffective treatments, and thereby reduce both direct and indirect medical costs. As such, it is important to identify and validate new prognostic and predictive molecular biomarkers that can be used to direct cancer treatment. This review will focus on existing and potential biomarkers in the context of castration-resistant prostate cancer management and discuss the need for continued discovery and validation of new biomarkers and biomarker panels for prostate cancer.

背景与目标： : 近年来，增加去势抵抗性前列腺癌患者生存率的批准疗法数量显着增加。当前的治疗指南提供了治疗管理建议，但这些建议主要基于临床因素，例如表现状态或转移部位 (骨与内脏)，而不是基于可能预测反应的疾病的潜在分子或细胞特征。根据疾病的分子或细胞特征定制治疗的能力可能会减少不必要的副作用和无效治疗的发生，从而减少直接和间接的医疗成本。因此，识别和验证可用于指导癌症治疗的新的预后和预测性分子生物标志物非常重要。这篇综述将重点关注去势抵抗性前列腺癌管理背景下的现有和潜在生物标志物，并讨论继续发现和验证前列腺癌新生物标志物和生物标志物的必要性。

BACKGROUND & AIMS: BACKGROUND:Major advances in our understanding of the underlying biology of prostate cancer have helped to herald a new era in the treatment of castration-resistant prostate cancer (CRPC), with 5 new agents having shown a survival advantage in the last 3 years and an impressive number of promising novel agents now entering the clinic. CONTENT:We discuss the challenges facing drug development for CRPC and strategies to meet these challenges, with a focus not only on the development of predictive and intermediate endpoint biomarkers, but also on novel hypothesis-testing, biomarker-driven clinical trial designs. SUMMARY:With several promising agents now entering the clinic, there is increasing pressure to rethink drug development for CRPC to ensure that novel agents are appropriately evaluated and that patients and resources are appropriately allocated. We envision that biomarker-driven, reiterative clinical trials will have a major impact on CRPC treatment through the testing of robust scientific hypotheses with rationally designed drugs and drug combinations administered to selected patients.

背景与目标：

BACKGROUND & AIMS: :Prostatic magnetic resonance images of 22 male volunteers less than 30 years old and with no known genito-urinary tract disease were obtained at 1.5 T. Normal anatomical features of the prostate were studied with spin-echo techniques. Different zones of the normal gland are shown by T2-weighted images: the anterior fibromuscular fascia, the central prostate, the peripheral prostate and the periurethral zone can be differentiated. The normal prostate gland is shown on T1-weighted images as a homogeneous appearance. It is important to recognize the normal zonal anatomy of the prostate since prostatic disorders arise in different anatomical zones.

背景与目标： : 在1.5 T时获得了22名30岁以下且没有已知生殖泌尿道疾病的男性志愿者的前列腺磁共振图像。使用自旋回波技术研究了前列腺的正常解剖特征。T2-weighted图像显示了正常腺体的不同区域: 可以区分前纤维肌筋膜，中央前列腺，外周前列腺和尿道周围区域。正常前列腺在T1-weighted图像上显示为均匀外观。重要的是要认识到前列腺的正常区域解剖结构，因为前列腺疾病发生在不同的解剖区域。

BACKGROUND & AIMS: :Terminally differentiated rhabdomyoblasts are common after or during therapy for rhabdomyosarcoma (RMS). Case reports have suggested that their presence after therapy does not indicate a poor prognosis, but significance and relationship to outcome has not been systematically studied. Management of patients with this finding can cause confusion. Slides and pathology reports from 44 patients with bladder/prostate RMS treated on Fourth Intergroup Rhabdomyosarcoma Study were examined by a pathologist experienced in RMS, and findings compared with institutional reports. Details regarding patient characteristics, outcome, and management were reviewed. Outcome of patients with various pathologic findings was assessed. One of 10 patients with only mature rhabdomyoblasts at their last procedure recurred, versus 4 of 17 patients with viable tumor and 2 of 17 patients with no viable tumor and no rhabdomyoblasts. Sixteen of 42 cases reviewed had results differing from our review. Mature rhabdomyoblasts are a discrete entity which may not be predictive of recurrence, but should be evaluated by a pathologist experienced with this entity. The presence of mature rhabdomyoblasts at the end of therapy for bladder/prostate RMS does not justify radical surgery. Sequential biopsies are subject to sampling error and should only be performed in the context of protocol-directed therapy to avoid unnecessary radical surgeries.

背景与目标： : 在横纹肌肉瘤 (RMS) 治疗后或治疗期间，晚期分化的横纹肌母细胞很常见。病例报告表明，治疗后它们的存在并不表明预后不良，但尚未系统地研究其意义和与结果的关系。对有此发现的患者进行管理可能会引起混乱。由RMS经验丰富的病理学家检查了在第四组间横纹肌肉瘤研究中接受治疗的44例膀胱/前列腺RMS患者的载玻片和病理报告，并将发现与机构报告进行了比较。回顾了有关患者特征，结果和管理的详细信息。评估了具有各种病理发现的患者的结局。最后一次手术中只有成熟横纹肌母细胞的10例患者中有1例复发，而17例有存活肿瘤的患者中有4例复发，而17例没有存活肿瘤且没有横纹肌母细胞的患者中有2例复发。在审查的42例病例中，有16例的结果与我们的审查不同。成熟的横纹肌母细胞是一个离散的实体，可能无法预测复发，但应由具有该实体经验的病理学家进行评估。膀胱/前列腺RMS治疗结束时存在成熟的横纹肌母细胞并不能证明根治性手术是合理的。顺序活检可能会出现采样误差，并且只能在方案指导的治疗中进行，以避免不必要的根治性手术。

BACKGROUND & AIMS: BACKGROUND:In a large number of studies a positive family history is documented as one of the main risk factors for the development of prostate cancer. In a US population an association between early-onset prostate cancer among familial patients and a more differentiated tumour was shown. The aim of this study was to compare clinical parameters between sporadic and familial or hereditary patients with an age at diagnosis < or =55 years. MATERIAL AND METHODS:The clinical data of prostate cancer patients with an age at diagnosis < or =55 years and who were recruited between July 1999 and the end of June 2004 to the database "familial prostate cancer in Germany" were analysed. The following data were documented for all patients: PSA at diagnosis, histopathological stage, grading, Gleason score and progression-free survival. RESULTS:The clinical data of 685 patients could be completed: 222 (32.4%) had one first-degree relative with prostate cancer, 48 of whom (7.0%) were hereditary; 463 (67.6%) were sporadic. The median age at diagnosis in the hereditary patients was 51.6 (41-55) years, in the familial patients 51.1 (35-55) years and in the sporadic patients 52.0 (38-55) years. The median follow-up was 24 months in hereditary, 36 months in familial and 35 months in sporadic patients. An initial curative therapy with radical prostatectomy or radiotherapy/brachytherapy was planned in 657/685 (95.9%) of the patients. There were no clear differences regarding PSA at diagnosis, the postoperative parameters (organ-confined disease, lymph node involvement, Gleason score, grading) and the progression-free survival in sporadic and familial or hereditary patients. CONCLUSIONS:Patients with an age at diagnosis < or =55 years have a positive family history more often than all prostate cancer patients in Germany. No association could be shown between pathohistological stage or clinical course and a positive family history in patients with an age at diagnosis < or =55 years.

背景与目标：

BACKGROUND & AIMS: :This paper reevaluates the recently reported excess mortality following transurethral resection of the prostate (TURP) for benign hypertrophy as compared with traditional open resection (OPEN). We studied survival through linkage of hospital discharge data with mortality data for the entire male population of Denmark (1977-85). For a maximum of 10.5 years 38,067 prostatectomy patients were followed. Adjusting for age and health status before surgery, TURP patients were subject to significantly higher levels of mortality than OPEN patients (RR = 1.19, 95% confidence interval (1.15-1.24). The extent to which this difference is attributable to the surgical intervention itself remains an open question. The two groups of patients are quite different with regard to age and preoperative health status, and available data may not be sufficient to control such differences through statistical analysis. On the other hand, the difference in mortality persisted over calendar time, even during periods when the pattern of utilization for the two procedures changed significantly (constant RR = 1.19, adjusting for age and comorbidity). The most important causes of death among Danish TURP patients differ from the causes suggested on the basis of previously reported Canadian data. The current evidence is thus ambiguous with regard to hypothetical biologic mechanisms behind the excess mortality over TURP patients. Further investigations are needed to evaluate the safety and effectiveness of prostate surgery.

背景与目标： : 本文重新评估了最近报道的经尿道前列腺切除术 (TURP) 与传统开腹切除术 (open) 相比，良性肥大的死亡率。我们通过将丹麦 (1977-85) 的整个男性人口的出院数据与死亡率数据联系起来研究了生存率。对38,067名前列腺切除术患者进行了最长10.5年的随访。调整手术前的年龄和健康状况，TURP患者的死亡率明显高于开放患者 (RR = 1.19，95% 置信区间 (1.15-1.24)。这种差异归因于手术干预本身的程度仍然是一个悬而未决的问题。两组患者在年龄和术前健康状况方面存在很大差异，并且可用的数据可能不足以通过统计分析来控制这种差异。另一方面，死亡率的差异在日历期间持续存在，即使在两种程序的使用模式发生显著变化的时期 (恒定RR = 1.19，调整年龄和合并症)。丹麦TURP患者中最重要的死亡原因不同于先前报告的加拿大数据所提出的原因。因此，目前的证据对于TURP患者死亡率过高背后的假想生物学机制是不明确的。需要进一步的研究来评估安全性和前列腺手术的有效性。

BACKGROUND & AIMS: BACKGROUND:Androgen regulation and prostate-specific expression of targeted genes in transgenic mice can be controlled by a small DNA fragment of the probasin (PB) promoter (-426 to +28 base pairs, bp). Although the small PB fragment was sufficient to direct prostate-specific expression, the low levels of transgene expression suggested that important upstream regulatory sequences were missing.

METHODS:To enhance transgene expression, a large fragment of the PB promoter (LPB, -11,500 to +28 bp) was isolated, linked to the bacterial chloramphenicol acetyl transferase (CAT) gene, and microinjected into CD1 mouse oocytes to generate transgenic mouse lines.

RESULTS:As shown by the immunohistochemical studies, CAT gene expression was restricted to the prostatic epithelial cells in a tissue-specific manner. High levels of CAT gene expression were observed in two of the six LPB-CAT transgenic lines. In Line 1, developmental regulation of LPB-CAT was detected early, from 1 to 4 weeks of age, with the activity of CAT increasing from 3 to 40,936 dpm/min/mg protein. Upon sexual maturation and elevated serum androgen levels (7 weeks of age), a further 18-fold rise in CAT activity occurred. Hormone ablation by castration in mature mice dramatically reduced transgene expression, whereas treatment with androgens returned LPB-CAT expression to precastration levels. In contrast, treatment with glucocorticoids had no significant effect on CAT gene expression. Zinc treatment of the castrated animals also increased LPB-CAT expression three- to four-fold in two prostatic lobes.

CONCLUSIONS:This study demonstrates that important regulatory DNA sequences located in the LPB fragment contribute to tissue-specific expression and greatly increase levels of transgene expression induced by androgens and zinc.

背景与目标： 背景 : 转基因小鼠中靶向基因的雄激素调节和前列腺特异性表达可以由probasin (PB) 启动子的小DNA片段 (-426至 + 28个碱基对，bp) 控制。尽管小的PB片段足以指导前列腺特异性表达，但低水平的转基因表达表明重要的上游调控序列缺失。
方法 : 为了增强转基因表达，PB启动子的大片段 (LPB，-分离出11,500至28 bp)，与细菌氯霉素乙酰转移酶 (CAT) 基因连接，并将其微注射到CD1小鼠卵母细胞中，以生成转基因小鼠品系。
结果 : 如免疫组织化学研究所示，CAT基因表达以组织特异性方式限制在前列腺上皮细胞中。在六个LPB-CAT转基因品系中的两个中观察到高水平的CAT基因表达。在第1行中，从1至4周龄早期检测到LPB-CAT的发育调节，CAT的活性从3 dpm/min/mg增加到40,936 dpm/min/mg蛋白。性成熟和血清雄激素水平升高 (7周龄) 后，CAT活性进一步增加了18倍。成熟小鼠中去势的激素消融显着降低了转基因表达，而雄激素治疗使LPB-CAT表达恢复到去势前水平。相反，糖皮质激素治疗对CAT基因表达没有显着影响。Cast割动物的锌治疗还使两个前列腺叶中的LPB-CAT表达增加了三到四倍。
结论 : 这项研究表明，位于LPB片段中的重要调控DNA序列有助于组织特异性表达，并大大提高了雄激素和锌诱导的转基因表达水平。

BACKGROUND & AIMS: BACKGROUND:The majority of patients receive HT after biochemical progression despite primary therapy of prostate cancer with curative intent. It is difficult to differentiate at a low rise in PSA level, e.g.,