Age-specific reference ranges for prostate-specific antigen among healthy Syrian men

Prostate-specific antigen (PSA) has become the most useful serum tumor marker in adjunct to digital rectal examination (DRE) for the management of prostate cancer (PC). The currently cited reference range of normal PSA levels (between 0 and 4.0 ng/mL) is deficient in terms of both sensitivity and specificity. Age-adjusted PSA have been proposed as an alternative to serum PSA. The primary objective of the present study is to determine the age-specific PSA and the percentage of free PSA (%FPSA) in healthy Syrian men. A total of 3,000 healthy Syrian men over 40 years old participated in this study. All men were asked to have total serum (TPSA) and free PSA (FPSA) tested, a DRE, and, when recommended, a prostate biopsy. Serum TPSA levels correlated with age (r=0.30, p<0.001). The 95th percentile TPSA values ranged from 1.7 ng/mL in the age group 40-49 years to 5.8 ng/mL in the group 70-80 years. The general pattern for medians and the percentile values for FPSA across age groups were similar to those seen for TPSA concentrations (r=0.37, p<0.001). However, the %FPSA was fairly constant across age groups except for the higher ratios in the youngest age group. These findings confirm that the serum TPSA and FPSA levels correlate with age. Interestingly, however, Syrian men have lower PSA values compared with other races. Racial differences of PSA concentrations were observed. Our results may help increasing the sensitivity and specificity of PSA measurements in the diagnosis of prostate cancer in Syria and probably in the surrounding regions.     

经直肠剪切波弹性成像技术联合血清CEA、PSA、FPSA对前列腺良恶性病变的鉴别诊断价值研究

摘要 目的：研究经直肠剪切波弹性成像技术（TRSWE）联合血清癌胚抗原（CEA）、前列腺特异性抗原（PSA）、游离前列腺特异性抗原（FPSA）对前列腺良恶性病变的鉴别诊断价值。方法：选取合肥市第二人民医院2019年1月～2022年6月收治的90例前列腺病变患者,根据病理检查分为前列腺癌组（47例）和前列腺良性病变组（43例）。对所有前列腺病变患者均行TRSWE检查,分析前列腺良恶性病变的图像差异以及弹性模量最大值（Emax）、弹性模量平均值（Emean）。检测所有前列腺病变患者的血清CEA、PSA、FPSA水平并进行对比。采用受试者工作特征（ROC）曲线分析明确Emax值、Emean值以及血清CEA、PSA、FPSA水平联合诊断前列腺良恶性病变的效能。结果：前列腺癌组Emax值、Emean值均高于前列腺良性病变组（均P＜0.05）。前列腺癌组血清CEA、PSA及FPSA水平均高于前列腺良性病变组（均P＜0.05）。经ROC曲线分析发现,Emax值、Emean值以及血清CEA、PSA、FPSA水平联合检测诊断前列腺良恶性病变的效能优于上述5项指标单独检测。结论：TRSWE联合血清CEA、PSA、FPSA对前列腺良恶性病变的鉴别诊断价值较高,可有效提升前列腺癌的检出率,可能值得临床推广应用。     

血清前列腺特异性抗原与前列腺增生的相关性研究

目的:探讨前列腺增生患者年龄,前列腺体积以及BMI与血清前列腺特异性抗原(PSA)之间的关系。方法:对224例前列腺增生患者的年龄,前列腺体积以BMI与PSA的相关性进行Spearman相关性分析。结果:224例前列腺增生患者有25%的患者PSA水平高于正常,并且年龄,前列腺体积与血清PSA存在明显的正相关:(r=0.672.P<0.01,r=0.785.P<0.01),而血清PSA与BMI指数存在明显的负相关:(r=-0.873,P<0.01)。结论:前列腺增生患者的血清PSA值随患者年龄增长和体积增大而增加,对于PSA轻度升高的前列腺增生患者,要考率到体重因素对结果的影响。     

血清PSA、EGF在不同类型良性前列腺增生患者中表达意义及其与术后疾病转归的相关性分析

摘要 目的：分析血清前列腺特异抗原（PSA)、表皮生长因子（EGF)在不同类型良性前列腺增生患者中低表达意义及其与术后疾病转归的相关性。方法：选择自2020年1月至2022年12月在我院接受手术治疗的128例良性前列腺增生患者作为研究对象,根据术后病理活检结果进行分组,间质结节组（16例）、腺肌性结节组（32例）、纤维腺瘤性结节组（12例）、腺性结节组（30例）和混合结节组（38例）,其中以间质增生为主60例、以腺体增生为主68例。检测所有患者血清PSA、EGF的表达水平,以术后6个月的国际前列腺症状评分（IPSS评分）<8分判定为预后良好,分析血清PSA、EGF在预后良好组与预后不良组之间的差异性及与IPSS评分的关系。结果：血清PSA、EGF表达水平在间质结节组、腺肌性结节组、纤维腺瘤性结节组、腺性结节组和混合结节组间比较有差异（P<0.05）;以腺体增生为主的良性前列腺增生患者血清PSA、EGF表达水平均明显高于以间质增生为主的患者（P<0.05）;经ROC曲线分析,血清PSA联合EGF预测以腺体增生为主的良性前列腺增生的敏感度为86.42%,特异度为65.34%,AUC为0.930;所有患者均获得随访6个月,预后良好98例、预后不良30例;预后不良组血清PSA、EGF表达水平均明显高于预后良好组（P<0.05）;经Pearson相关性分析,良性前列腺增生患者血清PSA、EGF表达水平均与IPSS评分呈负相关（r值分别为-0.348、-0.417,P值均为0.000）。结论：血清PSA、EGF在不同病理类型良性前列腺增生患者中表达差异显著,以间质增生为主的患者,以腺体增生为主的患者血清PSA、EGF表达水平更高,两者均与术后疾病转归密切相关,值得临床予以重视。     

Clinical utility of prostatic specific antigen and prostatic acid phosphatase serum levels in monitoring prostate cancer

We analysed 696 prostatic specific antigen (PSA) and prostatic acid phosphatase (PAP) serum samples by double antibody radioimmunoassay (RIA)I125 in the follow-up of 122 patients with prostate cancer under treatment. PSA levels were significantly correlated to response to treatment, whereas PAP results did not differentiate patients with partial or complete remission. Progression of the disease was detected in 95.2 and 85.4% of PSA and PAP samples, and increased to 99.9% using both simultaneously. On the whole, PSA was better than PAP in monitoring prostate cancer, and the efficacy was greater using both markers together.     

Impact of genotyping on outcome of prostatic biopsies: a multicenter prospective study

Single nucleotide polymorphisms (SNPs) have been associated with prostate cancer (PCa) risk and tumor aggressiveness in retrospective studies. To assess the value of genotyping in a clinical setting, we evaluated the correlation between three genotypes (rs1447295 and rs6983267[8q24] and rs4054823[17p12]) and prostatic biopsy outcome prospectively in a French population of Caucasian men. Five hundred ninety-eight patients with prostatic-specific antigen (PSA) >4 ng/mL or abnormal digital rectal examination (DRE) participated in this prospective, multicenter study. Age, familial history of PCa, body mass index (BMI), data of DRE, International Prostate Symptom Score (I-PSS) score, PSA value and prostatic volume were collected prospectively before prostatic biopsy. Correlation between genotypes and biopsy outcome (positive or negative) and Gleason score (≤6 or >6) were studied by univariate and multivariable analysis. rs1447295 and rs6983267 risk variants were found to be associated with the presence of PCa in univariate analysis. rs6983267 genotype remained significantly linked to a positive biopsy (odds ratio [OR] = 1.66, 95% confidence interval [CI]: 1.06-2.59, P = 0.026) in multivariable analysis, but rs1447295 genotype did not (OR = 1.47, 95% CI: 0.89-2.43, P = 0.13).When biopsy outcome was stratified according to Gleason score, risk variants of rs1447295 were associated with aggressive disease (Gleason score ≥7) in univariate and multivariable analysis (OR = 2.05 95% CI: 1.10-3.79, P = 0.023). rs6983267 GG genotype was not related to aggressiveness. The results did not reach significance concerning rs4054823 for any analysis. This inaugural prospective evaluation thus confirmed potential usefulness of genotyping PCa assessment. Ongoing clinical evaluation of larger panels of SNPs will detail the actual impact of genetic markers on clinical practice.     

Comparison of digital rectal examination and prostate specific antigen in early detection of prostate cancer

This study compares the value of digital rectal examination (DRE) and prostate specific antigen (PSA) determination in the detection of prostate cancer. 1,000 men aged > or = 50 from the Osijek surroundings were examined. The subjects with prostatitis were excluded from the study. The subjects with elevated concentration of total prostate specific antigen and/or digital rectal examination suspect of carcinoma underwent prostate biopsy. The rate of prostate cancer detection showed to be 3.3% for PSA > 4 ng/ml, 2% for abnormal finding of DRE, and 3.7% for combination of the two methods. Out of 35 patients with prostate cancer detected, 19 had suspect DRE finding and 32 had PSA exceeding 4 ng/ml. Thus, PSA pointed to the diagnosis of prostate cancer in 91.4%, and abnormal finding of DRE in 54.2% of cases, the difference being statistically significant. The positive predictive value was 48.7% for abnormal finding of DRE, 47% for PSA > 4 ng/ml, and 80.0% for the combination of both. Although PSA determination detected a considerable proportion of tumors missed on DRE, the former alone was found to be insufficient as a screening method because of its inadequate sensitivity. When combined with digital rectal examination, the probability of prostate cancer detection increased considerably.     

血清前列腺特异性抗原与前列腺增生的相关性研究

目的：探讨前列腺增生患者年龄,前列腺体积以及BMI与血清前列腺特异性抗原（PSA）之间的关系。方法：对224例前列腺增生患者的年龄,前列腺体积以BMI与PSA的相关性进行Spearman相关性分析。结果：224例前列腺增生患者有25％的患者PSA水平高于正常,并且年龄,前列腺体积与血清PSA存在明显的正相关：（r=0．672．P〈0．01,r=0．785．P〈0．01）,而血清PSA与BMI指数存在明显的负相关：（r=-0．873,P〈0．01）。结论：前列腺增生患者的血清PSA值随患者年龄增长和体积增大而增加,对于PSA轻度升高的前列腺增生患者,要考率到体重因素对结果的影响。     

Correlation of modified Gleason grading of prostate carcinoma with age, serum prostate specific antigen and tumor extent in needle biopsy specimens

OBJECTIVE: To investigate the correlation of biopsy grade with age, serum prostate specific antigen (PSA) and biopsy tumor extent using the conventional and modified Gleason grading systems. STUDY DESIGN: A total of 828 consecutive needle biopsy specimens of prostate carcinoma were collected from the years 1995 and 2000 (graded with conventional Gleason grading) and 2006 and 2007 (graded with modified Gleason grading). RESULTS: Both conventional and modified Gleason grading correlated with age, serum PSA, percent positive biopsies and percent cancer length. In 2006-2007, the patients were on average younger and more biopsy cores were taken per patient. Serum PSA and percent positive cores were lower than in the 1995 and 2000 group, indicating a stage shift downward, but the Gleason scores were nevertheless higher. CONCLUSION: Conventional and modified Gleason grading both correlated with age, serum PSA and cancer involvement in needle biopsies. With modified Gleason grading there is a grade shift upward despite the downstaging that has been observed in recent years.     

磁共振成像联合血清前列腺特异抗原、上皮钙黏蛋白、早期前列腺癌抗原-2诊断前列腺癌的临床价值探讨

摘要 目的：探究磁共振成像（MRI）联合血清前列腺特异抗原（PSA）、上皮钙黏蛋白（sE-cadherin）、早期前列腺癌抗原-2（EPCA-2）诊断前列腺癌的临床价值。方法：选取潍坊市人民医院2020年1月-2021年7月期间经病理证实的50例前列腺癌患者（前列腺组）以及50例前列腺增生患者（前列腺增生组）展开回顾性研究。100例研究对象均完善了MRI检查并测定血清PSA、EPCA-2、sE-cadherin水平,分析两组患者的MRI影像学特征,比较两组患者的PSA、EPCA-2、sE-cadherin水平以及各项检查方法的诊断准确性差异。结果：前列腺癌的MRI影像学特征为病灶主要位于外周带,外周带T2W呈低信号,病变侵及包膜、膀胱及周围组织具有T1加权消失或者不对称,具有信号异常、肌肉增厚的表现,盆腔淋巴结转移具有淋巴结部分融合或增大表现;前列腺增生的MRI影像学特征为边界清晰、包膜完整并且中央带增生、不均匀信号结节;前列腺癌、前列腺增生均存在不同程度的前列腺体积增大。相比于前列腺增生组,前列腺癌组患者的PSA、sE-cadherin、EPCA-2水平明显更高（P<0.05）。MRI、PSA、sE-cadherin、EPCA-2四项联合鉴别前列腺癌、前列腺增生的诊断符合率为96.00%,明显高于四项单独诊断的88.00%、79%、81%、82%（P<0.05）。结论：MRI联合PSA、sE-cadherin、EPCA-2鉴别诊断前列腺癌的准确性较高,具有作为临床前列腺癌早期诊断指导方案的潜力。     

The 4Kscore? Test Reduces Prostate Biopsy Rates in Community and Academic Urology Practices

There is significant concern regarding prostate cancer screening because of the potential for overdiagnosis and overtreatment of men who are discovered to have abnormal prostate specific antigen (PSA) levels and/or digital rectal examination (DRE) results. The 4Kscore® Test (OPKO Diagnostics, LLC) is a blood test that utilizes four kallikrein levels plus clinical information in an algorithm to calculate an individual’s percentage risk (< 1% to > 95%) for aggressive prostate cancer (Gleason score ≥ 7) on prostate biopsy. The 4Kscore Test, as a follow-up test after abnormal PSA and/or DRE test results, has been shown to improve the specificity for predicting the risk of aggressive prostate cancer and reduce unnecessary prostate biopsies. A clinical utility study was conducted to assess the influence of the 4Kscore Test on the decision to perform prostate biopsies in men referred to urologists for abnormal PSA and/or DRE results. The study population included 611 patients seen by 35 academic and community urologists in the United States. Urologists ordered the 4Kscore Test as part of their assessment of men referred for abnormal PSA and/or DRE test results. Results for the patients were stratified into low risk (< 7.5%), intermediate risk (7.5%–19.9%), and high risk (≥ 20%) for aggressive prostate cancer. The 4Kscore Test results influenced biopsy decisions in 88.7% of the men. Performing the 4Kscore Test resulted in a 64.6% reduction in prostate biopsies in patients; the actual percentage of cases not proceeding to biopsy were 94.0%, 52.9%, and 19.0% for men who had low-, intermediate-, and high-risk 4Kscore Test results, respectively. A higher 4Kscore Test was associated with greater likelihood of having a prostate biopsy (P < 0.001). Among the 171 patients who had a biopsy, the 4Kscore risk category is strongly associated with biopsy pathology. The 4Kscore Test, as a follow-up test for an abnormal PSA and/or DRE results, significantly influenced the physician and patient shared decision in clinical practice, which led to a reduction in prostate biopsies while increasing the probability of detecting aggressive cancer.Key Words: Prostate cancer, Prostate-specific antigen, Digital rectal examination, Biopsy rate, Gleason score, 4Kscore Test, Prostate cancer prognosisWidespread screening for prostate cancer with serum prostate-specific antigen (PSA) began in 1991, and subsequently a 45% decline in prostate cancer mortality has been observed.¹ A recent large European randomized clinical trial also reported a 29% reduction in death from prostate cancer in men undergoing routine screening.² However, because of a US study that showed no mortality benefits to organized PSA screening,³ and the net physical and psychologic burden of secondary adverse events triggered by PSA testing versus the number of lives saved, the United States Preventative Services Task Force (USPSTF) recently advised against routine PSA screening for prostate cancer.⁴ The concern of the USPSTF is based on the fact that most men diagnosed with prostate cancer have a tumor that is unlikely to pose a threat to life expectancy. A recent systematic analysis suggested that up to 60% of prostate cancers diagnosed in contemporary studies might be safely observed without a need for immediate intervention.⁵One of the primary challenges for urologists is the potential for under-grading of Gleason 6 prostate cancer due to biopsy sampling error; as a result, up to 90% of men with a Gleason 6 prostate cancer still proceed to prostate cancer treatment despite the advent of active surveillance programs. Approximately 66% of patients who are diagnosed with Gleason 6 disease at biopsy will be confirmed to have Gleason 6 cancer after radical prostatectomy.⁶ Some of these men are considered to have undergone overtreatment, because Gleason 6 cancer is not considered life threatening.⁷ This subset of men has the potential for developing complications following surgery, including erectile dysfunction, urinary incontinence, and changes in health-related quality of life with disruption of psychologic, sexual, and urinary function.^8–12The prostate biopsy procedure is invasive, and has significant costs and complications such as bleeding, urinary retention, and life-threatening infection. A recent population-based study from Ontario, Canada, revealed a fourfold increase to 4.1% for the rate of hospital admissions after prostate biopsy from 1996 to 2005, with 72% of admissions due to infection.¹³ These risks, combined with the anxiety involved in undergoing the procedure, present a significant burden to any man considering prostate cancer screening.The impact of the USPSTF has been a decrease in overall biopsy rates with a subsequent decline in the detection rate of Gleason 7 to 10 high-grade prostate cancers.¹⁴ The elimination of PSA screening means that the 20% to 30% of men who would have presented with an abnormal PSA level and been found to have high-grade prostate cancer may lose an opportunity for a possible cure.¹⁵ Clearly, there is a need for better risk-stratification tools for men presenting with an abnormal PSA level and/or digital rectal examination (DRE) result in order to both reduce the number of prostate biopsies performed and decrease the rate of Gleason 6 diagnosis and treatment.⁶The 4Kscore® Test (OPKO Diagnostics, LLC) incorporates measured blood levels of four kallikrein proteins: total PSA, free PSA, intact PSA, and human kallikrein 2 plus clinical information (age, DRE findings, and a history of prior negative biopsy result) into a proprietary algorithm to calculate an individual man’s percentage risk (< 1% to > 95%) of having Gleason score ≥ 7 if a prostate biopsy were to be performed. The 4Kscore Test has been extensively validated through a total of 12 prospective and retrospective studies published in peer-reviewed journals involving over 22,000 patients from both the United States and Europe.^16–23 These studies of men with elevated PSA levels involved cohorts of unscreened and screened men, and those with negative prior prostate biopsy results. Based on analyses published in these studies, the 4Kscore Test would have theoretically resulted in a 45% reduction in prostate biopsies while delaying the diagnosis of aggressive prostate cancer in only a few men (1.3%–4.7%).The 4Kscore Test is used to accurately determine percentage risk for aggressive prostate cancer (Gleason score ≥ 7) and provide additional information for men being considered for prostate biopsy because of abnormal PSA levels and/or DRE results. This allows urologists to better risk stratify men for biopsy and ultimately results in more selective treatment of those men with aggressive disease. Conversely, those men not harboring life-threatening disease are able to safely avoid prostate biopsy and overtreatment of indolent disease.With the introduction of any new diagnostic test such as the 4Kscore Test into clinical practice, it is important to assess whether its implementation, in this case as a follow-up test for an abnormal PSA and/or DRE result, influences and changes the physician-patient shared decision-making process and leads to an actual reduction in prostate biopsies. Herein we evaluated the influence of the 4Kscore Test on urologist-patient decisions about proceeding with biopsy in men who have an abnormal PSA and/or DRE result from multiple academic and community urology clinical practices in the United States.     

Summary of our clinical experience with the determination of serum prostate-specific antigen level in the first five years

The authors determined serum PSA levels in combination with digital rectal examination (DRE) and evaluated their role in the differential diagnosis of prostate diseases with special reference to cancer. The possible causes of differences between the observed cut-off level of PSA and the standard level PSA were analyzed. In the last few years the PSA determination found its clinical role in the diagnosis of prostate cancer.     

血清CD5L对肝脏疾病患者的临床意义研究

摘要 目的：检测CD5L水平在肝脏疾病患者血清中的变化,并分析其临床意义。方法：采用ELISA法检测41例慢性肝炎患者、192例肝硬化患者、69例肝癌患者和136例健康对照血清CD5L水平。全自动生化分析仪测定肝功能指标,Spearman相关性分析用于评估CD5L与肝功能指标的关系。受试者工作曲线（receiver operator characteristic, ROC）分析血清CD5L的潜在诊断价值。结果：与健康对照相比,CD5L水平在肝炎、肝硬化、肝癌患者中显著降低（P<0.01）。肝硬化患者血清CD5L水平较肝炎及肝癌患者显著降低（P<0.01）。肝硬化代偿期和失代偿期患者血清CD5L水平无显著差异。血清CD5L水平与FIB-4指数(肝纤维化评分)呈显著负相关（r=-0.2688,P=0.0001）。Spearman相关性分析结果显示：在肝炎患者中,血清CD5L与总胆红素（T-BIL）、直接胆红素（D-BIL）、间接胆红素（I-BIL）显著正相关;在肝硬化患者中,CD5L与其他肝功指标无显著相关性;在肝癌患者中,CD5L与碱性磷酸酶（ALP）显著正相关。以健康人为对照组,肝硬化患者为病例组,ROC分析显示血清CD5L的诊断特异性为85.3%,敏感性为77.1%。结论：CD5L水平在肝炎、肝硬化及肝癌患者血清中显著降低,且在肝硬化患者中最低。CD5L水平与肝纤维化评分FIB-4指数负相关,可作为监测肝纤维化进展的潜在生物标志物。     

Contribution of Genetic Variation rs266882 to Prostate-Specific Antigen Levels in Healthy Controls with Serum PSA Below 2.0 ng/ml

We evaluated the impact of genetic variation in the prostate-specific antigen (PSA) gene (rs266882) on serum PSA levels in healthy men as well as risk factors for benign prostate hypertrophy (BPH) and prostate cancer. The study population comprised 91 men with PSA levels below 2.0 ng/ml as healthy controls, 78 men with PSA 2–10 ng/ml as a BPH group, and 128 prostate cancer patients, all in Korea. DNA was amplified by polymerase chain reaction and the product was sequenced. We found that PSA levels were associated with a G/A polymorphism only in healthy controls. The transition, however, was not associated with PSA levels of BPH and cancer patients, nor was it a risk factor. In conclusion, this genetic factor is important for determining serum PSA levels in the naive group, whereas the disruption of prostatic architecture in BPH or prostate cancer may be a major determining factor for PSA levels.     

Effects on the prostate of environmental cadmium exposure--a cross-sectional population study in China.

To explore possible effects of environmental cadmium exposure on prostate in humans, and the possible relationship of serum sex hormones to occurrence of clinic signs of tissue changes in the prostate, a case-control study was undertaken in the southeast part of China in 1998. A total of 297 male volunteers from a control area and two cadmium-polluted areas were included as subjects in this study. All the subjects were required to answer a questionnaire and to undergo a complete physical examination including digital-rectal examination (DRE). Blood and urine samples were collected. Serum total prostate specific antigen (PSA), total serum testosterone (T), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured by radioimmunoassay and enzymeimmunoassay method, respectively. The data of urinary cadmium (U-Cd) and blood cadmium (B-Cd) were obtained by atomic absorption spectrometry (AAS) as an indicator of cadmium body burden. Statistical analysis was applied to investigate a possible relation between cadmium exposure and prostate pathological changes. The results show that there is a clear dose-response relationship between cadmium exposure and the prevalence of cases with abnormal PSA. The blood cadmium content in cases with positive DRE was significantly higher than that of subjects with negative DRE (P < 0.05). Significant differences in the level of FSH between cases with positive DRE and the normal subjects were also noted (P < 0.05). These results indicate that chronic environmental cadmium exposure is associated with injuries to human prostate. A possible relationship to changes in circulating sex hormones needs further investigation.     

Using Biopsy to Detect Prostate Cancer

Transrectal ultrasound-guided systemic biopsy is the recommended method in most cases with suspicion of prostate cancer. Transrectal periprostatic injection with a local anesthetic may be offered as effective analgesia; periprostatic nerve block with 1% or 2% lidocaine is the recommended form of pain control. On initial biopsy, a minimum of 10 systemic, laterally directed cores is recommended, with more cores in larger glands. Extended prostate biopsy schemes, which require cores weighted more laterally at the base (lateral horn) and medially to the apex, show better cancer detection rates without increasing adverse events. Transition zone biopsies are not recommended in the first set of biopsies, owing to low detection rates. One set of repeat biopsies is warranted in cases with persistent indication. Saturation biopsy (≥20 cores) should be reserved for repeat biopsy in patients who have negative results on initial biopsy but who are still strongly suspected to have prostate cancer.Key words: Prostate cancer, Biopsy, Transrectal ultrasound, Prostate-specific antigen, Anesthesia, NomogramsProstate cancer rarely causes symptoms until it is advanced. Thus, suspicion of prostate cancer resulting in a recommendation for prostatic biopsy is most often raised by abnormalities found on digital rectal examination (DRE) or by serum prostate-specific antigen (PSA) elevations. Although there is controversy regarding the benefits of early diagnosis, it has been demonstrated that an early diagnosis of prostate cancer is best achieved using a combination of DRE and PSA.Transrectal ultrasound (TRUS)-guided, systematic needle biopsy is the most reliable method, at present, to ensure accurate sampling of prostatic tissue in men considered at high risk for harboring prostatic cancer on the basis of DRE and PSA findings. In very rare circumstances, a biopsy of a metastatic site (bone lesion) or a suspicious lymph node may be easier and more advantageous. There are also circumstances in which the usual transrectal route is not feasible (eg, status post-anteroposterior resection of the rectosigmoid; see Tissue Diagnosis in Patients with No Rectal Access section, below). As nearly universal as the approach, as nearly universal is the technique, namely a TRUS-guided biopsy using an 18-gauge needle to obtain a tissue core. To be certain, the same biopsy device and needle may be used to perform a finger-guided biopsy, but this is reserved for unusual circumstances (eg, TRUS imaging not available, finger-guided directed biopsy of suspicious nodule not seen on TRUS). Last, whereas in decades past physicians in many countries performed fine-needle aspiration of the prostate, today this technique is less and less often used, although advocates claim that it is cheaper, faster, easier to perform, and results in lower morbidity than any other technique developed to date. Appropriate training in performing transrectal fine-needle aspiration of the prostate and in interpreting the smears is, of course, essential.¹ Fine-needle aspiration plays a major role in the aforementioned situations in which diagnosis is established from nonprostatic tissue sources, such as lymph nodes and others.^2,3Since the landmark study by Hodge and colleagues⁴ demonstrating the superiority of TRUS guidance compared with digitally guided biopsy, the TRUS-guided biopsy technique has become the worldwide accepted standard in prostate cancer diagnosis. Statistical performance (sensitivity, specificity, positive and negative predictive values) of all other diagnostic tests (eg, DRE and PSA assay) is calculated according to the assignment (cancer present vs absent) made by prostate biopsy. Recognizing the fact that all sampling procedures, including prostate biopsies, incur the risk of returning false-negative results (ie, cancer is present but missed by the biopsies), calculation of the statistical performance characteristics of all other tests using biopsy outcomes as the gold standard are inherently incorrect and biased. Similarly, when comparing the statistical performance of various biopsy strategies, usually the most extensive strategy is chosen as the gold standard to define disease presence or absence, and the performance of all other strategies is calculated on the basis of that particular strategy, again incurring a significant bias due to the remaining falsenegative rate of even the most extensive sampling strategy.     

Measurement of aberrant glycosylation of prostate specific antigen can improve specificity in early detection of prostate cancer

Introduction

We previously identified prostate cancer (PCa)-associated aberrant glycosylation of PSA, where α2,3-linked sialylation is an additional terminal N-glycan on free PSA (S2,3PSA). We then developed a new assay system measuring S2,3PSA using a magnetic microbead-based immunoassay. We compared the diagnostic accuracy of conventional PSA and percent-free PSA (%fPSA) tests.

Methods

We used MagPlex beads to measure serum S2,3PSA levels using anti-human fPSA monoclonal antibody (8A6) for capture and anti-α2,3-linked sialic acid monoclonal antibody (HYB4) for detection. We determined the cutoff values in a training test and measured serum S2,3PSA levels in 314 patients who underwent biopsy, including 138 PCa and 176 non-PCa patients with PSA of <10.0 ng/ml. Serum S2,3PSA levels were presented as mean fluorescence intensity (MFI). Receiver operating characteristic curves were used to evaluate the diagnostic accuracy of total PSA, %fPSA, and S2,3PSA.

Results

We determined an MFI cutoff value of 1130 with a sensitivity of 95.0% and specificity of 72.0% for the diagnosis of PCa in the training test. In the validation study, the area under the curve for the detection of PCa with S2,3PSA was 0.84, which was significantly higher than that with PSA or %fPSA.

Conclusions

Although the present study is small and preliminary, these results suggest that the measurement of serum S2,3PSA using a magnetic microbead-based immunoassay may improve the accuracy of early detection of PCa and reduce unnecessary prostate biopsy.     

Effects on the prostate of environmental cadmium exposure – A cross-sectional population study in China

To explore possible effects of environmental cadmium exposure on prostate in humans, and the possible relationship of serum sex hormones to occurrence of clinic signs of tissue changes in the prostate, a case-control study was undertaken in the southeast part of China in 1998. A total of 297 male volunteers from a control area and two cadmium-polluted areas were included as subjects in this study. All the subjects were required to answer a questionnaire and to undergo a complete physical examination including digital-rectal examination (DRE). Blood and urine samples were collected. Serum total prostate specific antigen (PSA), total serum testosterone (T), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured by radioimmunoassay and enzymeimmunoassay method, respectively. The data of urinary cadmium (U-Cd) and blood cadmium (B-Cd) were obtained by atomic absorption spectrometry (AAS) as an indicator of cadmium body burden. Statistical analysis was applied to investigate a possible relation between cadmium exposure and prostate pathological changes. The results show that there is a clear dose-response relationship between cadmium exposure and the prevalence of cases with abnormal PSA. The blood cadmium content in cases with positive DRE was significantly higher than that of subjects with negative DRE (P<0.05). Significant differences in the level of FSH between cases with positive DRE and the normal subjects were also noted (P<0.05). These results indicate that chronic environmental cadmium exposure is associated with injuries to human prostate. A possible relationship to changes in circulating sex hormones needs further investigation.     

Clinical behaviour of prostatic specific antigen and prostatic acid phosphatase: a comparative study

We assayed prostatic specific antigen (PSA) and prostatic acid phosphatase (PAP) serum levels in 1383 patients using a double antibody radioimmunoassay (RIA) I125. Establishing the upper normal limit in 10 ng/ml PSA and 2.5 ng/ml for PAP, the false positive results were only 1.9 and 5.1 percent in men with non-prostatic benign or malignant pathology and respectively 0 and 2.2 percent in women. We detected false positive levels for these two tumoral markers in 3.5 and 4.7 percent of patients with non-complicated benign prostatic hypertrophy, 64.8 and 19.2 percent in complicated benign prostatic hypertrophy, 24 and 16 percent in acute prostatitis and 3.3 percent in chronic prostatitis. The sensitivity in patients with prostate cancer was 87.2 percent for PSA and 64.1 percent for PAP, and there was a better correlation with PSA than PAP for tumoral spread and histological grading. Finally, clinical efficacy was higher with PSA and was no better when both markers were assayed.     

Decreased serum osteocalcin levels in patients with liver cirrhosis

Serum levels of osteocalcin (OC) have been found to be a specific biochemical parameter of bone formation. We measured serum levels of osteocalcin, parathyroid hormone (PTH) and 25-hydroxyvitamin D (25(OH)D) in 49 patients with liver cirrhosis, who are known to have an increased prevalence of metabolic bone disease, and a matched control group (n = 35). Serum levels of OC were significantly decreased in the patients with liver cirrhosis when compared to control subjects (P < 0.001). Serum levels of 25(OH)D were decreased (P < 0.001), whereas no statistical difference was found between the serum levels of PTH in the patients with liver cirrhosis and those of the controls. In a subgroup of 23 patients with cirrhosis of the liver and 34 control subjects, the bone mineral content (BMC) of the non-dominant forearm was determined by single photon absorptiometry. BMC was significantly lower in the patient with liver cirrhosis than the control subjects (P < 0.04). Our data demonstrate vitamin D deficiency, decreased bone formation and a decreased BMC in patients with liver cirrhosis.