Prospective identification of National Institutes of Health category IV prostatitis in men with elevated prostate specific antigen

PURPOSE: Although prostatitis may cause elevated prostate specific antigen (PSA), asymptomatic patients are not routinely screened for this diagnosis before transrectal biopsy is performed to rule out cancer. Many negative biopsies reveal evidence of prostatitis classified as National Institutes of Health (NIH) category IV prostatitis or asymptomatic inflammation. To our knowledge this report represents the initial study of the incidence of NIH category IV prostatitis in men before biopsy and its clinical significance. MATERIALS AND METHODS: From 1996 to 1998 asymptomatic men with elevated PSA levels were evaluated for laboratory signs of prostatitis. Patients with expressed prostatic secretions or post-prostate massage urine (voiding bottle 3 [VB3]) positive for greater than 20 and greater than 10 white blood cells per high power field, respectively, received antibiotics for 4 weeks and were reevaluated after 6 to 8 weeks. Men without these clinical signs promptly underwent biopsy. Those with acute urinary tract infection and PSA greater than 30 ng./ml., without a rectum or who refused biopsy were excluded from study. RESULTS: Of the 187 study patients 122 were evaluable with a mean PSA of 9.35 ng./ml., including 51 (42%) with laboratory signs of prostatitis. After treatment PSA was normal in 22 cases and remained elevated in 29, including 9 in which biopsy revealed cancer. The change or improvement in PSA was significantly greater in men with benign results than in those with prostate cancer (-21.32 versus -1.33%, p = 0.001). In the cohort with negative expressed prostatic secretion and VB3 results transrectal ultrasound guided biopsy was done promptly. Screening decreased the number of biopsies by 18% (22 of 122 cases). The positive predictive value of PSA for detecting biopsy proved cancer improved with screening for prostatitis (45 of 122 cases or 37% versus 36 of 71 or 51%). Long-term followup revealed continued normal or stable PSA in the prostatitis cohort. CONCLUSIONS: Screening for NIH category IV prostatitis should be considered in men with elevated PSA. Although patients may be asymptomatic, anxiety caused by prostate cancer and diagnostic procedures contributes to the clinical significance of this disorder.     

RATIO OF FREE-TO-TOTAL PROSTATE SPECIFIC ANTIGEN IN SERUM CANNOT DISTINGUISH PATIENTS WITH PROSTATE CANCER FROM THOSE WITH CHRONIC INFLAMMATION OF THE PROSTATE

Purpose

We demonstrate the effect of chronic inflammation of the prostate on the ratio of free-to-total prostate specific antigen (PSA) in serum calculated as a percentage of free PSA and, therefore, that percentage of free PSA is an unspecific means to distinguish among prostate cancer, chronic prostatitis and benign prostatic hyperplasia (BPH).

Materials and Methods

Total, free and percentage of free PSA was measured in 66 men with prostate cancer, 119 with BPH and 17 with asymptomatic chronic prostatitis. In all patients the diagnosis was histopathologically confirmed by microscopic examination of prostatic specimens after sextant biopsy, transurethral prostatic resection or prostatectomy.

Results

The median values of total, free and percentage of free PSA were 4.11 micro g./l., 0.75 micro g./l. and 20.4% in patients with BPH, 10.0 micro g./l., 0.84 micro g./l. and 8.5% in those with prostate cancer, and 7.60 micro g./l., 1.23 micro g./l. and 10.6% in those with chronic prostatitis. Patients with prostate cancer and chronic prostatitis had a significantly lower percentage of free PSA than those with BPH. Receiver operating characteristics curve analysis showed that percentage of free PSA as a discriminator between prostate cancer and BPH was not suitable for differentiating between prostate cancer and chronic prostatitis.

Conclusions

Chronic prostatitis is not characterized by elevated total PSA concentrations alone but also by a decreased percentage of free PSA, a tendency similar to that in prostate cancer. This unspecific change in percentage of free PSA must be considered to interpret the percentage of free PSA correctly.     

Prostate specific antigen and prostatitis. I. Effect of prostatitis on serum PSA in the human and nonhuman primate.

Prostate specific antigen (PSA) has become a mainstay in the diagnosis and management of patients with prostate cancer. We have found, as have others, that it may be elevated in patients with prostatic inflammation. Ten patients had clinical evidence of prostatitis and elevated PSA levels. Six of these had persistently elevated levels after antibiotic treatment. After transrectal ultrasonography and biopsy, two had findings of adenocarcinoma, and the rest had a pathologic diagnosis of acute or chronic prostatitis. We studied this process in an experimental model of prostatitis using a nonhuman primate. We infected six cynomolgus monkeys and followed their PSA levels until resolution of the infection. The PSA peaked between 5 and 7 days after inoculation and gradually returned to baseline in 8 weeks. The dramatically elevated serum PSA levels in bacterial prostatitis can cause confusion in the diagnosis of prostatic carcinoma.     

Treatment of chronic prostatitis lowers serum prostate specific antigen

PURPOSE: We evaluated men with documented chronic prostatitis and elevated serum prostate specific antigen (PSA) to determine whether treatment with antibiotics and anti-inflammatory drugs lowers serum PSA. MATERIALS AND METHODS: We retrospectively reviewed the records of 95 men who presented with serum PSA greater than 4 ng./ml. and were subsequently diagnosed with chronic prostatitis with greater than 10 white blood cells per high power field in expressed prostatic excretions. Patients meeting these criteria were treated with a 4-week course of antibiotics and a nonsteroidal anti-inflammatory agent. In all patients followup PSA was determined within 2 months of treatment. RESULTS: Mean PSA decreased 36.4% from 8.48 ng./ml. before to 5.39 after treatment (p <0.001). In 44 patients (46.3%) serum PSA decreased to below 4 ng./ml. (mean 2.48) and these patients no longer had an indication for biopsy. In the remaining 51 patients serum PSA remained elevated at greater than 4 ng./ml. and they underwent double sextant transrectal ultrasound guided biopsy. Pathological study showed prostate cancer in 13 cases (25.5%), chronic inflammation in 37 (72.5%) and only benign prostatic hypertrophy in 1 (1.05%). PSA in the 13 patients with prostate cancer decreased with treatment only 4.8% from 8.32 to 7.92 ng./ml. (p >0.05). Followup PSA at a mean of 11.4 months was determined in 19 of the 44 men who responded to treatment. Mean PSA increased only 4.5% from 2.35 to 2.46 ng./ml. (p >0.05) during this followup interval. CONCLUSIONS: In almost half of the patients diagnosed with elevated PSA and chronic prostatitis serum PSA normalized with treatment and there was no longer an indication for transrectal ultrasound guided biopsy. Our study suggests that chronic prostatitis is an important cause of elevated PSA and when it is identified, treatment can decrease the percent of negative biopsies.     

ROLE OF PROSTATE-SPECIFIC ANTIGEN AND DIGITAL RECTAL EXAMINATION IN THE DETECTION OF PROSTATE CANCER

Prostate-specific antigen (PSA) is a kallikrein-like serine protease that is secreted exclusively by the epithelial cells of all types of prostatic tissue, benign and malignant. Its serum concentration is raised in men with prostatic disease including cancer. We have evaluated its usefulness in the diagnosis of prostate cancer by measuring serum PSA concentrations in 260 men aged 50 years or over. All had abnormalities at digital rectal examination (DRE) involving suspected cancer, signs and symptoms of benign prostatic hyperplasia and equivocal findings on DRE, and miscellaneous other conditions, including hematospermia, chronic prostatitis and microscopic hematuria. Transrectal prostatic needle biopsies were performed in the men with abnormal findings on DRE or elevated serum PSA (above 4ng/ml). Serum PSA ranged from 4.0 to 9.9ng/ml in 14 (5%) of the 260 men. Four of the men in this group (31%) who underwent prostatic biopsy had prostate cancer. Serum PSA levels greater than or equal to 10.0 ng/ml were found in 8 (3%) of the 260 men. 5 of these 8 (63%) who underwent prostatic biopsy had cancer. If DRE alone had been used to screen the men having biopsies, 4 of the 10 cancers (40%) would have been missed. If PSA alone had been used to screen these men, only 1 of the 10 cancers would have been missed. Serum PSA measurement was more reliable than DRE for detecting prostate cancer. Since these two methods do not always detect the same malignant tumor, the combined use of DRE and PSA testing affords a more complete evaluation of the prostate gland for malignant involvement.     

Prostatic calculi do not influence the level of serum prostate specific antigen in men without clinically detectable prostate cancer or prostatitis

PURPOSE: Prostatic calculi are common but little is known of their effect on serum prostate specific antigen (PSA). We investigated whether prostatic calculi might influence serum PSA in men with clinically undetectable prostatic cancer or prostatitis. MATERIALS AND METHODS: Between November 1999 and November 2001, 581 consecutive patients underwent serum PSA determination and digital rectal examination. Of these patients 486 without detectable prostatic cancer, or a history or symptoms of prostatitis and with other specified exclusion criteria were included in the study. The detection and volume measurement of prostatic calculi, and the measurement of prostate volume were performed by transrectal ultrasonography. RESULTS: Prostatic calculi were detected in 198 of the 486 men (40.7%). Mean patient age, prostate volume and serum PSA were not significantly different in men with and without prostatic calculi. Prostate volume was significantly greater in patients with abnormally elevated serum PSA than in those with normal levels. However, no significant difference was found between the percent of men with prostatic calculi or the volumes of prostatic calculi in the 2 groups. Univariate logistic regression analysis indicated that the presence or volume of prostatic calculi was not a risk factor for elevated PSA. Multivariate analysis showed that age and prostate volume were associated with elevated PSA. CONCLUSIONS: The presence or volume of prostatic calculi had no significant effect on serum PSA. Our results suggest that the influence of prostatic calculi is irrelevant in men with elevated PSA.     

经直肠超声引导下“10+X”点法前列腺穿刺活检术在PSA值介于4～20ng/ml之间患者前列腺癌诊断中的价值

目的 探讨经直肠超声引导下“10 +X”前列腺穿刺活检术在PSA值介于4 ～20ng/ml之间患者前列腺癌诊断中的价值。方法 回顾性分析226例血清PSA值介于4～20ng/ml之间疑似前列腺癌患者临床资料,所有患者均行经直肠超声引导下前列腺穿刺术活检。结果 前列腺癌47例,前列腺增生158例,前列腺炎11例,前列腺上...     

Pilot and feasibility study of serum chemokines as markers to distinguish prostatic disease in men with low total serum PSA

BACKGROUND: The incidence and prevalence of both benign prostatic hypertrophy (BPH) and prostate cancer (PCa) increase with the aging process. Our laboratory recently showed that the chemokines CXCL5 and CXCL12, which normally function as inflammatory mediators, are secreted at higher levels by aging prostate stromal fibroblasts and elicit proliferative responses from both prostate stromal fibroblast and epithelial cells. Because both CXCL5 and CXCL12 are secreted molecules, we hypothesized that their levels in patient serum might serve as biomarkers to distinguish between BPH and PCa. METHODS: Serum CXCL5 and CXCL12 levels were determined using sandwich ELISAs for 51 men demonstrating low serum PSA values of < or =10 ng/ml who underwent diagnostic needle biopsy for the detection of PCa. The bivariate relationship of circulating chemokine levels, age, and disease status in the prostate was tested using the Wilcoxon rank-sum test. RESULTS: Total serum CXCL12 levels were significantly higher for men who were biopsy positive compared to those who were biopsy negative for cancer and histological prostatitis (P = 0.050). Among men who were biopsy negative for PCa, total serum CXCL5 levels were inversely associated with prostate volume and were significantly higher in men with concomitant BPH and histological prostatitis compared to those without evidence of prostatic disease (P < 0.003). CONCLUSIONS: The results of this pilot and feasibility study suggest that serum or plasma CXCL5 and CXCL12 levels may potentially distinguish between BPH and PCa among patients presenting with low serum PSA, and may be useful toward facilitating decisions to perform diagnostic needle biopsy in this patient population.     

Does normalizing PSA after successful treatment of chronic prostatitis with high PSA value exclude prostatic biopsy?

Objective

Evaluate male patients with diagnosed chronic prostatitis, elevated serum prostate-specific antigen (PSA) to find out whether medical treatment with antibiotics and anti-inflammatory drugs can lower serum PSA, and consequently decrease the prostate cancer detection rate in patients with post-treatment PSA<4 ng/mL.

Materials and methods

This prospective study evaluated 142 male patients aged 40-73 years whose presented with elevated serum PSA>4 ng/mL and were consequently diagnosed with chronic prostatitis as expressed prostatic excretions examination revealed more than 10 white blood cells per high power field. The Patients underwent treatment with antibiotics and nonsteroidal anti-inflammatory agents for 6-weeks. Subsequently, all patients are Followed-up by serum PSA and performed transrectal ultrasonography-guided prostate biopsy within 2 months of treatment.

Results

Mean patient age was (54.4±13.5) years. The mean PSA pretreatment was (8.11±3.7) ng/mL and after treatment, the mean PSA denoted a significant decrease to (4.7±3.5) ng/mL (P=0.002). The percent of changes in mean PSA was 41.9%. Prostatic biopsy after treatment showed that, cancer prostate in 31 patients (21.8%), chronic prostatitis in 71 patients (50.7%), chronic prostatitis plus benign prostatic hyperplasia (BPH) in 31 (21.8%) and BPH in 9 patients (6.3%) With regard to PSA values, cancer prostate patients were 3/25 (12%) if PSA<2.5 ng/mL, 6/47 (12.7%) if 4.0>PSA≥2.5 and 21/70 (30%) if PSA≥4.0. The numbers of cancer prostate detected patients were 30 (21.1%).

Conclusions

Chronic prostatitis is one of the causes that elevate serum PSA levels. Treatment of chronic prostatitis with elevated PSA by antibiotics and anti-inflammatory agents can decrease the elevated PSA to the normal levels. Nevertheless, the opportunities of potential prostate cancer still exist in patients with a decreased PSA level even also if PSA<2.5 ng/mL.     

The prevalence of men with National Institutes of Health category IV prostatitis and association with serum prostate specific antigen

PURPOSE: We evaluated the prevalence and relationship of serum prostate specific antigen (PSA) levels in a screening population of men diagnosed with National Institutes of Health (NIH) category IV prostatitis. MATERIALS AND METHODS: In September of 2001, 300 men were randomly selected from our prostate cancer awareness screening program to be evaluated for NIH category IV prostatitis. After informed consent was obtained all patients completed the NIH prostate cancer awareness survey and had a serum sample obtained for PSA before examination. Expressed prostatic secretions were obtained from 227 of the 300 participants. Patients were classified according to findings on examination of the expressed prostatic secretions. The records were entered into our data base and subsequently reviewed. RESULTS: The prevalence of NIH category IV prostatitis was 32.2% in our population of men. Patient age, American Urological Association symptom scores and clinical prostate gland size did not differ between men with or without evidence of prostatitis on expressed prostatic secretion examination. Men with NIH category IV prostatitis had a mean serum PSA level of 2.3 which was significantly higher (p <0.0004) than those without prostatitis (mean PSA 1.4). CONCLUSIONS: These data suggest that NIH category IV prostatitis is fairly prevalent (32.2%) among men in the general population who present for prostate cancer screening and appears to contribute to increased serum PSA levels in some men.     

High serum prostate-specific antigen levels in the absence of prostate cancer in Middle-Eastern men: the clinician's dilemma

OBJECTIVE: To investigate the common causes of total serum prostate-specific antigen (PSA) values of> 10 ng/mL in an Arab population, as in the USA and Europe the risk of prostate cancer is considered high in men with such PSA levels. PATIENTS AND METHODS: Serum total PSA was measured in men presenting to our hospital as part of the investigation for prostate cancer screening and/or in elderly men with prostatism. Men with a serum PSA level of> 10 ng/mL were further investigated by transrectal ultrasonography (TRUS) of the prostate and biopsy of suspicious lesions for histological diagnosis. In addition, the percentage of free PSA, PSA velocity and PSA density were determined. All the patients included in this study were men of Arab origin residing in Kuwait. RESULTS: In all, 1700 men (mean age 55.6 years, range 35-94) were assessed; of these, 161 had a serum PSA of> 10 ng/mL, attributable to benign prostatic hyperplasia (BPH) in 110 (68%), BPH with histological features of prostatitis in 33 (21%) and prostate cancer in 18 (11%). TRUS of the prostate in 143 of the 161 men with either BPH or BPH with prostatitis showed varying grades of intraprostatic calcifications in 22 (15%). Both PSA density and percentage free PSA did not contribute to determining the causes of total PSA levels of> 10 ng/mL. There was a progressive decline in PSA in all patients with BPH and prostatitis, except one who at re-biopsy had prostate cancer (T1N0M0, G1). CONCLUSION: Total PSA values of> 10 ng/mL in Arab men may be a result of BPH, BPH with prostatitis or prostate cancer, in that order. A gradual decline in total PSA (decreased PSA velocity) with time to < 4 ng/mL often confirms the diagnosis of BPH with prostatitis. The percentage of free PSA and PSA density may not be helpful in diagnosing prostate cancer with certainty in these patients. Compared with Caucasians in the USA and Europe, BPH and BPH with prostatitis appear to be more frequent causes of serum PSA levels of> 10 ng/mL in Arab men.     

Ⅳ型前列腺炎与前列腺特异性抗原的关系

目的 探讨Ⅳ型前列腺炎与前列腺特异性抗原(PSA)的关系. 方法回顾性分析245例前列腺疾病患者的临床病理资料,患者平均年龄68(32～87)岁,均无前列腺癌和穿刺活检史,均行PSA、全身骨扫描、磁共振成像(MRI)和前列腺穿刺活检.结果 245例经病理证实为良性前列腺增生(BPH)118例(48%)、BPH合并Ⅳ型前列腺炎(CP)127例(52%).BPH组患者f-PSA、t-PSA、f/t-PSA平均值分别为(1.70±1.70)、(9.40±8.10)ng/ml和0.19±0.09;合并CP组平均值分别为(2.83±4.37)、(16.87±20.51)ng/ml和0.20±0.14,2组比较差异有统计学意义(P＜0.05).多元线性回归分析结果显示t-PSA(P＜0.001)、f-PSA(P=0.003)和f/t-PSA(P=0.04)是BPH和CP最相关的指标.通过ROC曲线确定上述敏感指标的界值,以f-PSA≥0.85为界值诊断Ⅳ型前列腺炎的敏感度为77%,特异度为25%,ROC曲线下面积为0.60(P=0.014);t-PSA≥4.00 ng/ml为界值诊断Ⅳ型前列腺炎的敏感度为94%,特异度为20%,ROC曲线下面积为0.65(P=0.014);f/t-PSA≤0.16为界值诊断Ⅳ型前列腺炎的敏感度为56%,特异度为64%,ROC曲线下面积为0.61(P=0.003).结论 Ⅳ型前列腺炎是PSA升高的原因之一,以血清PSA作为前列腺癌的筛选指标时,应充分考虑前列腺炎的影响.对前列腺活检标本的病理报告,应包括对前列腺炎症的详细描述.     

Effect of NIH-IV prostatitis on free and free-to-total PSA

OBJECTIVE: To examine the effect of asymptomatic prostatic inflammation (NIH category IV prostatitis) on total PSA (tPSA), free serum PSA (fPSA) and the ratio of free-to-total prostate specific antigen (%fPSA). The role of free and %fPSA as a diagnostic tool for distinguishing between cancer and non-malignant diseases of the prostate was also investigated. MATERIAL AND METHODS: In a retrospective study 1090 prostate biopsies performed between January 2000 and September 2003 were evaluated and the levels of serum total and free PSA as well as the f/tPSA ratio were determined in samples obtained immediately before biopsy. 404 patients with full clinical and histological records were included in the study. All patients underwent 6 or 8 core primary prostate needle biopsies. RESULTS: A total of 404 patients were included in the analysis. 100 prostate cancer (PCa) (24.8%), 137 NIH-IV prostatitis (33.9%) and 143 patients with benign prostatic hyperplasias (BPH) (35.4%) were identified. 24 (5.9%) patients presented with both PCa and prostatitis on histology and were excluded from further analysis. The mean (median) levels of tPSA, fPSA and %fPSA were 11.94 ng/ml (8.0), 1.31 ng/ml (1.07) and 0.15 (0.14) for NIH-IV prostatitis; 11.94 ng/ml (8.35), 1.54 ng/ml and 0.13 (0.11) for prostate cancer; and 8.19 ng/ml (7.0), 1.48 ng/ml (1.03) and 0.18 (0.15) for BPH. No significant difference was found in tPSA levels between PCa and prostatitis (p = 0.32), while the difference in tPSA levels between PCa and BPH was significant (p = 0.007). Free PSA alone had no diagnostic power in distinguishing PCa from prostatitis (p = 0. 37) and BPH (p = 0. 61). By contrast, the f/tPSA ratio showed significant between-group differences (PCa versus prostatitis (p = 0. 011), PCa versus BPH (p = 0.0001). CONCLUSIONS: Chronic asymptomatic prostatitis NIH category IV has similar effects on total PSA and free PSA levels in serum as PCa. fPSA alone cannot distinguish prostate cancer from non-malignant inflammatory disease of the prostate. The ratio of free-to-total PSA is significantly different in PCa and NIH category IV prostatitis.     

Evaluation of prostate-specific antigen and prosttic acid phosphatase as prostate cancer markers

Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) have been evaluated in patients with prostate cancer, benign prostatic hypertrophy (BPH), and prostatitis. PSA has proved to be diagnostically more sensitive than PAP for the detection of prostate cancer: 95.0 per cent vs 60.0 per cent for 40 newly diagnosed cancer cases, and 97.1 per cent vs 65.7 per cent for 35 relapsed cases. This also holds true for those patients with early-stage disease: 71.4 per cent vs 0 per cent for 7 Stage A1 cases. The specificities of PSA and PAP are comparable, 96.8 per cent vs 98.9 per cent, respectively. PSA is also more sensitive for monitoring therapy, since it usually rises before PAP and always precedes clinical signs of relapse. Although PSA may be elevated more frequently than PAP in some patients with BPH and prostatitis, it is postulated that these patients with elevated serum PSA and normal serum PAP may fall into a high-risk sub-population which may have early prostate cancer or precancerous conditions not easily detectable by current clinical and diagnostic techniques. Our data suggest PSA is a sensitive useful tumor marker for the diagnosis and management of prostate cancer. In addition, PAP, in combination with PSA, may serve as a useful adjunct for differential diagnosis and confirmation of advanced stage prostate cancer.     

Evaluation of prostate-specific antigen and prostatic acid phosphatase as prostate cancer markers

Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) have been evaluated in patients with prostate cancer, benign prostatic hypertrophy (BPH), and prostatitis. PSA has proved to be diagnostically more sensitive than PAP for the detection of prostate cancer: 95.0 per cent vs 60.0 per cent for 40 newly diagnosed cancer cases, and 97.1 per cent vs 65.7 per cent for 35 relapsed cases. This also holds true for those patients with early-stage disease: 71.4 per cent vs 0 per cent for 7 Stage A1 cases. The specificities of PSA and PAP are comparable, 96.8 per cent vs 98.9 per cent, respectively. PSA is also more sensitive for monitoring therapy, since it usually rises before PAP and always precedes clinical signs of relapse. Although PSA may be elevated more frequently than PAP in some patients with BPH and prostatitis, it is postulated that these patients with elevated serum PSA and normal serum PAP may fall into a high-risk sub-population which may have early prostate cancer or precancerous conditions not easily detectable by current clinical and diagnostic techniques. Our data suggest PSA is a sensitive useful tumor marker for the diagnosis and management of prostate cancer. In addition, PAP, in combination with PSA, may serve as a useful adjunct for differential diagnosis and confirmation of advanced stage prostate cancer.     

前列腺特异性抗原升高的组织病理学基础

目的 探讨前列腺特异性抗原(PSA)与前列腺结节增生、Ⅳ型前列腺炎及前列腺癌之间的关系,探讨PSA升高的病理学基础.方法 有完整临床病理资料的前列腺疾病504例患者,均无前列腺癌和穿刺活检史,均行PSA、全身骨扫描、MRI和前列腺穿刺活检.直肠B超引导下以18G自动穿刺活检枪行双侧叶6-13点法前列腺穿刺活检.对患者穿刺的病理标本按前列腺结节增生、前列腺癌以及Ⅳ型前列腺炎病理诊断标准进行评价.结果 504例患者经病理证实前列腺癌185例(37%),Ⅳ型前列腺炎109例(21%),前列腺增生210例(42%).3组总PSA(t-PSA)分别为27.6(0.4～7116)、10.6(0.2～168)和9.2(0.3～60)ng/ml,3组间比较差异有统计学意义(P＜0.01);f-PSA分别为3.5(0.1～3356)、1.7(0.1～42)和1.5(0.06～15.8)ng/ml,3组间比较差异有统计学意义(P＜0.001);f/t-PSA分别为0.14(0＜0.94)、0.17(0.04～0.91)和0.16(0.02～0.75).3组间比较差异有统计学意义(P=0.019);3组间年龄、B超、直肠指诊结果比较差异无统计学意义(P＞0.05).前列腺癌分级与f-PSA(r=0.33,P＜0.001)、t-PSA(r=0.27,P＜0.001),f/t-PSA(r=0.22,P=0.003)具有显著相关性;多元线性回归分析发现前列腺癌分级与f-PSA(t=-2.34,P=0.02),t-PSA(t=2.77,P=0.006),f/t-PSA(t=3.97,P＜0.001)具有显著相关性.前列腺癌临床分期间f-PSA和t-PSA差异有统计学意义(P＜0.001).210例前列腺增生患者若按腺体增生为主和间质增生为主2类比较,t-PSA和f-PSA差异均有统计学意义(P＜0.05).多元线性回归分析发现t-PSA足前列腺增生病理结节类型最相关的指标,t-PSA≥2.5 ng/ml,确定腺体增生为主型前列腺增生的敏感性为96%,特异性为20%(P＜0.05).Ⅳ型前列腺炎109例和前列腺增生210例,2组间比较f-PSA,t-PSA,f/t-PSA差异有统计学意义(P＜0.05).通过ROC曲线确定前列腺癌敏感指标的界值:f-PSA≥0.85 ng/ml,t-PSA≥4 ng/ml和f/t-PSA≤0.16(P＜0.05).结论 血清PSA升高的病理基础为任何破坏前列腺上皮血屏障的病变;任何形成前列腺上皮增生,分泌更多PSA的病变;其中以破坏前列腺上皮血屏障最重要.     

Circulating levels of interleukin-6 in patients with hormone refractory prostate cancer.

BACKGROUND: Interleukin-6 (IL-6) is a cytokine that plays a central role in host defense due to its wide range of immune and hematopoietic activities. It is found in high levels in human ejaculate, and has recently been found to regulate prostate-specific protein expression in prostate cancer cells through nonsteroidal activation of the androgen receptor. IL-6 may be a candidate mediator of morbidity in patients with metastatic disease. We attempted to evaluate the potential of circulating IL-6 levels as a marker of disease progression. MATERIALS AND METHODS Serum IL-6, prostate specific antigen (PSA), percent free PSA (%fPSA), and prostate-specific membrane antigen (PSMA) were measured using commercially available assays in 407 men, including 15 controls. The rest of the study population had clinical or histologic evidence of prostate diseases, including 41 patients with chronic prostatitis, 167 with benign prostatic hyperplasia (BPH), 8 with high-grade prostatic intraepithelial neoplasia (PIN), 88 with localized prostate cancer, 22 with local recurrence after treatment of primary tumor, 4 with advanced untreated disease (nodal or bony metastases), 23 with advanced hormone dependent disease, and 39 with advanced hormone refractory disease (PSA > 1.0 ng/ml while on hormone treatment and/or evidence of disease progression). None had history of concurrent malignancy or acute inflammatory condition. Kruskal-Wallis analysis of variance and Spearman's correlation analysis were used for statistical analyses. RESULTS: Serum levels of IL-6 were significantly elevated in patients with clinically evident hormone refractory disease (5.7 +/- 1.9 pg/ml) and statistical significance was seen when comparing the elevated serum IL-6 levels to those in normal controls, prostatitis, BPH, and localized and recurrent disease, (P values < 0.01). Compared to serum levels of controls and BPH, PSA was significantly elevated in advanced untreated disease and hormone refractory groups (P < 0.05). Percent fPSA was significantly lower in all cancer patients but the hormone refractory. Serum PSMA was elevated in advanced untreated prostate cancer. Serum IL-6 showed positive correlation with PSMA and negative correlation with serum PSA but did not attain statistical significance. CONCLUSIONS: Serum IL-6 levels are significantly elevated in hormone-refractory prostate cancer patients and may be a surrogate marker of the androgen independent phenotype.     

Elevated prostate specific antigen serum levels after intravesical instillation of bacillus Calmette-Guerin

PURPOSE: We determined whether intravesical bacillus Calmette-Guerin (BCG) instillation is associated with elevated prostate specific antigen (PSA). MATERIALS AND METHODS: We treated 36 consecutive patients with bladder cancer with a 6-week course of BCG, followed by cystoscopy at 6 weeks. Blood samples for PSA determination were obtained before each BCG instillation and at cystoscopy with each patient also serving as a control. PSA elevation was defined as 2-fold the baseline level in at least 2 specimens and any PSA level greater than 4 ng./ml. was considered clinically significant. Digital rectal examination was done to identify firm nodules and prostate size. The prostate was examined histologically by transrectal ultrasound guided biopsy or after radical cystectomy. RESULTS: We observed elevated PSA in 27 men (75%) during BCG treatment, of whom 15 (41.6%) had a clinically significant elevation. Overall average PSA increased from 1.3 ng./ml. before BCG instillation to 3.8 during treatment (range 0.1 to 21.5, p <0.0001). In those with a clinically significant elevation average PSA increased from 2.31 ng./ml. at baseline to 6.97 during treatment (p <0.0001) and returned to 3.86 ng./ml. 3 months after treatment. Palpation demonstrated prostatic findings in 10 patients, including firm nodules in 7, while there was significantly elevated PSA in 5 with firm nodules and 2 with diffuse prostatic enlargement. Histological examination of the prostate in 10 patients was diagnostic for granulomatous prostatitis, nonspecific inflammation and benign prostatic hyperplasia in 3, 3 and 4, respectively, of whom none had prostate cancer. CONCLUSIONS: Intravesical BCG therapy is associated with significantly elevated PSA in up to 40% of cases. This effect is self-limited and PSA reverts to normal in 3 months. Therefore, we suggest that prostate biopsy be withheld in such patients and PSA monitored.     

Technical and anatomical essentials for transrectal ultrasound of the prostate

Transrectal ultrasound (TRUS) of the prostate is a specific urological examination. This morphological imaging technique is often capable of identifying the cause for raised values of prostate-specific antigen (PSA) or of clarifying hard tissue regions found during rectal palpation. Particulary in view of constantly increasing number of patients undergoing PSA tests, there is a rising need for further prostate diagnostics in otherwise asymptomatic men. Especially in the gray zone between 4 and 10 ng/ml the tissue marker PSA is frequently influenced by benign alterations, so that it is not possible—on the basis of the PSA value alone—to differentiate between benign and malignant causes. Only a clearly increased serum PSA value (>20 ng/ml) indicates the presence of a prostate carcinoma at a very high probability. However, it is necessary that all patients whose PSA is elevated, undergo a bioptical tissue sample procedure in order to try to diagnose prostate cancer. Today, we regard the technique of TRUS-based transrectal prostate biopsy, carried out with a semi-automatic coil spring device and an 18-gauge needle, as the gold standard. The core problem of visual TRUS assessment lies in its lack of specificity, especially if the examiner has only limited experience. There can be low-echo, cancer-suspicious areas that may be histologically either benign or malignant. Benign prostatic hyperplasia (BPH), vessels, centers of prostatitis as well as shadows and artefacts can often also be low in echo-density. Only adequate application of this technology and experience with this method can lead to satisfying biopsy and diagnostic results.     

Relationship between Serum Prostate Specific Antigen and the Pattern of Inflammation in Both Benign and Malignant Prostatic Disease in Middle Eastern Men

To determine the effect of prostatitis on serum prostate specific antigen in the diagnosis of prostate cancer in Middle Eastern men, H&E-stained sections of all consecutive prostate specimens were reviewed for diagnosis (malignant or benign) and pattern of inflammation. Inflammation was categorized into acute, active chronic and chronic inactive and graded semi-quantitatively according to previously published criteria. Results were correlated with serum PSA obtained from patients’ records. Of 513 prostate specimens reviewed; 435 (84.8%) were benign and 78 (15.2%) were malignant. Chronic inactive prostatitis was present in 259 (204 benign, 55 malignant) and active chronic prostatitis in 221 (204 benign, 17 malignant). Acute prostatitis alone was not observed and prostatitis was absent in 33 (27 benign, 6 malignant). There was no significant difference in the prevalence of inactive chronic prostatitis between benign and malignant specimens (p < 0.071), but active chronic prostatitis was more prevalent in benign specimens (p < 0.001). Increasing serum PSA was observed for increasing grades of both inactive and active chronic prostatitis in both benign and malignant disease. Prostate cancer showed higher serum PSA levels than benign, at different cut-off points (4 ng/ml = p < 0.0001; 8 ng/ml = p < 0.0001; 12 ng/ml = p < 0.0001). However, significant numbers of patients with benign prostate biopsies presented with PSA above 12 ng/ml (82/260 = 32%). We conclude that active chronic prostatitis is common in Middle Eastern men with benign prostatic disease and a significant number of these present with very high PSA levels, some over 300 ng/ml.