Alpha-methylacyl-CoA racemase: a multi-institutional study of a new prostate cancer marker.

AIM: To test whether alpha-methylacyl-CoA racemase (AMACR) is a sensitive and specific marker of prostate cancer. METHODS AND RESULTS: The expression levels of AMACR mRNA were measured by real-time polymerase chain reaction. A total of 807 prostatic specimens were further examined by immunohistochemistry specific for AMACR. Quantitative immunostaining analyses were carried out by using the ChromaVision Automated Cellular Imaging System and the Ariol SL-50 Imaging System, respectively. AMACR mRNA levels measured in prostatic adenocarcinoma were 55 times higher than those in benign prostate tissue. Of 454 cases of prostatic adenocarcinoma, 441 were positive for AMACR, while 254 of 277 cases of benign prostate were negative for AMACR. The sensitivity and specificity of AMACR immunodetection of prostatic adenocarcinomas were 97% and 92%, respectively. Both positive and negative predictive values were 95%. By automatic imaging analyses, the AMACR immunostaining intensity and percentage in prostatic adenocarcinomas were also significantly higher than those in benign prostatic tissue (105.9 versus 16.1 for intensity, 45.7% versus 0.02% and 35.03% versus 4.64% for percentage, respectively). CONCLUSIONS: We have demonstrated the promising features of AMACR as a biomarker for prostate cancer in this large series and the potential to develop automated quantitative diagnostic tests.

A novel diagnostic test for prostate cancer emerges from the determination of alpha-methylacyl-coenzyme a racemase in prostatic secretions.

PURPOSE: With the recent discovery that alpha-methlyacly-coenzyme A racemase (AMACR) is over expressed in a majority of prostate cancer (CaP) specimens we developed a novel polymerase chain reaction (PCR) based approach that would predict the presence of CaP from prostatic secretions. MATERIALS AND METHODS: A total of 21 patients were enlisted in this study, including 10 with CaP, 2 with high grade PIN and 9 cancer-free individuals (7 healthy men and 2 with benign hyperplasia). Total cellular RNA was extracted from prostatic secretions obtained from post-massage urine specimens. Levels of AMCAR transcripts and prostate specific antigen (PSA) transcripts in these samples were determined by quantitative reverse transcriptase-PCR analyses. Relative AMACR value scores (RAVSs) were calculated by normalizing the AMACR transcript level to that of PSA for each sample and multiplying by 100. An experimentally defined diagnostic cutoff RAVS value was determined in the cancer-free control group. RESULTS: Neither AMACR nor PSA mRNA levels were predictive of CaP when used alone. However, using RAVS values and imposing a diagnostic cutoff value of 2 SDs above the mean RAVS in the cancer-free control group all 9 (100%) cancer-free individuals, including those with benign prostatic hyperplasia, were below the cutoff and 7 of 10 (70%) with CaP had RAVS above the cutoff. Furthermore, 2 of the 3 false-negative cases showed clinically insignificant disease. The 2 patients with high grade PIN were above the cutoff in this test. CONCLUSIONS: In this study the quantification of AMACR transcripts normalized to PSA transcripts in prostatic secretions was shown to be predictive of CaP. Therefore, our novel approach using quantitative reverse transcriptase-PCR to detect the AMACR-to-PSA transcript ratio shows promise as a noninvasive screening test for CaP. Furthermore, early results demonstrate a trend toward excluding patients with clinically insignificant disease that may not yet require aggressive treatment due to a low cancer burden.

Monitoring the serological proteome: the latest modality in prostate cancer detection.

PURPOSE: Various strategies have recently emerged to improve the diagnostic prediction of prostate cancer (CaP). One such strategy includes the mass profiling of serum protein fractions selectively adsorbed onto chemically modified probes. In the current study we further validated this approach, while offering a more versatile, less expensive and yet equally predictive alternative to existing technologies. MATERIALS AND METHODS: A solid core lipophilic C-18 resin was used to extract and enrich the low molecular weight protein fraction from patient serum for further analysis by mass spectrometry. Mass spectra generated from a 48 patient training set were data mined using multivariate analysis to identify diagnostically significant protein peaks. These peaks were then used to test a blinded study set comprising 168 patients with common statistical algorithms and commercially available software packages. RESULTS: A total of 36 peaks generated from the training set were used to test the combined set of 168 serum samples obtained from 98 healthy individuals and 70 patients with CaP. We report a sensitivity of 94.1% and a specificity of 99.0% with 1 false-positive, 4 false-negative and 5 nondiagnosed cases. CONCLUSIONS: Our results further indicate that mass profiling of serological proteins provides a means for the accurate detection of CaP. In addition, our approach was found to be superior to chip based protocols, generating rich, sharp, highly reproducible spectra attainable in a high throughput manner and at minimal cost. This technique is also scaleable for subsequent protein characterization using multidimensional protein identification technologies. Finally, analyses of mass spectra with commercially available statistical applications was found to be highly effective in generating highly discriminatory m/z values for CaP diagnosis.

Can diet in conjunction with stress reduction affect the rate of increase in prostate specific antigen after biochemical recurrence of prostate cancer?

PURPOSE: Epidemiological and laboratory evidence indicates that a Western diet is associated with an increased incidence of prostate cancer. Specific components of the diet, such as high saturated fat, low fiber and high meat content, may have greatest clinical significance in the later stages of tumor promotion and progression. However, departure from the conventional diet is difficult to initiate and maintain. Therefore, we combined the well-known Mindfulness-Based Stress Reduction (MBSR) program with a low saturated fat, high-fiber, plant-based diet to determine the effect on the rate of change in prostate specific antigen (PSA) in patients with biochemical recurrence after prostatectomy. MATERIALS AND METHODS: We enrolled 10 men and their partners in a 4-month group-based diet and MBSR intervention. A pre-study post-study design in which each subject served as his own control was used to compare the rate of increase in and doubling time of PSA before and after intervention. RESULTS: The rate of PSA increase decreased in 8 of 10 men, while 3 had a decrease in absolute PSA. Results of the signed rank test indicated a significant decrease in the rate of increase in the intervention period (p = 0.01). Estimated median doubling time increased from 6.5 months (95% confidence interval 3.7 to 10.1) before to 17.7 months (95% confidence interval 7.8 to infinity) after the intervention. CONCLUSIONS: Our small study provides evidence that a plant-based diet delivered in the context of MBSR decreases the rate of PSA increase and may slow the rate of tumor progression in cases of biochemically recurrent prostate cancer. Larger-scale randomized studies are warranted to explore further the preventive and therapeutic potential of diet and lifestyle modification in men with prostate cancer.

Acute adrenal insufficiency as a complication of urological surgery.

Acute adrenal insufficiency postoperatively is an uncommon problem and, if unrecognized, it may cause serious morbidity and can be fatal. It can occur as the result of acute bilateral adrenal hemorrhage associated with anticoagulation, inadvertent injury to or removal of a solitary adrenal gland, or postoperative stress in an individual with incipient adrenal insufficiency. Its manifestations, such as fever, tachycardia, hypotension, lethargy, abdominal pain and gastrointestinal dysfunction, mimic the other more common postoperative complications and compound the difficulty in establishing the correct diagnosis. Once the diagnosis is made the condition is readily managed successfully. We report 3 cases of acute adrenal insufficiency occurring after salvage cystectomy, ileal replacement of the ureter and retropubic prostatectomy, which illustrate the salient clinical features, problems in diagnosis and predisposing risk factors. All 3 patients survived once the diagnosis of adrenal insufficiency was made. These cases emphasize the need to be aware of the possibility of this complication to make the correct diagnosis and to institute proper treatment.

Renal brush biopsy: survey of indications, techniques and results.

Urine cytology is inaccurate in the diagnosis of low grade tumors of the ureter and pelvis. In 1973 the retrograde brush biopsy technique was introduced in an effort to improve diagnostic capabilities. We herein review our experience with retrograde brushing of upper urinary tract radiolucent filling defects in 21 patients during a 6-year period. In addition, we have surveyed other urologists concerning their experience with this new technique. The data accrued from both sources, involving 68 procedures, were analyzed with respect to the results, technique and complications of this procedure. In lesions from which tissue was obtained we found an over-all diagnostic accuracy rate of 78 per cent. The major and minor complication rates were 7 and 34 per cent, respectively. Our results support the conclusion that this procedure is of value in the management of selected patients with problem radiolucent filling defects of the renal pelvis and ureter.

Isolated bladder neck obstruction of undetermined etiology (primary) in adult male: recognition and management.

Varying degrees of isolated bladder neck obstruction of undetermined etiology were identified with micturitional vesicourethral static pressure profiles. Our experience with the urodynamic studies in 15 patients suggests that isolated bladder neck obstruction is a real entity in young adult males. Our experience also suggests that pharmacologic success with alpha-adrenergic blockade of the dosage tolerated by the patients is inconsistent. Successful clinical results achieved with appropriate bladder neck surgery could be confirmed with uroflowmetry and detailed urodynamic studies during postoperative period.

Radiocolloid scintigraphic mapping of the lymphatic drainage of the prostate.

Radionuclide lymphoscintigraphy with the new microcolloid 99mtechnetium antimony sulfide is a diagnostic technique with potential application in patients with urologic malignancy. Scintigraphic images were obtained after simple interstitial injection into the prostate of 9 normal dogs and 2 patients with prostatic cancer and into the testis in 2 dogs. The images show the physiologic lymphatic drainage of the organs injected.

Immunologic indicators of prognosis in bladder cancer: the importance of cell surface antigens.

The loss of isoantigens on the surface of cells has been correlated with invasion in 89 patients with bladder cancer: 73 underwent cystectomy and 16 had stage A tumor and were followed. Tumors from these 89 patients were re-examined for the presence or absence of A, B and O (erythrocytic) isoantigens on the surface of neoplastic cells by the red cell adherence test. In 97% of the cystectomy patients with transitional carcinoma lacking superficial cellular antigens (red cell negative tumors) there was documented evidence of invasion and 71% of the patients with stage A, red cell negative tumors eventually had invasion. This high degree of correlation between the loss of cellular antigens and the presence of invasion lends credence to the usefulness of the specific red cell adherence test as an important adjunct in the decision for appropriate therapy of cancer of the bladder.