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Biomedical subjects

A N Vis

Publications and source records attributed to A N Vis.

18 recordsLinked to original sources
PubMed2003

Recurrence after radical prostatectomy for organ-confined prostate cancer.

BACKGROUND: Some patients from our radical prostatectomy (RPx) series with organ-confined (pT2) prostate cancer and negative surgical margins show a PSA (prostate specific antigen) relapse. Aim of the study was to analyze this cohort of patients that otherwise would have been considered to be cured. PATIENTS AND METHODS: Since the introduction of PSA measurement in the follow-up after RPx, 475 pelvic lymph node dissections with subsequent RPx were performed in our department from 1988 to 1997. Of these, 227 were classified as pT2, 34 (15%) exhibited positive surgical margins, and 4 others were excluded due to an inadequate follow-up. Of the remaining 189 patients (study cohort), 19 (10%) developed a biochemical progression, defined as a minimum of 2 consecutive PSA measurements > or = 0.1 ng/ml. Only in one of them a G3 tumor was present. Median follow-up was 19.1 months. RESULTS: The Kaplan-Meier analysis of biochemical progression showed that after 1, 2 and 5 years, 95% (confidence interval (Cl) 91-99%), 91% (Cl 86-96%), and 77% (Cl 55-89%) of the patients were free of progression, respectively. This means that roughly one fourth of pT2 tumors will become progressive despite negative surgical margins. These 19 patients were subdivided into 4 groups: 1: biopsy-proven local recurrence (n = 2); 2: suspected local recurrence defined as slowly rising PSA < or = 2 ng/ml, but negative biopsies (n = 12); 3: distant metastasis proven by radiologic imaging (n = 1); 4: suspected distant metastasis defined as rapidly rising PSA > 9 ng/ml without direct radiologic evidence (n = 4). Preoperatively all patients from groups 3 + 4 had negative bone scans and 4/5 had preoperative PSA values < 10 ng/ml. In total 7 patients with proven recurrence or with proven metastasis had positive biopsies. CONCLUSION: A pathological diagnosis of organ-confined prostate cancer (pT2) and a meticulous analysis of negative surgical margins do not exclude the occurrence of local relapses in 7% (14/189), and there is evidence for suspect hematogenic spread of PC cells in at least 2% (4/189) of patients.

Adult↗
PubMed2002

A phase II trial of methotrexate-human serum albumin (MTX-HSA) in patients with metastatic renal cell carcinoma who progressed under immunotherapy.

INTRODUCTION: Renal cell carcinoma (RCC) has a poor prognosis when metastasized to distant sites, although immunotherapy may offer a prolongation of survival in selected patient groups. Unfortunately, no treatment options remain when immunotherapy fails. In this phase IIa trial the tolerability and efficacy of the antifolate drug methotrexate-human serum albumin (MTX-HSA) were evaluated in patients with metastatic RCC who progressed after first-line immunotherapy. PATIENTS AND METHODS: A total of 17 patients started treatment, and 14 (12 men, 2 women) were evaluable for response according to the phase IIa Gehan design. Patients had had prior tumor nephrectomy, were in relatively good general condition, had no impairment of renal, liver or bone marrow function, and had progressive metastatic disease after treatment with interferon-alpha (IFN-alpha) with or without cis-retinoic acid (EORTC protocols 30951 and 30947). MTX-HSA was given once a week intravenously on an outpatient basis at a dose of 50 mg/m(2). The treatment interval was prolonged in those patients who had not yet recovered from previous toxicities. RESULTS: Toxicity was manageable, relatively mild to moderate and reversible in most cases. Grade 2/3 mucositis (10/17) and grade 3 elevated transaminase levels (4/17) were most frequent, and in only one patient was a grade 4 thrombocytopenia reported. Of three inevaluable patients, one discontinued treatment due to drug-related toxicities. The mean administration interval was 12.1 days, and 7 of 14 evaluable patients had treatment intervals of 1 or 2 weeks. No objective responses were seen, although eight patients had stable disease (stabilization >2 months) for up to 8 months (median 121 days). CONCLUSION: MTX-HSA was generally well tolerated and can be given on an outpatient basis, but no objective responses were seen in patients with metastatic RCC who had progressed after previous immunotherapy.

Adult↗
PubMed2002

Value of tissue markers p27(kip1), MIB-1, and CD44s for the pre-operative prediction of tumour features in screen-detected prostate cancer.

The pre-operative prediction of prognostic tumour features in the radical prostatectomy specimen using routine clinicopathological variables remains limited. The present study evaluated the predictive value of the cell-cycle protein p27(kip1), the proliferation marker MIB-1, and the cell-adhesion protein CD44s, determined on the diagnostic needle biopsy of asymptomatic men screened for prostate cancer. Of 81 screen-detected prostate cancers, representative biopsy cores and matched radical prostatectomy specimens were immunohistochemically stained for these tissue markers. Conventional pre-operative and post-operative clinicopathological variables were assessed and cancers were divided according to a validated tumour classification model (potentially harmless, clinically significant). Low (<50%) p27(kip1) expression, high (> or = 10%) MIB-1 expression, and low (<25%) CD44s expression were considered adverse prognostic signs. Binary logistic regression analysis was performed to assess the most valuable predictors of clinically significant disease. An adverse prognostic immunostaining assessment on the biopsy was found in 10 (12.3%), 17 (21.0%), and 25 (30.9%) cases for p27(kip1), MIB-1, and CD44s, respectively. The concordance in tissue marker assessment between the biopsy specimen and matched radical prostatectomy specimens was low for all three. The positive predictive value (PPV) of p27(kip1) was 90.0%, remarkably higher than that of MIB-1 and CD44s (41.2% and 52.0%, respectively), indicating that a low radical prostatectomy p27(kip1) score is expected if the biopsy p27(kip1) score is low. Logistic regression analysis revealed that biopsy Gleason score (p<0.01) and p27(kip1) assessment (p<0.01) remained the only significant predictors of clinically significant disease. All cases with low p27(kip1) expression were found to have clinically significant disease after radical prostatectomy. The assessment of p27(kip1) in the biopsy specimen might thus assist in distinguishing between potentially aggressive and potentially non-aggressive disease in prostate cancer screening.

Antigens, Nuclear↗
PubMed2002

Serendipity in detecting disease in low prostate-specific antigen ranges.

OBJECTIVE: To assess the magnitude of prostate cancer detection by serendipity (the coincidental detection of prostate cancer during the evaluation of an abnormal screening test result) when a digital rectal examination (DRE) and transrectal ultrasonography (TRUS) are used as initial screening tests for prostate cancer in men with low levels of prostate-specific antigen (PSA; 0.0-3.9 ng/mL). PATIENTS AND METHODS: In all, 117 participants of a population-based screening study were diagnosed with prostate cancer after a standard evaluation of an abnormal screening test result; 49 underwent radical prostatectomy. Serendipity was defined as either: (i) the presence of prostate cancer opposite to the side that raised suspicion for cancer on DRE and/or TRUS; (ii) a negative lesion-directed biopsy while cancer was present in one or more of the cores of the sextant biopsy; (iii) a tumour volume of < 0.5 mL on radical prostatectomy. RESULTS: Depending on the definition, 27-63% of prostate cancers detected at low PSA values were detected coincidentally and not as a result of a true-positive test result. The proportion of cancers detected by serendipity was inversely correlated with serum PSA level. CONCLUSION: A relatively high proportion of prostate cancers diagnosed in men with low PSA levels, and in which a biopsy was prompted by a suspicious DRE and/or TRUS, are considered to be detected by chance only. As these cancers are mostly small (< 0.5 mL), with potentially low biological aggressiveness, relying on serendipity seems disadvantageous in prostate-cancer screening. The level of serendipity in prostate cancer detection, the poor performance of the screening test, and high inter-observer variability, casts further doubt on the utility of DRE (and TRUS) as initial screening tests for prostate cancer in population-based screening.

Aged↗
PubMed2001

The predictive value for prostate cancer of lesions that raise suspicion of concomitant carcinoma: an evaluation from a randomized, population-based study of screening for prostate cancer.

BACKGROUND: Suspicion of prostate carcinoma may persist after an initial negative biopsy result, and repeated biopsy is suggested. The authors assessed whether diagnostic follow-up of men with an initial diagnosis of isolated, high-grade prostatic intraepithelial neoplasia (HPIN) and a prostate biopsy suspicious for malignancy (PBSM) is needed. METHODS: The frequency of isolated HPIN and PBSM was determined in 4057 participants of a population-based screening study who underwent systematic sextant transrectal biopsy. The predictive value for prostate carcinoma of HPIN and PBSM was determined by performing repeated biopsies at 6-week interval. The additional predictive value for malignant disease within a screened population was assessed by performing repeated biopsies at a 1-year interval in 462 consecutively recruited men with an initial benign biopsy result. Participants were subjected to a second screening at a 4-year interval. The biopsy and radical prostatectomy tumor features were determined. RESULTS: Isolated HPIN and PBSM were diagnosed in 0.8% and 2.6% of biopsied men, respectively. The detection rates on repeated biopsy were 10.0% (3 of 30 men) for isolated HPIN, 38.7% (36 of 93 men) for PBSM, and 11.0% (51 of 462 men) for those with initial benign biopsy results. Except for two men (one with PBSM and one with HPIN), all others remained free of prostate carcinoma at their second screening. Features of the tumors that were detected after PBSM were comparable to those that were detected on initial biopsy, whereas the few tumors that were diagnosed after HPIN had highly favorable features. CONCLUSIONS: Compared with men who have PBSM, men with isolated HPIN on initial biopsy are at no greater risk of being diagnosed with prostate carcinoma than if their initial biopsies were assessed as benign only. Moreover, the features of tumors that are diagnosed after an evaluation of HPIN warrant no early, extensive diagnostic follow-up.

Aged↗
PubMed2001

Pathologic features of prostate cancer found at population-based screening with a four-year interval.

BACKGROUND: The currently recommended frequency for prostate-specific antigen (PSA) screening tests for prostate cancer is 1 year, but the optimal screening interval is not known. Our goal was to determine if a longer interval would compromise the detection of curable prostate cancer. METHODS: A cohort of 4491 men aged 55-75 years, all participants in the Rotterdam section of the European Randomized Study of (population-based) Screening for Prostate Cancer, were invited to participate in an initial PSA screening. Men who received that screening were invited for a second screen 4 years later. Pathology findings from needle biopsy cores were compared for men in both rounds. Statistical tests were two-sided. RESULTS: A total of 4133 men were screened in the first round (the prevalence screen), and 2385 were screened in the second round. The median amount of cancer in needle biopsy sets was 7.0 mm (95% confidence interval [CI] = 5.4 mm to 8.6 mm) in the first round and 4.1 mm (95% CI = 2.6 mm to 5.6 mm) in the second round (P =.001). Thirty-six percent of the adenocarcinomas detected in the first round but only 16% of those detected in the second round had a Gleason score of 7 or higher (mean difference = 20% [95% CI = 10% to 30%]; P<.001). Whereas 25% of the adenocarcinomas detected in the first round had adverse prognostic features, only 6% of those detected in the second round did (mean difference = 19% [95% CI = 11% to 26%]; P<.001). Baseline PSA values were predictive for the amount of tumor in biopsies in men with cancer in the first round but not for that in the second round. CONCLUSION: Most large prostate cancers with high serum PSA levels were effectively detected in a prevalence screen. In this population, a screening interval of 4 years appears to be short enough to constrain the development of large tumors, although it is inconclusive whether this will result in a survival benefit.

Adenocarcinoma↗
PubMed2001

Tumor characteristics in screening for prostate cancer with and without rectal examination as an initial screening test at low PSA (0.0-3.9 ng/ml).

BACKGROUND: The value of rectal examination as initial screening test for prostate cancer at low PSA values (0.0-3.9 ng/ml) was determined by evaluating the number and tumor characteristics of the cancers detected. METHODS: Two study populations were subjected to screening with (n = 10,226) and without (n = 10,753) rectal examination as initial screening test. The number of cancers detected at low PSA values for both screening regimens, the corresponding biopsy and radical prostatectomy tumor characteristics were assessed. Possibly harmless cancers were defined as small (< 0.5 ml) organ-confined tumors without Gleason growth-patterns 4/5. RESULTS: At low PSA, 26.6% (117/440) of screen-detected cancers were detected after the evaluation of a suspicious rectal examination. The number of cancers and tumor aggressiveness features were highly associated with serum-PSA level. The proportion of possibly harmless disease steadily declined from 100% (PSA 0.0-0.9 ng/ml) to 15.4% (PSA 3.0-3.9 ng/ml). Rectal examinations were performed unnecessarily in 94.7-100% of cases, when detection of clinically significant disease was aimed at. Using PSA (and a cut-off of 3.0 ng/ml) as the only screening tool, 24.3% (121/498) of screen-detected cancers were in the PSA range 3.0-3.9 ng/ml, and 60.0% were assessed as clinically significant. CONCLUSIONS: Rectal examination as initial screening test for prostate cancer at low PSA values may be replaced by screening using serum-PSA only. At PSA levels below 3.0 ng/ml, 289 rectal examinations are required to find one case of clinically significant disease, and 96 rectal examinations are needed to diagnose prostate cancer of any size, grade, or stage.

Aged↗
PubMed2001

Defining the window of opportunity in screening for prostate cancer: validation of a predictive tumor classification model.

BACKGROUND: Subdividing cancers according to the natural course of disease, both at the time of diagnosis and after radical prostatectomy, may influence management decisions of patients with prostate cancer. We investigated whether categorization of prostate cancers into different prognostic subgroups is feasible. METHODS: In 218 screened participants of a randomized study, conventional post-operative tumor features were assessed for their accuracy in predicting PSA relapse after radical prostatectomy using Cox regression analysis. Independent prognostic tumor features were combined to identify subsets of cancers with similar biological potential. A cancer was defined that may be curable after its detection by screening tests, though is destined to progress to clinically manifest disease and cancer-related mortality in the absence of screening. RESULTS: After a median follow-up of 33.0 months, pathological stage (P = 0.03), tumor volume (P = 0.04), and margin status (P = 0.01) each independently predicted PSA relapse after surgery. The proportion of poorly differentiated cancer proved highly superior to the Gleason score and most strongly predicted PSA relapse (P < 0.0001). Based on combined independent prognostic tumor features, a tumor classification model powerfully predicted PSA relapse. CONCLUSIONS: Based on tumor characteristics, possibly harmless, and conversely, possibly non-curable disease, may be distinguished from cancers that are likely to show clinical progression in the absence of screening and treatment. Prediction of these subclasses prior to treatment may eventually lead to proper patient management.

Aged↗
PubMed2001

Molecular cytogenetic analysis of prostatic adenocarcinomas from screening studies : early cancers may contain aggressive genetic features.

No objective parameters have been found so far that can predict the biological behavior of early stages of prostatic cancer, which are encountered frequently nowadays due to surveillance and screening programs. We have applied comparative genomic hybridization to routinely processed, paraffin-embedded radical prostatectomy specimens derived from patients who participated in the European Randomized Study of Screening for Prostate Cancer. We defined a panel consisting of 36 early cancer specimens: 13 small (total tumor volume (Tv) < 0.5 ml) carcinomas and 23 intermediate (Tv between 0.5-1.0 ml) tumors. These samples were compared with a set of 16 locally advanced, large (Tv > 2.0 ml) tumor samples, not derived from the European Randomized Study of Screening for Prostate Cancer. Chromosome arms that frequently (ie, > or = 15%) showed loss in the small tumors included 13q (31%), 6q (23%), and Y (15%), whereas frequent (ie, > or = 15%) gain was seen of 20q (15%). In the intermediate cancers, loss was detected of 8p (35%), 16q (30%), 5q (26%), Y (22%), 6q, and 18q (both 17%). No consistent gains were found in this group. In the large tumors, loss was seen of 13q (69%), 8p (50%), 5q, 6q (both 31%), and Y (15%). Gains were observed of 8q (37%), 3q (25%), 7p, 7q, 9q, and Xq (all 19%). Comparison of these early, localized tumors with large adenocarcinomas showed a significant increase in the number of aberrant chromosomes per case (Rs = 0.36, P = 0.009). The same was true for the number of lost or gained chromosomes per case (Rs = 0.27, P: = 0.05; Rs = 0.48, respectively; P < 0.001). Interestingly, chromosomal alterations that were found in previous studies to be potential biomarkers for tumor aggressiveness, ie, gain of 7pq and/or 8q, were already distinguished in the small and intermediate cancers. In conclusion, our data show that chromosomal losses, more specifically of 6q and 13q, are early events in prostatic tumorigenesis, whereas chromosomal gains, especially of 8q, appear to be late events in prostatic tumor development. Finally, early localized tumors, as detected by screening programs, harbor cancers with aggressive genetic characteristics.

Adenocarcinoma↗
PubMed2001

Prostate-specific antigen-based early detection of prostate cancer--validation of screening without rectal examination.

OBJECTIVES: The evaluation of the screening procedures for prostate cancer (PCa) was a part of the protocol of the European Randomized Study of Screening for Prostate Cancer (ERSPC), section Rotterdam, The Netherlands. We sought to establish an improved strategy for the early detection of PCa using a prostate-specific antigen (PSA) cutoff of 3.0 ng/mL or greater as the only indication for prostate biopsy with omission of the digital rectal examination (DRE). METHODS: In June 1996, 8612 men, 55 to 74 years old, were randomized to screening and were screened within the ERSPC Rotterdam by a PSA level of 4.0 ng/mL or greater or positive DRE or transrectal ultrasound findings as the indication for biopsy. Four hundred thirty men had PCa. Those treated by radical prostatectomy provided the tumor characteristics considered essential for a change in the screening strategies. Various options were evaluated and predictions made by logistic regression analyses. The protocol change was implemented in February 1997. Another 7943 men were screened according to the new protocol (PSA 3.0 ng/mL or greater). The resulting data were used to compare the two protocols. RESULTS: The detection rate (proportion of PCa in those screened) turned out to be very similar, with rates of 5.0 and 4.7 at a PSA cutoff of 4.0 ng/mL or greater and 3.0 ng/mL or greater, respectively. This was due to a much larger number of cases of PCa per biopsy in the PSA range of 3 to 3.9 ng/mL than expected. The positive predictive value of the PSA range 3.0 to 3.9 ng/mL in the two protocols was 18.0% and 6.4%, respectively. Tumor characteristics were studied on radical prostatectomy specimens from the original protocol. PCa detected with the new screening regimen had a similar distribution of Gleason scores but a larger proportion of confined disease. Tumor volumes were smaller in patients with PSA levels of less than 2.9 ng/mL; the proportion of "minimal disease" in that group was 50% compared with 28% in the group with a PSA level between 3.0 and 3.9 ng/mL. CONCLUSIONS: Lowering the biopsy indication to a PSA cutoff of 3.0 ng/mL or greater without a DRE improved the positive predictive value from 18.2% to 24.3%. The number of biopsies necessary to detect 1 case of PCa accordingly changed from 5.2 to 3.4. The overall characteristics of the cases detected at that PSA cutoff differed very little from those detected with the regimen based on PSA, DRE, and transrectal ultrasound.

Aged↗
PubMed2001

Feasibility of assessment of promoter methylation of the CD44 gene in serum of prostate cancer patients.

BACKGROUND AND PURPOSE: CD44 is an important metastasis-suppressor gene in prostate cancer. Downregulation of the CD44 gene is attributed to transcription repression by methylation of CpG islands in the promoter region. The feasibility of CD44 promoter methylation measurement as a diagnostic tool was assessed in the serum of patients with cancer of the prostate (CAP). MATERIALS AND METHODS: Seven serum samples of patients with CAP were investigated for CD44 promoter methylation by methylation-specific PCR. Three patients had proven metastatic disease, and four were free of metastases. Tissues from a variety of normal epithelia were assessed as well. RESULTS: Methylation of the CD44 promoter was readily detectable in all serum samples, although no distinction could be made between patients with and those without metastatic disease on the basis of the signal intensity of methylation-specific PCR products. Remarkably, tissue specimens from different normal epithelia, especially those of the colon and rectum, repeatedly showed aberrant methylation of the promoter region of CD44. CONCLUSIONS: In the serum of CAP patients, assessment of the methylation status of CpG islands in the promoter region of the CD44 gene is feasible using methylation-specific PCR. However, because of physiologic promoter methylation in normal tissues, including the colorectal mucosa, assessment of methylation of tumor-derived DNA in the serum of cancer patients lacks tissue specificity and seems not to be applicable in clinical settings.

CpG Islands↗
PubMed2000

Staging prostate cancer.

Determining tumor stage provides a systematic way to describe the amount and the extent of a tumor at a certain point in time. In this short overview, the current version of the TNM system for prostate cancer is discussed. The TNM (tumor, lymph node, and metastasis) system is now used worldwide for determining tumor stage for prostate cancer. Tumor stage is essentially determined in two situations, at clinical evaluation of the patient (clinical stage) and after treatment by surgical removal of the prostate (pathological stage). In the ideal situation, clinical stage would be a reliable predictor of pathological stage, but in the current situation, tumors are clinically understaged in more than half of the cases. Additional clinical tools are needed to provide a firmer base on which the choice for patient treatment or management could be founded. Some of the criteria for the assessment of pathological stage are unclear. For instance, multifocal tumor, which occurs in more than half of the cases of prostate cancer, is not reckoned with in the current system, something that could hamper a correct and unambiguous assessment of pathological stage. In this report, we also discuss the criteria for extraprostatic extension, seminal vesicle invasion, and bladder neck invasion. Follow-up data obtained from a group of 123 patients that underwent radical prostatectomy at our hospital underline the importance of reporting the latter two.

Humans↗
PubMed2000

Detection of prostate cancer: a comparative study of the diagnostic efficacy of sextant transrectal versus sextant transperineal biopsy.

OBJECTIVES: The optimal biopsy strategy for the detection of prostate cancer still needs to be established, since a considerable proportion of clinically significant cancers remains undiagnosed on routine sextant transrectal biopsy. To assess the efficacy of transperineal biopsy to detect prostate cancer, we compared this approach to systematic sextant transrectal biopsy in a simulation experiment. METHODS: Ultrasound-guided sextant transverse (transrectal) biopsy and subsequent sextant longitudinal (transperineal) biopsy were performed on 40 radical prostatectomy specimens of patients with (transrectal) biopsy-detected prostate cancer. Conditions were simulative and may not be completely analogous to clinical settings. Ultrasound-determined prostate volume, biopsy tumor involvement, number of cores with cancer, and tumor volume were determined. Detailed mapping of radical prostatectomy specimens provided insight into the representativeness of the biopsy techniques. RESULTS: Of 40 cancers, 33 (82.5%) were redetected by the transperineal approach; 29 (72.5%) were detected by repeated transrectal biopsies. For both approaches, the tumor volume of the undiagnosed cancers was significantly smaller (P <0.01) and the prostate volume was significantly larger (P <0.01) than in the redetected ones. Between the two approaches, no difference was found for either of the variables determined in the redetected cancers. Prostate maps clarified that transperineal undiagnosed tumors were either small (0.2 cm(3) or less) or notably located at the prostatic base. CONCLUSIONS: The biopsy procedure in which the biopsy needles enter the prostate at the apex for a longitudinal direction may efficiently sample the prostatic peripheral zone. Since the experiment was artificial in design, caution should be observed in extrapolating these results to patient settings.

Biopsy↗
PubMed2000

Quantitative analysis of the decay of immunoreactivity in stored prostate needle biopsy sections.

Application of immunohistochemistry to assess the presence of prognostic tissue markers is used widely. The quantitation of these markers may be hampered by a time-related loss of antigenicity in formalin-fixed paraffin-embedded tissue stored on glass slides. Potential loss of immunohistochemical staining intensity was studied on prostatic needle biopsy sections stored for a maximum of 4 years with antibodies against p27kip1, CD-44s, MIB-1, and androgen receptor (AR). In benign tissue, the positive/total ratio for p27kip1 was determined, while CD-44s staining intensity was assessed semiquantitatively. For MIB-1 and AR, nuclear staining intensity was assessed using computed image analysis. An exponential and significant decay of immunoreactivity was seen for p27kip1, CD-44s, MIB-1, and AR, with half-lives of 587 days, 214 days, and 290 days for p27kip1, MIB-1, and AR, respectively. Immunohistochemical assessment of prognostic tissue markers on stored slides must be considered with care in research and clinical settings.

Antibodies, Neoplasm↗
PubMed2000

Prostate cancer detection at low prostate specific antigen.

PURPOSE: At low prostate specific antigen (PSA) the indication for prostate biopsy is usually an abnormal digital rectal examination. We evaluate the diagnostic value of PSA, digital rectal examination, transrectal ultrasonography and tumor characteristics at low PSA (0 to 4.0 ng./ml.). We confirm and add to recent evidence that digital rectal examination has a low predictive value and that many significant cancers at this PSA range may be missed. MATERIALS AND METHODS: From 1994 to 1997 a total of 10,523 participants 54 to 74 years old were randomized to screening in the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer. Of the participants 9,211 (87.5%) had PSA less than 4.0 ng./ml., and underwent digital rectal examination and transrectal ultrasonography. Expected rates of prostate cancer detection were calculated using logistic regression analysis. Radical prostatectomy was performed in about half of the 478 men diagnosed with prostate cancer. Tumors were characterized by pT category, Gleason score and cancer volume in 166 processed radical prostatectomy specimens. In 50 of these cases PSA was 0 to 4.0 ng./ml. RESULTS: The positive predictive value of digital rectal examination and transrectal ultrasonography at PSA 0 to 4.0 ng./ml. was only 9.7%. Positive predictive value strongly depended on PSA. Sensitivity was calculated by using estimates of the prevalence of sextant biopsy detectable prostate cancers. Of 760 detectable cancers 478 (67%) were diagnosed irrespective of PSA in men screened with digital rectal examination, transrectal ultrasonography and PSA. Only 127 of 348 detectable prostate cancers (36.5%) were actually diagnosed in men with PSA 2 to 4 mg./ml. The importance of these missed cancers was evaluated with parameters of tumor aggressiveness within PSA ranges. CONCLUSIONS: Approximately half of the tumors missed with PSA 0 to 4 ng./ml. had aggressive characteristics (Gleason score 7 or greater, Gleason 4-5 components) and were organ confined. These tumors should be diagnosed and treated according to the present understanding of their natural history. More sensitive and selective screening strategies are needed. Presently a wrong "window of opportunity" is used for early detection of prostate cancer.

Aged↗
PubMed2000

Prognostic value of cell cycle proteins p27(kip1) and MIB-1, and the cell adhesion protein CD44s in surgically treated patients with prostate cancer.

PURPOSE: Molecular tissue markers may give the clinician additional information about patients with prostate cancer at risk for treatment failure after retropubic radical prostatectomy. We substantiate the prognostic value of 3 tissue markers, the cell cycle proteins p27(kip1) and MIB-1, and the cell adhesion protein CD44s, in addition to more conventional pathological prognosticators in an historical (before prostate specific antigen) cohort of patients with prostate cancer. MATERIALS AND METHODS: Representative tumor sections from 92 patients who underwent retropubic radical prostatectomy were immunohistochemically stained with antibodies against p27(kip1), MIB-1 (Ki-67) and CD44s, and assessed in a semiquantitative manner. Gleason score and pathological tumor stage were recorded. All variables were correlated with clinical progression and disease specific survival on univariate and multivariate analyses. RESULTS: On univariate analysis low (less than 50%) p27(kip1), high (10% or greater) MIB-1 and loss of CD44s expression were significantly associated with clinical outcome parameters, although MIB-1 did not reach statistical significance for disease specific survival. All 3 molecules were highly correlated with Gleason score and pathological tumor stage. Multivariate analysis showed that low p27kip1 was independent of grade and stage in predicting clinical recurrence (p <0.001) and disease specific survival (p = 0.045), while loss of CD44s was an additional independent prognostic factor for clinical recurrence (p = 0.02). CONCLUSIONS: Reduced p27(kip1) expression is an independent predictor of poor outcome in prostate cancer, while MIB-1 is not. Decreased expression of CD44s yields additional information in predicting clinical recurrence. These tissue markers may identify patients at risk for disease recurrence after retropubic radical prostatectomy who may benefit from adjuvant therapy.

Aged↗
PubMed1996

Expression of oncoproteins and the amount of eosinophilic and lymphocytic infiltrates can be used as prognostic factors in gastric cancer. Dutch Gastric Cancer Group (DGCG).

Preoperative staging of gastric cancer is difficult. Several molecular markers associated with initiation and progression of cancer seem promising for obtaining preoperative prognostic information. To investigate whether these markers are indicative especially for the presence of lymph node metastases in patients with gastric cancer, we have examined primary tumour specimens from 105 patients with primary adenocarcinoma of the stomach entered in a surgical trial. In this trial, lymph node status was determined by strictly quality-controlled lymph node dissection and examination. The selected markers were growth regulators (p53, Rb and myc), metastasis-suppressor gene product (nm23), adhesion molecules (Ep-CAM, E-cadherin, CD44v5 and CD44v6) and urokinase-type plasminogen activator (u-PA). Also, the amount of eosinophilic and lymphocytic infiltrates available post-operatively was analysed with respect to its prognostic value for lymph node status. Moreover, the association of these parameters with survival and disease-free period (DFP) was evaluated. Of all molecular markers investigated, only Rb expression had a significant association with the presence of lymph node metastasis in both univariate and multivariate analysis. For curative resectability, a significant association was found with Rb and E-cadherin expression, while in multivariate analysis Rb and myc were selected as the combination with additional independent prognostic value, and E-cadherin had no additional independent value. For overall survival in univariate analysis, the amount of both eosinophilic and lymphocytic infiltrates and Rb and myc expression were of significant prognostic value. Only the amount of lymphocytic infiltrate had a prognostic significance for DFP. In stepwise multivariate analysis, TNM stage (I + II) and marked lymphocytic infiltrate were associated with better overall survival and longer DFP. We conclude that, if these results are confirmed in a larger series of patients, molecular markers can provide useful prognostic information.

Aged↗