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Hartwig Huland

Publications and source records attributed to Hartwig Huland.

At least 55 records · Page 3Linked to original sources

Epidemiology and statistical methods in prediction of patient outcome.

Substantial gaps exist in the data of the assessment of risk and prognosis that limit our understanding of the complex mechanisms that contribute to the greatest cancer epidemic, prostate cancer, of our time. This report was prepared by an international multidisciplinary committee of the World Health Organization to address contemporary issues of epidemiology and statistical methods in prostate cancer, including a summary of current risk assessment methods and prognostic factors. Emphasis was placed on the relative merits of each of the statistical methods available. We concluded that: 1. An international committee should be created to guide the assessment and validation of molecular biomarkers. The goal is to achieve more precise identification of those who would benefit from treatment. 2. Prostate cancer is a predictable disease despite its biologic heterogeneity. However, the accuracy of predicting it must be improved. We expect that more precise statistical methods will supplant the current staging system. The simplicity and intuitive ease of using the current staging system must be balanced against the serious compromise in accuracy for the individual patient. 3. The most useful new statistical approaches will integrate molecular biomarkers with existing prognostic factors to predict conditional life expectancy (i.e. the expected remaining years of a patient's life) and take into account all-cause mortality.

Adult↗

Comparison of predictive accuracy for pathologically organ confined clinical stage T1c prostate cancer using human glandular kallikrein 2 and prostate specific antigen combined with clinical stage and Gleason grade.

PURPOSE: Previously human glandular kallikrein 2 (hK2) has been implicated to predict pathologically organ confined prostate cancer (PCa) in patients with stage T2 disease. Now we evaluated the usefulness of hK2, as measured by 2 entirely different immunoassay designs, to enhance the discrimination of pathologically organ from nonorgan confined clinical stage T1c PCa. MATERIALS AND METHODS: A consecutive series of pretreatment serum from 148 men with clinical stage T1c PCa was used in 2 equally sensitive and specific methods to measure total hK2 with independent reagents and entirely different assay designs. Total prostate specific antigen (tPSA) and free PSA (fPSA) were measured and percent fPSA was calculated. We determined the algorithm, hK2*tPSA/fPSA, from data generated by each hK2 assay, calculated means, medians and ranges for each analyte and algorithm, and calculated the significance of differences on univariate analysis. Using pretreatment PSA, clinical stage and biopsy Gleason grade we then developed a multivariate logistic regression base model to predict organ confined cancer and we compared predictions of the base model supplemented by the different hK2 measurements. RESULTS: hK2 and hK2 based algorithms obtained by each hK2 assay were significantly different for pT2a/b vs pT3a or greater PCa (p = 0.034 to 0.0001) compared to tPSA (p = 0.06), fPSA (p = 0.90) or percent fPSA (p = 0.059). However, AUC (0.67 to 0.70) calculated by ROC analysis of the 4 models containing hK2 derived information was not significantly larger than that of the base model (AUC = 0.64, p = 0.52). CONCLUSIONS: The current data confirm that hK2 alone or hK2*tPSA/fPSA measured by 2 immunoassays is significantly lower in men with pT2a/b vs pT3a or greater PCa compared to tPSA, fPSA or percent fPSA on univariate analysis of a validation set of clinical stage T1c prostate cancer treated at an American center of excellence for prostate cancer surgery. However, the incorporation of preoperative hK2 into multiparameter predictive models for pT2 cancers did not increase predictive accuracy in this cohort of men.

Adult↗

Nomograms including nuclear matrix protein 22 for prediction of disease recurrence and progression in patients with Ta, T1 or CIS transitional cell carcinoma of the bladder.

PURPOSE: We developed and validated nomograms that accurately predict disease recurrence and progression in patients with Ta, T1, or CIS transitional cell carcinoma (TCC) of the bladder using a large international cohort. METHODS: Univariate and multivariate logistic regression models targeted histologically confirmed disease recurrence, and focused on 2,542 patients with bladder TCC from 10 participating centers. Variables consisted of pre-cystoscopy voided urine Nuclear Matrix Protein 22 (NMP22) assay, urine cytology, age and gender. Resulting nomograms were internally validated with bootstrapping. Nomogram performance was explored graphically with Loess smoothing plots. RESULTS: Overall 957 patients had recurrent TCC. Tumor grade and stage was available for 898 patients, including 24% grade I, 43% grade II, and 33% grade III; 45% stage Ta, 32% T1 and/or CIS, and 23% T2 or greater. Bootstrap corrected predictive accuracy for any TCC recurrence was 0.842; grade III Ta/T1 or CIS was 0.869; and T2 or higher stage TCC of any grade was 0.858. Virtually perfect performance characteristics were observed for the nomograms predicting any TCC recurrence or grade III Ta/T1 or CIS. The nomogram predicting T2 or higher stage TCC overestimated the observed probability for predicted values greater than 45%. CONCLUSIONS: We developed and internally validated nomograms that incorporate urinary NMP22, cytology, age and gender to predict with high accuracy the probability of disease recurrence and progression in patients with Ta, T1, and/or CIS bladder TCC. These nomograms could provide a means for individualizing followup in patients with Ta, T1, CIS bladder TCC.

Adolescent↗

Development and validation of a nomogram predicting the outcome of prostate biopsy based on patient age, digital rectal examination and serum prostate specific antigen.

PURPOSE: We developed and validated a nomogram which predicts presence of prostate cancer (PCa) on needle biopsy. MATERIALS AND METHODS: We used 3 cohorts of men who were evaluated with sextant biopsy of the prostate and whose presenting prostate specific antigen (PSA) was not greater than 50 ng/ml. Data from 4,193 men from Montreal, Canada were used to develop a nomogram based on age, digital rectal examination (DRE) and serum PSA. External validation was performed on 1,762 men from Hamburg, Germany. Data from these men were subsequently used to develop a second nomogram in which percent free PSA (%fPSA) was added as a predictor. External validation was performed using 514 men from Montreal. Both nomograms were based on multivariate logistic regression models. Predictive accuracy was evaluated with areas under the receiver operating characteristic curve and graphically with loess smoothing plots. RESULTS: PCa was detected in 1,477 (35.2%) men from Montreal, 739 (41.9%) men from Hamburg and 189 (36.8%) men from Montreal. In all models all predictors were significant at 0.05. Using age, DRE and PSA external validation AUC was 0.69. Using age, DRE, PSA and %fPSA external validation AUC was 0.77. CONCLUSIONS: A nomogram based on age, DRE, PSA and %fPSA can highly accurately predict the outcome of prostate biopsy in men at risk for PCa.

Adolescent↗

Detection of human telomerase RNA in the tumour-surrounding mucosa of bladder carcinomas as a marker for premalignant transformation.

OBJECTIVES: To investigate tumour tissue and non-malignant tumour-surrounding bladder mucosa (NTSBM) for expression of human telomerase RNA (hTR) as a possible marker for premalignant transformation of urothelial cells. MATERIAL AND METHODS: From 67 patients with superficial transitional cell carcinoma (TCC), sections with representative tumour tissue and NTSBM were selected for evaluation. Sections with moderate or severe dysplasia were omitted from evaluation. hTR expression was detected with in situ hybridization using a 35S-UTP-labelled riboprobe, and analysed semiquantitatively by counting the hybridization signals. RESULTS: In 45 of the 67 patients hTR expression was moderate or strong in tumour tissue, and in 20 hTR expression was moderate or strong in NTSBM. Moderate or strong hTR expression was detected in the NTSBM from 19 of 60 patients with pTa/pT1 tumours. Of the 56 patients who were treated conservatively, eight had tumour recurrence, of whom five had moderate or strong hTR expression in the TSBM, compared with only 14 of 48 patients without tumour recurrence. CONCLUSION: Detecting hTR expression and the morphological distribution of hTR hybridization signals in NTSBM by in situ hybridization might indicate premalignant alterations involved in tumour recurrence.

Adult↗

Extraction and processing of high quality RNA from impalpable and macroscopically invisible prostate cancer for microarray gene expression analysis.

Molecular analyses of early-stage prostate cancers are necessary to assess their potential clinical significance based on established and/or novel biomarkers for tailored clinical management. A prerequisite for the application of RNA-based analyses of such, mostly macroscopically-undetectable, small prostate carcinomas is the recovery and preservation of sufficient RNA quantities and quality. Furthermore, in prostate cancer, heterogeneity is a common phenomenon that includes a juxtaposition of different tissue compositions and variable histological grades within the same tumor focus. To better understand the molecular mechanisms of prostate cancer, it is essential to correlate molecular data with a specific cell type. Here, we present a tissue collecting protocol which is aligned with the preoperative evaluation of tumor localization. In combination with the technique of laser microdissection and pressure catapulting, we are able to preserve RNA of high quality from homogeneous cell populations of macroscopically-undetectable small prostate carcinomas. To obtain the necessary RNA quantities for whole genome cDNA microarrays, the isolated total RNAs were amplified by T7-based RNA-polymerase in vitro transcription. The microarray analyses (Human Unigene Set RZPD3.1) resulted in 216 differentially expressed genes (191 down-regulated, 25 up-regulated). Among these were several known prostate cancer relevant genes, such as AMACR, TARP, LIM, GPR160 (all up-regulated), CAV1, NTN1, MT1X; CLU, TRIM29, SPARCL1 and HSPB8 (all down-regulated).

Down-Regulation↗

Dual role of carcinoembryonic antigen-related cell adhesion molecule 1 in angiogenesis and invasion of human urinary bladder cancer.

Here, we show that carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is expressed in umbrella cells of bladder urothelium but is down-regulated in superficial bladder cancer, such as histologic tumor stage a (pTa) and transitional cell carcinoma in situ (pTis). Concurrently, CEACAM1 is up-regulated in the endothelia of adjacent angiogenic blood vessels. Mimicking the CEACAM1 down-regulation in the urothelium, CEACAM1 was silenced in bladder cancer cell lines 486p and RT4 using the small interfering RNA technique. CEACAM1 down-regulation was confirmed at the protein level by Western blot analyses. CEACAM1 silencing leads to a significant up-regulation of vascular endothelial growth factor (VEGF)-C and VEGF-D in quantitative reverse transcription-PCR. Correspondingly, supernatants from the CEACAM1-overexpressing bladder cancer cell lines reduce, but those from CEACAM1 silencing induce endothelial tube formation and potentiate the morphogenetic effects of VEGF. These data suggest that the epithelial down-regulation of CEACAM1 induces angiogenesis via increased expression of VEGF-C and VEGF-D. Inversely, CEACAM1 is up-regulated in endothelial cells of angiogenic blood vessels. This in turn is involved in the switch from noninvasive and nonvascularized to invasive and vascularized bladder cancer. CEACAM1 appears to be a promising endothelial target for bladder cancer therapy.

Antigens, CD↗

CXCR3 and CCR5 positive T-cell recruitment in acute human renal allograft rejection.

BACKGROUND: Experimental studies suggest that the infiltration of activated T cells into the allograft, the key event in the development of acute renal allograft rejection, depends on the expression of chemokines and their interaction with chemokine receptors expressed on T cells. METHODS: For a more detailed comprehension of the pathogenesis of T-cell recruitment in human acute rejection, the in situ expression of chemokines and chemokine receptors in allografts of 26 patients between day 3 and 9 after renal transplantation was examined in the present prospective study. RESULTS: Immunohistochemical staining showed a significantly increased number of CXCR3 (P<0.01) and CCR5 positive T cells (P<0.01) in the tubulointerstitium of patients with acute allograft rejection according to Banff grade Ia-IIb. Likewise the intrarenal RNA expression of the CXCR3 ligands IP-10 (5.2-fold) and I-TAC (7.2-fold) and the CCR5 ligand RANTES (5.7-fold), was significantly up-regulated in rejecting organs. In situ hybridization revealed that IP-10 but not I-TAC was predominantly expressed by infiltrating leukocytes in the tubulointerstitial area, co-localizing with CXCR3 positive T cells. To a lesser degree expression by tubular cells could be detected, providing a possible explanation for the increased urinary IP-10 excretion we found in patients with rejecting organs. CONCLUSIONS: These data from a prospective, biopsy-controlled study indicate that the local expression of IP-10 and RANTES leads to the directional movement of activated CXCR3 and CCR5 bearing T cells into the renal allograft and mediates acute rejection. Our data provide a rationale that blocking CXCR3 and CCR5 may offer a unique therapeutic approach to prevent episodes of acute rejection in the early phase after renal transplantation.

Acute Disease↗

Detection of methylated apoptosis-associated genes in urine sediments of bladder cancer patients.

PURPOSE: There is increasing evidence for a fundamental role for epigenetic silencing of apoptotic pathways in cancer. Changes in DNA methylation can be detected with a high degree of sensitivity, so we used the MethyLight assay to determine how methylation patterns of apoptosis-associated genes change during bladder carcinogenesis and whether DNA methylation could be detected in urine sediments. EXPERIMENTAL DESIGN: We analyzed the methylation status of the 5' regions of 12 apoptosis-associated genes (ARF, FADD, TNFRSF21, BAX, LITAF, DAPK, TMS-1, BCL2, RASSF1A, TERT, TNFRSF25, and EDNRB) in 18 bladder cancer cell lines, 127 bladder cancer samples, and 37 samples of adjacent normal bladder mucosa using the quantitative MethyLight assay. We also analyzed the methylation status in urine sediments of 20 cancer-free volunteers and 37 bladder cancer patients. RESULTS: The 5' regions of DAPK, BCL2, TERT, RASSFIA, and TNFRSF25 showed significant increases in methylation levels when compared with nonmalignant adjacent tissue (P < or = 0.01). Methylation levels of BCL2 were significantly associated with tumor staging and grading (P < or = 0.01), whereas methylation levels of RASSF1A and ARF were only associated with tumor stage (P < or = 0.04), and TERT methylation and EDNRB methylation were predictors of tumor grade (P < or = 0.02). To investigate clinical usefulness for noninvasive bladder cancer detection, we further analyzed the methylation status of the markers in urine samples of patients with bladder cancer. Methylation of DAPK, BCL2, and TERT in urine sediment DNA from bladder cancer patients was detected in the majority of samples (78%), whereas they were unmethylated in the urine sediment DNA from age-matched cancer-free individuals. CONCLUSIONS: Our results indicate that methylation of the 5' region of apoptosis-associated genes is a common finding in patients with bladder carcinoma. The ability to detect methylation not only in bladder tissue, but also in urine sediments, suggests that methylation markers are promising tools for noninvasive detection of bladder cancers. Our results also indicate that some methylation markers, such as those in regions of RASSF1A and TNFRSF25, might be of limited use for detection because they are also methylated in normal bladder tissues.

Adult↗

Comparison of the ImmunoCyt test and urinary cytology with other urine tests in the detection and surveillance of bladder cancer.

Despite several new urine markers urinary cytology remains the gold standard for the non-invasive detection of bladder carcinoma. The use of monoclonal antibodies against tumor associated antigens offers a promising approach to improve urinary cytology. The aim of this study was to compare fluorescence immunocytology (ImmunoCyt/Ucyt+ test), alone and in combination with the conventional cytology, with other urine markers. Urine samples from 126 patients undergoing cystoscopy were included in the study. Among them, 42 patients had urothelial carcinoma, two dysplasia, two other malignancies, and 78 had no evidence of bladder cancer. Urine samples were taken before any manipulation. We used the ImmunoCyt test and Papanicolaou staining for conventional cytology. The ImmunoCyt slides were examined under a fluorescence microscope. Evaluations of the tests were blinded to clinical and pathological data and were carried out by three independent observers. The results of cytology and ImmunoCyt were compared with the BTAstat, NMP22, Lewis X, 486p3/12, and Urovision tests. The sensitivity for the ImmunoCyt test was 78.3% and for conventional cytology 84.6%. The combination of ImmunoCyt and cytology showed a sensitivity of 89.1%. The specificity was 73.8% for the ImmunoCyt alone, 80.0% for the cytology, and 72.5% for the combination of ImmunoCyt and cytology. Sensitivities for the other tests were 68.8% for (FISH), 66.6% (BTA-Stat), 68.8% (486p3/12), 95.5% (Lewis X), and 71.1% for (NMP22). Specificity was 89.1% for (FISH), 78.2% (BTA-Stat), 76.4% (486p3/12), 32.8% (Lewis X), and 65.5% for (NMP22). Urinary cytology can be improved by immunostaining with monoclonal antibodies against tumor-associated antibodies. The combination of ImmunoCyt with conventional cytology offers a superior sensitivity to other commercial tests. The ImmunoCyt test provides a useful supplement to urinary cytology in the diagnosis of bladder cancer.

Fluorescent Antibody Technique↗

Prostate-specific antigen and related isoforms in the diagnosis and management of prostate cancer.

Despite its unparalleled merits for prostate cancer detection and staging, prostate-specific antigen (PSA) is not a marker for prostate cancer only, but also is expressed in benign conditions. For early detection, limitations of PSA are obvious. Its widespread use has led to an extensive amount of expensive and often unnecessary diagnostic procedures associated with significant morbidity. Total PSA derivatives may enhance the accuracy of prostate cancer diagnosis. The ratio of free-to-total PSA improves specificity while maintaining a high sensitivity for prostate cancer detection for men with a total PSA of 2.5 to 10 ng/mL. Human glandular kallikrein also has the potential to be a valuable tool in combination with total and free PSA for early diagnosis of prostate cancer. Complex PSA seems to be a reliable tool to improve specificity at high sensitivity levels in men with suspected prostate cancer (mainly in PSA levels below 4 ng/mL). Newly discovered isoforms of free PSA also may impact early detection of prostate cancer with encouraging preliminary results that warrant further clinical investigation.

Humans↗

Expression of Maspin in non-muscle invasive bladder carcinoma: correlation with tumor angiogenesis and prognosis.

OBJECTIVES: Maspin is a member of the serpin (serine protease inhibitor) family and has been shown to be a suppressor of tumor growth and an inhibitor of angiogenesis as well as metastasis in several types of tumors. We studied expression patterns of Maspin in pTa/pT1 urothelial carcinoma of the bladder and compared them with microvessel density (MVD) for two vascular markers (CD34 and CD105) and correlated the findings with clinical outcome. MATERIAL AND METHODS: We investigated tumor samples of 110 patients undergoing transurethral resection for pTa/pT1 bladder carcinoma (pTa, n=84; pT1, n=26; grade 1, n= 22; grade 2, n= 81; grade 3, n=7). Immunohistochemical studies were performed using the monoclonal antibodies, anti-human Maspin (NCL Maspin), anti-CD34 Class II and anti-CD105. Maspin expression level was classified according to the staining intensity (- to +++). The blood vessels (CD34) and specifically proliferating blood vessels (CD105) were counted as vessels per field (microvessel density, MVD). RESULTS: Of the 110 tumors, 27 showed a negative immunostaining for Maspin, 46 tumors stained +, 29 stained ++, and 8 stained +++. Maspin expression correlated inversely with CD34 reactivity. In tumors with loss of or only weak Maspin expression, the MVD for CD34 was 21.7 vessels per field, and 4.2 vessels per field for proliferating vessels (CD105), whereas Maspin-positive tumors had an MVD of 17.7 vessels per field (CD34), and of 6.0 vessels per field (CD105). Complete follow-up data are available in 92 patients. After a median follow-up of 25 months, 18 of the 92 patients (19.6%) had tumor recurrences. Tumors with decreased Maspin expression (-/+) had a shorter disease-free interval (23 months) than patients with stronger Maspin (++/+++) expression (29 months), whereas a Kaplan-Meier analysis and the log-rank test showed no significant difference in disease-free survival between the patients. CONCLUSION: The clinical importance of Maspin has been mainly investigated regarding tumor progression or metastasis. We found a decreased Maspin expression in a large portion of pTa/pT1 bladder tumors. Even if patients with decreased Maspin expression have a slightly shorter disease-free survival Maspin does not appear to be a promising prognostic marker.

Adult↗

Immunocyt and the HA-HAase urine tests for the detection of bladder cancer: a side-by-side comparison.

OBJECTIVES: The reliable detection of bladder cancer from urine specimen remains an unsolved problem. Especially superficial bladder cancer can be missed with urine tests. We assessed the sensitivity and specificity of the commercial Immunocyt test in a side-by-side comparison with the HA-HAase urine test and cytology. The Immunocyt test measures the immunocytological expression of sulfated mucin-glycoproteins and glycosylated forms of the carcinoembryonic antigen in urine. With the HA-HAase urine test the level of hyaluronic acid (HA) and its degrading enzyme hyaluronidase (HAase) are measured in an ELISA-like test. METHODS: A total of 94 consecutive patients were studied and among these 30 patients had bladder cancer and 64 were controls. Among bladder cancer patients, there were 14 pTa, 9 pT1, 5 pT2 and 2 carcinoma in situ (CIS) transitional cell carcinoma of the bladder, respectively. The controls consisted of 55 patients with a history of bladder cancer but no evidence of tumor at the follow-up cystoscopy and 9 benign prostatic hyperplasia (BPH) patients. The 30 transitional cell cancer specimens had 4 (13%) grade 1 tumors, 15 (50%) grade 2 tumors and 11 (37%) grade 3 tumors. Sensitivity and specificity as well as the positive and negative predictive values of each test were evaluated. RESULTS: The sensitivity of the HA-HAase urine test (83.3%; 25/30) was significantly higher than the Immunocyt at 63.3% (19/30) (p = 0.038, McNemar test) and cytology (73%; p < 0.05). The specificity of the HA-HAase test (78.1%; 50/64), Immunocyt (75%; 48/64) and cytology (79.7%; 51/64) were comparable. The prevalence of bladder cancer in our study was 31%. The positive predictive value (PPV) of the HA-HAase test (64.1%) was significantly higher than the Immunocyt test (54.3%). The negative predictive value (NPV) of the HA-HAase test (90.9%) was also higher than the Immunocyt test (81.3%). The PPV and NPV values for cytology were 62.9% and 86.4%, respectively. False negative patients in the HA-HAase urine test were 5 pTa tumors (2 G1, 2 G2 and 1 G3). False negative patients in the Immunocyt test were 7 pTa tumors (1 G1 and 6 G2), 3 pT1 (2 G2, 1 G3) and 1 pT2 G3, respectively. CONCLUSIONS: The sensitivity of the HA-HAase urine test is significantly higher than that of the Immunocyt test to detect bladder cancer. Specificity, as well as the PPV and NPV of the HA-HAase test were higher than that of the Immunocyt test. With a prevalence of 31% bladder cancer patients in all hematuria patients studied, a typical distribution of patients in a urological clinic is presented. Longer follow up of the study patients will give more information on the value of these tests in the detection of bladder cancer.

Biomarkers, Tumor↗

Assessment of the enhancement in predictive accuracy provided by systematic biopsy in predicting outcome for clinically localized prostate cancer.

PURPOSE: Current localized prostate cancer treatment outcome nomograms rely on prostate specific antigen (PSA), tumor stage and grade. We investigated whether the addition of prostate biopsy features may enhance the accuracy of a nomogram predicting recurrence after radical prostatectomy (RP). MATERIALS AND METHODS: Clinical data from 1,152 patients who underwent RP were used and included PSA, clinical stage, biopsy Gleason grade and systematic biopsy information that quantified the amount of cancer and high grade cancer. Predictive accuracy for freedom from recurrence after RP was assessed with and without tumor quantification in the biopsy by the area under the receiver operating characteristics curve (AUC). RESULTS: Percentage and number of cores with cancer, and percentage and number of cores with high grade cancer were predictors of outcome when added to models that included PSA, Gleason grade and clinical stage (all p <0.0001). Nomogram accuracy with 3 traditional variables (AUC 0.790) was minimally enhanced with the addition of percentage or number of positive cores (AUC 0.804 and 0.800, respectively), or percentage or number of cores with high grade cancer (AUC 0.802 and 0.800, respectively). Maximum predictive accuracy of 0.811 was achieved after supplementing the traditional 3-variable nomogram with various combinations of additional pathological predictors. CONCLUSIONS: The information provided by systematic biopsies substantially improves the ability to predict outcome following RP. However, some incremental predictive accuracy was achieved by adding systematic biopsy features.

Adult↗

Comparison of accuracy between the Partin tables of 1997 and 2001 to predict final pathological stage in clinically localized prostate cancer.

PURPOSE: We validated externally the predictive accuracy of the 2001 Partin tables and compared the 1997 and 2001 versions. MATERIALS AND METHODS: We used ROC derived AUC to test the predictive accuracy of organ confinement (OC), extraprostatic extension (ECE), seminal vesicle invasion (SVI) and lymph node involvement (LNI) of 1997 and 2001 Partin tables derived probabilities. These probabilities were defined by the pretreatment clinical stage, serum prostate specific antigen and biopsy Gleason grade of 2,139 patients treated with radical prostatectomy for clinically localized prostate cancer. RESULTS: OC, ECE, SVI and LNI were noted in 63.5%, 23.1%, 10.5% and 2.9% of cases, respectively. AUC of the 2001 tables was 0.787, 0.766, 0.775 and 0.790, for OC, ECE, SVI and LNI, respectively. These values were virtually the same as the respective 1997 Partin table AUC values, namely 0.784, 0.728, 0.791 and 0.799. CONCLUSIONS: This external validation of the 2001 Partin tables confirms good predictive accuracy of the updated tables. However, predictive accuracy in this external validation data set of 2,139 European men is virtually the same as that of the original 1997 tables. Therefore, a transition from the 1997 tables to the updated 2001 version does not appear warranted unless superior accuracy is demonstrated in other external cohorts.

Adult↗

Is year of radical prostatectomy a predictor of outcome in prostate cancer?

PURPOSE: We examined whether the year in which radical prostatectomy (RP) was performed is a predictor of treatment outcome after controlling for standard prognostic factors. MATERIALS AND METHODS: We examined the association between RP year and outcome in 6,556 patients from 7 centers using preoperative and pathological features. Patients underwent surgery between 1985 and 2000. The variables analyzed were RP year, clinical stage, pretreatment prostate specific antigen, biopsy Gleason sum, RP Gleason sum, margin status, level of extracapsular extension, seminal vesicle status, lymph node status, neoadjuvant hormones and adjuvant therapy. Median followup was 23 months (maximum 166). Separate Cox multivariate regression analyses were performed to analyze preoperative and postoperative factors. RESULTS: RP year was a predictor of outcome on preoperative analysis (p = 0.006) but not on postoperative analysis (p = 0.130). Patient outcome steadily improved with surgery through the mid 1990s and then it appeared to level off. CONCLUSIONS: When controlling for preoperative features, the year in which RP was performed is a predictor of outcome on multivariate analysis. This effect could not be explained by stage migration.

Adult↗

A side by side comparison of cytology and biomarkers for bladder cancer detection.

PURPOSE: The identification of accurate bladder tumor markers/tests could improve diagnosis, recurrence monitoring and treatment in patients with bladder cancer. In this study we compared the efficacy of the hyaluronic acid (HA)-hyaluronidase (HAase), BTA-Stat (Bard/Bion Diagnostics, Redmond, Washington), Hemastix (Bayer Corp., Elkhart, Indiana) (hematuria detection) and UBC-Rapid (IDL Biotech, Borlänger, Sweden) tests, and cytology to detect bladder cancer. The HA-HAase test measures urinary HA and HAase levels, BTA-Stat detects complement factor-H and H related protein in urine, the Hemastix hemoglobin dipstick detects hematuria and UBC-Rapid detects cytokeratin 8 and 18 fragments in urine. MATERIALS AND METHODS: A total of 138 urine specimens from 115 patients were collected at University Hospital Hamburg-Eppendorf, including 59 with active bladder cancer and 79 with a history of bladder cancer (73) or with benign genitourinary conditions (6). Specimens were assayed by the HA-HAase test, BTA-Stat, Hemastix (hemoglobin dipstick) and UBC-Rapid. Cystoscopy and histological findings were used to make the clinical diagnosis. Cytology results were available on 92 patients. RESULTS: In a side by side comparison the HA-HAase test, cytology, BTA-Stat, Hemastix and UBC-Rapid had 88.1%, 70.6%, 52.5%, 50.8% and 35.6% sensitivity, and 81%, 81%, 76.7%, 78.2% and 75% specificity, respectively. The accuracy, and negative and positive predictive values of the HA-HAase test were the highest (84.1%, 90.1% and 77.6%), followed by cytology (77.2%, 82.5% and 68.6%), Hemastix (66.4%, 67.8% and 63.8%), BTA-Stat (66.2%, 67.8% and 63.3%) and UBC-Rapid (57.8%, 60% and 52.5%), respectively. CONCLUSIONS: : The HA-HAase test is superior to cytology, BTA-Stat, Hemastix and UBC-Rapid for detecting bladder cancer recurrence. A side-by-side comparison of tumor markers should help identify a marker for monitoring bladder cancer recurrence.

Adult↗