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Biomedical subjects

Michael Marberger

Publications and source records attributed to Michael Marberger.

At least 37 records · Page 2Linked to original sources
PubMed2005

Are repeat biopsies required in men with PSA levels < or =4 ng/ml? A Multiinstitutional Prospective European Study.

OBJECTIVES: Pathological and biochemical features of prostate cancers detected on repeat biopsies in men with total PSA level between 2.0 and 4 ng/ml were evaluated and compared to those cancers detected on first biopsy. METHODS: 315 men with PSA level between 2.0 and 4 ng/ml underwent transrectal ultrasound guided sextant biopsy and two additional transition zone biopsies (Octant Biopsy). All subjects whose biopsy samples were negative for prostate cancer underwent a repeat biopsy after 6 weeks. Those with clinically localized cancers were offered surgery or radiation therapy. Pathological and clinical features of patients diagnosed with prostate cancer on initial and repeat biopsy were compared. RESULTS: Cancer detection rates on first and second biopsy were 24% (75/315) and 13% (29/224), respectively. Overall, of patients with clinically localized disease (83% of cancers detected), 87% underwent radical prostatectomy, 11% opted for radiation therapy and 2% opted for watchful waiting. Cancers found in the first biopsy group were more multifocal (p = 0.01) while cancers found on second biopsy were more located in the apical-dorsal region (p = 0.003). No significant differences were noted with respect to extracapsular extension, seminal vesical invasion, positive margins, final pathological stage, Gleason score, percentage Gleason grade 4/5, serum PSA and patient age between first and second biopsy. CONCLUSIONS: With an octant biopsy regime, biochemical and pathological features of cancers detected on initial and repeat biopsy in the PSA range 2.0 to 4 ng/ml are comparable in terms of PSA, grade, stage and cancer volume suggesting identical cancer characteristics, thus advocating for a repeat prostate biopsy in case of a negative finding on initial biopsy.

Aged↗
PubMed2005

Constant decline in sperm concentration in infertile males in an urban population: experience over 18 years.

OBJECTIVE: To investigate semen quality in infertile men from an urban population over an 18-year period. DESIGN: Retrospective study. SETTING: Andrology clinic at a city university hospital. PATIENTS: A total of 9,327 men were referred to the clinic for infertility investigation. After excluding those with azoospermia, 7,780 samples were evaluated. INTERVENTION(S): Semen samples were analyzed within half an hour of production using computer-automated semen analysis and phase microscopy. MAIN OUTCOME MEASURE(S): Sperm concentration, morphology, and motility; semen pH and leukocyte concentration; and patient age. RESULT(S): The median patient age over the study period was 31.6 years, with an increase from 30.8 years in 1986 to 34.4 years in 2003. The median sperm concentration was 10.25 million/mL for the entire period, with a decline from 27.75 million/mL in 1986 to 4.60 million/mL in 2003. The median proportion of normally shaped spermatozoa was 15%, and the proportion of motile spermatozoa was 21%. The pH increased from 7.4 in 1986 to 7.9 in 2003, and the median leukocyte concentration was 1.50 million/mL. CONCLUSION(S): A constant decline in median sperm concentration was found in the infertile men. The reason for this remains unclear, although the high pH and leukocyte concentration indicates the involvement of infection.

Adult↗
PubMed2005

Polymorphism in ARE-I region of prostate-specific antigen gene associated with low serum testosterone level and high-grade prostate cancer.

OBJECTIVES: To examine the impact of polymorphism in the androgen-responsive element I region of the prostate-specific antigen (PSA) gene on the serum testosterone level and Gleason score in patients with newly diagnosed, untreated prostate cancer (PCa). High-grade PCa is associated with a low serum testosterone level, and the testosterone level has been negatively correlated with the expression of PSA. METHODS: Endocrine factors (including testosterone, follicle-stimulating hormone, and luteotropic hormone), PSA level, prostate volume, and Gleason score were measured in 134 patients with untreated, biopsy-verified PCa. PSA polymorphism was determined by polymerase chain reaction-based methods using DNA from peripheral blood samples. RESULTS: Patients with the PSA G/G genotype had lower serum testosterone levels (3.5 +/- 1.2 ng/mL) than those with the A/A genotype (4.3 +/- 1.6 ng/mL) or the A/G genotype (4.4 +/- 1.5 ng/mL). The PSA level in the A/A and A/G genotype groups were significantly lower than that in the G/G genotype group (18.2 +/- 55.0 ng/mL versus 20.5 +/- 27.6 ng/mL, P = 0.013). In a multiple logistic regression model, the odds ratio for the G/G polymorphism was significantly increased for Gleason score (odds ratio 2.4, 95% confidence interval 1.6 to 10.4; P = 0.02) and serum testosterone level (odds ratio 0.44, 95% confidence interval 0.36 to 0.94; P = 0.01) relative to genotypes A/A and A/G. CONCLUSIONS: Our results showed that the PSA G/G genotype is associated with a greater Gleason score and serum PSA level but lower serum testosterone level and could be considered a risk factor for a poor outcome of PCa.

Adult↗
PubMed2005

Treatment of testicular cancer: influence on pituitary-gonadal axis and sexual function.

OBJECTIVES: To investigate the influence of treatment for testicular cancer on the pituitary-gonadal axis and sexual function in long-time survivors after unilateral orchiectomy. METHODS: Blood was drawn from patients treated for testicular cancer during routine oncologic follow-up for measurement of luteinizing hormone, follicle-stimulating hormone, sexual hormone-binding globulin, testosterone, and bioavailable testosterone. Sexual function was evaluated using the International Index of Erectile Function 15-item (IIEF-15) questionnaire. Patients were grouped according to treatment: group 1 followed a surveillance strategy, group 2 received two cycles of carboplatin monotherapy, and group 3 underwent cisplatin, etoposide, and bleomycin chemotherapy. RESULTS: No statistically significant difference was found in the serum hormonal levels among the three groups, and all hormonal levels were within the 95% confidence range, except for follicle-stimulating hormone. The median serum testosterone level was 3.5 ng/mL in group 1, 3.9 ng/mL in group 2, and 4.2 ng/mL in group 3. In group 1, the median IIEF-15 score was 64.0, and the median Erectile Function (EF) domain score was 28. The median scores in groups 2 and 3 were 62.5 for IIEF-15 and 27.5 for EF and 65.0 for IIEF-15 and 30.0 for EF, respectively. No correlation was found between testosterone level and IIEF-15 or EF score. CONCLUSIONS: None of the treatments investigated had a significant influence on the serum hormonal levels in long-time survivors of testicular cancer. Patients undergoing chemotherapy have no greater risk of developing a hormonal disorder than those following a surveillance strategy, and therapy for testicular cancer is not a risk factor for erectile dysfunction.

Adult↗
PubMed2005

Bladder tumor markers beyond cytology: International Consensus Panel on bladder tumor markers.

This is the first of 2 articles that summarize the findings of the International Consensus Panel on cytology and bladder tumor markers. The objectives of our panel were to reach a consensus on the areas where markers are needed, to define the attributes of an ideal tumor marker, and to identify which marker(s) would be suitable for diagnosis and/or surveillance of bladder cancer. Our panel consisted of urologists and researchers from Europe, Asia, and the United States who reviewed original articles, reviews, and book chapters on individual bladder tumor markers published in the English language mainly using the PubMed search engine. Panel members also met during 3 international meetings to write recommendations regarding bladder tumor markers. The panel found that the most practical use of noninvasive tests is to monitor bladder cancer recurrence, thereby reducing the number of surveillance cystoscopies performed each year. Markers also may be useful in the screening of high-risk individuals for early detection of bladder cancer. However, more prospective studies are needed to strengthen this argument. Case-control and cohort studies show that several markers have a higher sensitivity to detect bladder cancer. However, cytology is the superior marker in terms of specificity, although some markers in limited numbers of studies have shown specificity equivalent to that of cytology. Our panel believes that several bladder tumor markers are more accurate in detecting bladder cancer than prostate-specific antigen (PSA) is in detecting prostate cancer. However, bladder tumor markers are held to a higher standard than PSA. Therefore, use of bladder tumor markers in the management of patients with bladder cancer will require the willingness of both urologists and clinicians to accept them.

Biomarkers, Tumor↗
PubMed2005

Prognostic markers for bladder cancer: International Consensus Panel on bladder tumor markers.

The International Consensus Panel on cytology and bladder tumor markers evaluated markers that have the ability to predict tumor recurrence, progression, development of metastases, or response to therapy or patient survival. This article summarizes those findings. The panel mainly reviewed articles listed in PubMed on various prognostic indicators for bladder cancer. Based on these studies, most of which were case-control retrospective studies, various prognostic indicators were classified into 6 groups: (1) microsatellite-associated markers, (2) proto-oncogenes/oncogenes, (3) tumor suppressor genes, (4) cell cycle regulators, (5) angiogenesis-related factors, and (6) extracellular matrix adhesion molecules. The panel concluded that although certain markers, such as Ki-67 and p53, appear to be promising in predicting recurrence and progression of bladder cancer, the data are still heterogeneous. The panel recommends that identifying definitive criteria for test positivity, a clearly defined patient population, standardization of techniques used to evaluate markers, and clearly specified endpoints and statistical methods will help to bring accurate independent prognostic indicators into the clinical management of patients with bladder cancer.

Angiogenic Proteins↗
PubMed2005

The Vienna nomogram: validation of a novel biopsy strategy defining the optimal number of cores based on patient age and total prostate volume.

PURPOSE: We conducted a trial in patients with prostate specific antigen (PSA) levels from 2 to 10 ng/ml to validate a newly developed nomogram that defines the optimal number of biopsy cores required for prostate cancer (PCa) detection based on patient age and total prostate volume (Vienna nomogram). MATERIALS AND METHODS: A total of 502 patients underwent transrectal ultrasound guided prostate biopsy using the Vienna nomogram. These results were compared with those of a previous group of 1,051 patients who had standard octant biopsies followed by systematic repeat biopsies after 6 to 8 weeks if the initial biopsy result was negative for PCa. RESULTS: The overall PCa detection rate using the Vienna nomogram was 36.7% compared with 22% on first and 10% on repeat biopsy in the control group. The PCa detection rate using the Vienna nomogram was superior (p=0.002) to the octant biopsy technique, and comparable to a combination of first and repeat biopsy in the control group. Multivariate analysis of the Vienna nomogram showed that only PSA and the number of cores were independent predictors of PCa detection (chi-square = 49, p <0.001). Total prostate volume, transition zone volume and age were not independent predictors of PCa detection. CONCLUSIONS: The Vienna nomogram offers an easy tool to select the optimal number of prostate biopsy cores based on patient age and total prostate volume in PSA range 2 to 10 ng/ml. Cancer detection is significantly improved (66.4%) compared to the control group. The bias factor of larger prostate volume is eliminated by using the Vienna nomogram. Moreover, the Vienna nomogram is advantageous not only in terms of the improved PCa detection rate but also economically makes systematic repeat biopsies unnecessary.

Adult↗
PubMed2004

Differentiation between cell death modes using measurements of different soluble forms of extracellular cytokeratin 18.

Cytokeratins are released from carcinoma cells by unclear mechanisms and are commonly used serum tumor markers (TPA, TPS, and CYFRA 21-1). We here report that soluble cytokeratin-18 (CK18) is released from human carcinoma cells during cell death. During necrosis, the cytosolic pool of soluble CK18 was released, whereas apoptosis was associated with significant release of caspase-cleaved CK18 fragments. These results suggested that assessments of different forms of CK18 in patient sera could be used to examine cell death modes. Therefore, CK18 was measured in local venous blood collected during operation of patients with endometrial tumors. In most patient sera, caspase-cleaved fragments constituted a minor fraction of total CK18, suggesting that tumor apoptosis is not the main mechanism for generation of circulating CK18. Monitoring of different CK18 forms in peripheral blood during chemotherapy of prostate cancer patients showed individual differences in the patterns of release. Importantly, several examples were observed where the increase of apoptosis-specific caspase-cleaved CK18 fragments constituted only a minor fraction of the total increase. These results suggest that cell death of epithelially derived tumors can be assessed in patient serum and suggest that tumor apoptosis may not necessarily be the dominating death mode in many tumors in vivo.

Apoptosis↗
PubMed2004

Effect of keratinocyte growth factor and activin on cell growth in the human prostatic cancer cell line LNCaP.

Keratinocyte growth factor (KGF) has paracrine properties in the human prostate which stimulate epithelial cell growth. Activins have profound effects on cell growth and function in the human prostate, and are expressed in LNCaP, DU 145 and PC3 cells. LNCaP cells were characterized by immuncytochemistry, an immunoassay and polymerase chain reaction. A 3[H]thymidine assay was used with 0.01-10 nM dihydrotestosterone, 10 micro M flutamide, 1-100 ng/ml KGF and 3 nM activin. LNCaP cells expressed Ki67, PSA, cytokeratins (8, 18, 19, 14, 15) androgenreceptor but no KGF protein. LNCaP cells showed telomerase activity. Furthermore, ARmRNA (365 bp), but no KGF or KGFRmRNA were expressed. KGF ELISA detected no intracellular or secreted KGF. DHT (1, 10 and 100 nM) and KGF (10 and 100 ng/ml) significantly stimulated LNCaP cell proliferation. However, flutamide and 3 nM activin A significantly decreased cell proliferation in the presence and absence of KGF. The results of our experiments support the hypothesis that cell growth and proliferative characteristics of LNCaP cells are modulated by KGF and activin A.

Activins↗
PubMed2004

Response to sublethal heat treatment of prostatic tumor cells and of prostatic tumor infiltrating T-cells.

BACKGROUND: To investigate the possibilities offered by high intensity focused ultrasound (HIFU) in the field of tumor vaccination, we analyzed how prostatic cancer (CaP) cells react towards heat treatment and whether increased access to CaP cells by the immune system would be the result. METHODS: Heat/stress response of CaP cells in situ and of CaP cell lines was analyzed by immunohistochemistry, Western blotting, and Atlas array. A heat-induced change in immune recognition was analyzed functionally using human T-helper (Th)1 and Th2-cytokine release with tumor infiltrating T-lymphocytes (TIL) as responder and autologous CaP cells either heated or untreated as stimulator cells. RESULTS: Transcription of 68 out of 500 genes was upregulated by sublethal heat in LNCaP and PC3 cells. Significantly upregulated stress protein (SP) expression (HSP-72, -73, GRP-75, -78) was seen at the border zone of HIFU treatment. Remarkably, even untreated benign prostatic hyperplasia (BPH) specimens revealed relative overexpression of heat shock protein (HSP)-72, -73 and glucose regulated protein (GRP)-75, -78. Heated CaP cells increased Th1-cytokine (IL-2, IFN-gamma, TNF-alpha) release but decreased Th2-cytokine (IL-4, -5, -10) release of TIL. CONCLUSIONS: HIFU treatment may alter the presentation of prostate tissue and tumor antigens and this presentation is most likely stimulatory. HSP-72/73 overexpression in untreated BPH may suggest a mechanism by which BPH can incite inflammation.

Antigens, Neoplasm↗
PubMed2004

DD3PCA3 RNA analysis in urine--a new perspective for detecting prostate cancer.

OBJECTIVES: Serum tPSA lacks specificity. The DD3(PCA3) gene is highly specific for prostate cancer and is detectable in prostate cancer cells shed into urine after rectal palpation. A newly developed nucleic acid sequence based amplification assay (uPM3) for detecting DD3(PCA3) RNA in urine samples was evaluated prospectively in patients referred for prostate cancer detection. METHODS: The uPM3 assay simultaneously detects the relative expression of DD3(PCA3) RNA and PSAmRNA as a marker for prostate cells in urine. Urine samples were collected after attentive digital rectal palpation prior to transrectal guided prostate biopsy. Samples were provided as a single void specimen (20-30 ml), stabilized in phosphate buffer and centrifuged. Lysis was performed on cell pellets DD3(PCA3) RNA and PSAmRNA were extracted and amplification was performed using isothermic nucleic acid based amplification (NASBA). The two targets were detected in real-time using specific beacons as probes in a thermostated spectrofluorimeter. Parameters of the amplification curve were defined after a logistic curve fitting routine and a classification tree model was constructed to predict the outcome of patients (i.e. cancer and non-cancer). RESULTS: 201 patients were included in this prospective study. 158/201 analyzed urine samples contained enough prostate cells sufficient for DD3(PCA3) analysis (79% adequacy rate). Prostate cancer was found in 62 (39%) of the evaluable patients. Overall sensitivity, specificity, positive predictive value and negative predictive value for the uPM3 assay at a cut-off 0.5 probability were 82%, 76%, 67% and 87% respectively as compared to 98%, 5%, 40% and 83% respectively for tPSA (at a cutoff of 2.5 ng/ml). In the tPSA categories <4, 4-10 and >10 ng/ml sensitivity was 73%, 84% and 84% and specificity was 61%, 80% and 70%, respectively. The AUC (area under the curve) was 0.87 (CI 0.81-0.92). CONCLUSION: The uPM3 assay showed excellent clinical performances and a specificity far superior to tPSA.

Adult↗
PubMed2004

Longitudinal study of men with mild symptoms of bladder outlet obstruction treated with watchful waiting for four years.

OBJECTIVES: To determine the risk of clinical progressions in men with mild lower urinary tract symptoms of bladder outlet obstruction and identify the predictors for progression in this group of men. METHODS: A total of 397 men who presented to the urology clinics with mild symptoms of bladder outlet obstruction (International Prostate Symptom Score less than 8) were analyzed in this longitudinal study conducted during a 4-year period. They began with the watchful waiting protocol and were followed up every 3 months for 48 months. Age, International Prostate Symptom Score (IPSS), divided into obstructive symptom score and irritative symptom score, serum prostate-specific antigen level, total prostate volume, transitional zone volume, urinary flow rates, and postvoid residual urine volume were documented. RESULTS: The cumulative incidence of clinical progression, defined as worsening of the IPSS with migration to the moderate symptom group (IPSS 8 to 18) or severe symptom group (IPSS 19 to 35) and an increase in IPSS of more than 2 points, was 6%, 13%, 15%, 24%, 28%, and 31% at 6, 12, 18, 24, 36, and 48 months, respectively. Nineteen patients (4.9%) developed acute urinary retention within the 48-month follow-up period. Of these 19 patients, only 2 (0.6%) required transurethral resection of the prostate. The variables of importance for disease progression in the artificial neural network analysis were, in order of statistical significance, prostate-specific antigen level, obstructive symptom score, and transitional zone volume. CONCLUSIONS: The risk for men with mild symptoms of bladder outlet obstruction to progress clinically and develop complications such as acute retention of urine is moderate. Prostate-specific antigen, obstructive symptom score, and transitional zone volume were identified as important risk factors.

Aged↗
PubMed2004

Benign prostatic hyperplasia progression and its impact on treatment.

PURPOSE OF REVIEW: Management of men with benign prostatic hyperplasia should reduce the lifetime risk of acute urinary retention and the need for benign prostatic hyperplasia-related surgery. A number of recent studies demonstrate that 5alpha-reductase inhibitors are unique in providing a long-term combination of improvements in symptoms and flow, and reductions in the risks of acute urinary retention and surgical intervention. RECENT FINDINGS: The 5alpha-reductase inhibitor finasteride was shown to reduce the risk of retention and surgery in men with large prostate volumes and/or high PSA. Recent studies have examined the role of adding an alpha1-blocker to 5alpha-reductase inhibitor in short- or long-term combination. The Medical Therapy of Prostatic Symptoms study randomised 3,047 men with benign prostatic hyperplasia to treatment with a 5alpha-reductase inhibitor (finasteride), an alpha1 blocker (doxazosin), a combination of both, or placebo. Only treatment arms containing 5alpha-reductase inhibitor therapy were associated with longer-term significant reductions in the risk of acute urinary retention and invasive therapy for benign prostatic hyperplasia. Three randomised, two-year, placebo-controlled studies have assessed the clinical relevance of the >93% DHT suppression provided by dutasteride. Dutasteride was also associated with a reduction in the risk of acute urinary retention of 57%, and a reduction of 48% in the risk of surgical intervention compared with placebo after 2 years. SUMMARY: Short-term combination of 5alpha-reductase inhibitor and alpha-blockade are optimal in providing symptomatic improvement among patients who require symptom relief, while enabling the initiation of 5alpha-reductase inhibitor therapy to reduce the risk of subsequent acute urinary retention or benign prostatic hyperplasia-related surgery in men who are at greater risk of disease progression.

Adrenergic alpha-Antagonists↗
PubMed2004

Improved detection of urothelial carcinoma in situ with hexaminolevulinate fluorescence cystoscopy.

PURPOSE: In this European multicenter study we compared hexaminolevulinate (HAL) fluorescence cystoscopy and standard white light cystoscopy for the detection of carcinoma in situ (CIS) in patients suspected of having high risk bladder cancer. MATERIALS AND METHODS: This study was a prospective controlled, within-patient comparison of standard and HAL fluorescence cystoscopy. Eligible patients received an intravesical instillation of 50 ml HAL 8 mM solution. Cystoscopy was performed using a D light system, which provided white and blue light at 375 to 440 nm. The bladder wall was inspected and mapped, first under white light, followed by blue light. All tumors and suspicious areas identified under white light and by red fluorescence were resected or biopsied. Histological findings were assessed by an independent central pathologist blinded to the identity of the biopsies. RESULTS: Of 211 evaluable patients 83 (39%) had CIS, of whom 18 (22%) were detected by HAL cystoscopy only, 62 (75%) were detected by standard and HAL cystoscopy, 2 (2%) were detected by standard cystoscopy only and 1 (1%) was detected by nonguided biopsy. Therefore, HAL cystoscopy identified 28% more patients with CIS than standard cystoscopy. The side effects of HAL instillation were negligible and no unexpected events were reported. CONCLUSIONS: HAL fluorescence cystoscopy improves the detection of bladder CIS significantly, which has consequences for clinical management and may improve the patient prognosis. The procedure is easily implemented as an adjunct to standard cystoscopy and it adds no significant risk of complications.

Adult↗