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Biomedical subjects

Wolfgang Horninger

Publications and source records attributed to Wolfgang Horninger.

At least 19 recordsLinked to original sources
PubMed2007

Value of contrast-enhanced ultrasound and elastography in imaging of prostate cancer.

PURPOSE OF REVIEW: Prostate cancer is the most commonly diagnosed malignancy in men. Gray-scale ultrasound-guided systematic biopsy is the standard of care for prostate cancer detection in men with an elevated prostate-specific antigen or an abnormal digital rectal examination. Systematic biopsy may miss up to 35% of clinically relevant cancers. Color and power Doppler ultrasound, ultrasound contrast agents, and elastography have and will dramatically change the role of ultrasound in prostate cancer diagnosis. RECENT FINDINGS: Several reports have demonstrated that contrast-enhanced ultrasound investigations of the blood flow of the prostate allow for prostate cancer visualization and therefore, for targeted biopsies. Comparisons between systematic and contrast-enhanced ultrasound-targeted biopsies have shown that the targeted approach detects more cancers with a lower number of biopsy cores. Furthermore, contrast-enhanced ultrasound has been shown to detect cancers with higher Gleason scores compared with the systematic approach, which seems to improve prostate cancer grading. In addition, elastography is a new ultrasound technique that allows for the assessment of tissue elasticity. SUMMARY: Contrast-enhanced ultrasound and elastography improve prostate cancer detection and may be useful for prostate cancer grading and staging. Future clinical trials will be needed to determine the promise of these new advances for ultrasound of the prostate evolving into clinical applications.

Humans↗
PubMed2006

Relapse after radical prostatectomy correlates with preoperative PSA velocity and tumor volume: results from a screening population.

OBJECTIVES: To evaluate, in a screening population, the impact of tumor volume and prostate volume on prostate-specific antigen (PSA) velocity (PSAV) and to find predictors of biochemical failure after radical prostatectomy. Longitudinal PSA changes in men with prostate cancer have been reported to be significantly different from those without prostate cancer. METHODS: PSAV was assessed in 102 men undergoing radical retropubic prostatectomy. The pathologic findings of specimens obtained at radical retropubic prostatectomy and pelvic lymph node dissection were analyzed separately for all patients. RESULTS: The median preoperative PSA in the 102 patients was 6.4 ng/mL, the median prostate volume was 32.8 cm3, and the median tumor volume was 1.27 cm3. The PSAV correlated significantly with tumor volume (P <0.05) but not with prostate volume (P = 0.142). The median tumor volume in men with biochemical progression after radical retropubic prostatectomy was 2.55 cm3 versus 0.94 cm3 in men who were free of disease 5 years after surgery. The median PSAV in the year before diagnosis in men with relapse after radical prostatectomy was 1.98 ng/mL/yr versus 1.05 ng/mL/yr in men who had no evidence of disease. CONCLUSIONS: The results of our study have shown that the main factor contributing to the PSAV in patients with prostate cancer is cancer load and that prostate volume is not significantly associated with the PSAV. Men with a PSAV of more than 2 ng/mL/yr in the year before cancer diagnosis are at a high risk of relapse. The PSAV may be helpful in identifying patients with small tumors and thus increase the detection rate of potentially curable prostate cancers.

Adult↗
PubMed2006

Growth curves of the fetal prostate based on three-dimensional reconstructions: a correlation with gestational age and maternal testosterone levels.

OBJECTIVE: To create a nomogram of the fetal growth of the human prostate corresponding to gestational age, and to investigate the relationship between the expansive growth of the fetal prostate and the maternal testosterone surge during pregnancy. MATERIALS AND METHODS: In all, 27 fetal prostates at 11-40 weeks of gestation, and seven neonatal specimens at 1-20 weeks after birth, were analysed. Serial sections of prostates were immunostained and examined using light microscopy. After modular image acquisition the volumes were calculated using three-dimensional reconstruction. The prostate volumes were correlated with gestational age, and related to reference testosterone levels during pregnancy. RESULTS: There was exponential growth of the fetal prostate with gestational age. The increasing volume of the prostate during the fetal period corresponded with maternal testosterone levels. In the second trimester there was a significant increase in prostate volume in relation to the bladder. In infants, macroscopically there was an inverse proportion between bladder size and prostate volume. CONCLUSIONS: Starting from the second trimester there is distinct growth of the fetal prostate, obviously triggered by the maternal testosterone surge. In neonates there is an inversion of the dimensions between bladder and prostate. These results indicating exponential growth of the fetal prostate provide evidence of a gender-related transient infravesical obstruction in human fetuses.

Female↗
PubMed2006

Atherosclerosis as a risk factor for benign prostatic hyperplasia.

OBJECTIVES: To evaluate the relationship between clinical benign prostatic hyperplasia (BPH) and atherosclerosis, using colour Doppler ultrasonography (CDUS) and symptom scores. PATIENTS, SUBJECTS AND METHODS: CDUS was used to evaluate prostatic vascularity in four groups of men, comprising young healthy subjects, patients presenting with coronary artery disease (CAD), diabetes mellitus, or peripheral arterial occlusive disease (PAOD). Resistive index (RI) measurements and computer-assisted quantification of colour pixel density (CPD) were used to objectively evaluate perfusion. The International Prostate Symptom Score (IPSS) and the International Index of Erectile Function were used to quantify symptoms. RESULTS: In diabetic patients and men with PAOD, perfusion of the transition zone (TZ) of the prostate was significantly lower (P < 0.001) and the RI of the TZ was significantly higher (P < 0.001) than in healthy controls and men with CAD. In diabetics and men with PAOD, the mean prostate volume was greater than in healthy controls and men with CAD. The IPSS in patients with vascular damage (diabetes, PAOD) was significantly worse than in the control group. CONCLUSIONS: The significantly lower CPD and higher RI values of the TZ in patients with vascular disease than in healthy subjects support the hypothesis that an age-related impairment of blood supply to the prostate has a key role in the development of BPH.

Aged↗
PubMed2006

Reduction of prostate cancer mortality in Tyrol, Austria, after introduction of prostate-specific antigen testing.

The objective of this study was to analyze in detail the time trend in prostate cancer mortality in the population of Tyrol, Austria. In Tyrol, prostate-specific antigen tests were introduced in 1988-1989 and, since 1993, have been offered to all men aged 45-74 years free of charge. More than three quarters of all men in this age group had at least one such test in the last decade. The authors applied the age-period-cohort model by Poisson regression to mortality data covering more than three decades, from 1970 to 2003. For Tyrol, the full model with age and period and cohort terms fit fairly well. Period terms showed a significant reduction in prostate cancer mortality in the last 5 years, with a risk ratio of 0.81 (95% confidence interval: 0.68, 0.98) for Tyrol; for Austria without Tyrol, no effect was seen, with a risk ratio of 1.00 (95% confidence interval: 0.95, 1.05). Each was compared with the mortality rate in the period 1989-1993. Although the results of randomized screening trials are not expected until 2008-2010, these findings support the evidence that prostate-specific antigen testing offered to a population free of charge can reduce prostate cancer mortality.

Aged↗
PubMed2006

Vascular resistance in the prostate evaluated by colour Doppler ultrasonography: is benign prostatic hyperplasia a vascular disease?

OBJECTIVE: To evaluate prostatic vascular resistance by measuring the resistive index (RI), and flow velocity using colour Doppler ultrasonography (CDUS), in normal prostates and in patients with benign prostatic hyperplasia (BPH) or prostate cancer, as BPH is considered to be a result of urogenital ageing and studies suggest that hyperplasia in the stromal and glandular compartments might be induced by stromal growth secondary to hypoxia, which in turn results from abnormal blood flow patterns. PATIENTS, SUBJECTS AND METHODS: Ninety-two men (22 with normal prostates, 45 with BPH and 25 with prostate cancer; mean age 56 years) were prospectively evaluated by CDUS. The RI values for the peripheral, central and transition zones were assessed by one investigator. The diagnosis of BPH and prostate cancer was established from histological findings. RESULTS: The mean (sd) RI in the transition zone was significantly higher only in patients with BPH, at 0.77 (0.05), vs 0.65 (0.05) in the other two groups. In the peripheral and central zones there was no significant difference in the RI among the three groups. Arterial CDUS flow velocity was increased in the transition zone of patients with BPH, but not in the peripheral and central zones. CONCLUSIONS: The present results support the hypothesis that an age-related impairment of blood supply to the lower urinary tract might have a role in the development of BPH. Although prostate cancer cannot be excluded by measuring RI, high RI values (>0.75) in the transition zone are indicative of BPH.

Adult↗
PubMed2006

The expression of transcription factor activating transcription factor 3 in the human prostate and its regulation by androgen in prostate cancer.

PURPOSE: ATF3 is a member of the basic leucine zipper/cyclic adenosine monophosphate responsive element binding protein family of transcription factors. There is overwhelming evidence that it is a stress inducible factor acting in a signal-type and cell-type dependent manner, and it is involved in cell proliferation and survival. We found that ATF3 was differently expressed in an in vitro prostate cancer tumor progression model and we investigated the possible role of ATF3 in prostate cancer. MATERIALS AND METHODS: ATF3 up-regulation in vivo/in vitro and androgen regulation were assessed by immunohistochemistry and immunoblot analysis. Results after forced ATF3 transfection were evaluated by proliferation assay and cell cycle analysis. RESULTS: Immunohistochemistry and immunoblot analysis revealed ATF3 up-regulation in prostate cancer in vitro and in vivo, and stimulation of expression by androgens. Antiandrogen treatment decreased ATF3 expression in androgen sensitive cells but acted as a stimulator in long-term androgen ablated cells representing a model for therapy refractory disease. Expression in tumors increased with higher Gleason scores and highest expression was observed in samples of therapy refractory tumor tissue. Forced ATF3 over expression in a prostate cancer cell line induced cell proliferation and accelerated cell cycle progression from G1 to S-phase. CONCLUSIONS: These data provide new insight into the role of ATF3 in prostate cancer development and/or progression. They indicate that ATF3 is an androgen regulated gene that is highly expressed in prostate tumors and stimulating cell proliferation. It represents a possible target for prostate cancer therapy.

Activating Transcription Factor 3↗
PubMed2006

The proximal neurovascular plate and the tri-zonal neural architecture around the prostate gland: importance in the athermal robotic technique of nerve-sparing prostatectomy.

OBJECTIVE: To review the neural architecture around the prostate gland, as it is relevant for nerve-sparing robotic prostatectomy, including in particular the anatomy of the proximal neurovascular tissue, the neurovascular bundle (NVB), and accessory neural pathways (ANPs). MATERIALS AND METHODS: The aims of this study were achieved in collaboration between the Cornell Institute of Robotic Surgery, New York, NY, USA and the Institute of Urology at the University of Innsbruck, Austria. The broad steps were: (i) anatomical studies of 10 fresh and two fixed male cadavers; and (ii) collection of videotape and still image data from 200 men undergoing radical prostatectomy by the athermal robotic technique at the Cornell Institute. RESULTS: From a surgical standpoint there was a tri-zonal neural architecture including the proximal neurovascular plate (PNP), the predominant NVB (PNB) and ANPs. The PNP was a mean (range) of 5 (3-10) mm lateral to the seminal vesicles, was 3 (2-7) mm thick, 7 (5-25) mm wide and 9 (4-30) mm long. It was within 6 (4-15) mm of the bladder neck, 5 (2-7) mm of the endopelvic fascia and overlapped 5 (0-7) mm of the proximal prostate. The PNB varied in shape and size from the proximal to distal end, was thickest at the base and most variable near the apex. In eight of 12 cases, there was a medial extension behind the prostate, which converged medially at the apex in four cases. ANPs were noted within the layers of levator fascia and/or lateral pelvic fascia on the anterolateral aspect in five cases and in three on the posterior aspect of the prostate. In nine cadavers, the proximal third of the prostate was covered by the PNP where these ANPs were most prominent. The ANPs formed a plexus on the posterolateral aspect of the apex in four cases. CONCLUSION: We have created an anatomical map of neurovascular tissue relevant to robotic prostatectomy. A tri-zonal neural architecture is described which has helped in standardizing the steps of robotic prostatectomy.

Adult↗
PubMed2005

Are transition zone biopsies still necessary to improve prostate cancer detection? Results from the tyrol screening project.

OBJECTIVES: The present retrospective study was designed to investigate the value of transition zone (TZ) biopsies for prostate cancer (PC) detection rate in a combined contrast enhanced color Doppler targeted (CECD) and gray-scale systematic biopsy (SB) approach. METHODS: PSA screening participants totalling 1475 with tPSA of >1.25 ng/ml (fPSA< or =18%) were assessed. Ten SB and additionally 5 or fewer CECD were performed. The impact of TZ biopsies on the PC detection rate and the biological significance of the detected TZ-cancers were analyzed. RESULTS: Out of 1475 biopsied patients, 395 (26.8%) were identified as PC patients; 5925 biopsy cores from these patients were analyzed. In 86 patients (21.8% of PC), we found 102 PC- positive cores in the TZ, and only in 9 of them solitary TZ-cancers without any other PC-location (2.3% of PC or 0.6% of all investigated patients). Pathologic findings after retropubic prostatectomy (RPE) revealed multifocal adenocarcinoma including involved peripheral zone (PZ) in eight of these nine patients, and solitary TZ-cancer in one patient. There was no positive correlation between prostate volume and TZ-detection rate and no patient with solitary TZ-PC after rebiopsy. CONCLUSION: Biopsy revealed 9 solitary TZ cancers (1.8%) and RPE revealed only one of them to be truly TZ-confined cancer (0.6%). Furthermore PC-detection did not improve, even in patients with rebiopsy, and there was no correlation between detection of TZ-cancers and prostate volume. A combined use of CECD and SB to investigate participants of a PSA-screening program suggests that TZ-biopsies do not improve PC detection rate and are therefore unnecessary.

Adult↗
PubMed2005

Longitudinal PSA changes in men with and without prostate cancer: assessment of prostate cancer risk.

BACKGROUND: To determine longitudinal PSA changes over a period of 10 years in patients with and without prostate cancer. METHODS: Serial PSA measurements performed over 10 years were evaluated in 353 men who eventually developed prostate cancer and in 2.462 participants of a screening program without prostatic malignancy. RESULTS: In men with cancer, mean tPSA increased from 2.28 ng/ml at 10 years before diagnosis to 6.37 ng/ml at the time of postive biopsy (PSA velocity: 0.409 ng/ml/year). PSA velocity was significantly associated with Gleason scores and pathologic stage. In the benign group (n=2.462), mean tPSA increased from 1.18 to 1.49 ng/ml over a period of 10 years (PSA velocity of 0.03 ng/ml/year). Of the subjects with tPSA levels of 2 ng/ml or less, 2 years prior to cancer diagnosis, 11.4% had tPSA values of more than 4 ng/ml at the time of biopsy. Of the 972 men with tPSA below 1 ng/ml 2 years before the most recent measurement was obtained, 966 (99.4%) had no evidence of prostate cancer 2 years later, while six were found to have malignancies (0.6%). CONCLUSIONS: Longitudinal PSA changes in men with and without prostate cancer are significantly different. Annual testing may not be required in men with baseline tPSA levels of 1 ng/ml or below, whereas in patients with levels higher than 1 ng/ml, it seems to be indicated because of the significant percentage of men presenting with tPSA levels of more than 4 ng/ml two years later.

Adult↗
PubMed2005

Ability of PSA-positive circulating macrophages to detect prostate cancer.

BACKGROUND: Prostate-specific antigen (PSA) is a widely used serum marker for prostate cancer, but has a poor specificity for early detection at levels below 10 ng/ml, because it can also result from benign conditions. Our aim was to determine the frequencies of circulating PSA+ macrophages in a blinded study and to examine the suitability of this new method for differentiating between benign and malignant prostate disease. METHODS: Between October 2002 and February 2003, 126 patients undergoing transrectal biopsy were enrolled in this study. Peripheral blood macrophages were stained for intracellular content of PSA in all patients. Ten patients' peripheral blood mononulear cells (PBMCs) were also supplementarily stained for cytokeratin (CK) and epithelial membrane antigen (EMA). Macrophages were analysed by flow cytometry. Patients were grouped according to their biopsy histology and bone scan results. FINDINGS: Based on histological data, patients were classified as having no evidence of malignancy (NEM) (n = 59), prostatitis (n = 20), or localised prostate cancer (n = 37). Significantly higher levels of circulating PSA+ macrophages were found in prostate cancer compared to benign conditions. Calculating a 2% cut-off level enabled the detection of localised prostate cancer with 89% sensitivity and 80% specificity. In a subset of patients (65%) with a serum PSA below 4 ng/ml and confirmed prostate cancer, the percentage of PSA+ macrophages was significantly higher compared to NEM and prostatitis. Macrophages of ten patients tested with prostate cancer contained significantly higher amounts of PSA, EMA, and CK compared to ten with NEM. INTERPRETATION: Intracellular PSA in combination with CK and EMA can be found in permeabilized blood macrophages, indicating phagocytosis of complete cancer cells. This study further suggests, that this new method might be suitable for differentiating between prostate cancer and benign conditions especially in patients with low serum PSA.

Aged↗
PubMed2005

Access of tumor-derived macromolecules and cells to the blood: an electron microscopical study of structural barriers in microvessel clusters in highly malignant primary prostate carcinomas.

BACKGROUND: The neo-angiogenetic microvessels forming a major reactive stromal element in highly malignant prostate neoplasms may exhibit fine-structural features relevant to our understanding of the passage of macromolecules from tumor to blood, on the one hand, and of events facilitating the metastatic cascade, on the other hand. METHODS: Ensuring rapid, optimal fixation in buffered glutaraldehyde was a foremost concern. Thin parings from radical prostatectomy specimens of Gleason scores (GS) 5-9 were taken from the tumor and from the contralateral side of the gland, glutaraldehyde-fixed, diced to smaller than 1 mm(3), postfixed in osmium tetroxide, embedded in Epon, ultrathin-sectioned, contrasted with lead and uranyl salts, and viewed in a transmission electron microscope. RESULTS: In dysplastic tissue areas, intraductal microvessels located in gland ducts were occasionally observed, and found to be aggressively invasive and highly active in producing neo-angiogenetic sprouts. Closely spaced microvessel clusters contained almost exclusively neo-angiogenetic microvessels, which were in cell-cell contact with numerous ameboid migratory cells, some of which were likely to be tumor cells. In these microvessel clusters, all structural barriers hindering passage of tumor-derived molecules or cells to the blood were eliminated. CONCLUSION: In microvessel clusters, the ultrastructural equivalent of microvascular hotspots, tumor invasion of microvessels is facilitated, but equally microvessels are observed invading the gland duct epithelial walls. This reciprocal invasivity of tumor cells and microvascular endothelial cells generates ideal conditions for tumor products and metastatic cells to enter the blood.

Aged↗
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

Suprapubic electroresection of prostate in three patients with benign prostatic hyperplasia and previous surgery for long urethral stricture.

The treatment of patients presenting with severe symptoms of obstruction due to benign prostatic hyperplasia and a history of previous surgery for long urethral stricture is still a matter of discussion. We report on 3 patients in whom resection of the prostate was performed using a dilated cystostomy approach under spinal anesthesia. All men had undergone dorsal onlay urethroplasty for long urethral stricture before prostate resection. The good outcome demonstrated the feasibility and safety of prostate resection using a suprapubic approach, which may become a treatment option in this group of patients.

Aged↗
PubMed2005

Detection rates and biologic significance of prostate cancer with PSA less than 4.0 ng/mL: observation and clinical implications from Tyrol screening project.

OBJECTIVES: To investigate the prostate cancer (PCa) detection rates and Gleason scores in patients with serum prostate-specific antigen (PSA) levels of 2.0 to 3.9 ng/mL and 4.0 to 10 ng/mL (free PSA 18% or less), in a population-based screening project. With the use of prostate-specific antigen (PSA) screening, more PCa is being diagnosed at PSA values of less than 4 ng/mL. METHODS: A total of 3446 consecutive screening volunteers with a PSA level of 2.0 to 10.0 ng/mL (free PSA 18% or less) were assessed. Ten systematic prostate biopsies and an additional five Doppler-enhanced targeted biopsies were performed on the basis of age-specific PSA reference ranges. The cumulative frequency of detection and the Gleason scores were analyzed. RESULTS: The PCa detection rate for patients with a PSA value of 2.0 to 3.9 ng/mL (n = 1522, group 1) and 4.0 to 10.0 ng/mL (n = 1924, group 2) was 21% (n = 320) and 30% (n = 572), respectively. Of the PCa cases detected, 37% were in men with a PSA level of 2 to 4 ng/mL. Statistically significant differences were found in age and prostate volume between groups 1 and 2, with patients in the lower PSA group younger and having a smaller mean prostate volume (P = 0.0001). Of 313 patients with PCa and a PSA value of 2 to 3.9 ng/mL, 24% had a Gleason score of 7 or greater compared with 33% of 560 patients with a PSA value of 4.0 to 10.0 ng/mL (P = 0.004). CONCLUSIONS: Our data suggest that in a screening population, more than one third of PCa cases in men with a PSA level of 2 to 10 ng/mL will occur in those with a PSA value of 2 to 3.9 ng/mL. Also, PCa cases with a low PSA level occur in younger patients and at lower stages with a smaller prostate volume.

Adult↗
PubMed2005

Prostate cancer detection in men with prostate specific antigen 4 to 10 ng/ml using a combined approach of contrast enhanced color Doppler targeted and systematic biopsy.

PURPOSE: Transrectal gray scale ultrasound guided biopsy is the standard method for diagnosing prostate cancer (PC). Improved cancer detection with ultrasound contrast agents is related to better detection of tumor vascularity. We evaluated the impact of a combined approach of contrast enhanced, color Doppler targeted biopsy (CECD) and systematic biopsy (SB) for the PC detection rate in men with prostate specific antigen (PSA) 4.0 to 10 ng/ml. MATERIALS AND METHODS: We examined 380 screening volunteers with a total PSA of 4.0 to 10 ng/ml (percent free PSA less than 18). CECD was always performed before SB. Another investigator blinded to contrast enhanced findings performed 10 SBs. The cancer detection rate for the CECD, SB and combined approaches was assessed. RESULTS: PC was detected in 143 of 380 patients (37.6%, mean total PSA 6.2 ng/ml). The PC detection rate for CECD and for SB was 27.4% and 27.6%, respectively. The overall cancer detection rate with the 2 methods combined was 37.6%. For targeted biopsy cores the detection rate was significantly better than for SB cores (32.6% vs 17.9%, p <0.01). CECD in a patient with cancer was 3.1-fold more likely to detect PC than SB. CONCLUSIONS: CECD allows for the detection of lesions that cannot be found on gray scale ultrasound or SB. CECD allows for assessment of neovascularity associated with PC. However, the combined use of CECD and SB allows for maximal detection of PC with a detection rate of 37.6% in our patients with PSA 4 to 10 ng/ml.

Adult↗