Biomedical subjects

W Horninger

Publications and source records attributed to W Horninger.

31 records · Page 2Linked to original sources

PubMed1998

Interleukin-6 regulates prostate-specific protein expression in prostate carcinoma cells by activation of the androgen receptor.

Interleukin-6 (IL-6) levels are frequently elevated in sera of patients with metastatic prostate cancer. IL-6 receptors are expressed in prostate cancer cell lines, as well as in benign prostate hyperplasia and prostate cancer tissue specimens. The androgen receptor (AR) is a key transcription factor that is present in all stages of prostate carcinoma, even in therapy-refractory tumors. In an attempt to investigate possible cross-talk between IL-6 and androgen signal transduction cascades, we tested the effects of this cytokine on AR transcriptional activity. The regulation of AR activity by IL-6 was studied in DU-145 cells, which were cotransfected with the androgen-responsive reporter plasmid ARE2TATACAT and the AR expression vector pSG5AR. We show that IL-6 up-regulates AR activity in a ligand-independent manner, as well as synergistically, with very low doses of the synthetic androgen methyltrienolone (5-10 pM). Therefore, AR activation by IL-6 may be operative in prostate cancer patients who have decreased androgen levels because of androgen ablation therapy. The maximal induction of reporter gene activity by IL-6 alone (50 ng/ml) was 67% of that stimulated by 1 nM of methyltrienolone. The nonsteroidal antiandrogen bicalutamide (Casodex) nearly completely inhibited AR activation by IL-6. IL-6 effects on AR activity were also abolished or greatly reduced by inhibitors of protein kinase A and C and mitogen-activated protein kinase pathways. In concordance with the results obtained in DU-145 cells, IL-6 induced AR-regulated prostate-specific antigen mRNA and protein in LNCaP cells. Stimulation of prostate-specific antigen protein secretion by IL-6 was antagonized by bicalutamide and inhibitors of protein kinase A and mitogen-activated protein kinase signaling pathways. Taken together, our data show for the first time that IL-6 is a nonsteroidal activator of the AR and that this activation is implicated in the regulation of prostate-specific proteins. Keeping in mind that IL-6, its receptor, and the AR are expressed in prostate cancers, cross-talk between IL-6 and AR signaling pathways may have clinical significance.

Down-Regulation↗

PubMed1997

Prostate carcinoma screening in the county of Tyrol, Austria: experience and results.

BACKGROUND: This article summarizes the experience and results of different prostate carcinoma screening projects using total prostate specific antigen (PSA) as the initial test and different diagnostic tests to improve specificity. METHODS: The seven projects studied included 1) a mass screening study using PSA as the initial test in 21,079 volunteers; 2) an investigation of the usefulness of normal and age-referenced PSA cutoffs in 1618 men; 3) a PSA-based screening study of 2272 asymptomatic blood donors; 4) an investigation of the incidence and clinical significance of transitional zone carcinoma in 340 men with negative rectal examination findings and clearly visible prostatic zones on three-dimensional transrectal ultrasound; 5) determination of percent free PSA in one retrospective and two prospective screening studies to define the optimal range of total PSA and determine the appropriate cutpoints for percent free PSA within this range; 6) evaluation of the diagnostic benefit of PSA transitional zone density in 308 screening volunteers; and 7) a study of the impact of PSA-based screening on the percentage of incidental prostate carcinoma diagnosed in 1543 men undergoing transurethal resection of the prostate. RESULTS: 1) Of the 21,078 volunteers, 1618 (8%) had elevated PSA levels. Of these men, 778 (48%) underwent biopsies; 197 biopsies (25%) were positive for prostate carcinoma and 135 patients underwent radical prostatectomy. Ninety-five of the 135 pathologically staged lesions (70%) were found to be organ-confined. 2) A PSA cutoff of 2.5 ng/mL in men age 45-49 years and of 3.5 ng/mL in men age 50-59 years with normal digital rectal examination findings resulted in an 8% increase in both the number of biopsies (66 of 778) and the detection rate of organ-confined disease. 3) Of the 2272 men, 284 had elevated PSA levels and prostate carcinoma was detected in 62 men. All patients underwent radical prostatectomy and histologic examination revealed organ-confined disease in all but eight men. 4) Ninety-eight of 340 men (28.8%) had biopsies positive for carcinoma; 28 of these patients (28.5%) had carcinoma that originated in the transitional zone only. 5) In the retrospective study, receiver operating characteristic curve analysis showed that by using a percent free PSA of 18% as a biopsy criterion in men with an elevated PSA serum level, 37% of the negative biopsies could be eliminated although 94% of all carcinomas would still be detected. In the first prospective study, 106 of 158 men with elevated total PSA values between 2.5 and 10.0 ng/mL were further evaluated and 37 prostate carcinomas were detected. By using a percent free PSA of < or =22% as a biopsy criterion, 30% of the negative biopsies could be eliminated although 98% of the carcinomas would still be detected. In the second prospective study, 120 of 465 men with total PSA levels between 1.25 and 6.49 ng/mL, a percent free PSA of <18%, and normal digital rectal examination findings were further evaluated and 27 (22.5%) were found to have prostate carcinoma. 6) Receiver operating characteristic curve analysis for PSA transitional zone density showed that by using a PSA transitional zone density of >0.22 ng/mL/cc as a biopsy criterion, 24.4% of negative biopsies could be avoided without missing the detection of a single carcinoma. 7) In the prescreening era the incidence of T1a Grade 1 and 2 carcinomas was 3.1% and the incidence of T1a Grade 3 and T1b carcinoma was 2.3%, whereas in the years after the establishment of PSA-based screening the incidence was 4.6% and 1.03%, respectively. CONCLUSIONS: These data suggest that PSA-based screening increases the detection rate of clinically significant and organ-confined tumors. Percent free PSA and PSA transitional zone density provide an additional diagnostic benefit over total PSA.

Age Factors↗

PubMed1997

Are contact laser, interstitial laser, and transurethral ultrasound-guided laser-induced prostatectomy superior to transurethral prostatectomy?

BACKGROUND: In order to assess the value of various new therapeutic modalities in the management of benign prostatic hyperplasia (BPH), we performed a prospective study comparing transurethral resection of the prostate (TURP) to contact Laser, interstitial Laser, and transurethral ultrasound-guided laser-induced prostatectomy (TULIP). METHODS: The following parameters were evaluated preoperatively as well as 3, 6, and 12 months after surgery: prostatic volume, urinary flow rate, postvoid residual volume, and the AUA symptom score. The diagnosis of bladder outlet obstruction was established preoperatively by means of pressure/flow studies which were repeated 1 year after the operation. RESULTS AND CONCLUSIONS: In conclusion, TURP is still the gold standard in the treatment of BPH. The results of TULIP, contact laser, and interstitial laser are about the same. The time intervals within which the patients become free of symptoms, however, vary widely. Contact laser is limited to prostates below 50 cc, while interstitial laser is ideal for patients in poor general health who present with large prostates. Furthermore, our results demonstrate that the only reliable data for determining the degree of posttherapeutic disobstruction can be provided by urodynamic investigations including pressure/flow diagrams.

Humans↗

PubMed1997

PSA-based screening for prostate cancer in asymptomatic younger males: pilot study in blood donors.

BACKGROUND: The efficacy and success of a screening program for prostate cancer in young and healthy asymptomatic volunteers are described. METHODS: In the present study, prostate specific antigen (PSA) samples obtained from 2,272 males (aged 40-65 years) who donated blood at the local Red Cross Blood Bank were evaluated. Two groups of donors were distinguished, which were investigated in different ways. Group 1 comprised individuals aged 40-49 years (n = 568), while group 2 consisted of males aged 50-65 years (n = 1,704). Volunteers in group 2 who had PSA levels greater than 4 ng/ml (n = 302) were referred for ultrasound guided biopsy irrespective of findings on digital rectal examination (DRE). In group 2, individuals with PSA levels exceeding 4 ng/ml and positive DRE findings biopsy specimen was ordered (n = 2). In patients with unremarkable findings on DRE, serum PSA was determined 1 year later and in case of more than 20% increase in the PSA level biopsy was obtained under ultrasound guidance. RESULTS: The biopsy specimen yielded prostatic carcinoma in 58 patients in group 1. As a screening test, serum PSA determination was superior to digital rectal examination. On digital palpation only 2 presented with abnormal prostates. These 58 patients underwent radical prostatectomy and histological examination revealed organ-confined disease in all but 8. In group 2, in 4 of 12 males the biopsy specimen yielded prostatic carcinoma. CONCLUSIONS: This study shows that PSA measurement in blood donors is a useful method for recruiting screening volunteers, and therefore represents an additional possibility for early detection of prostate cancer in asymptomatic younger males. Furthermore, it represents an effective tool for following relatively young patients known to have a significant risk of prostate cancer.

Adult↗

PubMed1996

Anatomy and innervation of the rhabdosphincter of the male urethra.

The striated sphincter of the male urethra and its innervation are still a subject of controversy. Essentially, two concepts of its anatomy can be found in the literature. Some authors describe the rhabdosphincter as part of the urogenital diaphragm caudal to the prostate, others as a striated muscle which extends from the base of the bladder to the "urogenital diaphragm." In a combined anatomic-histologic study the striated sphincter and the pudendal nerve were examined by means of anatomical dissections and serial anatomical as well as histological sections of 12 male pelves. Furthermore, radical prostatectomy was performed in a cadaver specimen; subsequently, the so-called "urogenital diaphragm" was excised and then examined histologically. The varying number of striated muscle fibers caudal to the prostate is of particular interest. In fetuses, there are abundant striated muscle fibers dorsal to the membranous urethra, where they are arranged as a circular collar around the urethra. In the adult male, hardly any striated muscle fibers can be found dorsal to the urethra; in a majority of cases this region is devoid of striated muscle fibers. Inserting dorsally in the perineal body, the fibers form an omega-shaped loop around the anterior and lateral aspects of the membranous urethra. The existence of a "urogenital diaphragm" and a strong, circular, striated "external sphincter urethrae" completely encircling the urethra caudal to the apex of the prostate could not be confirmed by our anatomical and histological investigations. Our study shows that the striated muscle fibers run in a cranial direction from the bulb of the penis to the base of the bladder along the anterior and lateral aspects of the prostate and the membranous urethra. Further dissection studies revealed that the rhabdosphincter is supplied by branches of the pudendal nerve after leaving the pudendal canal.

Aged↗

PubMed1996

Transurethral prostatectomy: mortality and morbidity.

In 1989 two large-scale multicenter studies on the mortality and morbidity of transurethral resection of the prostate were published [Mebust et al.: J Urol 141:243-247, 1989; Roos et al.: N Engl J Med 320:1120-1124, 1989]. These studies caused us to perform a retrospective study on a total of 1,211 consecutive patients who underwent transurethral resection of the prostate at our department between January 1988 and July 1991. The mortality rate in the 1,211 patients subjected to transurethral resection of the prostate was 0.00%; none of the patients died of intraoperative or postoperative complications. Intraoperative complications were observed in 8.9% of the patients, while the rate of early postoperative complications was 15.8%. Of the 1,211 patients operated on, 775 were followed for at least 1 year postoperatively. Late complications were noted in 11.2% of the patients. Repeat resection had to be performed in 0.9% of patients within 1 year, and in 2.5% within 3 years after surgery. A comparison of the studies by Mebust et al. and Roos et al. yielded similar rates of intraoperative and postoperative complications, whereas our mortality rate and repeat transurethral resection rate were significantly lower.

Adult↗

PubMed1996

Usefulness of the ratio free/total prostate-specific antigen in addition to total PSA levels in prostate cancer screening.

OBJECTIVES: Two different studies were performed. The aim of the first study was to define whether the measurement of the ratio between free and total prostate-specific antigen (f/t PSA) in serum may enhance the ability of PSA-based screening for early detection of prostate cancer in men with elevated serum PSA levels. A second study was undertaken to investigate the value of f/t PSA ratio in serum to improve the specificity of prostate cancer screening in men with serum PSA levels between 2.5 and 10.0 ng/mL. METHODS: In a retrospective study of 266 men with elevated PSA levels and proven biopsy results, f/t PSA levels were measured using deep frozen serum samples. In a second study we enrolled 158 men with elevated PSA levels according to age reference ranges apparent from our current PSA screening study with additional measurement of the f/t PSA ratio. All study volunteers with a free f/t PSA ratio cutoff point of < or = 22% underwent digital rectal examination, transrectal ultrasonography, and biopsy of the prostate. Free and total PSA levels were measured with the Delfia PSA dual label f/t PSA kit (Wallac Oy Turku, Finland). RESULTS: 106 of 158 men with elevated total PSA values between 2.5 and 10.0 ng/mL (group 1) have been further evaluated and 37 prostate cancers were detected. Mean percentage of free PSA was 10% in men with cancer and 22% in men with benign prostatic hyperplasia. Using a f/t PSA ratio of < or = 22% as a biopsy criterion 30% of the negative biopsies could be eliminated while still detecting 98% carcinomas. CONCLUSIONS: Measurement of f/t PSA reduces the number of unnecessary biopsies in PSA screening without missing many cancers.

Aged↗

PubMed1995

Comparison of different prostate-specific antigen cutpoints for early detection of prostate cancer: results of a large screening study.

OBJECTIVES: This study was designed to compare the usefulness of the normal prostate-specific antigen (PSA) level and the age-referenced PSA level in a large screening study for early detection of prostate cancer. METHODS: A total of 21,078 subjects (aged 45 to 75 years) were participants in a 1-year prostate cancer screening project with PSA as the initial test. Of the volunteers, 1618 (8%) showed an elevated PSA level according to age-specific reference ranges, and using the normal PSA cutoff point (4.0 ng/mL), 1872 (9%) had elevated PSA levels between 4.0 and 6.5 ng/mL. RESULTS: Biopsies in both groups were performed if the PSA level was elevated. We evaluated the effect on biopsy rate and cancer detection. A PSA cutoff point of 2.5 ng/mL in men 45 to 49 years old and a PSA cutoff point of 3.5 ng/mL in men 50 to 59 years old with normal digital rectal examination findings resulted in an 8% increase in the number of biopsies (66 of 778) and an 8% increase in organ-confined cancer detection. An increasing cutoff of 4.5 ng/mL in men 60 to 69 years old and 6.5 ng/mL in men 70 to 75 years old resulted in 21% fewer biopsies (205 of 983) and would have missed 4% of organ-confined tumors (8 of 220). CONCLUSIONS: We conclude that the use of PSA age-specific reference ranges increases the detection of clinically important and organ-confined cancers in young men and decreases the number of biopsies in older men.

Aged↗

PubMed1995

Three-dimensional sonographic guidance for interstitial laser therapy in benign prostatic hyperplasia.

In recent years, interstitial laser therapy was introduced to provide a new treatment of benign prostatic hyperplasia (BPH). However, the precise positioning of the laser fibers has remained a major unsettled issue. Three-dimensional (3-D) transrectal ultrasound scanning permits precise differentiation of the prostatic zones, in particular the transition zone, which is enlarged in BPH. Initially, a volume scan of the prostate is obtained. On the monitor, three sections of the prostate in the coronal, sagittal, and horizontal planes are displayed simultaneously. This new 3-D technology enables precise and reproducible positioning of the laser fibers at any selected site in the adenoma under sonographic guidance, thus providing the basis for complete laser prostatectomy. Placement of the laser fibers proved to be precise, quick, and uncomplicated.

Humans↗

PubMed1995

[Hormonal therapy of benign prostatic hyperplasia].

In the last 30 years transurethral prostatectomy (TURP) has been the standard treatment for benign prostatic hyperplasia. While the mortality rate of TURP has been reduced to zero, the postoperative morbidity rate has remained unchanged at 15-18% for several decades. Increasing costs and the preference of many patients for non-surgical treatment have now led to the development of new pharmacological treatment options. All hormone therapeutic modalities known to date, such as GnRH-agonists, cyproteronacetate and flutamide, have acted on the male hypothalamic-pituitary-gonadal system. Because of their side effects they are rarely used for the treatment of symptomatic benign prostatic hyperplasia. The 5-alpha-reductase inhibitor finasteride is a new endocrinological treatment option. It can be used to reduce the volume of enlarged prostates and to improve flow rates without severe side effects. According to the available data, finasteride is a safe treatment option for symptomatic patients with benign prostatic hyperplasia if surgery is not yet indicated. It should not, however, be regarded as an alternative to surgical treatment of benign prostatic hyperplasia.

5-alpha Reductase Inhibitors↗

PubMed1993

Modified retroperitoneal lymphadenectomy for testicular tumor: anatomical approach, operative technique and results.

Between January 1988 and June 1992, 56 patients underwent nerve-preserving retroperitoneal lymphadenectomy at the Department of Urology, University of Innsbruck. In 23 patients stage I, and in 33 patients stage II testicular tumors were found (staging according to the criteria recommended in Lugano 1979). Orchiectomy and subsequent lymphadenectomy within the boundaries described by Weissbach's group were performed for stage I tumors. In patients presenting with stage IIa or IIb tumors modified retroperitoneal lymphadenectomy within the boundaries suggested by Colleselli's group was performed. In stage IIc patients the residual tumor was resected after three cycles of polychemotherapy. If possible, nerve-sparing lymphadenectomy was performed. By adapting the operative technique to the respective tumor stage antegrade ejaculation could be preserved in 47 of these 56 patients. Semen analysis was carried out in 22 patients. The results in patients with stages I and IIa tumors were excellent, while in stages IIb and IIc patients' exocrine testicular function was considerably worse due to inductive polychemotherapy. None of the patients had a retroperitoneal recurrence. Of all 56 patients only one had a relapse in the lung (1.7%). The average follow-up period was 29 months.

Adolescent↗

PubMed1993

[Modified retroperitoneal lymph node excision in testicular tumors. Anatomy, surgical technique and results].

Between January 1988 and June 1992, 56 patients suffering from malignant testicular tumors underwent nerve-preserving retroperitoneal lymphadenectomy at the University Hospital in Innsbruck. The tumors were staged according to the nomenclature recommended by the Workshop for Staging and Treatment of Testicular Cancer (Lugano 1979). According to this nomenclature 23 patients had stage I and 33 patients stage II. Thirty-nine patients presented with malignant teratoma, 3 with seminoma and 14 with teratoma and seminoma. The patients with stage I tumors were treated after orchiectomy with nerve-preserving retroperitoneal lymphadenectomy according to the dissection fields of Weissbach et al. In cases of nodal involvement in the retroperitoneum (stage IIa and IIb) a retroperitoneal modified lymphadenectomy according to the margins of Colleselli et al was performed. Patients with stage IIc tumors were treated with three cycles of polychemotherapy. Subsequently, the residual tumor was removed and, if possible, a nerve-sparing lymphadenectomy was performed. Since the nerve-preserving technique was modified in accordance with the tumor stage, antegrade ejaculation could be preserved in 47 of the 56 patients. In 22 patients exocrine testicular function was assessed by sperm analysis. The findings for the patients with stage I and IIa were considerable. The patients who had undergone induction chemotherapy for stage IIb and IIc had poor exocrine testicular function. The follow-up time was 29 months. At follow-up none of the patients presented with recurrent retroperitoneal tumor. Only one patient was found to have tumor progression (solitary pulmonary metastasis 1.7%). These results show that nerve-preserving retroperitoneal lymphadenectomy is the treatment of choice in stage I non-seminomatous testicular tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMedDate not supplied

Contrast-enhanced transrectal color doppler ultrasonography (TRCDUS) for assessment of angiogenesis in prostate cancer.

BACKGROUND: The clinical relevance of tumor angiogenesis has been investigated in several human tumors, including prostate carcinoma (PC). Previously, we found angiogenesis, measured as microvessel density (MVD), to be an independent prognostic factor in PC. Therefore, we evaluated contrast-enhanced Transrectal Color Doppler Ultrasonography (TRCDUS) for assessment of angiogenesis in PC. MATERIALS AND METHODS: We investigated 15 patients with PC before radical prostatectomy (RP) and 3 control patients before radical cystoprostatectomy. TRCDUS was performed using a micro-bubble-based ultrasound enhancer Levovist for identifying hypervascularized areas within the prostate. Computer-assisted quantification of color pixel intensity (PI) was used to evaluate objectively the hypervascularized areas; resistive index (RI) measurements were also obtained in these areas. After histopathological examination of the entire prostate gland for tumor confirmation, immunohistochemical evaluation of MVD using a polyclonal antibody against factor VIII was performed as described by Weidner et al. (N Engl J Med 324: 1-8, 1991). TRCDUS findings were correlated with the immunohistochemical data. RESULTS: All patients showed hypervascularized areas (range: 1-9) on contrast-enhanced TRCDUS. Hypervascularized areas showed a sensitivity of 50.8% and a specificity of 95.2% for detecting PC. Analysis of TRCDUS data and immunohistochemistry revealed a significant correlation between PI and MVD in PC specimens, demonstrating a correlation coefficient of r2 = 0.977 (p<0.001). RI did not correlate with MVD. CONCLUSION: Contrast-enhanced TRCDUS showed a high specificity in identifying PC. PI correlated significantly with MVD. Therefore, quantification of color Doppler signals seems to be helpful for assessment of angiogenesis in PC.

Adenocarcinoma↗