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H Rogatsch

Publications and source records attributed to H Rogatsch.

At least 19 recordsLinked to original sources
PubMed2005

Successful management of recurrent Epstein-Barr virus-associated multilocular leiomyosarcoma after cardiac transplantation.

BACKGROUND: In contrast to Epstein-Barr virus (EBV)-associated posttransplant lymphoproliferative disorders (PTLD), EBV-associated leiomyomatous tumors have thus far only rarely been described. CASE REPORT: Two years after heart transplantation with ATG induction, cyclosporine (CsA; trough levels of 250 ng/mL)-based triple drug immunosuppression), a 23-year-old patient developed a small round lesion within the left lateral liver segment. The patient underwent ultrasound-guided biopsy followed by liver resection. Histological and immunohistological examination showed a leiomyosarcoma. In situ hybridization using EBV-specific EB endoplasmic reticulum-RNA showed an intensive signal in almost all tumor cells. The tumor stained for EB nuclear antigen (EBNA)-2-protein. Immunosuppression was drastically reduced, namely, CsA levels <100 ng/dL, prednisolone 5 mg, azathioprine withdrawn, and antiviral chemotherapy initiated with 10 days of IV gancyclovir and acyclovir followed by oral famcyclovir. During the follow-up, anti-EBV-IgM, anti-early antigen antibodies, and anti-EBNA antibodies were continuously monitored excluding significant EBV replication. Eighteen months post-liver resection, and high-resolution computed tomography scan demonstrated two paravertebral tumors. These lesions and a small nodule at the left ankle were resected revealing identical leiomyosarcomata. Immunosuppression was further reduced (CsA levels 75 ng/dL) and famcyclovir maintenance therapy started. Nevertheless, 2 years later the patient again developed tumor recurrence (perirectal, liver, and right adrenal gland); the tumors were surgically removed. The therapy was switched to Rapamycin and famcyclovir was continued. Three years after the last surgical intervention, the patient is well and recurrence-free. CONCLUSION: Long-term survival in patients with posttransplant EBV-associated leiomyosarcoma can be achieved by combined surgical intervention, reduction of immunosuppression, switch to Sirolimus, and antiviral chemotherapy.

Acyclovir↗
PubMed2004

Characteristics of prostate cancers detected at low PSA levels.

BACKGROUND: When age-referenced PSA levels as recommended by Oesterling et al.1 were used as a biopsy criterion, only 25% of the cancers detected in a population based PSA Screening Project were organ-confined. This observation led to the decision to use low PSA levels as the sole indication for biopsy. Since 1995 age-referenced PSA levels of 1.25-3.25 ng/ml have been used in combination with a percentage free PSA cutoff of 18%. This PSA cutoff reduction led to a statistically significant migration to lower pathological stages with a decreased prostate cancer mortality in the years 1996-2001. However, concerns have been raised that screening with low PSA levels may detect clinically insignificant cancers. MATERIALS AND METHODS: We evaluated prostate cancer patients with low PSA levels in terms of heterogeneity, clinical significance, multifocality, and tumor biology including ploidy and proliferation index. RESULTS: Concerning heterogeneity the Gleason score of the needle biopsy failed to predict the Gleason score of the radical prostatectomy specimen in nearly 40% of prostate cancer patients; regarding multifocality 65% of patients with low PSA levels showed multifocal lesions and 36% exhibited tetraploid DNA distribution; more than 50% of tetraploid tumors were found in patients with tumor volumes of less than 0.5 cm(3). Ploidy correlated with the Ki-67 proliferation index, but not with tumor volume. CONCLUSIONS: These results demonstrate that small prostate cancers with low PSA levels and low tumor volumes exhibit all features of prostate cancers with higher tumor volumes and show the characteristics of malignant cancers, i.e., multifocality, tetraploidy, and high proliferative activity.

Adult↗
PubMed2004

Prognostic significance of tenascin-C expression in superficial and invasive bladder cancer.

AIMS: Tenascin-C (Tn-C) is an extracellular matrix glycoprotein that is upregulated in malignant tumours. Tn-C promotes cell growth, cell migration, and angiogenesis. It has been suggested to be a prognostic factor in various types of malignant tumours, but there is little information on its significance in bladder cancer with regard to overall survival (OS) and recurrence free survival (RFS). METHODS: Tn-C expression was studied in 106 patients with bladder cancer diagnosed between 1994 and 1997. Immunohistochemistry was performed using a monoclonal antibody against Tn-C. RFS and OS were estimated by the Kaplan-Meier method and compared by the log rank test in univariate analysis and by the Cox multistep regression method in multivariate analysis. RESULTS: Within the mean follow up period of 126 months, patients with diffuse Tn-C staining in the tumour stroma had a significantly worse OS than those with negative staining or only moderate Tn-C expression (p = 0.025). Patients with cytoplasmic expression of Tn-C had a significantly better OS than those without (p = 0.001). Multivariate analysis, taking into consideration age, grade, stage, tumour associated carcinoma in situ, progression, and Tn-C staining in tumour stroma, showed that only expression of Tn-C in invasive tumour cells was an independent positive prognostic factor for OS (p = 0.049). CONCLUSIONS: Tn-C may provide important prognostic information in bladder cancer depending on the expression pattern in the tumour stroma or cytoplasm of the tumour cells.

Adult↗
PubMed2002

Primary lymphatic metastatic spread in testicular cancer occurs ventral to the lumbar vessels.

OBJECTIVES: To analyze whether primary metastatic spread occurs behind the lumbar vessels and whether removal is necessary for accurate staging in diagnostic retroperitoneal lymph node dissection, because dissection of lymphatic tissue behind the lumbar vessels is a challenging maneuver. METHODS: One hundred thirty-nine patients were included in our study. Twenty-nine patients with clinical Stage I tumor underwent laparoscopic staging lymph node dissection, including removal of the lymph nodes behind the lumbar vessels. Sixty-four patients with Stage II testicular cancer were retrospectively examined by computed tomography to determine the localization of the enlarged lymph nodes in relation to the lumbar vessels. On the basis of these results, 49 patients with clinical Stage I underwent laparoscopic lymph node dissection within the same template but without dissection of the lymphatic tissue behind the lumbar vessels. RESULTS: In the first group, 10 of 29 patients had pathologic Stage IIA tumors, with positive nodes exclusively ventral to the lumbar vessels. In group 2, 39 patients with solitary metastatic lesions had enlarged lymph nodes, which were always ventral to the lumbar vessels. Only in 3 of 25 patients with multiple metastases was one enlarged node found behind the lumbar vessels. In group 3, no tumor recurrence either before or behind the lumbar vessels could be found in 46 patients after a mean follow-up of 27.8 months. CONCLUSIONS: On the basis of these data, we believe that primary lymphatic metastatic spread in testicular cancer always occurs ventral to the lumbar vessels. Therefore, the removal of lymphatic tissue behind the lumbar vessels for diagnostic procedures is not necessary.

Humans↗
PubMed2001

Predictive value of total and percent free prostate specific antigen in high grade prostatic intraepithelial neoplasia lesions: results of the Tyrol Prostate Specific Antigen Screening Project.

PURPOSE: We evaluate the predictive values of total and percent free prostate specific antigen (PSA) in regard to high grade intraepithelial lesions in volunteers who participated in the Tyrol PSA Screening Project. MATERIALS AND METHODS: Between June 1995 and December 1998, 1,474 patients undergoing transrectal biopsy of the prostate were evaluated. The primary detection rates of prostate cancer and high grade intraepithelial lesions were evaluated. In addition, the rate of prostate cancer detected on biopsy in patients diagnosed with high grade prostatic intraepithelial neoplasia on the previous biopsy was assessed. Mean total PSA values and mean percent free PSA levels were determined for each study group and compared using the Mann-Whitney U test. RESULTS: A total of 1,077 (73.1%) volunteers had benign prostatic hyperplasia or prostatitis, and 327 (22.2%) had prostate cancer. The primary detection rate for high grade intraepithelial lesions was 4.7% (70 patients) and on repeat biopsy was 38.6% (27). Mean total PSA for the benign prostatic hyperplasia, prostate cancer, high grade and intraepithelial cancer groups were 6.0, 8.7, 5.9 and 5.2 ng./ml., respectively. Mean percent free PSA values for the various groups were 21.9, 12.1, 15.0 and 12.0, respectively. In regard to total PSA there was a statistically significant difference between the prostate cancer and high grade prostatic intraepithelial neoplasia groups (p = 0.016), as well as the prostate cancer and intraepithelial cancer groups (p = 0.028). However, the high grade and intraepithelial cancer groups did not differ significantly. In regard to percent free PSA there were statistically significant differences between the prostate cancer and high grade prostatic intraepithelial neoplasia groups (p = 0.0001), and the high grade and intraepithelial cancer groups (p = 0.013). CONCLUSIONS: In regard to percent free PSA our data indicate a significant difference between high grade intraepithelial lesion and intraepithelial cancer. Due to a substantial overlap in percent free prostate specific antigen between the 2 groups, a clinically useful cutoff point could not be established. Therefore, we recommend repeat biopsy in all patients with high grade intraepithelial lesions regardless of the percent free PSA.

Adult↗
PubMed2001

Treatment of giant ancient pelvic schwannoma.

A 32-year-old patient presented with urinary retention and chronic constipation. Computerized tomography and magnetic resonance imaging showed a 10 x 11cm encapsulated tumor with cystic areas lying ventral to the sacrum. There was no evidence of invasion of bladder or rectum. At laparotomy, a 10 x 11 cm mass was found in the left pelvis. Final pathology revealed an ancient schwannoma. In most large series, 80% to 90% of the primary retroperitoneal tumors are malignant. Retroperitoneal schwannomas can be benign or malignant, roughly half of the reported cases showed malignancy. Benign schwannomas may arise along the course of any myelinated nerve, with the acoustic neuroma being the most frequent site. Immunostaining showed a strong expression of S-100 protein. The staining for this protein is helpful for differentiation of a benign schwannoma from a malignant peripheral nerve sheath tumor and from other benign spindle cell tumors. The treatment of choice for benign schwannomas is complete excision. Recurrence or persistence seems to be associated with incomplete resection, which occurred in 10% of the reported cases. After surgery, the patient had normal erection, normal micturition, and normal defecation but no symptoms of motor and sensory disturbances.

Adult↗
PubMed2000

Optimized preembedding method improves the histologic yield of prostatic core needle biopsies.

BACKGROUND: The aim of this study was to optimize the core shape of prostatic core needle biopsies using a novel preembedding method, and to investigate the influence of the number of cores per tissue block on the histologic yield per section level. METHODS: Twenty-four core needle biopsies were taken from a fresh prostatectomy specimen, using an 18-gauge needle. Twelve core needle biopsies were conventionally fixed floating free in formalin-filled containers, whereas 12 biopsies were stretched between two nylon meshes, and placed in tissue cassettes before fixation. The total number of tissue sections per paraffin block necessary for complete workup of the tissue was determined. Using image analysis, the relation of the area of every fifth section level was calculated in relation to the total projected area of the biopsies. Both methods of tissue processing were compared for both parameters. RESULTS: In contrast to the curved biopsies after conventional processing, the optimized preembedding method generally led to stretched cores after fixation and embedding. This method led to a 100% decrease in total number of tissue sections necessary for complete workup and to higher percentages of the tissue amount per section level compared to the total projected core area. These parameters were also influenced by the number of cores per paraffin block, but to a minor degree. CONCLUSIONS: This study shows that optimized preembedding of prostatic needle biopsies improves the histologic yield per section level. The continuous occurrence of representative sections could improve diagnostic accuracy in the histological examination of prostatic core needle biopsies.

Biopsy, Needle↗
PubMed2000

Immunohistochemical localization of interleukin-6 and its receptor in benign, premalignant and malignant prostate tissue.

Interleukin-6 (IL-6) is a pleiotropic cytokine that interacts with its receptor in prostate cells, thus regulating proliferative response and differentiation. It also activates the human androgen receptor in prostate cancer cell lines. In order to assess the significance of these findings in vivo, the expression of key elements of the IL-6 signalling pathway, IL-6 and its receptor, was investigated in tissue samples obtained on radical prostatectomy from prostate cancer patients. IL-6 immunohistochemistry was performed on 17 frozen prostate cancer specimens. IL-6 receptor immunostaining was evaluated in 21 paraffin-embedded prostate tumour specimens. In both groups, adjacent areas of high-grade prostatic intraepithelial neoplasia and benign tissue were also investigated. In benign prostatic epithelium, IL-6 was localized predominantly in basal cells, whereas in prostate cancer tissues more IL-6-positive glandular cells were identified. No IL-6 expression was detected in stromal cells on immunohistochemistry, although IL-6 protein was measured in the supernatants obtained from cultured stromal cells by ELISA. IL-6 receptor was expressed in benign prostatic tissue in both epithelial and stromal cells. Furthermore, IL-6 receptor expression was observed in all tumour specimens investigated and the majority of Gleason patterns analysed had more than 50% of cells showing a positive reaction. IL-6 and IL-6 receptor expression patterns in high-grade prostatic intraepithelial neoplasia lesions were similar to those observed in tumour tissues. Taken together, the results of the present study imply that there are paracrine and autocrine IL-6 loops in benign and neoplastic prostate.

Adenocarcinoma↗
PubMed2000

Prostate cancer screening in the Tyrol, Austria: experience and results.

This article summarises the experience and results of different prostate carcinoma screening projects using total prostate specific antigen (PSA) and per cent free PSA as the initial test. Of the 21078 volunteers 1618 (8%) had elevated PSA levels. Of these men 778 (48%) underwent biopsies; 197 (25%) biopsies were positive for prostate carcinoma and 135 (17%) underwent radical prostatectomy. 95 were found to be organ-confined. A PSA cut-off of 2.5 ng/ml in men aged 45-49 years and of 3.5 ng/ml in men aged 50-59 years resulted in an 8% increase in the detection rate of organ-confined disease. 284/2272 men (13%) had elevated PSA levels and prostate carcinoma was detected in 62 men (3%). All patients underwent radical prostatectomy and histological examination revealed organ-confined tumour in all but 8 men. 98/340 men (29%) had biopsies positive for carcinoma; 28 of these patients (29%) had carcinoma that originated in the transition zone only. In the retrospective study, receiver operating characteristic curve analysis showed that by using a per cent free PSA of less than 18% as a biopsy criterion, 37% of the negative biopsies could be eliminated although 94% of all carcinomas would still be detected. In the first prospective study, 106/158 men (67%) with elevated PSA levels below 10.0 ng/ml were further evaluated and 37 (35%) prostate carcinomas were detected. By using a per cent free PSA of <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, 120/465 men (26%) with total PSA levels between 1.25 and 6.49 ng/ml and a per cent free PSA<18% were further evaluated and 27 (23%) were found to have prostate carcinomas. Receiver operating characteristic curve analysis for PSA transition zone (TZ) density showed that by using a PSA transition zone density of >22 ng/ml/cc as a biopsy criterion, 24.4% of negative biopsies could be avoided without missing a single carcinoma. In the prescreening era the incidence of T1a Grade 1 and 2 carcinomas was 3.1% and the incidence of T1a and T1b Grade 3 carcinoma was 2.3% whereas in the years after the establishment of PSA-based screening the incidence was 4.6 and 1.03% respectively. The rate of organ-confined tumours increased from 28.7% in 1993 to 65.7% in 1997. In this evaluation a new approach, to proceed with a prostate biopsy based upon the individual risk of having prostate cancer rather than a single PSA cut-off point was developed. High total PSA levels, PSA density and PSA transition zone density correlated significantly with high Gleason scores, capsular penetration, a high percentage of cancer in the prostatectomy specimen and a high cancer volume. In this evaluation all of the 95 patients with PSA levels below 3.99 ng/ml who underwent radical prostatectomy showed clinically significant, organ-confined prostate cancer with negative surgical margins. The results of this evaluation suggest that older men have larger tumour volumes compared with younger men with the same PSA levels. These data suggest that PSA-based screening with low PSA cut-off values increase the detection rate of clinically significant, organ confined and potentially curable prostate cancer. Per cent free PSA and PSA transition zone density provide an additional diagnostic benefit over total PSA.

Age Distribution↗
PubMed2000

Selective expression of trophoblastic hormones by lung carcinoma: neurendocrine tumors exclusively produce human chorionic gonadotropin alpha-subunit (hCGalpha).

Recent findings suggest that glycoprotein- and protein hormones act as local auto/paracrine growth/differentiation factors in normal and malignant tissue. An imbalanced or even selective production of human chorionic gonadotropin-alpha (hCGalpha) by neuroendocrine tumors in various organs has been reported. In this context, the ectopic production of trophoblastic hormones by lung carcinoma has not been investigated systemically. Because the determination of serum levels of hCGalpha are flawed by a number of factors, we designed an immunohistochemical study to precisely assess the comprehensive paraneoplastic auto-/paracrine hormone production by lung carcinoma of various histological types. To this end, 90 patients with primary lung neoplasms (40 neuroendocrine tumors, 29 adenocarcinomas, 20 squamous cell carcinomas, and 1 adenosquamous carcinoma) were analyzed by our well characterized monoclonal antibodies (mabs) against the glycoprotein hormones hCG, and its derivatives hCGalpha, hCGbeta, hCGbeta core-fragment (hCGbetacf), luteinizing hormone (LH, LHbeta), follicle-stimulating hormone (FSH, FSHbeta), and the protein hormones placental lactogen (PL) and growth hormone (GH). Overall, trophoblastic hormone immunoreactivity was found in 31% (28/90) of all lung carcinomas, regardless of histological differentiation. Detailed analysis showed 23% (21/90) hCGalpha-, 7% (6/90) hCGbeta, and 2% (2/90) hCGbetacf-positive cases. The tumors produced neither the intact heterodimer hCG, nor the other placental protein hormones PL-A/B and GH-V, or the hCG-related pituitary gonadotropins FSH/FSHbeta and LH/LHbeta. With regard to histological differentiation, it appeared that neuroendocrine tumors exclusively produced free hCGalpha in a distinct expression pattern depending on histological tumor grade. Thirty-eight percent (15/40) of all neuroendocrine neoplasms were hCGalpha-positive, and marker positivity increased with more mature, highly differentiated tumors (20% of small cell neuroendocrine carcinomas versus 90% of atypical and typical carcinoids). This is in striking contrast not only to trophoblastic malignancies and testicular germ cell tumors, but also to nontrophoblastic tumors, such as gynecological and urothelial malignancies, 60% of which produce hCGbeta and where marker positivity correlates with poor histological tumor differentiation. In conclusion, free hCGalpha, but not hCGbeta, is a useful marker for neuroendocrine differentiation in primary lung tumors. The fact that it is preferentially produced by the differentiated tumor types (carcinoids) points to a putative biological function in these tissues. The few hCGbeta-positive NSCLC must not be confounded with primary mediastinal choriocarcinoma.

Adult↗
PubMed2000

Diagnostic effect of an improved preembedding method of prostate needle biopsy specimens.

The authors compared the influence of a conventional and an optimized submitting method of prostate core needle biopsy specimens on the frequency of cancer detected and the pathologic characteristics of the adenocarcinoma bearing biopsy specimens. The patients included were part of the prostate-specific antigen (PSA) screening program of Tyrol/Austria. Of the systematic core needle biopsy specimens from 500 unselected men obtained within 1 year from the Urological Department, University of Innsbruck, the core biopsy specimens of 250 cases were submitted conventionally, floating free in formalin-filled containers, whereas the biopsy specimens of the other 250 cases were stretched and orientated between 2 meshes in tissue cassettes at the time of biopsy before formalin fixation. On 136 cases diagnosed as adenocarcinoma the number and the length of cores as well as number of the cores involved by cancer and the tumor size were morphometrically determined. The diagnosis of benign prostatic hyperplasia, isolated high-grade prostatic intraepithelial neoplasia (PIN), atypical foci suspicious for cancer, and carcinoma was made in 66%, 5.6%, 4.8%, and 23.6% after conventional submission and in 61.6%, 6.4%, 1.2%, and 30.8% of the cases after optimized preembedding respectively. In the adenocarcinoma cases the optimizedly preembedded material showed higher mean total core length (126.5 mm versus 93.9 mm; P < .0001), a higher mean total tumor length (14.1 mm versus 8.6 mm; P = .01), and more cores involved by cancer (2.9 versus 2.4; P = .01) compared with the conventionally worked-up biopsy specimens. Optimized preembedding of core needle biopsy specimens in tissue cassettes could be quickly and routinely done by the assistance of the urologists at the time of biopsy. The significant improvement of the histologic yield of optimizedly preembedded prostatic needle biopsy specimens led to a higher frequency of cancer diagnosis, a reduction of cases with atypical foci suspicious for cancer and a significantly lower number of cases with only 1 core biopsy involved by cancer.

Adenocarcinoma↗
PubMed2000

Epstein-Barr virus-associated multicentric leiomyosarcoma in an adult patient after heart transplantation: case report and review of the literature.

Epstein-Barr virus (EBV)-associated smooth muscle tumors following solid organ transplantation are extremely rare, with only 12 cases reported in the literature thus far. The exact pathogenetic role of EBV infection in the oncogenesis of these soft tissue tumors in immunodeficient patients and the biologic behavior of such tumors is still unclear. We report a 26-year-old man in whom multiple smooth muscle tumors developed 36 to 51 months after heart transplantation. All tumors, two synchronous liver nodules, two subsequently occurring paravertebral tumors, and a single tumor in a vein at the left ankle were surgically resected. The tumor tissue was processed for routine histology and immunohistochemical (IHC) stains. Additionally, competitive polymerase-chain-reaction (PCR), reverse-transcriptase PCR (RT-PCR), as well as in situ hybridization (ISH) were used for EBV particle quantification and gene transcription analysis. The histologic features and immunohistochemical profiles were consistent with leiomyosarcoma in all tumor nodules. EBV infection was detected in >95% of tumor cell nuclei by EBER 1/2 ISH. Competitive PCR revealed 3105 EBV particles per milligram of tumor tissue. The EBV gene expression pattern analyzed by RT-PCR and IHC corresponded to the latency type III with specific expression of EBNA1, EBNA2, LMP1, and LMP2A genes. Under continuous antiviral therapy (famcyclovir) the patient currently shows no evidence of disease. Our data indicate that EBV infection plays a causal role in the development of smooth muscle tumors following organ transplantation. A latency type III, identical to EBV-associated posttransplant lymphoproliferative disorders, was identified and suggests a common pathogenetic mechanism in the development of these histogenetically distinct neoplasms. The fact that the patient currently shows no evidence of disease may be the result of the continuous administration of antiviral therapy because the soft tissue recurrences of the leiomyosarcoma occurred while the patient was not receiving antiviral prophylaxis.

Adult↗
PubMed2000

Radical prostatectomy: the value of preoperative, individually labeled apical biopsies.

PURPOSE: Involvement of the prostatic apex with adenocarcinoma is a relatively common finding, as is a positive surgical margin at this location. We evaluated whether a positive apical core biopsy provides preoperative information that may be used as a basis for the subsequent surgical approach in individuals. MATERIALS AND METHODS: We evaluated apical prostate cancer in 240 individually labeled, preoperative apical core biopsies and the corresponding prostatectomy specimen in 120 patients who underwent radical prostatectomy for clinically localized prostate cancer. Sensitivity, specificity, and positive and negative predictive values were calculated for the ability of an individual apical core to predict the side of tumor in the surgical specimen using 2 x 2 contingency tables. Moreover, univariate subset analysis was done for positive biopsies to assess the ability of histopathological characteristics, including Gleason score, cancer length, percent of cancer in the core and distance of cancer from the inked rectal core end, to predict a positive surgical margin at the apex. RESULTS: The positive predictive value of a single positive apical core for identifying tumor location correctly in the prostatectomy specimen was 71.1%, while absent cancer in the apical biopsy had a negative predictive value of 75.5%. Sensitivity was 44.5% for a positive biopsy core. In this context the predictive value of an individual positive apical core biopsy was only 28.8% for predicting surgical margin positivity at the apex. CONCLUSIONS: Cancer and its histopathological characteristics in an individual core biopsy failed to predict apical tumor involvement as well as a positive apical margin at subsequent radical prostatectomy.

Adenocarcinoma↗
PubMed1999

Correlation between preoperative predictors and pathologic features in radical prostatectomy specimens in PSA-based screening.

BACKGROUND: Measurement of percent free prostate-specific antigen (PSA), PSA density, and PSA-transition zone density (PSA-TZ density) in addition to total PSA is known to improve the specificity of PSA-based prostate cancer screening. We evaluated the ability of total PSA, percent free PSA, PSA density, and PSA-TZ density to predict pathologic features in radical prostatectomy specimens. METHODS: The levels of total PSA, percent free PSA, PSA density, and PSA-TZ density assessed prior to the diagnosis of prostate cancer were correlated with the pathologic findings in 102 prostate glands with cancer obtained at radical prostatectomy. The entire organs were examined histologically; Pearson correlation coefficients were used for statistical analysis. RESULTS: High levels of total PSA, PSA density, and PSA-TZ density correlated significantly with capsular penetration, high Gleason scores, and large cancer volumes in the prostatectomy specimens. Free PSA was found to correlate well with high Gleason scores, high percentages of cancer, and large cancer volumes, but not with capsular penetration. The four parameters were evaluated by means of logistic regression, which showed that only percent free PSA and total PSA were significant predictors of Gleason scores > or =7 and cancer volumes > or =0.5 cc. With regard to clinically insignificant cancers, only percent free PSA and the Gleason score obtained at biopsy were significant predictors. CONCLUSIONS: In men whose prostate cancers are detected by PSA-based screening, high total PSA levels in combination with low percent free PSA levels are suggestive of a potentially more aggressive type of prostate cancer. This may help both patient and clinician in selecting the most appropriate therapeutic approach.

Adult↗
PubMed1999

Modulation of the differentiation status of cultured prostatic smooth muscle cells by an alpha1-adrenergic receptor antagonist.

BACKGROUND: Prostatic stromal cells are believed to be a key factor in the pathogenesis of benign prostatic hyperplasia (BPH). The effect of phenylephrine, an alpha1-adrenergic receptor agonist, and doxazosin, an alpha1-adrenergic receptor-specific antagonist, on the expression of smooth muscle myosin-heavy-chain isotypes SM-1 and SM-2 was tested in an in vitro model of prostatic smooth muscle cells (SMC). METHODS: Primary prostatic stromal cells, grown in SMC-specific medium, were treated with 10 microM of phenylephrine or 1 microM of doxazosin or a combination of both. SM-2 to SM-1 mRNA ratios and expression of alpha1-adrenergic receptor subtypes were determined by means of reverse transcriptase polymerase chain reaction (RT-PCR) techniques. Cell growth was measured by a cell viability assay. RESULTS: SM-1 mRNA and only very low levels of SM-2 mRNA were detected in prostatic SMC cultures grown for 4 days in a serum-free base medium. After 6 days of treatment, SM-2 expression increased, highest in the doxazosin-treated cultures. In comparison to unstimulated cells, a statistically significant 10-fold increase of the SM-2:SM-1 ratio was measured in doxazosin-treated cultures. Analysis of alpha1-adrenergic receptor subtype expression revealed the presence of mRNAs of subtypes 1d and 1b mRNAs. Subtype 1a was not expressed. Phenylephrine and doxazosin showed no significant effect on cell proliferation and on alpha1d-adrenergic receptor expression. CONCLUSIONS: SMC can differentiate from a proliferative to a contractile phenotype, which is accompanied by increased expression of isotope 2 of smooth muscle myosin heavy chain. Our results suggest that doxazosin seems to have a long-term effect on the differentiation of prostatic stromal cells, indicating that alpha1-adrenergic receptor antagonists do not act solely on SMC contractility.

Adrenergic alpha-1 Receptor Agonists↗
PubMed1999

Basic fibroblast growth factor synthesis by human peritoneal mesothelial cells: induction by interleukin-1.

Peritoneal mesothelial cells are uniquely located to regulate cellular events in the peritoneal cavity and are an important source for various cytokines and growth factors. This study was conducted to analyze the capacity of human peritoneal mesothelial cells (HPMCs) to synthesize and release basic fibroblast growth factor (bFGF) and to characterize its regulation by inflammatory cytokines. HPMCs constitutively synthesized and released considerable amounts of bFGF as detected by a specific immunoassay. Almost 80% of bFGF (1547 +/- 173 pg/10(5) cells) was localized intracellularly. Approximately 20% of the bFGF (357 +/- 27 pg/10(5) cells) was associated with extracellular matrix components on the HPMC surface. Small amounts of bFGF (<1%) were detectable in tissue culture supernatants (8.4 +/- 1.4 pg/10(5) cells). Treatment of HPMCs with interleukin-1beta (IL-1beta; 1 ng/ml) resulted in a significant increase in bFGF production. The intracellular bFGF content showed a rapid but only transient increase, which was significant above background levels after 24 hours (41% increase; P < 0.05). This increase in intracellular bFGF concentration was associated with an induction of the release of bFGF. Within 96 hours, the release of bFGF to the cell surface and into the supernatant increased by 58% (564 +/- 52.4 pg/10(5) cells; P < 0.01) and by 214% (26.4 +/- 3.2 pg/10(5) cells; P < 0.001), respectively. Neither tumor necrosis factor-alpha nor interferon-gamma affected bFGF synthesis by HPMCs. Stimulation of HPMCs with IL-1beta increased steady-state levels of bFGF-specific mRNA. Immunohistochemical analyses of peritoneal tissue revealed constitutive expression of bFGF by HPMCs. This in situ expression proved to be most pronounced in areas of serosal inflammation in activated HPMCs. Our study demonstrates that HPMCs synthesize and release significant amounts of bFGF and that the expression of this growth factor is significantly up-regulated by the proinflammatory cytokine IL-1beta. The data support the view that HPMCs are key regulators of abdominal disease processes such as peritonitis, peritoneal fibrosis, or peritoneal tumor metastasis.

Cells, Cultured↗
PubMed1999

Prostate cancer screening in 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) and percent free PSA as the initial test. METHODS: The twelve 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 cut-offs in 1,618 men; (3) a PSA-based screening study of 2,272 asymptomatic blood donors; (4) an investigation of the evidence and significance of transition zone carcinoma in 340 men with negative digital rectal examination findings; (5) determination of percent free PSA in one retrospective and two prospective studies to determine the appropriate cutpoints for percent free PSA; (6) evaluation of the diagnostic benefit of PSA transition zone density in 308 screening volunteers; (7) a study of the impact of PSA-based screening on the percentage of incidental prostate carcinoma in 1, 543 men undergoing transurethral resection of the prostate; (8) an evaluation of the changes in total PSA and pathologic stages in radical prostatectomy over 5 years in a PSA-based mass screening program; (9) a study evaluating the probability of having prostate cancer given the patient's age, total PSA and digital rectal examination findings; (10) an evaluation of the correlation between preoperative predictors and pathologic features in radical prostatectomy specimens; (11) an investigation of the correlation of total PSA with pathologic stage and tumor volume in patients undergoing radical prostatectomy with low PSA cut-off level, and (12) a study whether age has an impact on the extension of prostate cancer. RESULTS: (1) of the 21,079 volunteers, 1,618 (8%) had elevated PSA levels. Of these men, 778 (48%) underwent biopsies; 197 biopsies were positive for prostate carcinoma and 135 underwent radical prostatectomy. Ninety-five were found to be organ-confined. (2) A PSA cut-off of 2.5 ng/ml in men aged 45-49 years and of 3.5 ng/ml in men aged 50-59 years resulted in an 8% increase in the detection rate of organ-confined disease. (3) Of the 2,272 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 tumor in all but 8 men. (4) Ninety-eight of 340 men had biopsies positive for carcinoma; 28 of these patients (28.5%) had carcinoma that originated in the transition 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, 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 PSA levels <10.0 ng/ml were further evaluated and 37 prostate carcinomas were detected. By using a % free PSA of <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 and a % free PSA <18% were further evaluated and 27 (22.5%) were found to have prostate carcinomas. (6) Receiver-operating characteristic curve analysis for PSA transition zone density showed that by using a PSA transition zone density of >22 ng/ml/cm3 as a biopsy criterion, 24.4% of negative biopsies could be avoided without missing 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. (8) The rate of organ-confined tumors increased from 28.7% in 1993 to 65.7% in 1997. (9) In this evaluation a new approach to proceed with a prostate biopsy based upon the individual risk of having prostate cancer rath

Adult↗