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Biomedical subjects

K Pummer

Publications and source records attributed to K Pummer.

At least 19 recordsLinked to original sources

Molecular markers and their prognostic impact in patients with advanced prostate cancer undergoing intermittent androgen suppression.

OBJECTIVE: Tumour features were evaluated during intermittent androgen suppression (IAS), and their prognostic impact on the first off-treatment time was analysed. PATIENTS AND METHODS: Twenty patients with advanced prostate cancer underwent three consecutive prostate biopsies during the first cycle, namely at the beginning of androgen deprivation, 8 months after continuous therapy and at the time of prostate-specific antigen (PSA) progression above 20 ng/ml. Biopsy specimens were immunohistochemically processed and analysed for the apoptotic index (AI), Ki-67, p53 and Bcl-2 to investigate eventual changes over time. Correlations and regression analysis were performed to assess the prognostic significance of clinical and pathological parameters in predicting the first off-treatment time. RESULTS: In contrast to the AI, p53 and Bcl-2, Ki-67 was the only marker that significantly changed over time (P=0.008). The first off-treatment time correlated significantly with pretreatment PSA (r=-0.594; P<0.01), testosterone recovery time (r=0.590; P=0.013) and biopsy grade (r=-0.738; P<0.01); only the latter gaining an independent factor in the multivariate analysis (P=0.022). CONCLUSIONS: During IAS, Ki-67 was the only molecular marker that consistently changed over time. However, it did not correlate with off-treatment time that was predicted independently by the initial biopsy grade only. First off-treatment time was best predicted by clinical parameters and molecular markers from needle biopsies did not further contribute to a better patient selection.

Aged↗

Distribution of prostate carcinoma foci within the peripheral zone: analysis of 8,062 prostate biopsy cores.

The aim of this study was to evaluate the distribution of prostate cancer within the peripheral zone by prostate biopsies excluding the influence of the transition zone. A prospective, multicenter study was carried out using a consecutive series of men who underwent transrectal ultrasound guided prostate biopsies using different biopsy techniques at six institutions. Biopsies were directed strictly within the peripheral zone or strictly within the transition zone. A model of the peripheral zone with 18 sectors of similar volume was established and the biopsy cores obtained were associated with these sectors and analysed with respect to prostate cancer detection rate. A total of 904 men (mean age 66.8 years, range 42-86) with a median serum PSA of 8.1 ng/ml (2.2-940 ng/ml) entered the study. A total of 8,062 biopsy cores (mean 8.92/patient) were obtained. Each of the peripheral zone sectors tested by biopsies yielded a similar percentage of prostate cancer ( P=0.6). There was no increase in the incidence of cancer toward the lateral sectors compared to midline sectors ( P=0.53) of the peripheral zone. Biopsy sampling of the peripheral zone from the apex to the base yielded a similar percentage of prostate cancer ( P=0.47). Our data suggest that the distribution of cancer foci detected by biopsies in the peripheral zone of the prostate is homogeneous.

Adult↗

Long-term results of nephron-sparing surgery for renal cell carcinoma in 114 patients: risk factors for progressive disease.

OBJECTIVES: To evaluate risk factors for metastatic disease after nephron-sparing surgery (NSS) for renal cell carcinoma (RCC). PATIENTS AND METHODS: NSS for RCC was used 117 times in 114 patients at our institution; 61 had a normal contralateral kidney and were selected for elective NSS, and in 56 cases (53 patients) the indication for NSS was imperative. Univariate and multiple regression analysis was used to evaluate the risk factors for metastatic disease. RESULTS: After a mean follow-up of 80 months, there was tumour progression in 17 of the 114 patients (15%). In the univariate analysis, the tumour diameter (P = 0.03) and imperative indication (P = 0.009), and in multiple regression analysis only imperative indication, were significant risk factors for metastatic disease (P = 0.016). CONCLUSIONS: Elective NSS for RCC provides excellent long-term results in selected patients, whereas those undergoing NSS imperatively are at a significantly higher risk of metastatic disease and require a close follow-up.

Adult↗

[Value of intensive thyroid assessment in male infertility].

In infertile men thyroid hormone and antibody testing was performed and correlated with the results of semen analyses. Evaluation included semen analyses, physical examination, evaluation of sex steroid hormones, thyroid hormones (bTSH, fT4, fT3) and thyroid antibody testing (TGA, TPO-Ab, TRAK). Furthermore 45 men with normal thyroid function were scheduled for TRH testing. No one was diagnosed as having manifest hypo- or hyperthyroidism. Latent thyroid dysfunction had no effect on semen parameters. Elevated TPO-Ab were significantly correlated with reduction in motility of spermatozoa. The routine assessment of thyroid hormones and antibodies in infertile men is not recommended. Subclinical hypothyroidism as a result of TRH testing is a rare finding in infertile men.

Gonadal Steroid Hormones↗

Radiotherapy of testicular intraepithelial neoplasia (TIN): a novel treatment regimen for a rare disease.

PURPOSE: Testicular intraepithelial neoplasia (TIN) is a consistent precursor of most invasive germ cell tumors, currently treated by radiotherapy with 20 Gy, which destroys TIN but preserves Leydig cells. Nevertheless, analysis has shown dose-dependent dysfunction even with low therapeutic doses of 20 Gy in some cases. Therefore, we tested a dose reduction regimen by delivering smaller fractional doses to enhance the tolerance of Leydig cells. METHODS AND MATERIALS: Between 1993 and 1999, 9 patients were treated for TIN in a prospective multicenter trial. A total dose of 13 Gy was administered in 10 fractions of 1.3 Gy. Hormonal levels of follicle-stimulating hormone, luteinizing hormone, and testosterone were assayed serially. RESULTS: During a median follow-up time of 36 months, no patient showed evidence of local disease. A first postradiation biopsy was obtained 3-12 months after radiotherapy; 5 patients underwent a second biopsy 2-3 years after treatment. All biopsies showed a Sertoli cell-only pattern. Follicle-stimulating hormone levels continued to increase 1 year after radiotherapy, signaling eradicated spermiogenesis. Luteinizing hormone and testosterone remained within the normal range 2 years after radiotherapy. CONCLUSIONS: In the treatment of TIN, there seems to be a dose reduction potential to 13 Gy by lowering single fractional doses, which enhances the therapeutic ratio in favor of the Leydig cells.

Adult↗

Identification of tumor antigens in renal cell carcinoma by serological proteome analysis.

We have investigated the suitability of proteomics for identification of tumor-associated antigens. First, we compared the proteomes of nontumorous kidney and renal cell carcinoma (RCC) by two-dimensional gel electrophoresis (2-DE) and silver staining. Protein patterns were markedly different (approximately 800 spots in RCCs versus approximately 1400 spots in kidney). 2-DE immunoblotting revealed five RCC-specific spots, reproducibly reactive with RCC-patient but not healthy donor control sera. Two of these antigens were isolated by preparative 2-DE, and identified by Edman sequencing of tryptic peptides. The first antigen, smooth muscle protein 22-alpha (SM22-alpha), is an actin-binding protein of unknown function predominantly expressed in smooth muscle cells. In situ hybridization revealed that SM22-alpha is not expressed in the malignant cells but in mesenchymal cells of the tumor stroma. The second antigen represents carbonic anhydrase I (CAI), an isoform usually not expressed in kidney. Interestingly, a different isoform (CAXII) has previously been identified by serological expression cloning as an antigen overexpressed in some RCCs. In additional assays, antibodies to recombinant CAI or SM22-alpha were detected in sera from 3/11 or 5/11 RCC patients, respectively, whereas sera from 13 healthy individuals did not react. In conclusion, serological proteome analysis may be a new tool for the identification of tumor-associated antigens.

Amino Acid Sequence↗

Thyroid hormones and thyroid antibodies in infertile males.

OBJECTIVE: To investigate the incidence of thyroid dysfunction, thyroid antibodies, and the correlation with semen and hormonal parameters in infertile men. DESIGN: Prospective study. SETTING: University-based andrology laboratory. PATIENT(S): Three hundred five infertile men with idiopathic infertility. INTERVENTION(S): Medical history, clinical examination, semen analysis, measurement of free thyroxin (fT4), free triiodothyronine (fT3), basal thyroid-stimulating hormone (bTSH), LH, FSH, T, free testosterone (fT), PRL, E2, sex hormone-binding globulin (SHBG), DHEAS, and the thyroid antibodies thyreoglobulin antibody (TGA), thyroid peroxidase antibody (TPO-Ab), and thyroid receptor antibody (TRAK). MAIN OUTCOME MEASURE(S): Incidence of thyroid dysfunction and thyroid antibodies, as well as the correlation with hormones and the results of semen analyses. RESULT(S): No manifest thyroid dysfunction was observed. Latent thyroid dysfunction and latent hypothyroidism were diagnosed in 11.5% and 3% of infertile men, respectively. No correlation between thyroid dysfunction and semen parameters was detected. bTSH correlated significantly with PRL (P<.001). Thyroid antibodies were elevated in 7.5%. Elevated TPO-Ab were significantly correlated with pathozoospermia (P=.036) and asthenozoospermia (P=.049). CONCLUSION(S): Latent thyroid dysfunction had no impact on semen parameters. In patients with elevated TPO-Ab levels, pathozoospermia or asthenozoospermia should be considered.

Adult↗

Therapeutic strategies for localized prostate cancer I: surgery, ultrasound, adjuvant and neoadjuvant therapy.

Over the past decade, because of the introduction and widespread availability of prostate-specific antigen determinations, carcinoma of the prostate that is localized and potentially curable has been diagnosed in an increasing number of men. Advances in surgical management with preservation of the neurovascular bundles, in addition to hormone therapy, have added to the success and improved quality of life of patients undergoing treatment. New forms of treatment (including laparoscopic prostatectomy and high-intensity focused ultrasound) are advances that are continuing to be developed and that may have a significant role in the management of this disease. With further investigation and technologic advancement, it is anticipated that more and more men with localized disease will be identified and cured, with preservation of sexual and urinary function.

Journal Article↗

[Radiologic staging of renal cell carcinoma].

The routine staging work-up for renal cancer includes a contrast-enhanced multiphasic spiral CT and a chest radiograph. If there is doubt regarding the presence and extent of (supradiaphragmatic) IVC thrombus, MR imaging should be performed. Dynamic contrast-enhanced MR imaging should be used in place of CT in any patient with severe renal dysfunction, symptomatic polycystic kidney disease, or a history of allergy to iodinated contrast media. Cavography is no longer needed in the era of (adaptive array detector) spiral CT and MR venography.

Adult↗

Diagnosis and staging of prostatic carcinoma: what is really necessary?

Diagnosis and staging of prostatic carcinoma should be considered in men in whom treatment with curative intent is possible. The primary tools for detection of cancer are digital rectal examination (DRE) and serum prostate-specific antigen (PSA), whereas transrectal ultrasonography is best used to guide the needle for biopsy. Staging should be based on the TNM system. The most reliable staging methods include a combination of DRE, PSA and systematic biopsies for local tumor extension, pelvic lymphadenectomy for regional lymph nodes, and PSA and bone scintigraphy for distant metastases. Computed tomography and magnetic resonance imaging are not necessary in most cases.

Humans↗

Hormonal therapy of prostate cancer: is there any news?

Androgen ablative therapy was introduced in the early 1940s and, even today, has remained the golden standard for the treatment of advanced prostate cancer. During the past decades, a variety of improvements have been achieved which, however, primarily aimed at a better tolerance or improved acceptance of androgen deprivation. However, after almost six decades of hormonal therapy it is appropriate to ask whether progress was also made in terms of efficacy, particularly as far as prolongation of survival or quality of life is concerned. During the last few years, two therapeutic strategies, maximal androgen blockade and intermittent androgen suppression, have been considered true conceptual advances. However, despite tremendous efforts and a huge number of studies so far, these concepts appear to produce more questions rather than answers. Therefore, it seems appropriate to raise some critical issues of maximal androgen blockade and intermittent androgen suppression.

Androgen Antagonists↗

Randomized comparison of total androgen blockade alone versus combined with weekly epirubicin in advanced prostate cancer.

Hormone deprivation is the gold standard for the treatment of metastatic prostate cancer. However, prostate cancer being primarily a heterogeneous tumor comprising hormone-dependent, hormone-sensitive, and hormone-insensitive cells, at least the latter remain unaffected by hormonal manipulations, thus making disease progression almost inevitable. In quest of a more comprehensive therapy we therefore studied the concept of early combined chemoendocrine therapy in a prospective randomized multicenter trial. The purpose of this study was to evaluate whether patients with previously untreated advanced prostate cancer benefit from combining total androgen blockade (TAB) with weekly epirubicin chemotherapy (E-TAB). From April 1988 to January 1991, 145 previously untreated patients with either metastatic (n = 117) or locally advanced (n = 28) histologically confirmed prostate cancer were randomly allocated to treatment with TAB by bilateral orchiectomy and flutamide 250 mg t.i.d. or TAB plus weekly epirubicin 25 mg/m2 i.v. for 18 weeks (E-TAB). The study endpoints were progression-free survival and overall survival. In addition the effects of treatment on quality of life were assessed by two methods. At regular intervals patients self-assessed ten qualities of physical, functional and emotional health using 5-point scales. In order to evaluate the time without disease progression and treatment-induced adverse effects, a modified Q-TWiST (quality-adjusted time without symptoms and toxicity) model was applied. At a median follow-up of 81 months, progression-free survival and overall survival in the TAB and E-TAB groups were 12 and 18 months (p < 0.02) and 22 and 30 months (p = 0.12), respectively. In patients with > 5 sites of bone metastasis (D2max), the corresponding periods were 9 and 14 months (p = 0.005) and 17 and 27 months (p = 0.06), respectively. Subjective quality of life assessment showed no impairment of quality of life by epirubicin treatment. Stage D and D2max patients treated with E-TAB had an average gain in Q-TWiST of 5 months (p = 0.098) and 8 months (p = 0.03), respectively, compared to the TAB treatment. Objective toxicities were generally mild with either treatment. In conclusion, the combination of TAB and epirubicin was well tolerated by patients with advanced prostate cancer and resulted in a significant extension of progression-free survival. This effect of E-TAB on objective treatment outcome was accompanied by prolonged time without treatment-induced adverse effects and tumor progression, i.e., time with good quality of life. Therefore, further studies with E-TAB appear warranted in patients with advanced prostate cancer.

Aged↗

Restoration of micturition in patients with acontractile and hypocontractile detrusor by transurethral electrical bladder stimulation.

The aim of transurethral electrical bladder stimulation (TEBS) treatment in patients with diminished detrusor contractility is to attain complete voiding, i.e., micturition without residual urine, which is under volitional control. In contrast to other types of electrical bladder stimulation, the physiological basis for this kind of treatment is sensitizing of the bladder mechanoreceptor afferents. The latency of afferent stimuli in normal conditions indicates that myelinated A-delta-fibers are used for neurotransmission from these mechanoreceptors. Forty-eight patients with hypocontractile or acontractile detrusor underwent intravesical electrical stimulation. All patients had a history pointing to neurogenic pathology. Forty patients had an acontractile and 8 a hypocontractile bladder. Prior to therapy, the mean residual urine volume was 461 ml. After stimulation, 32 of 48 patients were able to void with a mean residual of 57 ml. Detrusor contraction was achieved in 39% and bladder sensation was perceived by 75% of patients who failed these conditions before treatment. Following therapy, 19 of 35 patients were able to empty their bladder without the previously needed catheterization. Side effects were epididymitis in 1 and cystitis in 7 patients.

Adult↗

Adrenalectomy--still a must in radical renal surgery?

OBJECTIVE: To investigate the incidence of adrenal involvement and survival in patients with renal cell carcinoma. PATIENTS AND METHODS: A retrospective, multicentre trial was initiated by the Austrian Association of Urologic Oncology (AUO); between January 1980 and December 1984, 225 patients were eligible for the study. All patients had unilateral renal tumours and nephrectomies were performed either with (group A, 109 patients) or without (group B, 116 patients) adrenalectomy. The two groups were matched for sex, age, laterality and nodal status. The mean follow-up time was 78 months. RESULTS: The location of the intrarenal tumour had no significant effect on adrenal involvement. By univariate and multivariate analysis (Cox's proportional hazards model) significant differences in outcome were found only for pT stages. The mean survival times of patients in group A were 122.9 months in those with stage pT1/2, 76.6 months with stage pT3 and 75.3 months with stage pT4. In group B, survival times were 109 months in those with stage pT1/2 (not significant) and 111 months in stage pT3 (P = 0.0076). Eight patients had adrenal involvement and died from their tumours after a median of 15.3 months (range 4-63). The slightly longer survival of patients in group B with stage T1/2 tumours and the significantly better survival of patients with stage T3 disease may be attributable to statistical bias, but there was no benefit from adrenalectomy. CONCLUSION: The effect of adrenalectomy on the prognosis was at best comparable to that of lymphadenectomy and no curative effect was demonstrated. The removal of a healthy adrenal may be detrimental and cause subsequent problems in those patients requiring hormone replacement.

Adrenalectomy↗

Effect of extracorporeal shock wave lithotripsy on prostate specific antigen.

PURPOSE: We evaluated the effects of extracorporeal shock wave lithotripsy (ESWL) of distal ureteral calculi on serum prostate specific antigen (PSA). MATERIALS AND METHODS: A total of 29 consecutive men with distal ureteral calculi at a maximum of 25 mm. from the ureteral orifice, and without any history of urinary tract infection, benign prostatio hyperplasia or prostate cancer underwent ESWL with the Dornier MPL 9000 X lithotriptor. The therapeutic focus size was 48 X 7 mm. PSA was measured exactly 5 minutes before ESWL, as well as 120 minutes, 24 hours and 7 days after termination of treatment. RESULTS: Fragmentation rate was 100% and all patients were stone-free within 1 week of therapy. There was no statistically significant difference between PSA values before and after treatment. Only 15 patients had a slight increase in PSA at 120 minutes after treatment (range 0.01 to 0.41 ng./ml., mean 0.07). CONCLUSIONS: ESWL can be performed in men at risk for prostate cancer without impairing the predictive value of PSA.

Adult↗

Serum immunosuppressive acid protein predicts lymph node metastases in patients with renal cell carcinoma.

OBJECTIVE: To evaluate the usefulness of serum immunosuppressive acid protein (IAP) as a marker for lymph node metastases in patients with renal cell carcinoma. PATIENTS AND METHODS: Serum IAP levels were studied in 73 patients with renal cell carcinoma, prior to therapy. Serum IAP levels were correlated with the clinical and the post-operative histopathological stage. A threshold value of 800 micrograms/ml was applied. RESULTS: Statistical analysis revealed a better correlation between IAP concentration and disease than with any other variable. Sensitivity and specificity were 94% and 84%, respectively, thus providing good positive (65%) and negative (98%) predictive values regarding lymph node involvement. CONCLUSION: Measuring serum IAP levels can be a valuable contribution to lymph node staging in patients with renal cell cancer. The choice of cut-off value of 800 micrograms/ml has yet to be supported by a larger series.

Adult↗

Fleroxacin versus norfloxacin in the treatment of urinary tract infections: a multicenter, double-blind, prospective, randomized, comparative study.

In a multicenter, double-blind, prospective, randomized, comparative study, fleroxacin, 400 mg once daily orally, was compared with norfloxacin, 400 mg twice daily orally. Each drug was given for 10 days to study efficacy and safety in the treatment of uncomplicated, recurrent, or complicated urinary tract infection (UTI). A total of 587 patients from 22 centers were enrolled and randomly assigned to fleroxacin (n = 291) or norfloxacin (n = 296). Of these, 163 patients in each group were included in the efficacy analysis, and 287 in the fleroxacin group and 292 in the norfloxacin group were included in the safety analysis. There was no difference between the two groups in terms of bacteriologic or clinical efficacy, with cure rates for each diagnostic subgroup of 93-100% in the fleroxacin group and 91-96% in the norfloxacin group. Superinfection, reinfection, or relapse, as well as development of resistance to the administered drugs, were infrequent and comparable in the two groups. Adverse events were documented in a significantly higher number of patients treated with fleroxacin and involved mainly the digestive system, the central nervous system, and the skin. However, > 90% of such adverse events were judged as mild or moderate in severity and did not lead to premature termination of treatment. Fleroxacin exhibited a clinical and bacteriologic efficacy comparable to that of norfloxacin in this group of patients, with cure rates similar to those of other 4-quinolones, suggesting a promising role for fleroxacin in the treatment of both uncomplicated and complicated UTIs. However, the higher incidence of adverse events with fleroxacin warrants further investigation with special focus on adverse reactions.

Adolescent↗