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Biomedical subjects

U Tunn

Publications and source records attributed to U Tunn.

At least 19 recordsLinked to original sources
PubMed2003

[Gemcitabine/cisplatin vs. MVAC. 5 year survival outcome of the phase III study of chemotherapy of advanced urothelial carcinoma in Germany].

Of 405 patients with stage IV transitional cell carcinoma from an international multicenter phase III trial, 70 were randomized in Germany to receive either gemcitabine/cisplatin or standard MVAC systemic chemotherapy for locally advanced or metastatic urothelial cancer. Overall survival as the primary endpoint of the study was similar in both arms (median survival GC 15.4 months vs MVAC 16.1 months), as were tumor-specific survival and time to progressive disease. In the intent-to-treat analysis, the 5-year overall survival rate was 10% for patients randomized to GC and 18% randomized to MVAC. Tumor overall response rates (GC 54%, MVAC 53%) were similar. The toxic death rate was 0% in the GC arm and 3% (one patient) in the MVAC arm. Significantly more GC than MVAC patients experienced grade 3/4 anemia (GC 52%, MVAC 20%) with significantly more red blood cell transfusions in the GC arm.Significantly more GC than MVAC patients had grade 3/4 thrombocytopenia (GC 54%, MVAC 17%) without grade 3/4 hemorrhage or hematuria in either arm. More MVAC patients experienced grade 3/4 neutropenia (GC 56%, MVAC 61%, p=1.000), neutropenic or leukopenic fever (GC 0%, MVAC 10%, p=0.237), mucositis (GC 0%, MVAC 7%, p=0.495), and alopecia (GC 6%, MVAC 36%, p=0.004). GC represents a reasonable alternative for the palliative treatment of patients with locally advanced and metastatic transitional cell carcinoma. Sustained long-term survival was only found for patients with locally advanced cancer, lymphatic metastases, or solitary distant metastasis but not for visceral metastatic disease.

Adult↗
PubMed2003

Management of locally advanced prostate cancer: a European consensus.

This report summarises the findings of a European Consensus Group review of current standards of care in locally advanced prostate cancer defined as (a) untreated cancer extending clinically beyond the prostatic capsule in patients with no evidence of lymph node invasion or distant metastases, and (b) residual disease remaining after local treatment with positive surgical margins, seminal vesicle invasion, persistent prostate-specific antigen (PSA) and/or secondary PSA relapse. There was no overall consensus as to the standard of care in clinically apparent locally advanced prostate cancer. It was agreed, however, that hormonal therapy (e.g. with a gonadotrophin releasing hormone analogue [GnRHa]) represents a valid treatment in these patients. Treatment practices and regimens vary considerably between European countries, but GnRHa is widely used, either alone or in combination with antiandrogens. Hormonal therapy alone is a valid option, though the optimal modality, timing and duration of treatment remain to be defined. Adjuvant therapy with a GnRHa has been shown to improve survival in patients undergoing external beam radiotherapy. It is a viable option after prostatectomy in patients with persistent or secondary relapsing PSA. It was determined that optimal treatment will be different according to PSA, clinical staging and Gleason score, and the treatment of locally advanced disease should be individually tailored after discussion between physician and patient. In many instances, patients prefer and expect some form of treatment in preference to watchful waiting. Treatment nomograms such as the Kattan nomograms provide precise, comprehensive and invaluable tools for everyday use and may be used to predict outcomes and guide treatment decisions.

Androgen Antagonists↗
PubMed2002

Endogenous pro-inflammatory cytokines in children and adolescents during chemotherapy-induced neutropenia.

Monocyte-derived pro-inflammatory cytokines such as GM-CSF, IL-12, and IP-10 might protect patients with chemotherapy-induced neutropenia against infections. In settings with abundant neutrophils, G-CSF has been described as a suppressor of IL-12, but also as an inducer of GM-CSF. In 25 pediatric patients with chemotherapy-induced neutropenia the authors measured plasma levels of these four cytokines. GM-CSF was detectable in only a minority of patients (6/25). It was, however, positively correlated with high plasma levels of IL-12 and IP-10. G-CSF levels, however, were in no way correlated with the levels of any of these three cytokines.

Adolescent↗
PubMed2000

3D interstitial HDR brachytherapy combined with 3D external beam radiotherapy and androgen deprivation for prostate cancer. Preliminary results.

BACKGROUND: Evaluation of feasibility, tolerance and efficiency for a new 3D interstitial HDR brachytherapy technique combined with 3D external beam radiotherapy and androgen deprivation for prostate cancer. PATIENTS AND METHODS: Between January 1997 and August 1998 we treated 35 patients with stage cT1-3 N0 M0 prostate cancer. Thirty-two patients with a follow-up of 12 to 28 months (median: 18 months) were evaluated. After ultrasound-guided transrectal implantation of 4 non-parallel needles, CT based 3D brachytherapy treatment planning ("Offenbach system") was performed. All patients received 4 fractions brachytherapy using a fractional dose of 5 or 7 Gy. Time between each fraction was 14 days. After brachytherapy 3D external irradiation followed up to 39.6 or 45.0 Gy. All patients received androgen deprivation, starting 2 to 19 months before brachytherapy, ending 3 months after 3D external radiotherapy. RESULTS: Posttreatment PSA levels dropped to < 1.5 ng/ml in 29/32 patients (91%). In 25 patients PSA levels were < 0.5 ng/ml, in 4 patients 0.5 to 1.5 ng/ml. In 2 patients we noted biochemical relapse. Transrectal implantation was very well tolerated. Grade 3 acute urinary toxicity occurred in 1 patient. We noted no Grade 2 or higher acute gastrointestinal toxicity. One patient developed a Grade 3 late urinary toxicity. No patient showed late gastrointestinal side effects. All 140 dose-volume histograms for 3D HDR brachytherapy were analyzed. CONCLUSIONS: The new 3D HDR brachytherapy technique, combined with 3D external irradiation and androgen deprivation, is a feasible, so far well-tolerated and effective treatment in the short-time follow-up of median 18 months.

Adenocarcinoma↗
PubMed1999

New interstitial HDR brachytherapy technique for prostate cancer: CT based 3D planning after transrectal implantation.

We have developed a new interstitial HDR brachytherapy technique for the treatment of prostate cancer using CT based 3D planning after transrectal implantation of four non-parallel needles. CT based needle reconstruction, target definition, evaluation and documentation, including DVHs and 3D imaging, is a feasible, safe and well tolerated treatment concept.

Adenocarcinoma↗
PubMed1998

[Strategy for multimodal therapy of soft tissue sarcomas of the trunk and extremities].

The aim of surgical therapy for soft tissue sarcoma is local tumor control with the best possible functional result. Only small, superficial, well-differentiated or strictly intracompartmental lesions should be treated by surgery alone. In all other cases, especially for recurrent lesions, multimodality treatment strategies should be applied. For locally advanced lesions, neoadjuvant therapy can achieve tumor response. Aside from systemic chemotherapy and preoperative radiation therapy, isolated limb perfusion with tumor necrosis factor and melphalan can aid local control, and thus enable limb-sparing resection. The application of adjuvant systemc chemotherapy must be further investigated in prospective trials before a general recommendation can be given. If the patient has distant metastases, decisions regarding treatment of the local lesion must take into account quality-of-life aspects. Should complete resection not be possible, multimodality strategies may be able to control the tumor for a longer period.

Chemotherapy, Adjuvant↗
PubMed1997

Adjuvant chemotherapy for superficial transitional cell bladder carcinoma: long-term results of a European Organization for Research and Treatment of Cancer randomized trial comparing doxorubicin, ethoglucid and transurethral resection alone.

PURPOSE: We compared the efficacy of transurethral resection alone or transurethral resection followed by bladder instillations of doxorubicin or ethoglucid for 1 year in patients with superficial bladder carcinoma, and followed them long term for the incidence of progression to muscle invasion. MATERIALS AND METHODS: A total of 443 patients with superficial transitional cell carcinoma of the bladder was randomized. After randomization of 206 patients the control arm was closed to patient entry based on the results of an interim analysis showing a significant difference in favor of those receiving adjuvant chemotherapy. RESULTS: Final analysis of treatment results for recurrence included 432 patients at a median followup of 3.4 years for time to first recurrence, 5 years for analysis of time to invasion (Category T2 disease or worse) and 10.7 years for duration of survival. Time to first recurrence was significantly prolonged by both drugs compared to transurethral resection alone (doxorubicin versus transurethral resection alone p < 0.001 and ethoglucid versus control p < 0.001). Recurrence rate per year was 0.30 for both adjuvant treatment arms and 0.68 for the resection only group. Progression to muscle invasion was rare (15.1% of cases) and not apparently different in the 3 treatment arms. Of the 423 patients death from any cause in 199 and from malignant disease in 59 was not correlated with treatment. However, there was a strong correlation between death from malignant disease, and T category and tumor grade. CONCLUSIONS: In regard to time to first recurrence and recurrence rate per year this study indicates that adjuvant chemotherapy with doxorubicin and ethoglucid using the indicated schedule is superior to transurethral resection alone. However, progression in stage or survival was not influenced by the treatment regimen.

Aged↗
PubMed1990

Comparison of the effects of high dose Estramustine phosphate and mitomycin C on the time to progression and length of survival of patients with progressive, advanced endocrine-independent prostatic cancer: an interim analysis of EORTC-GU Group study no. 30865.

Patients with hormone escaped advanced progressive prostate cancer were randomized either to receive either high-dose Estramustine phosphate orally or Mitomycin C by i.v. injection every 6 weeks until signs of progression or death supervened. Patients on both arms progressed rapidly, with a median time to progression of 5 months and a median length of survival of only 10 months. Toxicity was very considerable in both arms.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Adjuvant chemotherapy of superficial transitional cell bladder carcinoma: preliminary results of a European organization for research on treatment of cancer. Randomized trial comparing doxorubicin hydrochloride, ethoglucid and transurethral resection alone.

Patients with superficial transitional cell carcinoma of the bladder were entered in a randomized clinical trial to compare the efficacies of transurethral resection alone or followed by bladder instillation of doxorubicin hydrochloride or ethoglucid (Epodyl) for 1 year. Results showed that adjuvant chemotherapy with the selected drugs prolonged the mean interval between recurrences. Mild systemic toxicity and chemical cystitis were observed in 3 and 3 per cent, respectively, of the patients given ethoglucid, and in 5 and 4 per cent, respectively, of those taking doxorubicin.

Carcinoma, Transitional Cell↗
PubMed1982

Phenotypic modulation of the canine prostate after long-term treatment with androgens and estrogens.

Fine structural alterations of the canine prostate induced by long-term treatment of castrated adult animals with estrogens and/or androgens and also in combination with antiandrogens and/or antiestrogens for six months have been studied with particular respect to their topographic location within the gland. Three major patterns of structural responses of the epithelium have been distinguished: squamous metaplasia, atrophy, and hypertrophy, while in stroma, regression, hypertrophy, or sclerosis were observed. In addition to cellular alterations of stromal fibrocytes and smooth muscle cells, characteristic changes in the arrangement, distribution, and pattern of the different stromal elements occurred. General squamous metaplasia of the epithelium and regressive alterations of stromal cells were most obvious in animals treated with estradiol plus androstanediol. Atrophy of the epithelium and stromal sclerosis were the salient features of antiandrogen-treated castrated animals, while hypertrophy or hyperplasia of both the epithelium and stroma was a major finding in androstanediol-substituted castrated animals. Combined treatment caused rather heterogeneous structural patterns seemingly dependent on the location within the gland. The results indicate that the prostatic epithelial cells dispose of a broad variety of structural reaction patterns that, in case of combined hormonal treatment, are expressed in a manner typical for their locations within the ductal system of the gland. However, with the exception of combined treatment with estradiol, tamoxifen, and androstanediol of castrated dogs, none of the experimental protocols used induced a morphologic response of the gland comparable to that seen in human benign prostatic hyperplasia. The canine prostate therefore is of rather limited value as a model for human BPH.

Androgens↗
PubMed1980

Fine structure of the canine prostatic complex.

The canine prostatic complex, including the prostatic urethra, the urethral openings of the prostatic gland ducts, the prostate gland proper and the ejaculatory ducts has been studied with the transmission and scanning electron microscopes. The urethral epithelium was found to be a modified transitional epithelium; it extended a short distance from the urethra into the orifices of the ducts where it gradually lost height. The columnar cells were replaced by cuboidal superficial cells in the terminal ducts of the gland. With increasing distance from the urethral openings of the ducts, the superficial cuboidal cells developed secretory activity and finally were indistinguishable from regular prostatic secretory cells. The latter formed typical prostatic acini, consisting of secretory cells which were merocrine in nature, and flat lentilate basal cells. In addition to exocrine cells, three different types of presumptive endocrine cells occurred, predominantly in the periurethral ducts of the prostate gland. It has been concluded from this study that, firstly, fluid absorption and spermatophagy are the main functions of the epithelia of the ejaculatory ducts and the ampulla of the vas deferens. Secondly, it has been concluded that the different functions of the various structures of the prostatic complex can be related to their different embryological origins.

Animals↗
PubMed1980

Effects of cyproterone acetate on experimentally induced canine prostatic hyperplasia. A morphological and histochemical study.

The effect of 3 alpha-androstanediol (3 alpha-diol), 17 beta-estradiol (E2) and cyproterone acetate (CA) on prostates in castrated beagle dogs were investigated by histological and histochemical examinations. A significant increase of prostatic weight occurred after 6 months' treatment with 3 alpha-diol alone and in combination with E2. Histologically and histochemically, two different types of prostatic enlargement were observed: first, administration of 3 alpha-diol resulted in diffuse glandular hyperplasia with replacement of functional activity monitored by strongly positive reactions for acid phosphatase, aminopeptidase and zinc. Second, 3 alpha-diol plus E2 produced stratified squamous metaplasia with cystic lumina and loss of the typical morphological structure. These glands showed negative reactions for acid phosphatase, aminopeptidase and zinc. In both types of prostatic hyperplasia CA abolished epithelial or metaplastic proliferation and induced atrophy of glandular epithelium. In estrogenized dogs activation of the fibromuscular stroma was obvious. CA prevented prostatic hyperplasia by atrophying epithelial effects.

Acid Phosphatase↗
PubMed1979

[Concentrations of cefradine in renal tissue (author's transl)].

After a single bolus injection of two grams of cefradine the concentrations of antibiotic in serum and renal tissues of 21 patients were estimated. After 30 minutes the mean serum concentrations were 159 microgram/ml, after 60 mins 62 microgram/ml and after 95 mins 22 microgram/ml. The tissue concentrations in normal renal tissue (group I) after 30 minutes were 348 microgram/ml and with tissue of chronically inflamed kidneys (group II) 118 microgram/ml in the same period. After 90 minutes the concentrations of group I were 214 microgram/g, and in group II 28 microgram/g, e.g. 8 times lower. The estimated cefradine concentrations in serum and in normal and impaired renal tissue within the time interval of 10 to 90 minutes are above the minimal inhibition concentrations for most cefradine sensitive pathogens.

Cephalosporins↗
PubMed1979

Role of the pituitary gland in experimental hormonal induction and prevention of benign prostatic hyperplasia in the dog.

The antiandrogen, cyproterone acetate (CPA), prevents development of prostatic hyperplasia, induced in castrated dogs by a 6 month-treatment with 5 alpha-androstane-3 alpha, 17 beta-diol (A)alone or in combination with 17 beta-oestradiol (E2). The immunoperoxidase technique was used to study functional cell types in the pars distalis of the pituitary gland and to detect growth hormone (GH) and prolactin (PRL) target sites in the prostate gland. Homologous radioimmunoassays for estimation of serum canine GH and PRL concentrations were also performed. Treatment with the combinations A + E2 and A + E2 + CPA resulted in morphological indications of stimulated GH and PRL cells and depressed gonadotrophs. This correlates well with an increase in PRL-dependent staining in glandular epithelium and fibromuscular tissue of the prostate gland. However, basal serum PRL and GH levels were not significantly affected. Treatment with A and A + E2 stimulated, while additional treatment with CPA clearly suppressed adrenocorticotrophin/melanotrophin (ACTH/MSH) cells. These findings indicate that an endocrine imbalance in hypothalamic-pituitary-adrenal function may be involved in induction and prevention of prostatic hyperplasia in the dog.

Androstane-3,17-diol↗
PubMed1979

Biochemical and histological studies on prostates in castrated dogs after treatment with androstanediol, oestradiol and cyproterone acetate.

The effect of cyproterone acetate (CA) on experimentally induced benign prostatic hyperplasia (BPH) in the castrated dog was investigated. BPH was induced by 6 months' treatment with 3 alpha-androstanediol (3 alpha-diol) alone and in combination with 17 beta-oestradiol (Oe2). RNA, DNA and zinc content of the glands were determined in addition to histological examination and measurement of the prostates. Two different types of prostatic enlargement were observed. First, 3 alpha-diol induced typical diffuse canine hyperplasia with replacement of functional activity. DNA, RNA and the zinc content of total glands were increased compared with intact controls. Second, 3 alpha-diol plus Oe2 produced on the one hand a more striking increase of prostatic weights, but on the other a loss of typical morphological structure and function. Histologically, transformation of simple glandular epithelium into stratified squamous metaplasia occurred in addition to stimulation of fibromuscular tissue. Biochemically, a relative decrease of DNA per mg tissue was measured with a fall in the RNA to DNA ratio and zinc to the values of castrates. Administration of CA resulted in an abolition of the 3 alpha-diol effect. Biochemical determinations and histological examinations revealed an effect similar to castration after treatment with 3 alpha-diol plus CA. After treatment with 3 alpha-diol plus Oe2 plus CA fibromuscular stimulation as an oestrogen effect predominated in addition to glandular atrophy and metaplastic changes, especially in prostatic ducts. Epithelial hyperplasia is an effect of 3 alpha-diol, whereas metaplastic proliferation only occurs in oestrogenized and androgenized dogs. In both types of prostatic enlargement CA prevents development of hyperplastic prostate.

Androstane-3,17-diol↗
PubMed1979

[Lipid A antibody titers in patients after ureterosigmoidostomy (author's transl)].

Lipid A antibody titers were determined over a period of 6 months by passive hemolysis test in 10 patiens who underwent cystectomy and ureterosigmoidostomy. Preoperative the sera of all patients had no detectable anti lipid A activity. After 4 weeks 4 patients showed significant elevation of lipid A antibody titers. Only in these 4 patients the titers remained elevated up to six months. The significant elevation of lipid A antibody titers in these patients were caused by a non-obstructive infection of the kidneys. The serological determination of lipid A antibody titers appears to be an appropriate method for detecting pyelonephritis after ureterosigmoidostomy.

Aged↗