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M Kuczyk

Publications and source records attributed to M Kuczyk.

52 records · Page 3Linked to original sources
PubMed1998

[Molecular pathogenesis and prognostic factors in testicular tumor].

Aim of this review article was to critically analyse the recently described zytogenetic and molecular markers for testicular germ cell tumors with regard to their clinical utility. The isochromosome i(12p) represents the most common and characteristic cytogenetic finding which already appears in testicular carcinoma in situ. A number of proto-oncogenes (Cyclin D and PTHLH) as well as putative tumor suppressor genes are localized on 12p; however, their role in pathogenesis and prognosis of testicular germ cell tumors has not been defined yet. Clinical characteristics of patients with familial testicular germ cell tumors indicate a genetic background for the development of testicular tumors. Although a number of chromsomal loci encoding potential testicular tumor susceptibility genes have been identified, the genetic basis of testicular cancer pathogenesis is still unknown. With regard to molecular prognostic risk factors most of the reported data on proliferation markers, tumor suppressor genes, proteases and adhesion molecules have to be confirmed in prospective randomized trials prior to their widespread clinical use. Based on the available data on prospective studies percentage of embryonal carcinoma and vascular invasion appear to be the most significant prognosticators. Investigation and identification of those factors determining the aggressive biologic behavior of embryonal carcinoma compared to all other histological components appear to be most promising in research for prognosticators of metastatic disease. In conclusion, the increasing knowledge of molecular genetic events involved in pathogenesis and prognosis of testicular germ cell tumors will not only help to better understand development and progression of testicular cancer, but it also will define new approaches to classification and management of germ cell tumors.

Cell Transformation, Neoplastic↗
PubMed1998

Urodynamics and transurethral microwave thermotherapy.

In this paper the role and value of urodynamic measurements in symptomatic benign prostatic hyperplasia (BPH) patients selected for transurethral microwave thermotherapy (TUMT) reviewed. Although pressure-flow studies alone can diagnose benign prostatic obstruction, the level of acceptance of urodynamic investigations in BPH remains low, reportedly due to their cost and to their invasive and time-consuming nature. Furthermore, the observation that extremely different treatment modalities in BPH have nearly the same symptomatic outcome, independently of their influence on obstruction, has played a part in raising doubt as to the value of baseline urodynamics as a predictor of clinical success. Pre- and posttherapy urodynamic investigations in TUMT-treated patients have shown that urodynamic algorithms must be capable of distinguishing between compressive and constrictive types of obstruction to document the limited effects of low-energy TUMT on obstruction. Furthermore, it has been shown that urodynamics evaluated in this way seems to be the only predictor of the clinical success of TUMT when improvements in the objective parameters Qmax (peak uroflow) and residual urine are included in the definition of outcome.

Diathermy↗
PubMed1998

Expression of E-cadherin in primary prostate cancer: correlation with clinical features.

OBJECTIVE: To correlate the immunohistochemically detected loss of E-cadherin expression with patient age, clinical and biological variables, and to investigate the prognostic value of these variables for the relapse-free and overall survival of patients with different stages of newly diagnosed prostate cancer. PATIENTS AND METHODS: Sixty-seven patients (median age 63 years, range 48-78) undergoing radical prostatectomy for the treatment of primary prostate cancer were assessed to determine whether age, tumour stage, histological grading, serum levels of prostate specific antigen and prostatic acid phosphatase, regional lymph node status and E-cadherin expression were prognostic factors for relapse-free and overall survival. RESULTS: With a median (range) follow-up of 54 (3-193) months, there was no independent prognostic value of decreased E-cadherin expression for the long-term or recurrence-free survival of patients, using a threshold value of 40% for the relative amount of positively stained tumour cells, or for any other threshold value calculated (25%, 60% or 75%). However, comparing a follow-up of 16 months in patients with < 40% positivity and 46 months in patients with > or = 34% positivity, those patients retaining E-cadherin expression had a significantly longer recurrence-free interval after radical prostatectomy (P < 0.01). CONCLUSION: The value of E-cadherin expression as an additional independent prognostic variable for patients with primary prostate cancer is questionable.

Adenocarcinoma↗
PubMed1998

Secondary leukemia following high cumulative doses of etoposide in patients treated for advanced germ cell tumors.

PURPOSE: High cumulative epipodophyllotoxin dosages are reported to be associated with an elevated risk for secondary acute myeloid leukemia (s-AML). This study examined the risk of s-AML following cumulative etoposide doses greater than 2 g/m2 in patients with metastatic germ cell tumors (GCT). PATIENTS AND METHODS: The incidence of s-AML was retrospectively assessed in patients treated within clinical trials between January 1986 and February 1996 at four university centers. All patients received high-dose chemotherapy (HDCT) plus autologous stem-cell support for metastatic GCT, including high cumulative etoposide doses (> 2 g/m2). Minimum patient follow-up was 12 months. Standardized morbidity ratio (SMR) was calculated to estimate the risk associated with high cumulative etoposide doses, as compared with the general population. RESULTS: A total of 302 patients with a median age of 29 years (range, 15 to 55) received a median cumulative etoposide dose of 5 g/m2 (range, 2.4 to 14 g/m2). Four cases of s-AML were observed, which resulted in a cumulative incidence of 1.3% (95% confidence interval [CI], 0.38% to 3.59%) at 52 months of median follow-up (range, 12 to 198). Two cases of secondary myelodysplasia (s-MDS) developed in patients with primary mediastinal GCT. Based on the observed four cases of AML, which are most likely etoposide-related, the risk for developing s-AML (SMR, 160 [95% CI, 43.7 to 411.2]) is significantly increased in comparison to the age-matched general population. CONCLUSION: Due to the low incidence of AML in the general population, the significantly elevated risk for developing s-AML affects only 1.3% of all patients who receive etoposide doses greater than 2 g/m2. HDCT, including etoposide doses greater than 2 g/m2, is associated with an acceptably low incidence of s-AML in patients with advanced GCT.

Acute Disease↗
PubMed1997

Surgery for metachronous solitary liver metastases of renal cell carcinoma.

PURPOSE: The postoperative outcome and survival of patients undergoing surgery for metachronous solitary liver metastases of renal cell carcinoma were evaluated. MATERIALS AND METHODS: Between 1983 and 1993, 17 patients with metachronous liver metastases of renal cell carcinoma underwent laparotomy for metastatic liver disease. All patients had undergone radical nephrectomy a mean of 3.6 years before the diagnosis of liver metastases. RESULTS: Surgical resection was feasible in 13 of 17 patients with right hemihepatectomy in 9 (3 multivisceral resections), wedge resection in 4 and ex situ (mobilization and eversion out of the abdomen) resection in 1. Stage R0 resection (complete removal, negative surgical margins with no macroscopic disease left behind) was possible in 11 of 13 cases (85%). In patients with metastatic liver tissue resection the mortality rate was 31% (4 of 13) with additional significant morbidity in another 2. Mean survival of patients with nonresectable disease was 4 months, which increased to 16 months after resection. CONCLUSIONS: Complete resection of metachronous liver metastases can be achieved in the majority of patients. However, significant morbidity and mortality as well as the limited prognosis even after R0 resection strongly suggest careful patient selection.

Adult↗
PubMed1996

Effects of various phosphodiesterase-inhibitors, forskolin, and sodium nitroprusside on porcine detrusor smooth muscle tonic responses to muscarinergic stimulation and cyclic nucleotide levels in vitro.

The cyclic nucleotides cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) are second messengers involved in the regulation of contractility in various smooth muscle organs including detrusor smooth muscle. They are synthesized by activation of adenylate and guanylate cyclases, respectively, and inactivated by phosphodiesterases (PDEs). In order to delineate the intracellular regulation of porcine detrusor contractility by cyclic nucleotides and phosphodiesterases, functional organ bath studies and determinations of intracellular cyclic nucleotide contents were performed after incubation of porcine detrusor strips with forskolin (adenylate cyclase activator), sodium nitroprusside (guanylate cyclase activator), and various phosphodiesterase-inhibitors. Significant relaxant responses were achieved only by forskolin, the nonspecific phosphodiesterase-inhibitor papaverine, and the phosphodiesterase 1-inhibitor vinpocetine (62.4 +/- 5.6%, 73 +/- 4.3%, and 53 +/- 7.9%, respectively). Sodium nitroprusside and the selective PDE-inhibitors milrinone, rolipram, zaprinast, and dipyridamole were significantly less efficacious (26.9 +/- 3.9%, 15.5 +/- 3.8%, 15.3 +/- 3.0%, 13 +/- 4.0%, and 13.2 +/- 2.1%, respectively). Forskolin, papaverine, and vinpocetine elevated intracellular cAMP concentrations (7.3-, 1.9-, and 1.7-fold increase at 100 microM, respectively), whereas the other substances failed to enhance cAMP levels. cGMP levels were only increased by sodium nitroprusside (7.8-fold). The adenylate cyclase-cAMP system seems to be the more important signal transduction system involved in the relaxation of carbachol induced smooth muscle tone of the porcine detrusor. The role of the guanylate cyclase-cGMP system is less clear. In addition, the calcium/calmodulin-stimulated PDE I seems to be of major functional importance in regulating cAMP hydrolysis in the porcine detrusor smooth muscle in vitro.

Adenylyl Cyclases↗
PubMed1996

Cyclic nucleotide phosphodiesterase (PDE) isoenzymes in the human detrusor smooth muscle. I. Identification and characterization.

Phosphodiesterases (PDEs) are key enzymes involved in the regulation of intracellular cyclic nucleotide metabolism. The aim of the present study was to identify and to characterize the PDE isoenzymes present in the human detrusor smooth muscle. Human detrusor PDE isoenzymes were separated by Q-Sepharose anion exchange and calmodulin-agarose affinity chromatography and characterized upon their kinetic characteristics and their sensitivity to allosteric modulators and inhibitors. All five presently known PDE isoenzyme families were identified: one high-affinity, low-Km calcium/calmodulin-stimulated PDE I with a slight preference for cGMP over cAMP, one cGMP-stimulated PDE II, one cGMP-inhibited PDE III, one cAMP-specific PDE IV and one cGMP-specific PDE IV. All five known PDE isoenzyme families exist in human detrusor smooth musculature. The kinetic characteristics, together with functional in vitro studies, suggest that the PDE I may be of importance in the intracellular regulation of the human detrusor smooth muscle tone.

Anion Exchange Resins↗
PubMed1996

Prostate-specific antigen density--a reliable parameter for the detection of prostate cancer?

We compared the prostate-specific antigen density (PSAD) in clinically and surgically staged patients with specimen-confined prostate cancer (n = 57) and in patients with benign hyperplasia (n = 69), who underwent transvesical adenomectomy. The PSAD was calculated from the preoperative PSA level and the specimen volume. The prostate volume was determined by dividing the prostate weight by the specific gravity of the tissue. The mean tissue values used for PSAD calculation were 51.9 g in men with prostate cancer (PCA) and 62.9 g in men with benign prostatic hyperplasia (BPH). The PSAD values showed significant differences (BPH 0.19 versus PCA 0.37, P = 0.029). Receiver operator characteristic (ROC) curves demonstrated the best cutoff value to be 0.15, with the sensitivity being 58%; the specificity, 51% and the positive predictive value of PCA, 49%. At a serum PSA level below 10ng/ml, the best cutoff value was 0.1 and the positive predictive value was 51%. The PSAD results we calculated from an accurate prostate volume (surgical estimate) show that PSAD is not a significant predictor of prostate cancer.

Aged↗
PubMed1995

Denovo urothelial carcinoma of the upper and lower urinary tract in kidney--transplant patients with end-stage analgesic nephropathy.

Patients with end-stage analgesic nephropathy bear a higher risk for urothelial cancer than do patients with other renal diseases. In a retrospective study in patients with analgesic nephropathy and kidney transplants we analyzed the prevalence and clinical course of de novo urothelial cancer. Diagnosis of analgesic nephropathy was based on the patients' history and clinical data. Only patients under cyclosporine treatment were included. Between 1968 and 1993, 2,371 kidney transplants were performed on 2,072 patients in the Department of Abdominal and Transplant Surgery. The prevalence of analgesic nephropathy was 3.1%. Of 65 patients with analgesic nephropathy and kidney transplants, 10 (15.4%) developed urothelial carcinoma; 10.8%, bladder cancer; and 9.1%, renal pelvic cancer. The mean age at diagnosis was 56.1 years. Urothelial cancer occurred on average at 33.6 months posttransplantation. On average, 6 of 10 patients with urothelial cancer died of the disease at 16.9 months after the diagnosis. All patients with urothelial bladder cancer had a muscle-infiltrating tumor of moderate or high grade. Since urothelial renal pelvic cancer occurred in 9.1% of our patients with analgesic nephropathy and urological screening is insufficient in patients on dialysis, we suggest that prophylactic nephroureterectomy be performed on one side before transplantation and on the contralateral side at 3-6 months after transplantation. An aggressive approach is indicated in patients with urothelial cancer of the bladder.

Analgesics↗
PubMed1995

Renal-cell carcinoma with intracaval neoplastic extension: stratification and surgical technique.

Surgical removal continues to be the mainstay in the treatment of renal-cell carcinoma with neoplastic venous extension. The steady improvement of surgical and anesthesiological techniques and the introduction of complete circulatory arrest has dramatically improved the morbidity even of patients with extensive thrombi. If ultrasound or computerized tomography (CT) scanning suggests the presence of a venous extension in a patient with renal-cell carcinoma, cavography, magnetic resonance imaging (MRI), transesophageal color-coded ultrasound, and echocardiography may be needed to resolve the questions of cranial extension and vascular wall infiltration. Surgical stratification and, thus, classification of the venous extension depend on the potential need for complete circulatory arrest. Surgical removal is done en bloc for smaller venous extensions and in a two-step procedure (radical nephrectomy followed by thrombectomy) for more extensive thrombi. In patients with infiltration of the suprahepatic inferior vena cava, the hepatic veins or atrium, pending thrombotic embolism, or large masses of suprahepatic thrombotic material, the use of cardiopulmonary bypass and complete circulatory arrest is recommended.

Aged↗
PubMed1995

[Thermotherapy of benign prostatic hyperplasia].

Transurethral microwave thermotherapy (TUMT) differs from hyperthermia in the higher intraprostatic temperatures reached and in the irreversible damage it causes to intraprostatic tissue. Both subjective symptoms and objective data, such as peak flow and residual urine, are influenced differently by TUMT and by sham treatment. As expected, no improvement of the objective data was documented with TUMT, in contrast to transurethral resection of the prostate (TURP), whereas the improvement in subjective symptoms was comparable. The complication rate in terms of morbidity is clearly lower with TUMT than with TURP. TUMT can be performed as an outpatient procedure without a general anaesthetic. TUMT had a specific effect on outflow obstruction, but it was less pronounced than that achieved with TURP. Therefore, TUMT is indicated for patients with typical symptoms of BPH and a mild mechanical obstruction. In this patient group TUMT seems to be the optimal treatment, whereas TURP would constitute "overtreatment" owing to its higher complication rate and the unnecessary tissue resection. At this stage of BPH, TURP is justifiable only with reservations; it should be reserved for BPH with moderate and severe mechanical obstruction.

Follow-Up Studies↗
PubMed1994

Long-term gonadal toxicity after therapy for Hodgkin's and non-Hodgkin's lymphoma.

With the increasing cure rate of patients treated for Hodgkin's and non-Hodgkin's lymphoma, the evaluation of late effects on gonadal function remains an important issue. The gonadal function of relapse-free long-term survivors with high-grade non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) were studied; 24 of 119 patients with NHL treated between 1980 and 1990 and 66 of 364 patients with HD treated between 1975 and 1990 at Hannover University Medical School, who were younger than 45 years of age and in complete remission at the time of evaluation for at least 24 months after completion of therapy, were included into the analysis. Of 24 patients with NHL, 1/10 women (10%) and only 3/14 men (21%) showed signs of gonadal dysfunction. Three of these four patients had been treated with combined modality therapy followed by maintenance COP chemotherapy, resulting in high cumulative doses of cyclophosphamide (range: 12-43 g). In comparison, 13/26 (50%) women with HD suffered from premature ovarian failure, and 26/40 (65%) men showed signs of gonadal dysfunction with significant FSH elevations. No significant difference in the incidence of gonadal toxicity existed in patients treated with combined modality who received irradiation to either supra- or infradiaphragmatic radiation fields in combination with chemotherapy (70% versus 62%). A comparison of the chemotherapy regimens used in patients with NHL or HD shows that patients from both groups had received comparable median cumulative doses of cyclophosphamide, vincristine, and adriamycin, but only patients with HD had additionally received a median cumulative dose of 13.3 g of procarbazine per patient. A tendency towards a higher incidence of gonadal toxicity with higher cumulative doses of procarbazine received was found in patients with HD. The frequency of gonadal dysfunctions is markedly lower in patients treated for non-Hodgkin's lymphoma than in patients treated for Hodgkin's disease, approximately half of whom will be affected by long-term gonadal toxicity. Although the use of more intensive radiotherapy in patients with HD compared with NHL patients makes the evaluation of the influence of radiotherapy on gonadal toxicity more difficult, the current retrospective analysis raises the concern that, in addition to infradiaphragmatic radiotherapy, the use of procarbazine in regimens for the treatment of HD, like COPP or MOPP, may be a possible explanation for the differences in gonadal toxicity observed between patients with HD and those with NHL. Regimens including procarbazine should be avoided in patients wanting to preserve fertility since alternative chemotherapies with at least equal efficacy are available.

Adolescent↗
PubMed1994

Intracavernous calcitonin gene-related peptide plus prostaglandin E1: possible alternative to penile implants in selected patients.

The implantation of a penile prosthesis is still the ultima ratio for patients with erectile dysfunction who fail other treatment options such as pharmacotherapy and penile venous surgery. Despite mostly favorable results regarding restoration of erectile capacity, penile allografts are often not accepted for various reasons. Therefore, pharmacotesting with a mixture of calcitonin gene-related peptide and prostaglandin E1 (CGRP/PGE1) was offered to different selected patients populations: 28 patients with erectile dysfunction and venous leakage who failed penile venous surgery, 28 patients with erectile dysfunction and venous leakage (who refused penile venous surgery) and 12 patients without venous leakage, but poor response to maximum doses of papaverine/phentolamine, received 5 micrograms CGRP plus 10 micrograms PGE1. Erections sufficient for intercourse were noted in 19/28 (67.9%), 20/28 (71.4%) and 11/12 (91.7%) patients, respectively. Our data show that a combination of CGRP and PGE1 may be an alternative to penile implants in selected patients.

Alprostadil↗
PubMed1993

Followup results of a combination of calcitonin gene-related peptide and prostaglandin E1 in the treatment of erectile dysfunction.

Recent human and animal studies have shown a possible role for calcitonin gene-related peptide in penile erection and a therapeutic benefit in combination with prostaglandin E1 for autoinjection therapy. The ethical committee approved calcitonin gene-related peptide-prostaglandin E1 combination for cases of nonresponse or cavernous fibrosis to papaverine-phentolamine. Since June 1990, 65 patients (59 nonresponders and 6 with fibrosis) were injected with 5 micrograms. calcitonin gene-related peptide plus 10 micrograms. prostaglandin E1. Of the 59 nonresponders to papaverine-phentolamine 31 and of the 6 patients with fibrosis 5 had full erectile response. Of these 36 patients 2 experienced pain during the pharmacologically induced erection. A total of 39 patients who had had at least 20 autoinjections of calcitonin gene-related peptide plus prostaglandin E1 was available for minimum followup. There were no side effects, such as pain (the 2 patients with pain mentioned previously were not included in the autoinjection therapy group), systemic side effects or (increased) fibrosis. Our results show that a combination of calcitonin gene-related peptide and prostaglandin E1 may be beneficial to the treatment of impotence in carefully selected patients.

Alprostadil↗
PubMedDate not supplied

Analysis of the cyclin-dependent kinase inhibitor p27Kip1 in muscle invasive bladder cancer.

It has been suggested that a deregulated cell cycle control contributes to the development of human malignancies due to the loss of critical antiproliferative mechanisms. The cell cycle is controlled at two checkpoints, one at the G1-S and another at the G2-M transition. Several genes including the structurally related p21WAF/CIP1 gene, the downstream mediator of the p53 tumor suppressor gene, and the p27Kip1 gene have been identified as inducers of cell cycle arrest at the G1 checkpoint when substantial DNA damage has occurred to avoid further replication of the altered genome. Recently, a heat stable 27 kDa protein, the transcript of the p27Kip1 gene, has been identified and was suggested to substantially participate in cell cycle control at the G1 checkpoint. Previous investigations have correlated decreased expression of the p27Kip1 protein with an increased biological aggressiveness of breast and small cell lung cancer. However, the molecular-genetic analysis of a variety of human malignancies including prostate cancer failed to identify any alteration at the p27Kip1 gene locus, therefore suggesting a loss of p27Kip1 protein expression to result from post-transcriptional/post-translational events or from so far unknown regulatory mechanisms. So far, bladder cancer specimens have neither been investigated for p27Kip1 alterations on the DNA level, nor has the result of molecular genetic analysis been correlated with an immunohistochemically detected expression of the gene product, the p27Kip1 protein. The present study is the first to describe p27Kip1 gene alterations on the DNA level in 3 of 42 muscle invasive bladder cancer specimens. In contrast, loss of p27Kip1 protein expression was observed in 14 of 42 (33%) tumors. According to the previously reported observation in a variety of human malignancies, in bladder cancer loss of p27Kip1 protein expression seems to result from post-transcriptional or post-translational events.

Adult↗