Biomedical subjects

U Jonas

Publications and source records attributed to U Jonas.

At least 145 records · Page 8Linked to original sources

PubMed1997

[Dorsal ligation of the penile vein--prognostic factors and long-term outcome].

Poor longterm success has been reported for penile vein ligation the last few years. Therefore, we decided to re-investigate our group of 147 patients who were operated on between 1987 and 1996. All patients showed a negative response to intracavernous injection therapy at the time of diagnosis and revealed a maintenance flow > 15 ml/min, as well as a pathological venous flow with pharmacocavernosometry or pharmacocavernosography. These patients underwent ligation of all superficial dorsal veins and resection of the deep dorsal vein of the penis. An up-to-date record of the success of the operation was kept either by a renewed clinical visit or by a standardized telephone interview or questionnaire. A total of 126 patients were available here for long-term follow-up. We divided the findings into three groups: complete spontaneous erection, postoperative response to cavernous autoinjection therapy and no changes in erectile competency postoperatively. The short-term success rate for these groups after 1-3 months was an outcome of 31 (24.6%), 25 (19.8%) and 70 (55.6%) patients; 86% of the cases whose results deteriorated after the initial operation success rate had this happen within the first postoperative year (p < or = 0.001). Favorable prognostic factors were preoperative erectile dysfunction of < or = 7 years, a normal CC-EMG and a maintenance flow of < or = 45 ml/min. If all three parameters were present, the long-term success rate (spontaneous erection plus response to intracavernous injection) of 30% of all patients was found to rise to 67% in this selected group of patients (p < or = 0.001). This study reveals that long-term success for unselected patients undergoing penile venous surgery is disappointing; however, careful selection of patients by certain prognostic factors can improve long-term results.

Adult↗

PubMed1997

Long-term results following dorsal penile vein ligation in 126 patients with veno-occlusive dysfunction.

One hundred and forty-seven patients who had dorsal penile vein ligation (DPVL) between 1987 and 1996 were re-investigated either during clinical consultation or by standardised telephone interview respectively questionnaire. One hundred and twenty-six patients were available for long-term follow-up. Postoperative outcome was classified into complete spontaneous erection, postoperative response to pharmacotherapy or no satisfactory improvement. The short-term success after 1-3 months according to this classification was 31 (24.6%), 25 (19.8%) and 70 (55.6%). These results were found to have deteriorated on long-term observation; with only 14 (11.2%), 24 (19.0%) and 88 (69.8%) respectively. Positive prognostic factors were preoperative duration of erectile dysfunction of < or = 7 y, a normal CC-EMG and a maintenance flow of < or = 45 ml/min. With all three parameters present, longterm success (spontaneous erection plus responder to intracavernous injection) rose from 30 to 67% in this selected group (P < or = 0.001). Our study shows that long-term success for unselected patients undergoing DPVL is disappointing; however, careful patient selection significantly improves long-term results.

Electromyography↗

PubMed1997

Prognostic relevance of intracaval neoplastic extension for patients with renal cell cancer.

OBJECTIVE: To assess the diagnosis of vena caval thrombosis (VCT) in patients with renal cell carcinoma (RCC) as an independent indicator of prognostic importance and when combined with additional tumour characteristics in a controlled multivariate analysis. PATIENTS AND METHODS: The clinical course of 53 patients (41 men and 12 women, mean age 60 years, range 35-79) with RCC and VCT was compared with that of a control group of 47 patients (37 men and 10 women, mean age 57 years, range 32-76) with RCC but no neoplastic extension into the vena cava. RESULTS: With a follow-up of 1-154 months and a mean long-term survival of 32 and 35 months, respectively, for patients with and without VCT, neither the propagation of the tumour into the vena cava (P = 0.391) nor the cranial extension of the thrombosis (P = 0.158) were identified as having any prognostic value during univariate or multivariate statistical analysis. The presence of regional lymph node (P < 0.001) or distant metastases (P = 0.009) was an independent prognostic variable for patients with RCC, with a significant decrease in long-term survival (13 and 14 months for patients with lymph node and distant metastases, respectively). CONCLUSION: A radical surgical approach is essential as standard therapy for the treatment of patients with RCC and neoplastic extension into the vena cava. Because they have a significantly decreased life expectancy, asymptomatic patients with lymph node or distant metastases should be treated conservatively.

Adult↗

PubMed1997

Computer-assisted evaluation of the smooth-muscle electromyogram of the corpora cavernosa by fast Fourier transformation.

OBJECTIVE: The aim of our study was to investigate analogous and digital recording of corpus cavernosum EMGs (CC-EMGs) in normal men according to criteria that were recently agreed upon in an international consensus workshop. METHODS: CC-EMGs were analogously and digitally registered from 37 normal subjects. Power spectra in the frequency domain were determined via fast Fourier transformation (FFT). RESULTS: Thirty-one of men showed identical or at least very similar electrical activity patterns in the analogous and digital registration. Needle penetration artifacts (investigated in 18 subjects) were found in 17/18 CC-EMGs during the first 20 min. Power spectra show a maximum of power at a frequency of 0.3 Hz with more than 90% of the power located between 0 and 5 Hz. CONCLUSIONS: Registration of CC-EMGs in normal men resulted in interindividually reproducible recordings. Age hardly affected CC-EMGs. Computer-assisted evaluation by FFT after elimination of artifacts was feasible. Thus, interpretation of the CC-EMG signals by a computer-aided expert system seems to be promising for clinical routine, in particular with respect to an increase in objectivity and a decrease in time needed for interpretation.

Adolescent↗

PubMed1997

[Pharmacological therapy in erectile dysfunction--current standards and new viewpoint].

Intracavernous pharmacotherapy of erectile dysfunction has been established for over 10 years, with prostaglandin E1 (PGE1) being the standard substance with the lowest rate of side effects. Recent investigations deal with the identification of intracellular mechanisms of smooth muscle relaxation in cavernous tissue as the most important aspect of penile erection. Nitric oxide and specific phosphodiesterase-isoenzymes seem to play a central role. This resulted in clinical studies with the intracavernous injected nitric oxide-donor linsidomine (SIN 1) and the orally given phosphodiesterase-inhibitor sildenafil. Furthermore new ways of pharmaco-application are tested, e.g. transdermal treatment with nitroglycerin, minoxidil or papaverine, as well as intraurethral injection of prostaglandin E1.

Alprostadil↗

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↗

PubMed1997

Corpus cavernosum electromyography: technique and clinical implications.

Recently, corpus cavernosum EMG (CC-EMG) has been introduced into the diagnostic evaluation of erectile dysfunction. It has been demonstrated that CC-EMG may be a valuable tool in the evaluation of the integrity of the autonomic innervation of the corpus cavernosum. The interpretation and comparison of the recorded data still remains problematic due to a lack of standardization of recording procedures, technical equipment and of data analysis software. The assessment of recorded data was originally performed visually and nonquantitatively, however, more recently, computer-aided analysis of digitized measurements has proved to be more objective, less time-consuming and more reliable. Future efforts should be aimed at creating larger databases and differentiating between the various sources of lesions within the autonomic neural network of the corpus cavernosum.

Electromyography↗

PubMed1996

Alterations of the p53 tumor suppressor gene in carcinoma in situ of the testis.

BACKGROUND: Carcinoma in situ (CIS) is regarded as the precursor of all histologic variants of testicular germ cell tumors except spermatocytic seminoma. For a variety of human malignancies, alterations of the p53 tumor suppressor gene have been identified as prognostic factors for a poor clinical course. Discussions of the occurrence of p53 gene alterations in testicular carcinoma have been controversial. Immunohistochemical detection of the p53 oncoprotein has been reported in four of eight CIS cell areas adjacent to mature teratoma. The majority of investigations have failed to demonstrate p53 gene alterations on the DNA level in testicular carcinoma specimens. However, the genetic analysis of testicular carcinoma is complicated by the histologic variety of tumors, resulting in a mixture of subtypes undergoing moleculargenetic analysis. In the present study, CIS cells identified in normal testicular tissue adjacent to different testicular tumors were examined for alterations of the p53 tumor suppressor gene. The authors believed that the detection of p53 alterations in CIS of the testis would not only support the idea of malignant potential in CIS but might also demonstrate the involvement of the p53 tumor suppressor gene in the development of germ cell cancers. METHODS: CIS cells were identified in the normal testicular tissue adjacent to 18 seminomatous and nonseminomatous germ cell tumors by histopathologic criteria and the immunohistochemical staining reaction for placental-like alkaline phos phase, a highly specific marker for testicular CIS. About 20-50 CIS cells per tumor were collected by a microdissection technique and were subjected to RNA. SSCP analysis and additional DNA-sequence analysis. RESULTS: In 12 of 18 cases (66%), RNA-SSCP analysis of the microdissected CIS cells revealed mutational band shifting at the p53 gene locus. In 7 of 18 cases (39%). the results of SSCP analysis were confirmed by DNA sequencing. DNA-sequence analysis revealed missense point mutations in the p53 gene in four cases (exon 5, codons 158, 170, and 176; exon 6, codon 213) and silent mutations in two cases (exon 5, codon 178; exon 6, codon 213). In one case, the identical missense point mutation (exon 5, codon 176) was detected in the CIS cells and also in the associated germ cell tumor. In two of six cases, different mutations were found in the CIS cells and the testicular tumor. In three cases in which DNA sequencing revealed point mutations in CIS cells, alterations of the p53 gene could not be detected in the examination of the associated tumor specimen. CONCLUSIONS: These findings appear to support the concept that malignant biologic characteristics are present in the in situ stage of testicular germ cell tumors. This is the first report demonstrating monoclonal development of a manifested testicular carcinoma from associated CIS cells on the basis of a certain mutational event in the p53 gene sequence. The involvement of p53 gene alterations in precursor cells of testicular carcinoma appears likely.

Alkaline Phosphatase↗

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

The role of paclitaxel in chemosensitive urological malignancies: current strategies in bladder cancer and testicular germ-cell tumors.

Recent results demonstrate an emerging role for paclitaxel in patients with urothelial-tract cancer and in patients with testicular cancer. Yielding response rates in the range of 40-50% as a single agent, paclitaxel is one of the most active drugs in metastatic bladder cancer. Ongoing trials of paclitaxel combination chemotherapy with cisplatin or cisplatin and ifosfamide demonstrate substantial objective remission rates above 70% and, in addition, a high range of complete responses. Thus, paclitaxel appears to be an important drug when used as part of first-line combination chemotherapy for metastatic bladder cancer. Ongoing clinical trials focus on the combination of paclitaxel with cisplatin, ifosfamide, gemcytabine, and carboplatin. Furthermore, paclitaxel administration has been demonstrated to be easily applicable to patients with reduced renal function, requiring no dose reduction and producing no increase in toxicity. Future strategies will have to compare the most active paclitaxel combination regimen with first-line MVAC (methotrexate, vinblastine, adriamycin, cisplatin) chemotherapy. Finally, the role of paclitaxel combination regimens needs to be explored in the adjuvant and neoadjuvant setting in patients with bladder cancer. In testicular cancer, paclitaxel has initially been tested in patients with cisplatin-refractory disease. Among 4 consecutive trials involving a total of 83 patients a response rate of 26% has been observed using dose schedules varying from 3-h to 24-h infusions and doses ranging from 175 to 250 mg/m2. The major toxicities of paclitaxel include neutropenia, neurotoxicity, and fatigue syndrome. Currently, combinations of paclitaxel with cisplatin +/- ifosfamide are used as first- or second-line salvage therapy in patients with relapsed metastatic testicular cancer. The German Testicular Cancer Study Group uses a paclitaxel (Taxol, ifosfamide, cisplatin; TIP) combination regimen as salvage treatment. Following the TIP regimen and the application of granulocyte colony-stimulating factor (G-CSF), peripheral blood stem cells (PBSC) are harvested and the patients subsequently receive high-dose chemotherapy with PBSC rescue. Since only a few drugs have demonstrated substantial activity in cisplatin-refractory disease, paclitaxel will be used in early salvage strategies and, possibly, as first-line chemotherapy as a part of platinum-based combination regimens in patients with testicular cancer. Further trials confirming the important role of paclitaxel in this highly curable malignancy and a thorough investigation of its acute and long-term toxicity will be the future tasks.

Antineoplastic Agents, Phytogenic↗

PubMed1996

The renal paracrine peptide system--possible urologic implications of urodilatin.

Cardiodilatin/atrial natriuretic peptide (CDD/ ANP) is a hormone system of great clinical importance. The prohormone CDD/ANP-1-126 is a peptide synthesized in the heart and cleaved during exocytosis into the circulating form CDD/ANP-99-126. Urodilatin (CDD/ ANP-95-126) is a homologue natriuretic peptide that differs from CDD/ANP-99-126 by four amino acids. Whereas CDD/ANP-99-126 circulates in blood plasma and is not excreted into the urine, urodilatin is detected only in urine. Urodilatin exerts its renal effects in a paracrine fashion. After its secretion from cells in the distal tubule, it interacts with luminally located receptors in the collecting duct, resulting in increased diuresis and natriuresis. Results suggest that urodilatin plays an important role in the physiologic regulation of fluid-balance and sodium homeostasis. Pharmacology studies reveal significant differences when urodilatin and CDD/ANP-99-126 are given intravenously, showing that stronger diuresis and natriuresis are induced by urodilatin as compared with those induced by CDD/ANP-99-126. Clinical studies indicate the prophylactic and therapeutic effect of urodilatin in patients suffering from acute renal failure following heart and liver transplantation. A significant reduction in requirements for hemodialysis/hemofiltration can be achieved using urodilatin. Postobstructive diuresis and natriuresis is probably due to a defective urinary concentrating mechanism and is usually resistant to treatment with antidiuretic hormone. The distal tubule and collecting duct have often been considered to be the site of altered sodium and water excretion following relief of obstruction. Since circulating CDD/ANP-99-126 levels are markedly elevated during obstruction and decrease upon relief of the obstruction, natriuretic peptides may play an important role in this clinical feature. On the basis of recent findings attributing an important role in sodium homeostasis to urodilatin in contrast to CDD/ANP-99-126, future studies have to clarify whether urodilatin, not CDD/ANP-99-126, might be responsible for the altered renal sodium excretion observed in postobstructive diuresis. In the past decade a considerable amount of research has led to the identification and characterization of hormones of the natriuretic peptide family [13]. These peptides are involved in the regulation of salt and water homeostasis. The prototype of the natriuretic hormones is cardiodilatin/atrial natriuretic peptide (CDD/ANP), or A-type natriuretic peptide. CDD/ANP is primarily produced in the heart [6]. It is synthesized as a precursor molecule, CDD/ ANP-1-126, in specific granules in atrial myoendocrine cells [15]. The prohormone, upon appropriate stimuli for release, is cleaved into the C-terminus CDD/ANP-99-126 and excreted into the circulation via exocytosis [16]. Further members of the natriuretic peptide family are brain natriuretic peptide (BNP, or B-type natriuretic peptide) [45] and C-type natriuretic peptide (CNP) [46]. All the members of this family share many common features, including tissue distribution of gene expression, biosynthetic pathways, and pharmacologic effects in target organs [13,26]. The main biologic effects of these hormones are natriuresis, diuresis, and vasodilation [5, 6, 14, 22], but these vary among the individual peptides. Natriuretic effects such as increased glomerular filtration, inhibition of aldosterone production, and secretion result from direct inhibition of sodium absorption in the collecting duct. Urodilatin (INN: Ularitide) is a member of the natriuretic peptide family, discovered in 1988 by Schulz-Knappe et al. [43]. This hormone is presumably synthesized in the kidney and exerts potential paracrine renal effects [17]. Results of clinical phase I-II trials suggest a potent therapeutic effect of urodilatin in the treatment of acute renal failure in patients following organ transplantation [4, 27, 33].

Acute Kidney Injury↗

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

Cyclic nucleotide phosphodiesterase (PDE) isoenzymes in the human detrusor smooth muscle. II. Effect of various PDE inhibitors on smooth muscle tone and cyclic nucleotide levels in vitro.

Phosphodiesterases (PDEs) regulate intracellular cyclic nucleotide metabolism and, thus, contraction and relaxation of smooth musculature. The aim of the present study was to evaluate the functional effects of isoenzyme-selective inhibitors and their effects on cyclic nucleotide levels in the human detrusor smooth muscle. In addition, the functional relevance of the cAMP versus the cGMP pathways in the regulation of the detrusor smooth muscle tone was assessed. Relaxant responses to various PDE inhibitors, forskolin and sodium nitroprusside (SNP) were investigated in vitro using a standard organ bath setup. Cyclic nucleotide levels were measured after incubation with the same substances using cAMP and cGMP radioimmunoassays (RIAs). Significant relaxant responses were only induced by non-selective PDE inhibition, the PDE I inhibitor vinpocetine and the adenylate cyclase activator forskolin. Relaxant responses to these substances were paralleled by increases in cyclic nucleotide levels. Our data suggest that the cAMP pathway and calcium/calmodulin-stimulated PDE (PDE I) may be of functional importance in the regulation of the human detrusor smooth muscle tone in vitro.

Cyclic AMP↗

PubMed1996

Application of factor analysis for the determination of specific frequency bands in corpus cavernosum EMG power density spectra.

Corpus cavernosum electromyogram (CC-EMG) recording provides diagnostic information on cavernous autonomic innervation and the intact state of cavernous smooth muscle cells. Evaluation of these signals is time consuming and complex. Therefore, we attempted to facilitate their interpretation and to increase their objectivity by using computer-based digital signal processing. Spectral parameters were used as a starting point for this analysis, which were calculated from the Fourier-transformed time domain CC-EMGs. Factor analysis was applied to determine specific frequency bands in the CC-EMG power density. Two hundred power spectra, taken from normal subjects (n = 66) and from patients suffering from erectile dysfunction (n = 134), constituted the basic data. As a result of applying factor analysis, four specific frequency bands were depicted: 0.0-0.3, 0.3-3.5, 3.5-6.0 and 6.0-10.0 Hz. The results of this study form the basis for further mathematical evaluation and calculation of the CC-EMG for clinical and diagnostic purposes.

Adult↗

PubMed1996

A possible role for nitric oxide in the regulation of human ureteral smooth muscle tone in vitro.

There is ample evidence that nitric oxide (NO) is an important neurotransmitter in many tissues of the urogenital tract. The aim of the present study was to examine the possible role of NO in ureteral relaxation. Human ureteral rings were mounted in organ bath chambers and precontracted in KCl. Increasing doses of the NO donor linsidomine (SIN-1) were added with and without prior blockade of the NO/cGMP pathway by methylene blue and protein kinase (PK) inhibitors Rp-8-pCPT-cGMPS and RP-8-CPT-cAMPS. Electrical filed stimulation (EFS) was done before and after incubation with L-NOARG (NG-nitro-L-arginine) and TTX (tetratodoxin). For detection of neuronal NO synthase (NOS), ureters were stained immunohistochemically. Ureteral strips were dose dependently relaxed by SIN-1; preincubation with methylene blue and protein kinase G inhibitor significantly reduced the SIN-1-induced relaxations. No effects of L-NOARG and TTX on EFS-induced tone alterations were found. NOS-positive neuronal axons and nerve-ending-like structures were found in the muscular layers. Our in vitro findings suggest that ureteral relaxation may involve the NO pathway.

Cyclic GMP↗

PubMed1996

Treatment of clinical stage I testicular cancer and a possible role for new biological prognostic parameters.

Three different treatment strategies for patients with stage I non-seminomatous testicular cancer are available that will all result in long-term survival in more than 98% of the patients: a "wait and see" strategy with follow-up and chemotherapy in cases of tumour progression, retroperitoneal lymphadenectomy, with or without application of systemic chemotherapy, in cases of retroperitoneal metastases (pathological stage II disease) or primary adjuvant chemotherapy following inguinal orchiectomy. Each treatment strategy is associated with specific side-effects. In several studies histological characteristics of the primary tumour, particularly the presence of vascular invasion and of embryonal carcinoma cells, have been demonstrated to be significant prognostic factors for the risk of occult retroperitoneal metastases in patients with stage I disease. In addition, new biological prognostic factors determined by flow cytometry, cytogenetic analysis or molecular-biological DNA or RNA analysis have been investigated, among which alterations of the p53 tumour-suppressor gene may represent a promising new prognostic factor. Although alterations of p53 gene expression seem to be associated with advanced tumour stage and may predict retroperitoneal metastatic disease, the independent role of these molecular genetic alterations needs to be prospectively studied. Currently a risk-adapted treatment strategy based on the histological criteria of vascular invasion and the presence of embryonal carcinoma can be used to stratify patients into a "high-" and "low-risk" group with respect to tumour progression. While primary-nerve-sparing retroperitoneal lymphadenectomy or adjuvant chemotherapy with two cycles of platinum, etoposide and bleomycin may be appropriate for patients with a high risk (above 40%) for tumour progression, a "wait-and-see" strategy can be used for "low-risk" (less than 15% risk of progression) patients. Molecular investigations of prognostic factors may be able to improve further the stratification of patients into these different risk categories.

Humans↗

PubMed1996

Expression of stem-cell factor and its receptor c-kit protein in normal testicular tissue and malignant germ-cell tumours.

The proto-oncogene c-kit and its ligand stem-cell factor (SCF) may play an important role in the development of normal and malignant testicular tissue. This study investigates the presence of SCF and c-kit protein in 32 orchiectomy specimens of patients with testicular cancer, in 5 specimens of normal testicular tissue and in three established non-seminomatous germ-cell cancer cell lines (H12.1, H32, 577ML) by an immunohistochemical approach. Out of 9 testicular cancer specimens classified as pure seminomas, 7 (78%) showed a strong immunohistochemical reaction for both SCF and c-kit protein on the surface of the tumour cells. Fourteen non-seminomatous germ-cell tumours composed of embryonal carcinoma were completely negative for both SCF and c-kit proteins and only faint positivity was found in 6 tumours (26%). Differentiated teratomatous structures within the specimens on non-seminomatous tumours showed a strong immunohistochemical reaction for SCF and c-kit protein in 8 of 11 (73%) cases. All three testicular cancer cell lines showed only faint staining reactions for c-kit protein and none for SCF. No secretion of SCF by the three lines in vitro was detected. The addition of high concentrations of SCF (100 ng/ml) to the testicular cancer cell lines in culture conditions without fetal calf serum resulted in a 1.4 to 3-fold growth stimulation compared to cell growth in serum-free medium alone. This effect was not detectable when the cells were cultured in serum-containing media. In the normal testicular tissue the germ-cells displayed a strong immunohistochemical reaction for c-kit protein while SCF positivity was found at the tubular membrane and on the surface of Sertoli cells. The SCF/c-kit system may possess a regulatory function in normal testicular tissue by possibly providing the microenvironment necessary for spermatogenesis. With the development of testicular cancer, this regulatory system seems to be lost, particularly in non-seminomatous germ-cell tumours. A growth-stimulatory effect of high concentrations of SCF on non-seminomatous testicular cancer cell lines can be detected only in culture conditions with serum-free media. The effects achievable by the combination of SCF with other growth factors need to be further studied, as well as the role of the c-kit/SCF regulatory system for normal spermatogenesis and its possible implications for the understanding and treatment of male infertility.

Germinoma↗

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↗