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Biomedical subjects

U Räth

Publications and source records attributed to U Räth.

At least 19 recordsLinked to original sources
PubMed1996

A randomized trial of cisplatin, etoposide and bleomycin (PEB) versus carboplatin, etoposide and bleomycin (CEB) for patients with 'good-risk' metastatic non-seminomatous germ cell tumors.

BACKGROUND: Cisplatin-based combination chemotherapy will cure 70% to 80% of patients with metastatic non-seminomatous germ cell tumors but is associated with the possibility of severe neuro-, oto- and nephro-toxicities. Carboplatin, a cisplatin analogue, is an active drug in testicular cancer with a more favourable spectrum of side effects. In a randomized trial, the German Testicular Cancer Study Group compared a combination regimen of carboplatin, etoposide and bleomycin (CEB) to standard cisplatin, etoposide and bleomycin (PEB) chemotherapy for patients with 'minimal-' and moderate-disease' non-seminomatous germ cell tumors, according to the Indiana University classification. PATIENTS AND METHODS: PEB was given for three cycles at standard doses (given days 1-5), and the CEB regimen consisted of carboplatin (target AUC of 5 mg/ml x min) on day 1, etoposide 120 mg/m2 on days 1 to 3 and bleomycin 30 mg on days 1, 8 and 15. Four cycles of CEB were given, with the omission of bleomycin in the fourth cycle. Thus, the cumulative doses of etoposide and bleomycin applied in the two treatment arms were comparable. Fifty-four patients were entered on the trial, 29 were treated with PEB and 25 with CEB chemotherapy. Patients were stratified according to disease extent (minimal versus moderate) and the degree of tumor marker elevation. Thirty-two patients (59%) belonged to the group with minimal disease and low markers. RESULTS: No significant difference in response to chemotherapy was seen between the two arms, with CR rates of 81% for the PEB arm and 76% for CEB treatment. However, more patients treated with CEB (32% versus 13%) have relapsed after therapy, and 4 patients (16%) have died of disease progression after CEP in contrast to 1 (3%) after PEB therapy. The first interim analysis of negative events (relapse, vital tumor at secondary resection, death from disease and therapy-associated death) showed a significantly higher rate after CEB than after PEB therapy, and the trial was terminated early. After a median follow-up of 33 months for all patients, the calculation of negative events is still significantly in favour of PEB-treated patient, particularly since three late relapses > 2 years have been observed in the CEB arm (P = 0.03). CONCLUSION: This randomized trial demonstrates that even with the use of adequate doses of etoposide and full-dose bleomycin, carboplatin cannot altogether replace cisplatin in patients with testicular cancer. Treatment with the PEB regimen remains the standard approach in patients with 'good-risk' non-seminomatous germ cell tumors.

Adolescent↗
PubMed1995

Lack of association of Helicobacter pylori seroprevalence and gastric cancer in a population with low gastric cancer incidence.

BACKGROUND: Previous studies have suggested that infection with Helicobacter pylori is associated with an increased risk of gastric adenocarcinoma. METHODS: We examined the sera of 111 Caucasian patients with histologically confirmed gastric cancer (36 with cancer of the cardia, 70 with cancer of the body or antrum, and 5 with stump carcinomas after Billroth-II procedures) and 111 age-matched controls with colorectal carcinomas for the presence of H. pylori IgG antibodies by enzyme-linked immunoassay. RESULTS: The overall prevalence of H. pylori infection was 58.6% (65 of 111) in gastric cancer patients as compared with 50.5% (56 of 111) in matched control subjects (odds ratio, 1.39; 95% confidence interval, 0.82 to 2.36). Carcinomas of the cardia were not linked to H. pylori infection (odds ratio, 1.25; 95% confidence interval, 0.65 to 2.46), nor diffuse or intestinal-type carcinomas (odds ratios, 1.79 and 1.0; 95% confidence intervals, 0.69 to 4.67 and 0.34 to 2.91, respectively). Age, sex, and height of the IgG immune response did not affect risk. CONCLUSIONS: In contrast to previous results, these data do not provide evidence that the contribution of H. pylori infection to the carcinogenesis of gastric cancer is of major significance in a population with low gastric cancer rates and with high socioeconomic status.

Adenocarcinoma↗
PubMed1994

[Somatostatin receptor scintigraphy in the primary diagnosis and follow-up care of gastrinoma].

Somatostatin receptor scintigraphy (SRS) was performed in 14 patients (five men, nine women; mean age 51.5 [20-71] years) with Zollinger-Ellison syndrome (ZES), a gastrinoma proven in 7 and suspected on clinical or biochemical grounds in 7. The results were compared with those obtained by other methods (ultrasound, computed tomography, angiography). All 12 known tumour manifestations were demonstrated by SRS in seven patients with histologically confirmed gastrinoma. In four patients previously non-localized tumour was revealed by SRS, while in seven other patients the procedure led to modification of the treatment (primary tumour resection: n = 3, resection of metastases: n = 2, percutaneous radiation or chemoembolization: one each). These results suggest the following indications for SRS: (1) staging or re-staging in histologically proven gastrinoma and (2) search for primary tumour in clinically and biochemically suspected ZES.

Adult↗
PubMed1994

p53 overexpression is frequent in European hepatocellular carcinoma and largely independent of the codon 249 hot spot mutation.

Mutations in the p53 tumour suppressor gene have been recently described in hepatocellular carcinomas (HCC) from high risk areas such as China and South Africa. Our study was designed to assess the importance of p53 aberrations in HCCs from Europe, where the major risk factors in hepatocarcinogenesis, aflatoxin exposure and chronic hepatitis B virus (HBV) infection, do not play a dominant role. We investigated 22 HCCs and, as controls, their corresponding tumour-free liver tissues, seven livers with primary biliary cirrhosis and four morphologically normal livers. p53 overexpression, which is usually associated with point mutations of the p53 gene, was detected in 10 of the 22 HCCs by immunoblotting and immunohistochemistry. p53 expression was restricted to the nucleus in the positive cells, while all cells in the control tissues were negative. There was no obvious etiological preference in the p53 positive tumours. Particularly, underlying chronic HBV infection did not appear to be associated with an increased rate of p53 overexpression in European HCCs. SSCP and sequence analysis of exons 5-8 of the p53 gene revealed point mutations in six out of eight tumours with increased steady state levels of p53. In conclusion, our study demonstrates increased p53 levels due to point mutations in a significant proportion of European HCCs. The codon 249 mutation, which was detected in one of the cases, is not predominant in these tumours.

Adult↗
PubMed1993

[Diagnostic significance of parathyroid hormone-related protein in tumor patients with hypercalcemia].

The clinical utility of measuring parathormone-related protein (PTHrP) was investigated in 94 patients (48 men, 46 women, mean age 56 [18-82] years) with tumour-associated hypercalcaemia, using a radioimmunoassay directed against the middle portion (53-84) of PTHrP (reference range < 5-21 pmol/l). Increased levels of the middle portion of PTHrP were found in 44 of the 73 patients (60%) with hypercalcaemia associated with solid tumours (median 49 [22-333] pmol/l). There was a positive correlation between the serum calcium concentration and the PTHrP (P = 0.018). The frequency of a raised PTHrP, indicating hormone-induced hypercalcaemia, was similar in patients with and without bone metastases (48% vs 66%). Elevated PTHrP was particularly frequent in patients with squamous cell carcinomas (17 out of 21; 81%), while PTHrP levels were normal in 18 out of the 21 patients with hypercalcaemia associated with haematological malignancies. PTHrP levels were normal in 37 out of 38 normocalcaemic tumour patients and in 30 out of 32 patients with primary hyperparathyroidism. Hypercalcaemia associated with benign disease was found in only one case, a female with marked benign breast hypertrophy.--The measurement of PTHrP allows the demonstration of a pathogenetic factor in tumour-associated hypercalcaemia, and differentiation from other causes of hypercalcaemia, in particular primary hyperparathyroidism.

Adolescent↗
PubMed1993

Improved visualization of carcinoid liver metastases by indium-111 pentetreotide scintigraphy following treatment with cold somatostatin analogue.

Five patients with hepatic metastases of midgut carcinoid underwent somatostatin receptor scintigraphy with indium-111 pentetreotide before and during treatment with octreotide. Octreotide treatment changed the biodistribution of 111In-pentetreotide significantly. Whereas the radioactivity in liver, spleen and kidney decreased, hepatic metastases showed increased contrast. In one patient, liver metastases could only be detected during octreotide treatment. These data suggest that the diagnostic reliability of somatostatin receptor scintigraphy in carcinoid liver metastases is not necessarily compromised by octreotide therapy. Because of different biodistributions, the detection of liver metastases may even be improved during octreotide therapy.

Carcinoid Tumor↗
PubMed1993

Comparison of 5 vs 10 micrograms/kg per day of GM-CSF following dose-intensified chemotherapy with cisplatin, etoposide, and ifosfamide in patients with advanced testicular cancer.

Despite the increasing use of granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment of chemotherapy-induced neutropenia, few studies have focused on the activity and toxicity of the different clinically used dosages of GM-CSF. Forty-four patients with "poor-risk" (advanced disease, according to the Indiana University classification) testicular cancer were treated with a dose-intensified chemotherapy regimen of cisplatin (30 mg/m2), etoposide (200 mg/m2), and ifosfamide (1.6 g/m2), given on days 1-5 for a total of four cycles at planned intervals of 21 days. Patients (pts) received GM-CSF, either 10 (22 pts; 70 cycles evaluable) or 5 micrograms/kg body wt. daily s.c. (22 pts; 72 cycles evaluable), starting the first day after chemotherapy for 10 consecutive days. Overall, 34 patients (78%) achieved a favorable response (CR or PR with negative tumor markers), six patients (14%) failed this chemotherapy regimen, and four patients (9%) died of therapy-related complications. The durations of both neutropenia and thrombocytopenia increased with the number of treatment cycles given. The duration of granulocytopenia after the fourth PEI cycle was significantly shorter for patients receiving 10 micrograms/kg than for those with 5 micrograms/kg per day of GM-CSF (9 vs 13 days; p < 0.05). The median duration of thrombocytopenia < 20,000/microliters after the fourth cycle of PEI was also significantly reduced in favor of patients receiving 10 micrograms/kg of GM-CSF (4 vs 9 days; p < 0.02). However, there were no differences in the frequency of severe infections or in the achieved dose intensity. Five patients (11%) discontinued GM-CSF due to side effects (three anaphylactoid-type reactions, one myalgia and fever, one cutaneous toxicity). No difference in the frequency of side effects was seen between patients receiving 5 and those receiving 10 micrograms/kg per day of GM-CSF. The dose of 5 micrograms/kg per day of GM-CSF may be sufficient to ameliorate neutropenia following standard-dose chemotherapy, while higher dosages of GM-CSF may be advantageous in patients receiving repetitive cycles of dose-intensified chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

A phase I/II study of a stepwise dose-escalated regimen of cisplatin, etoposide and ifosfamide plus granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with advanced germ cell tumours.

In order to improve the survival of patients with metastatic advanced disease germ cell tumours (according to Indiana University classification), 77 patients were treated by a stepwise dose-escalated combination regimen of platinum (P), etoposide (E) and ifosfamide (I) (PEI) followed by application of granulocyte-macrophage colony-stimulating factor (GM-CSF) (10 micrograms/kg subcutaneously per day at levels 2 and 3) starting the first day after chemotherapy for 10 consecutive days. The maximally tolerated dose was reached at the third dose level with P 30 mg/m2, E 200 mg/m2 and I 1.6 g/m2, all given for 5 days, once every 21 days, for a total of four cycles. Sixty-seven per cent of patients had three or more metastatic sites. Twenty-two per cent of patients had extragonadal primary tumours. 49 (65%) patients achieved complete remission, and 9 additional patients (12%) achieved marker normalisation with unresectable residual disease. After a median follow-up of 27 months, the overall survival is 80%, with 67% of patients remaining free from progression. The dose-limiting toxicities were WHO grades 3/4 mucositis/enteritis in 33% of patients and prolonged thrombocytopenia < 20.000/microliters (> 10 days). Adverse reactions to GM-CSF occurred in 13% of patients. The use of a single haematopoietic growth factor allowed only a moderate increase in dose intensity (factor 1.37). Peripheral blood stem cells will be additionally incorporated into the treatment protocol in order to deliver multiple cycles of an upfront dose-intensified PEI regimen in patients with "poor risk" germ cell tumours with less toxicity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

[Somatostatin receptor scintigraphy. A new imaging procedure for the specific demonstration of carcinoids of the small intestine].

Scintigraphy with a radiolabelled somatostatin analog represents a new highly specific approach in the diagnostic work-up of receptor-positive APUD tumours and their metastases. We present our preliminary results with somatostatin receptor scintigraphy in 15 patients with histologically proven midgut carcinoid. 5 out of 6 primary tumour sites (83%) and 90% of the known metastatic lesions could be detected; unknown metastatic lesions were seen in 5 patients. Compared with other nuclear medicine procedures somatostatin receptor scintigraphy is able to detect all tumour sites within hours. This advantage will promote the acceptance of this sensitive and specific imaging modality by the clinicians with regard to preoperative work-up and symptomatic therapy with a somatostatin analog.

Adult↗
PubMed1993

The humoral immune response to p53 in patients with hepatocellular carcinoma is specific for malignancy and independent of the alpha-fetoprotein status.

Recently, p53 gene aberrations have been recognized as a relevant factor in hepatocarcinogenesis, in tumors from both high-risk and low-risk areas. Because p53 gene mutations typically result in increased p53 levels in tumor cells, this cellular protein might become immunogenic during tumor development. To test this hypothesis, we have analyzed sera from 80 European patients with hepatocellular carcinoma for the presence of p53 antibodies. For this purpose we developed an immunoblot assay using recombinant p53 as antigen. Sixty-seven sera from patients with different acute and chronic liver diseases were used as controls. In addition, serum alpha-fetoprotein assays were performed. Circulating antibodies against p53 were found in 25% (20 of 80) of the sera from patients with hepatocellular carcinoma but not in various nonmalignant liver diseases. The association of p53 antibodies with malignancy was highly significant (p < 0.00003). In 73.8% (59 of 80) of the hepatocellular carcinoma sera the alpha-fetoprotein levels were elevated. Among the 21 alpha-fetoprotein-negative hepatocellular carcinoma sera, 5 were found to contain p53 antibodies (23.8%). In conclusion, an antibody response against p53 developed in a significant proportion of patients with hepatocellular carcinoma but not in those with nonmalignant liver diseases. Serological testing for p53 antibodies gives the opportunity to identify a subgroup of patients with hepatocellular carcinoma not detected by conventional tests for serum alpha-fetoprotein.

Adult↗
PubMed1993

Diagnostic reliability of somatostatin receptor scintigraphy during continuous treatment with different somatostatin analogs.

In order to evaluate the diagnostic reliability of somatostatin receptor scintigraphy (SRS) in patients treated with somatostatin analogs, ten patients with metastatic neuroendocrine tumors were investigated before and during continuous treatment. Different somatostatin analogs were used for therapy: five patients received octreotide (Sandostatin, Sandoz, Switzerland) and five were treated with BIM 23014 (Lanreotide, Ipsen Biotech, France) within the scope of a clinical phase II study. The SRS findings were analyzed in terms of biodistribution of the labeled somatostatin analog and tumor visualization comparing the two studies in each patient. Whereas liver, spleen, and kidney uptake were decreased during octreotide treatment and increased on lanreotide therapy, tumor accumulation was intensified in all but one patient. Our results suggest that the diagnostic value of SRS is not necessarily restricted during treatment with somatostatin analogs. Indeed, tumor visualization may even be enhanced in this therapeutic setting.

Adult↗
PubMed1993

Pen-based remote data entry system. A pilot clinical trial.

This study assesses the feasibility of pen-based remote data entry and measures the acceptance of such systems by patients and physicians. Three clinical investigators participated in a phase-I/II clinical trial of escalated doses of chemotherapy followed by Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF). The study included 20 patients with testicular cancer who were treated at three university hospitals. The patients' data obtained in this trial were recorded and stored on a pen-based computer system. A total of 798 data points were recorded for each patient using 33 electronic forms resembling the paper forms used during an earlier phase of the study. The data recorded include the past medical history, inclusion/exclusion criteria, disease staging, therapy documentation, laboratory values and side effects. Both physicians and patients were interviewed directly after using the pen-based remote data entry system. Patients accepted that their physician was taking notes on an electronic form rather than on paper. All patients noted that a pen-based system is superior to a desktop computer when used during an interview. For the investigators electronic data entry takes additional effort, but time savings are realized later with less data clearing and increased data quality. These benefits are important for the study sponsor as well. In conclusion, pen-based remote data entry is a feasible new mode of recording clinical data with concrete benefits to both investigators and sponsors.

Data Display↗
PubMed1991

Computerized ultrasound B-scan texture analysis of experimental diffuse parenchymal liver disease: correlation with histopathology and tissue composition.

By means of statistical pattern recognition procedures, a quantitative description of the ultrasound B-scan images of experimental diffuse liver disease has been carried out. Fatty livers, fatty fibrosis/cirrhosis, and cirrhosis without fatty infiltration of the liver were studied in female Wistar rats. Separation accuracies of more than 80% between the tissue classes "normal" vs "fatty infiltration," or "normal" vs "fatty cirrhosis," using only two statistical image parameters were found. A subclassification of the diffuse parenchymal liver disease was not possible. It is shown by multiple linear regression analysis that the image parameter "mean grey level" correlates better with total lipid content than with the amount of connective tissue. Furthermore it is demonstrated that connective tissue leads only to a weak increase in "mean grey level," whereas the addition of connective tissue to a given tissue lipid can lead to a reduction in image brightness.

Animals↗
PubMed1991

Cisplatin/etoposide/ifosfamide stepwise dose escalation with concomitant granulocyte/macrophage-colony-stimulating factor for patients with far-advanced testicular carcinoma.

In order to develop a more dose-intensive induction regimen for the treatment of far-advanced testicular tumours, the German Cooperative Group for Testicular Tumours started a dose-escalation trial of cisplatin, etoposide and ifosfamide. At the first dose level 18 patients with advanced testicular cancer (Indiana University classification) received cisplatin 25 mg/m2, etoposide 120-150 mg/m2 and ifosfamide 1.2 g/m2 for 5 days every 3 weeks. Of these, 13 patients (72%) became tumour-free, 2 achieved a stable, marker-negative partial remission, 2 had progressive disease and 1 patient died of Clostridium sepsis. The main toxicity was myelosuppression with a white blood cell nadir of 900/microliters and a thrombocyte nadir of 47,000/microliters. Granulocytopenic fever occurred in 43% of all cycles. At the second dose level 15 patients received cisplatin 30 mg/m2, etoposide 150 mg/m2 and ifosfamide 1.6 g/m2 five times every 3 weeks together with s.c. recombinant granulocyte/macrophage-colony-stimulating factor (GM-CSF) 10 micrograms/kg on days 6-15. Acute toxicity was severe with a white blood cell nadir of 300/microliters and thrombocyte nadir of 11,000/microliters. The duration of the thrombocytopenia increased with cycle number; 63% of all cycles were associated with granulocytopenic fever and in 83% platelet transfusions were required. One patient died from acute renal failure and Aspergillus sepsis; 3 patients experienced adverse reactions to GM-CSF, requiring omission of this drugs in 2; 33% had grade 3 or 4 mucositis. At this dose level 8 patients (53%) became tumour-free, 4 patients (26%) had marker normalization with irresectable residual disease and 2 patients were treatment failures. Though acute toxicity was severe at this dose level, there was no unexpected or unmanageable organ toxicity and thus patients are now entered at dose level 3, which consists of cisplatin 30 mg/m2, etoposide 200 mg/m2 and ifosfamide 1.6 g/m2 for 5 days and GM-CSF 10 micrograms kg-1 day-1 on days 6-15 s.c.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Effect of intraperitoneal recombinant human tumour necrosis factor alpha on malignant ascites.

29 patients with refractory malignant ascites due to metastatic peritoneal spread of adenocarcinomas originating from the ovary, gastrointestinal tract, liver, breast and uterus were treated in a phase I trial of intraperitoneal infusions of recombinant human tumour necrosis factor alpha (rhTNF-alpha). Patients received 40-350 micrograms/m2 rhTNF-alpha intraperitoneally once weekly for 2 months or for a shorter period in case of early resolution of ascites. Systemic side-effects resembled those reported for rhTNF-alpha given intravenously. No dose-limiting toxicities were found and thus a maximum tolerated dose of intraperitoneal rhTNF-alpha was not established. Out of 29 patients, 22 responded with a complete (16) or partial (6) resolution of their ascites. There was a less than 50% reduction in 4, and no increase in ascites in 1. 1 patient showed progressive ascites formation, and another patient was not eligible because of early death unrelated to treatment. Trials in patients with smaller tumour burden are warranted.

Adenocarcinoma↗