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R Klapdor

Publications and source records attributed to R Klapdor.

At least 19 recordsLinked to original sources
PubMed2003

Clinical utility of biochemical markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines.

In recent years, numerous serum and cell/tissue-based markers have been described for colorectal cancer (CRC). The aim of this article was to provide guidelines for the routine clinical use of some of these markers. Lack of sensitivity and specificity preclude the use of any available serum markers such as carcinoembryonic antigen (CEA), CA 19-9, CA 242, CA 72-4, tissue polypeptide antigen (TPA) or tissue polypeptide-specific antigen (TPS) for the early detection of CRC. However, preoperative measurement of CEA is desirable as this may give independent prognostic information, help with surgical management and provide a baseline level for subsequent determinations. For patients with stage 2 (Dukes' B) and 3 (Dukes' C) disease who may be candidates for liver resection, CEA levels should be measured every 2-3 months for at least 3 years after diagnosis. For monitoring treatment of advanced disease, CEA should also be tested every 2-3 months. Insufficient evidence is presently available to recommend the routine use of other serum markers for monitoring purposes. Similarly, the new cell and tissue-based markers (e.g, ras, P53) cannot yet be recommended for routine clinical use.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1999

CA 125 and its relation to cardiac function.

BACKGROUND: CA 125, known as a marker for ovarian cancer with hypothetical but hitherto uncharacterized biologic functions, was reported to be elevated in some not-well-defined benign conditions. There are no reports on fluctuations of CA 125 related to cardiac function, especially the failing heart and neurohumoral factors such as norepinephrine or atrial natriuretic peptid/e. METHODS AND RESULTS: CA 125 blood levels were determined in patients with heart failure before and after heart transplantation (HTx). In 71 patients, parallel determinations of norepinephrine, atrial natriuretic peptide, pulmonary capillary wedge pressure, and right atrial filling pressure were done. CA 125 levels also were prospectively studied in patients with heart failure with stabilization (n = 25) or worsening of the clinical status (n = 9) and after HTx (n = 25). Parallel determinations of the tumor markers CEA, CA 199, CA 153, TPS, and TPA were also done. The results were grouped according to the clinical status (New York Heart Association class) of the patients. CA 125 was significantly correlated with neurohormones and filling pressures. Follow-up investigations revealed a decrease of CA 125 levels after HTx (401 +/- 259 U/L vs 33 +/- 22 U/L, P <.001, n = 25) or stabilization (429 +/- 188 U/L vs 78 +/- 35 U/L, P <.001, n = 25) and an increase during worsening of heart failure (42 +/- 25 U/L vs 89 +/- 32 U/L, P <.01, n = 9). In 4 patients after HTx, unexpected death was preceded by rising CA 125 levels. CEA, CA 199, CA 153, TPS, or TPA did not correlate with heart failure status or clinical events. CONCLUSIONS: CA 125 is a marker of the clinical and hemodynamic status and the course of patients with heart failure before and after heart transplantation. The determination of CA 125 serum levels may be an additional tool in the management of these patients. In patients with cancer, these "nonspecific" changes must be considered when CA 125 levels are determined. Whether CA 125 has a specific biologic role in heart failure deserves further studies.

Atrial Natriuretic Factor↗
PubMed1999

Tumor marker determination after orthotopic heart transplantation.

BACKGROUND: Because the risk of developing malignant tumors after heart transplantation is approximately 100-fold higher, methods for rapid diagnosis must be developed to allow early and aggressive treatment in these patients. Although tumor markers have been used frequently for surveying already detected cancer, we studied their value in screening for tumors in heart transplant patients. METHODS: The levels of the tumor markers CEA, CA19-9, CA125, CA72-4, TPA, TPS, and CYFRA 21-1 were determined prospectively in 3-month intervals in 91 heart transplant patients between 1993 and 1998. RESULTS: In eight patients a definite diagnosis of cancer was made during the marker survey (mean observation time 2.85 +/- 1.3 years), including bronchogenic carcinoma in six, renal carcinoma in one, and colon cancer in one. All patients with bronchogenic carcinoma were smokers. The markers had a sensitivity below 60% to detect cancer. Given a 2-fold cutoff level (10 ng/mL), the CEA was the only marker with sufficient specificity (93.8%, only one false-positive result). Two patients were symptom-free even though they had elevated CEA levels. In one of those patients, disseminated intractable cancer was diagnosed at first evaluation, whereas no tumor was found in the other case at first evaluation. Subsequently, by means of fluorodeoxyglucose positron emission tomography, a hypermetabolic region was found in the right upper mediastinum. Control computed tomographic scan 4 weeks after the first investigation showed disseminated intractable disease also in this patient. Another heart transplant patient with colon cancer showed a normalization of the CEA after hemicolectomy and an increase in the CEA when liver dissemination developed. There was a relationship between cardiac death and CA125 and TPS in some heart transplant patients. CONCLUSIONS: We conclude that the CEA is the only tumor marker with adequate sensitivity and specificity to detect subclinical malignancies in the follow-up of heart transplant patients. However, because of several limitations (limited diagnostic and therapeutic possibilities and enormous costs), we cannot recommend screening by tumor markers on a regular basis. Because of the elevated risk of cancer in patients who had organ transplantation, further prophylactic measures, especially smoking cessation programs, must be developed. Once a malignancy is diagnosed, tumor markers can help target clinical decisions. Additionally, nonspecific increases in CA125 and TPS levels might be related to nonmalignant circulatory disturbances and cardiac death.

Adult↗
PubMed1992

Detection of colorectal carcinomas by intraoperative RIS in addition to preoperative RIS: surgical and immunohistochemical findings.

The immunoscintigraphic detection of tumour foci less than 1 cm in diameter fails even with single photon emission tomography (SPET) owing to low contrast against background activity. In an attempt to improve detection of macroscopically invisible tumour spread, intraoperative scintimetry (IOSM) with a hand-held gamma-probe was performed in addition to SPET 24-30 and 41-48 h after injection of the technetium-99m carcinoembryonic antigen (CEA MoA) on 12 patients with colorectal carcinoma and 3 patients with different neoplastic and inflammatory diseases. Tumour specimens were measured in vitro in a gamma well counter. For comparison, the presence and amount of CEA in the tumour cells were evaluated immunohistochemically. After modification, the gamma-probe originally designed for iodine-131 was 20 times more sensitive; activities of 99mTc located close to the collimator hole were measured with absolute sensitivity of 100 cps = 2.5 kBq 99mTc. The unfavourably high background activity affected both the in vitro and in vivo analysis: SPET results had been considered positive in 8 of 15 cases. In vitro tumour/non-tumour (t/nt) ratios greater than 2.0 were found in 4 cases. In vivo IOSM resulted in t/nt ratios greater than 2.0 in only 3 patients. In most cases, there was no coincidence of elevated t/nt ratios from the different methods. A correlation was derived between positive immunoscintimetric in vitro findings and immunohistochemically proven interstitial localization of CEA in tumor cells. In conclusion, the measurement technique of IOSM seems adequate, but clinical success will depend on a more specific enrichment of MoA in tumour tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

A randomized controlled trial of adjuvant immunotherapy (murine monoclonal antibody 494/32) in resectable pancreatic cancer.

In a prospective randomized multicentric trial, 61 patients from six hospitals with resectable pancreatic cancer were recruited between 1987 and 1989. All patients underwent a Whipple resection. Two weeks after surgery, the patients were randomized to be given either intravenous (IV) treatment with 370 mg (100 mg loading dose, 9 x 30 mg continuing within 10 days) of monoclonal antibody (MoAb) 494/32 (Behringwerke AG, Marsburg, Germany) or no additional anti-cancer treatment. This murine immunoglobulin (Ig) G1 antibody has been shown to strongly bind to human pancreatic cancer cells and to induce an antibody-dependent cellular cytotoxicity (ADCC). Both study groups were well matched with respect to age, sex, tumor staging, and grading. Six patients suffered from minor toxicity (vomiting and abdominal pain) after immunotherapy. Ten months after the end of the recruitment period, 65% and 53% of the patients in the treatment and control groups, respectively, had died. Of the living patients, 60% and 53% are alive with recurrent or progressive cancer disease. Median survival time was 428 days (range, 248 to 510 days) and 386 days (range, 296 to 509 days) in the treatment and control groups, respectively. The authors concluded that repeated IV treatment with the antibody 494/32 is not helpful in resectable pancreatic cancer. This study provides the first controlled data on passive immunotherapy in solid cancer.

Adult↗
PubMed1991

Radioimmunodiagnosis of pancreatic cancer disease.

From a theoretical point of view, immunoscintigraphy of exocrine pancreatic cancer offers itself as a promising diagnostic method. However, the actually available clinical and experimental data point out that the indication for diagnostic application in patients with pancreatic carcinoma has to be viewed more critically than in the case of, e.g., colorectal cancer disease. The quality of imaging depends on a lot of factors, such as the cellular antigen expression, the affinity of the MAbs to the corresponding antigens expressed by the cells, tumor vascularization, tumor size, and unspecific background activity as well as on labeling techniques, the kind of antibodies used, and the technical equipment. All these factors may vary from one patient to the other and from one center to the other. In summarizing the available clinical data, we have to state that immunoscintigraphy does not allow early detection of pancreatic cancer and, consequently, does not allow screening for early stages in asymptomatic patients. Even nowadays primary diagnosis and staging should be based on the imaging methods of ultrasound, CT and/or ERCP, and angiography. With respect to detection of local recurrence and especially peritoneal carcinosis, immunoscintigraphy, however, may be superior when compared to the other imaging methods. The potential clinical value for followup and as a preinvestigation to assess the probability of effective MAb treatment has still to be evaluated in prospective clinical studies. Altogether, a lot of experimental and clinical work remains to be done to introduce immunoscintigraphy of pancreatic cancer into clinical practice as a routine method.

Animals↗
PubMed1990

[Is there an advantage to neo- or adjuvant chemotherapy in pancreatic cancer?].

In view of the lack of representative clinical studies indication and potential value of neo-/adjuvant chemotherapy of pancreatic cancer has still to be discussed on the basis of palliative treatment results, prognostic and pathohistological data, theoretical considerations and experimental data. A critical analysis, however, indicates that the widespread therapeutical nihilism at least with regard to adjuvant trials should be obsolete today. On the contrary, adjuvant chemotherapeutic trials should be recommended, alone or in combination with radiation or immunotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

[Individualization of chemotherapy through in vitro predictive determination of the cytostatic sensitivity of malignant tumors].

An in-vitro test was developed for predicting the efficacy of anti-tumour chemotherapy. Cell cultures were grown from freshly removed tumours and it was then demonstrated by DNA cytophotometry and immuno-cyto-chemistry whether the growing tumour cells corresponded to those of the original tumour cells. Several cytostatic agents were then tested for their efficacy of inhibiting growth at clinically customary dosage. Growing cell cultures were established in 306 of 413 submitted tumours (74%). They responded quite differently to the various drugs that were tried. The clinical course in 94 cases was observed for minimally four and a mean of eight months to obtain an in-vitro to in-vivo correlation of response, with 178 individual correlations. A discrepancy was recorded in 16% of cases, a false-positive in-vitro sensitivity result was 3.6 times more frequently associated with an in vivo resistance than the reverse. Concordance between test results and clinical tumour response occurred in 84%. The monolayer proliferation assay correctly indicated resistance in 93.8%, sensitivity in 72.8%.

Antineoplastic Agents↗
PubMed1989

[Insulin reserve and morphology of the tail of the pancreas following resection of the head of the pancreas using various surgical methods].

Four modifications of dealing surgically with the remaining pancreas after resection of the pancreatic head were compared to each other in dogs. Insulin response and corresponding blood sugar levels were controlled, the remaining pancreas was examined histologically. The obstruction of the pancreatic ducts by prolamine showed mainly sclerosis of the exocrine tissue whereas the duct ligation was followed by atrophy. The free intraperitoneal draining of the duct system showed both alterations, the pancreatojejunostomy did hardly impair the exocrine pancreas. According to the grade of sclerosis of the exocrine tissue, the insulin response was delayed followed by a pathologic glucose tolerance. This was shown particularly for the obstruction of the ducts by prolamine.

Amylases↗
PubMed1989

Increase in B-cells in the pancreatic remnant after partial pancreatectomy in pigs. An immunocytochemical and functional study.

The regenerative and functional capacity of B-cells in the remaining pancreatic tissue after surgical removal of 40%, 60% and 80% of the pancreas was examined in 7 month old pigs (three animals in each group). Prior to resection and 1, 3 and 6 weeks after surgery, basal and glucose-stimulated levels of insulin and blood glucose were determined and compared with the preoperative data and that of sham-operated controls. For quantitative morphology, the volume of the resected specimen and the residual pancreatic tissue, 6 weeks after surgery, was determined and sections evaluated by immunocytochemistry (insulin, glucagon, somatostatin, pancreatic polypeptide) combined with morphometry. In the remaining pancreas, the volume density of the B-cells was increased by 19% (1.57-1.92 after 60% resection; p less than 0.02) and 56% (1.57-2.38 after 80% resection; p less than 0.02) 6 weeks after surgery, compared with the respective resected portion of the pancreas and the controls (n = 12). The non-B-cells gained between 0-10% (PP-cells), 10-20% (D-cells) and 30-40% (A-cells) in the different resection groups. As the number of B-cells per given islet area remained unchanged (mean 4.12 cells/0.25 mm2), the increased volume density was due to an increase in cell number rather than cell size. Insulin secretion (integrated values, 0-120 min), was not significantly impaired after 40% and 60% resection (2711 +/- 250 all preoperative samples; 3215 +/- 474 40% at 6 week intravenous glucose tolerance test (IV-GTT); 1677 +/- 109 60% at 6 week IV-GTT), although the glucose levels (integrated values) were increased during the IV-GTT. The 80% resected animals showed a significant decrease in the insulin response only 1 week after surgery (integrated values: 2711 +/- 250 all preoperative samples, compared with 1250 +/- 508 1 week IV-GTT; p less than 0.05), while the integrated glucose values during IV-GTT (0-120 min) were significantly elevated throughout the observation period. These results suggest a B-cell hyperplasia in the residual pancreas after resection, which may cope with a normal functional demand, but disclose functional abnormalities when challenged with an increased glucose load.

Animals↗
PubMed1989

Cytokines and pancreatic cancer. The effect of rIFN-gamma, HuLeIFN, rTNF-alpha, and LAK-cells on pancreatic and other gastrointestinal tumors in vitro.

A panel of 10 digestive tract carcinoma cell lines (6 pancreatic carcinomas) was assayed for their sensitivity to HuLeIFN, human rIFN-gamma, rTNF-alpha and allogeneic human LAK-cells in vitro. In addition, a combination of rIFN-gamma + rTNF-alpha was tested on 3 pancreatic carcinoma cell lines. Whereas 6/7 cell lines were completely resistant to HuLeIFN, rIFN-gamma and rTNF-alpha did inhibit growth of some carcinomas tested. The individual sensitivity was heterogenous as is already known from cytostatics. Response to rIFN-gamma tended to increase with increment of cell doubling time. Only high concentrations (greater than 1000 U/ml) of rIFN-gamma displayed cytotoxicity on sensitive tumors. The antitumoral effect of rIFN-gamma was stimulated by rTNF-alpha. As revealed by isobole analysis this interaction was synergistic in all pancreatic carcinomas tested. In comparison to rIFN-gamma or rTNF-alpha the response to LAK-cells was slightly superior at high effector target ratios, even though heterogenous.

Biological Factors↗
PubMed1989

Combined therapy of xenografts of human pancreatic carcinomas with rTNF-alpha and mitomycin C.

Based on previously published experimental studies in nude mice indicating that rTNF-alpha as well as mitomycin C are able to induce significant growth inhibition of xenotransplants of gastrointestinal and pancreatic carcinomas we have investigated the antitumor effects of rTNF-alpha (0.8 mg/kg daily for 21 days) and mitomycin C (2.4 mg/kg once weekly, day 1, 7, 14) as single drugs and in combination (0.8 + 2.4) in nude mice bearing xenografts of 4 human pancreatic carcinomas and 1 colorectal cancer. Serum CA 19-9 was measured additionally to tumor growth rate. The results demonstrate that combined treatment is more effective compared to rTNF-alpha and mitomycin C alone. Combined therapy resulted in a significant inhibition of tumor growth in 3 of 5 xenografts and in decrease of tumor volume to less than 50% of the initial values in 2 of 5 tumors. The results support the concept that combinations of cytokines with cytostatics might be of value for treatment of gastrointestinal and pancreatic cancer in vivo.

Animals↗