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Biomedical subjects

K H Berghäuser

Publications and source records attributed to K H Berghäuser.

17 recordsLinked to original sources

The efficacy of adjuvant cytostatic therapy after organ transplantation for malignancy: an experimental study with a combined transplantation/tumor model.

New data show that perioperative cytostatic therapy is beneficial in the case of liver transplantation for hepatic cancer. However, it has not been established clearly whether chemotherapy interferes with graft rejection. We therefore studied the interactions between tumor growth and graft rejection, especially with regard to chemotherapy, using a combined tumor/transplantation model. As a tumor model, we used the Novikoff hepatoma, a malignant hepatoma that was injected subcutaneously into the backs of rats. Heterotopic heart grafting served as the transplantation model. In a first step (a), we studied the effect of cytostatic therapy on tumor growth: tumor cells were injected, and in four groups epirubicin, cyclosporine, epirubicin + cyclosporine, and placebo were applied, in corresponding groups, transplantation was additionally performed. Tumor growth was measured and the resected tumors were examined by histology and immunohistology. In a second step (b), we studied the effect of chemotherapy on graft rejection: transplantation was performed and the above-mentioned drugs were applied; in corresponding groups, a solid tumor was additionally induced and resected immediately before transplantation. The results of these procedures were as follows: (a) Epirubicin decreased tumor growth and diminished the volume-increasing effect of cyclosporine significantly. After transplantation, tumor growth was similar. (b) Epirubicin prolonged graft survival significantly, and the combination with cyclosporine had an augmenting effect. In the corresponding groups, graft survival was similar. In conclusions. chemotherapy diminishes the tumor-increasing effect of cyclosporine and does not interfere negatively with graft survival. It might therefore be beneficial after transplantation for malignancy.

Animals↗

[Primitive neuroectodermal tumor].

The primitive neuroectodermal tumor is a rare soft tissue neoplasm occurring in children and young adults. It derives from a carcinogeneic alteration of pluripotent neural crest cells, caused by a balanced reciprocal translocation t(11;22) (q24;q12). Treatment of this undifferentiated, extremely malignant small cell tumor is carried out in compliance with the soft tissue trail (CWS) from the German Society of Pediatric Oncology. Biopsy-proven diagnosis is followed by primary chemotherapy, which in 95% of cases leads to remission, allowing excision of the remainder of the tumor without mutilation and avoidance of intraoperative tumor cell dissemination. After excision, irradiation of the tumor site and two further sequences of chemotherapy are performed. If PNETs of the paravertebral region cause symptoms of paralysis and immediate surgery is required, postoperative chemotherapy, a second-look operation and irradiation are mandatory. Between 1986 and 1994, in cooperation with our pediatric and radiotherapy colleagues, we treated ten patients. In four patients (median age, 14 years) the PNET originated from the chest wall, in six patients from the paravertebral and retroperitoneal region. Five patients died after 20 months on average, while the remaining five patients are in full remission after 31, 46, 50, 51 and 91 months, respectively.

Adolescent↗

The prognostic significance of tumor cell detection in intraoperative pleural lavage and lung tissue cultures for patients with lung cancer.

METHODS: Three hundred forty-two patients with lung cancer and 99 patients with nonneoplastic lung diseases (control group) underwent intraoperative pleural lavage with 300 ml physiologic saline solution before (lavage I) and after resection (lavage II). RESULTS: Studies of the lavage fluid in all control patients were negative, that is, there were no false positive findings. Tumor cells were found in lavage I in 132 patients (38.6%) and also in lavage II in 99 of them. In stage I (pT1 N0, pT2 N0) lung cancer, tumor cell detection was possible in 47 patients (28.6%). The 4-year survival of patients with resected non-small-cell lung cancer was 24% (95% confidence interval, 16% to 32%) if lavage I results were positive and 52% (95% confidence interval, 45% to 59%) if lavage I results were negative (all stages, p = 0.007). For patients with stage I disease (n = 164) the 4-year survival was 35% (95% confidence interval, 18% to 52%) if lavage I results were positive (n = 47), and 69% (95% confidence interval, 60% to 78%) if lavage I results were negative (n = 117) (p = 0.037). On multivariate analysis the positive cytologic result in intraoperative pleural lavage was an additional prognostic factor for our patients. To prove how the tumor cells enter the pleural cavity, we performed tissue cultures of tumor-free parenchyma in 23 cases of lung cancer. Tumor cell detection by histology and immunohistology was possible in 16 cases (69.6%). Detection of tumor cells in pleural lavage fluid before resection proves that tumor cells have spread into the pleural cavity. CONCLUSION: The positive result in pleural lavage seems to be a prognostic predictor for patients with lung cancer.

Bronchoalveolar Lavage↗

[Intrapulmonary tumor cell dissemination and intraoperative pleural lavage as prognostic factors in bronchial carcinoma].

319 patients with the first manifestation of lung cancer underwent intraoperative pleural lavage (lavage I = after opening the chest; lavage II = after resection of lung cancer). Tumor cells were found in lavage I in 122 patients (38.2%), in 94 of them also in lavage II. In only 9 cases we found tumor cells in lavage II cytologically. The cumulative five-year survival rate of non-small cell lung cancer in stage I (n = 154) was 22.1% if lavage was positive (lavage I and II, n = 44), and 64.3% if lavage was negative (n = 110) (p < 0.05). Additionally, we performed tissue cultures of tumor-free parenchyma in 23 cases of lung cancer. In 16 cases (69.6%) we detected tumor cells by histology and immunhistology. Intraoperative pleural lavage should be done when assessing the final tumor stage. A positive result should be added to the pTNM-classification of lung cancer.

Adult↗

[Intrapulmonary tumor cell spread and intraoperative pleural lavage as prognostic factors in bronchial carcinoma?].

Tumor cell detection in lavage fluids might be a prognostic factor in solid tumors. Therefore, 342 patients with the first manifestation of lung cancer underwent intraoperative pleural lavage (lavage I = after opening the chest; lavage II = after resection of lung cancer). Tumor cells were found in lavage I in 132 patients (38.6%), in 99 of them also in lavage II. We found tumor cells in only nine cases in lavage II cytologically. The cumulative 5 year survival rate of non-small cell lung cancer in stage I (n = 164) was 25.9% if lavage was positive (lavages I and II, n = 47), and 69.2% if lavage was negative (n = 117) (p < 0.05). Additionally, we performed tissue cultures of tumor-free parenchyma in 23 cases of lung cancer. In 16 cases (69.6%), we detected tumor cells by histology and immunohistology. Cytologic tumor cell detection in intraoperative pleural lavage in lung cancer seems to be an additional prognostic factor and should be done when assessing the final tumor stage. A positive result should be added to the pTNM classification.

Carcinoma, Bronchogenic↗

[Localized benign pleural mesothelioma].

Benign mesothelioma of the pleura is a very rare tumor. The cells responsible originate from either the mesothelium or the submesothelium. This is why such tumors are described in the literature as fibroma of the pleura, mesothelial fibroma, localized fibrous mesothelioma and monophasic spindle cell tumor. Their growth, is very slow taking several years or even decades. In contrast to the more common malignant mesothelioma of the pleura, it is not related to asbestos exposure. This report deals with a 47-year-old woman patient with a giant benign mesothelioma of the pleura in the region of the right thorax, which was completely removed by thoracotomy.

Female↗

Interactions between malignant tumor growth and allogeneic graft rejection in an experimental rat model.

We describe a combined tumor and simultaneous transplant model in rats in tended to investigate interactions between tumor growth and graft rejection. To study the influence of tumor growth on graft rejection. Novikoff hepatoma cells were injected subcutaneously into the back of Lewis rats. Eight days later, the grown solid tumor was resected, and allogeneic heart transplantation was performed. Four groups were formed, receiving 5-fluorouracil (5-FU), cyclosporin A (CsA), 5-FU + CsA, and placebo, respectively. In the corresponding groups, tumor injection was omitted. Graft survival was significantly prolonged when CsA was given 5-FU did not abrogate or augment CsA efficiency nor influence graft survival when given alone. In the corresponding control groups, graft survival was similar, thus excluding an immunomodulating effect of the prior tumor growth on graft survival. To study the reverse interaction of allogeneic graft on tumor growth, heart grafting and tumor cell injection were performed on the same day. In different groups, 5-FU, CsA, 5-FU + CsA, and placebo was given. For the control, no transplantation was carried out. The tumor was resected on the 8th postoperative day and examined by immunohistology. A slight decrease of tumor growth by 5-FU, but a marked increase by CsA were found, whereas the graft alone showed no immunomodulation.

Animals↗

[Carcinoembryonic antigen in serum and pleural fluid to distinguish between bronchial carcinoma and pleural mesothelioma].

The concentrations of carcinoembryonic antigen (CEA) were measured, partly retrospectively and partly prospectively, in 94 patients with diffuse malignant mesothelioma and in 79 with bronchial carcinoma and pleural involvement. Serum concentrations were measured in all patients, pleural-fluid concentrations additionally in 53 patients of the former and 39 of the latter group. The concentrations were significantly higher in those with bronchial carcinoma (P less than 0.001). The two groups could be distinguished by serum concentrations, using 5.2 ng/ml as the limit, with a sensitivity of 68%, specificity of 98% and a predictive value of 96%. Measurement of CEA in pleural fluid (at a limit of 4.5 ng/ml) had a specificity of 94% and a positive predictive value of 90%, sensitivity being similar to that for serum. The negative predictive value for serum CEA concentration was 79%, for pleural fluid it was 81%. Thus in most cases measurement of CEA in serum and, to a lesser extent in pleural fluid, is a very simple method to exclude mesothelioma with a high degree of certainty. If the CEA concentration is below the stated level, either may be present.

Adult↗

Distinction of mesothelioma from carcinoma in pleural effusions. An immunocytochemical study on routinely processed cytoblock preparations.

The study was designed to find out whether the commercially available antibodies BMA 130 c, BMA 120, V 9, KL 1, B 72.3 TAG, HEA 125 and Ber-EP 4 would be of help in distinguishing carcinomas from a mesothelial process (mesothelioma/pleuritis) in pleural effusion specimens routinely processed by the cytoblock method. All of the 20 carcinomas included in the study but also 19 of the 20 mesotheliomas expressed cytokeratin (KL 1), whereas vimentin expression was found in 7 of the 20 carcinomas and 19 of the 20 mesotheliomas. 19 of the 20 carcinomas reacted with the epithelial markers B 72.3 and HEA 125, and 18 of them with Ber-EP 4. In contrast, only a few of the 20 mesotheliomas showed a weak reaction to these markers (1 with HEA 125, 2 with B 72.3, and 3 with Ber-EP 4). BMA-130 c was detected in 10/20 carcinomas but in none of the mesotheliomas. BMA-120 was observed in the effusions from 17/20 mesotheliomas and in cover cells which had undergone reactive changes, but also in 2 cases of ovarian carcinoma. The results show that reaction to the "epithelial markers" B 72.3, HEA 125 and Ber-EP 4 is strongly indicative of carcinoma and not of mesothelioma, whereas a positive reaction with the antibody BMA-120 in the absence of reaction to the epithelial markers makes a mesothelial process very likely. However, immunocytochemical distinction cannot be made as yet between mesothelioma cells and pleuritic cells. If simultaneous positivity for BMA-120 and an "epithelial marker" in a pleural effusion is observed the primary tumor could be an ovarian carcinoma.

Antibodies, Monoclonal↗

Tumor cells in intraoperative pleural lavage. An indicator for the poor prognosis of bronchogenic carcinoma.

Fifty-nine patients with bronchogenic carcinoma and 21 patients with nonneoplastic lung diseases underwent intraoperative pleural lavage with 300-ml physiologic saline before (Lavage I) and after resection (Lavage II). The presence of tumor cells in the lavage fluid was established cytologically in 29 patients with bronchogenic carcinoma. Twenty-seven had positive findings in Lavage I and 23 of these also in Lavage II. Two patients had positive findings in Lavage II only. All controls were negative. In all 40% of patients with Stage I bronchogenic carcinoma had positive lavage results. The cumulative two-year survival rate of this group is 40%, which differs significantly (P less than 0.01) from the 97% survival rate of the patients with the same tumor stage whose lavage findings were negative. Detection of tumor cells in pleural cavity washings before resection proves that tumor cells have spread into the pleural cavity. Cytologic examination of an intraoperative pleural lavage should be done when assessing the tumor stage.

Adenocarcinoma↗

[Determining the prognosis in bronchial carcinoma by intraoperative pleural lavage].

Pleural lavage with 300 ml physiological saline was undertaken at thoracotomy (before and after resection) in a prospective study of 59 patients (49 males and 10 females; average age 59.7 years, range 41-76 years) with first manifestations of a bronchial carcinoma. The aim was to find out whether, even at an early stage of the tumour, there are tumour deposits in the pleural cavity. The lavage fluid was centrifuged and the sediment then embedded in paraffin and prepared for cytological examination. Tumour cells were demonstrated before resection in 27 patients (45.8%), in 23 of them also after the resection. Among 38 patients, previously classified as being in stage I, the lavage material was positive in 15 (39.5%); tumour cells were demonstrated in 5 of 18 patients in stage pT1. The cumulative two-year survival rate of non-small-cell bronchial carcinoma in stage I (n = 32) was 39.9% if the lavage was positive, 97.4% if negative (P less than 0.01). The results indicate that a positive finding on pleural lavage corresponds to a pT4 stage with a poor life expectancy.

Adenocarcinoma↗

Immunocytochemical identification of osteogenic bone tumors by osteonectin antibodies.

18 bone-forming tumours and tumour-like lesions were investigated immunocytochemically for the presence of osteonectin. A group of non-bone-forming skeletal tumours (five cartilage-forming tumours, four Ewing sarcomas and five extraskeletal sarcomas) served as controls. The studies showed that osteonectin antibodies react reliably with benign and malignant bone-forming tumours (two cases of fibrous dysplasia, three osteoid osteomas, 13 osteosarcomas). This finding was supported by protein blot studies. Osteonectin is formed by cells which do not yet possess the morphological phenotype of osteoblasts and may be regarded as a "differentiation marker" of the osteoblastic lineage. Only chondroid bone (tissue in which chondrocytes were surrounded by osteoid matrix containing type I and type II collagen) showed a positive reaction. All other primary skeletal tumours and extraskeletal soft tissue tumours were completely negative.

Antibodies↗

Immunohistochemical study of osteonectin in various types of osteosarcoma.

Polyclonal antibodies against osteonectin, a 32 kd non-collagenous bone protein, were applied for the histogenetic identification of variously differentiated osteosarcoma tissues. A strong positive reaction was found in matrix-producing osteosarcoma cells of the osteoblastic type, but pleomorphic or fibrosarcomatous osteosarcoma tissues reacted focally positive as well. Because the production of osteonectin depends on the osteoblastlike function of the individual tumor cell, a homogeneous immunocytochemical staining of all tumor cells cannot be expected. Nevertheless, the immunocytochemical demonstration of osteonectin in osteolytic tumors that produce no or scarcely any matrix seems to be a valuable tool for establishment of their osteogenic origin.

Animals↗

Osteonectin--a differentiation marker of bone cells.

Bone matrix consists of type-I collagen and non-collagenous proteins. The latter represent only 10% of its total protein content. Since type-I collagen is also present in various other connective tissue sites (e.g., skin) it cannot be considered as bone specific. Among the non-collagenous components osteonectin--a 32 kilodalton (KD) glycoprotein linking mineral to collagen fibrils--is thought to be bone specific due to its biochemical properties. In the present study various skeletal and non-skeletal tissues were investigated for the presence of osteonectin by means of immunocytochemical methods. Two polyclonal antibodies against human and bovine osteonectin were applied. Immunocytochemically, osteonectin could be demonstrated in active osteoblasts and osteoprogenitor cells as well as in young osteocytes, while aged, quiescent osteocytes did not contain the protein, suggesting that the protein is a marker of the osteoblastic functional differentiation of bone cells. Osteonectin was absent in all non-skeletal tissues with the exception of chondrocytes in so-called mineralizing chondroid bone.

Antibodies↗