[The effect of air pollutants on cultured lung cells].
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Publications and source records attributed to K Kayser.
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Survival, pTN stages, and cell type of patients operated on for bronchus carcinoma were evaluated in a retrospective study and compared with data obtained in a prospective study. One thousand three hundred thirty-two patients with potential curative resected lung carcinoma were included in the retrospective study. Two hundred eighty-two patients with potential curative resected lung carcinoma were analyzed in the prospective study. Data showed similarities in distribution of cell type and relative frequency of pT1 stage in both collectives. Major differences between both studies were obtained in relative frequencies of pT3, and pN0, pN1, and pN2 stages. Survival of patients grouped according to cell type revealed differences between patients suffering from epidermoid-adeno carcinoma and patients suffering from small anaplastic carcinoma--large cell anaplastic carcinoma in both studies. Patients stated as pN0 stages showed more favourable prognosis in the prospective study compared with patients of the retrospective study. Two-year survival rates of patients grouped into a pT1pN0 stage and into a pT2pN0 stage had similar survival rates in both studies. Survival of these cohorts compared with patients staged as pT1pN1 and pT2pN1 was statistically significantly better. The data indicate that patients suffering from pT1pN1 or pT2pN1 tumors should be classified as Stage II tumors.
TNM stage, immunostaining with various monoclonal and polyclonal antibodies, analysis of distance of neighboring cells, remission rates, and survival were analyzed in 60 patients suffering from small cell anaplastic carcinoma of the lung. The majority of patients showed advanced tumors at the time of admission to hospital (T2, T3 stage). Distant metastases prior to chemotherapy were detected in 34 patients. Partial remissions lasting 2-4 months were observed in 38 patients, and complete remission was documented in 7 patients. The remission rate was independent of cell type but dependent on the stage of the tumor. Some 30 patients showed positive staining with an antibody recognizing epitopes detectable on carcinoembryonic antigen, whereas 60% of the tumors were positive to a polyclonal neuron-specific enolase antibody. Tissue polypeptide antigen was found to stain positively in 5 cases only. Some 14 patients with negative staining against the monoclonal antibody BMA 406/14 showed prolonged survival compared to patients with positive staining (P less than 0.05). Patients suffering from tumors with smaller distances between neighboring cells had worse prognoses compared to patients with larger distances (P less than 0.01). Survival of patients was found to be indistinguishable if cohorts were grouped according to T stage, N stage, or existence of distant metastases. Ten patients who underwent surgical treatment of tumors did not show prolonged survival compared to 50 patients treated by combined chemotherapy only.
One hundred cavitating pulmonary foci were examined by CT; the appearances have been analysed and compared with the histological findings. Three types of disease have been characterised: bronchial carcinomas, lung metastases and benign lesions. Compared with benign lesions, malignant disease shows a significantly higher incidence of cystic or multiple cavities: thick cavity walls; radiation of tumour tissue; enlarged mediastinal lymph nodes; ipsilateral displacement of the mediastinum; intrapulmonary satellite foci and infiltration of the thoracic wall. Morphologically, tumours can be most easily distinguished from metastases by their ill-defined outer contours. Non-epidermoid primary lung tumours have a higher incidence of pleural effusions and other pleural reactions than have tumours of other origins. 80% of cavitating lung tumours are squamous cell carcinomas, the remaining 20% consist of adeno- and large cell carcinomas. Small cell carcinomas practically never show cavitation.
A case with advanced diffuse pulmonary ossification is described. The patient underwent surgical treatment of a malignant nodular melanoma of the right shoulder followed by postoperative cytostatic therapy for 6 months. He developed renal insufficiency and pulmonary infiltrates 3 years after the operation. Two metastases into the lung were operated 4 years after extirpation of the melanoma. Histopathological findings revealed two major metastases of a malignant amelanotic melanoma and multiple tumour thromboses in lymphatic and venous vessels. Severe interstitial lung damage including diffuse pulmonary ossification and focal interstitial fibrosis was noted. Morphometric measurements of ossified nodules revealed increased ossification in fibrotic lung areas. Immunohistology for differentiating immunoglobulins and lymphocytic subpopulations was insuspicious. The findings suggest that diffuse intraalveolar ossification is probably not related to pulmonary congestion.
In vivo invasion of human carcinoma of the lung into the cartilage of the bronchus was studied by light microscopy. Tumor spread into the cartilage was found in 26% (60/229). It occurred in 38/128 epidermoid carcinoma (30%) and in 14/55 adenocarcinoma (25%), but was observed in only 1/17 large cell anaplastic carcinoma (6%). Degradation of cartilage matrix was found to be limited. Destroyed area measured 9.9 +/- 1.8 mm2 on average. Tumors able to destroy bronchus cartilage were similar in size compared to tumors without detectable invasion into cartilage. Analysis of pTN stages revealed no differences between both groups. Tumor volume in extrapulmonary lymph nodes was significantly larger in case of cartilage degradation. Patients with tumors degrading bronchus cartilage showed poorer survival (median survival 360 vs. 780 days, p less than 0.10). Immunohistology differentiating inflammatory cells (B lymphocytes, T lymphocytes, monocytes, granulocytes, macrophages) revealed no participation of inflammatory cells in tumorous degradation of cartilage. The findings suggest that hyalin cartilage is highly resistant to invasion of human lung carcinoma although evidence exists for proteolytic activity of human lung carcinoma.
Clinical history and wedge biopsy specimen findings of a Vietnam veteran suffering from progressive severe tissue damage of lung are presented. The patient served as a soldier in defoliated areas for 2 years and developed severe chest pain and dyspnoea with chronic postnasal dripping, maxillary sinusitis and allergic asthmoid bronchitis with pronounced obstructions and eosinophilia. Recurrent onsets of symptoms over a period of 10 years led to wedge biopsies of the left upper lobe, right lower lobe and mediastinal lymph node. Histology is consistent with chronic, slightly progressive diffuse alveolar damage including moderate interstitial fibrosis. Total destruction of mediastinal lymph node with deposits of amorphous material and foreign body giant cells were noted. Histology findings and clinical course favor hypersensitivity reaction of lung and congestion of exogeneous material probably related to exposure to herbicides.
A total of 126 resection specimens from malignant lung tumors were cut into serial sections, and tumor volume and macroscopic growth pattern were computed. Four characteristic tumor growth patterns could be separated: Tumors growing in bizarre, irregular shapes; Tumors growing in spheroid shapes; Tumors growing in ellipsoid shapes; Tumors growing in mixed growth pattern. The immunologic response of the host tissue was analyzed grading the number of lymphocytes, plasma cells, macrophages in and at the boundary of the tumor tissue. Lymphocytic subpopulations were analyzed in 46 cases using monoclonal antibodies (BS3/BS4; T3, OKT4, OKT8, OKT11, OKT14). The majority of lymphocytes were T-lymphocytes and monocytes in cases with inflammatory response of host tissue. The ratio of inducer/helper subset (OKT4+) compared to suppressor/cytotoxic subset (OKT8+) was similar in expression as reported for circulating peripheral T-lymphocytes. The different growth patterns depend upon cell type of tumor, immunologic response of the host tissue, and tumor volume. The findings indicate that tumor progression into lung tissue is partly due to "localized metastatic growth" of different tumor cell subpopulations.
From 1973 to 1983 170 patients underwent surgical treatment of small cell lung cancer. In 2/3 of the cases we performed lobectomy resp. bilobectomy including bronchoplastic and arterioplastic resections, the other third of patients underwent pneumonectomy. 26 patients (15%) died within 30 days. Postoperative mortality in patients with pneumonectomy was 17% and in patients undergoing lobectomy 7%. Since 1978 lethality rate dropped from 20% to 7%. Due to polychemotherapy, estimated time of survival (according to Kaplan and Meier) has increased significantly, adding up to 3-years- and 5-years-survival rates of 31% and 20% respectively.
A new algorithm analyzing neighborhood conditions of adenomatous tissue is is introduced. Using O'Callaghan's definition of neighborhoods, a graph theory approach for measuring histomorphological structures can be created as follows: glands are defined as vertices and the coherence of neighboring glands as edges. The procedure leads to an unoriented, well-defined graph which contains information usually not measurable by conventional morphometric analysis. Measurements on healthy mucosa, tubulo-villous adenoma and highly to moderately differentiated adenocarcinoma of colon revealed statistically significant differences (p less than or equal to 0.05) for the following parameters: number of vertices, number of edges, frequency distribution of n-stars and of n-closed paths. Correct separation and reclassification of 83% of cases could be carried out using discriminant analysis. 11/15 cases (73%) could be classified correctly in a prospective group based upon the learning set. The significance of these findings for automatic pattern recognition in histopathology is discussed.
Poor long-term results following the surgical management of small cell carcinoma have contributed to the opinion that small cell carcinoma is a non-surgical disease; polychemotherapy is generally given preference. As nowadays adequate therapy (chemotherapy) achieves control of local tumor growth as well as of extended metastases, surgical resections should be discussed from a different viewpoint: "Does surgery profit from modern chemotherapy?" In our clinic, 1332 patients have been operated on for bronchogenic carcinoma from 1973 to 1983: 170 (12.8%) suffered from small cell carcinoma. The indications for surgery were either non-histologically classified tumors (e.g. peripheral coin lesions) or small cell carcinomas stage I, and only in rare cases for palliative reasons. Lobectomy, including bronchoplastic and arterioplastic resections (n = 108), was the most common procedure. The postoperative mortality was 15%, the average survival 341 days, the latter having improved significantly since 1979 when a postoperative polychemotherapy (ACO) was instigated. Recent results of surgical resection after primary chemotherapy are encouraging. Nevertheless, this new concept is reserved for the few cases of strictly limited disease and must be controlled by future studies.
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Three hundred and fifty-three resection specimens with primary lung carcinomas were cut into serial sections, and the tumor volume was computed. Resected lymph nodes were cut into 0.3-mm serial sections and analyzed for metastasis. The inflammatory reaction of lung tissue was analyzed by grading the amount of inflammatory infiltrations of a complete tumor cross section. Survival of patients was evaluated by consulting the house physician every 3 months after surgical treatment. Percentage of specimens with severe inflammatory reaction of host tissue increased remarkably in tumors with a volume of 35-60 cm3. Percentage of patients with detectable lymph node metastasis increased with tumor volume but decreased at the tumor volume of 35-45 cm3. Mean tumor volume in patients with no detectable lymph node metastasis was increased if severe inflammatory response of host tissue existed. Survival of patients with severe inflammatory infiltrations was superior to survival of patients with no inflammatory infiltrations if grouped for tumor volume. Data indicated that inflammatory infiltrations in primary lung carcinoma may partly be related to the immunologic response of host tissue to tumor growth. Inflammatory infiltrations may delay tumor cell propagation into lymph nodes or may be even able to destroy small tumor cell agglutinations.
Three murine monoclonal antibodies (MAbs) reactive to different epitopes on CEA were selected according to their ability to bind to various human tissue sections. The most selective MAb, BW 431/31, bound to the majority of colon carcinomas but only faintly to normal colon mucosa. In addition to the tissues stained by MAb BW 431/31, MAb BW 250/183 reacted with granulocytes, colon mucosa and faintly with pancreatic ducts. The third MAb, BW 374/14, reacted with granulocytes, colon mucosa, strongly with pancreatic ducts and with alveolar and bronchial epithelium. The antigenic determinants recognized by the 3 MAbs in human tissue sections were resistant to formaldehyde fixation and paraffin embedding as well as to periodic acid oxidation and neuraminidase treatment. The last two treatments suggest that the epitopes are protein in nature. Using MAb affinity chromatography, 3 antigen preparations were isolated from a human colon carcinoma xenograft with an approximate molecular weight of 180 kd. These preparations were shown to bear the epitopes from each of the MAbs and from a polyclonal antiserum specific for purified CEA. Furthermore, the ability of MAb BW 431/31 to localize its antigenic determinant in vivo on a human colon carcinoma xenograft is evaluated and its possible application in the patient is suggested.
126 resected malignant lung tumours were cut into serial sections. The tumour volume, the pTN-stage and the macroscopic growth pattern were computed. The average tumour volume was found to be 28.5-35.8 cm3 (confidence limits, p greater than or equal to 95%) and to be independent of the major cell type of the carcinomas. The cell types grow in different macroscopically distinguishable tumour growth patterns: epidermoid carcinomas grow mostly in bizarre finger-like shapes and small cell anaplastic and adenocarcinomas more frequently in ball-like shapes. The different growth patterns depend on the cell type, the cellular response of the host tissue and the tumour volume. Due to irregular growth pattern the tumour volume computed by X-ray diameter is likely to be overestimated by 50%-300%.
All cases of the Regional Cancer Registry, North Baden who developed a gastro-intestinal cancer during the period 1975-1980 were re-examined according to the following parameters: tumor volume, pT stage, pN stage, grading. In the period considered, 8424 cases out of 14,061 cases with histologically proven gastrointestinal cancer could be grouped according to the pT stage. Most of the cases were operated at the pT2 or pT3 stage. Remarkable differences in the different tumor localizations were obtained. Stomach carcinoma had the highest percentage of the pT4 stage (36.2%), rectum carcinoma the lowest (7%). In all primaries a close coherence of tumor volume and pT stage was noted. Carcinoma at the pT1 stage measured 20 cm3 on average, those at the pT4 stage 170 cm3. No coherence of staging and age of the patients could be obtained. Younger patients showed a higher percentage of undifferentiated carcinoma than older patients. Survival data could not be obtained due to the data protection law.
A small primary lung lesion had remained unchanged in size over a period of 8 years. Within the ensuing 2 years rapid tumor growth occurred. On operation the surgical specimen revealed a tumor mass of 87.2 cm3. Within 6 months after resection, the tumor occurred on the same side. Extensive tumor infiltration of the chest wall prevented any further surgery. The histo-morphologic picture of both lesions was consistent with a lymphangiosarcoma without evidence of high grade malignancy. The patient died of cardio-respiratory insufficiency due to extension of the tumor mass. Unfortunately no autopsy was performed. Tumor growth rates, macroscopic reconstruction and electron microscopic evaluations are presented. This case report again points out that size and long-time stability of solitary lung nodules are not necessarily reliable criteria for assessing prognosis.
Population-based data of malignomas of the gastro-intestinal tract were evaluated from the regional cancer registry North-Baden for the period of 1971-1980. The age standardized incidence of oesophagus carcinomas shows a steady level of 4.5/100,000 (males) and 0.5/100,000 (females); the age standardized incidence of stomach carcinomas increased from 1971 to 1974, then shows a decline for both males and females, where the colon carcinomas show an increase of 80% for the same time period, also the cancer of the small intestines and of the rectum, increased slightly. Compared to data of other cancer registries the world standardized incidence of rectum carcinomas is of the same level as the data from the cancer registry of Bas-Rhin and is with an incidence of 25.8/100,000 males; 16.2/100,000 females above the incidence of all other cancer registries. The post-operative TNM-stage differs for the different primary topographies. Especially patients with colon carcinomas were operated when the carcinoma was in an advanced stage, patients with rectum carcinomas were operated at a less advanced stage. Male patients with an oesophagus carcinoma showed in a significant percentage an advanced smoking and alcohol consumption, compared to patients suffering from stomach, colon or rectum carcinomas. The specialized organisation of the cancer registry shows a high efficiency due to the requirements of the public health system, and is very useful in the evaluation of descriptive and analytic population-based cancer data.