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Biomedical subjects

A Burkhardt

Publications and source records attributed to A Burkhardt.

At least 73 records · Page 4Linked to original sources

Giant cell stromal reaction in squamous cell carcinomata. Electronmicroscopic and ultrahistochemical observations on the genesis and functional activity of multinucleated giant cells in bleomycin-induced tumor regression.

Ten cases of oral squamous cell carcinoma, treated by bleomycin, were studied by electron microscopy with particular regard to the stromal reaction. The genesis and phagocytic function of multinucleated giant cells of foreign body type were observed. These cells phagocytize devitalized, keratinized tumor cells in particular. Their genesis from monocytic macrophages and endocytosis of large keratinized tumor cells are described in detail. Both phenomena are connected and the mode of formation of the cells results in functional specialization. The initial stages of intracellular digestion do not seem to take place within membrane limited vacuoles but in specialized cytoplasmatic areas which are formed around the ingested material. These contain high concentrations of hydrolases, sealed off from the rest of the cell by a clear zone of organell-free cytoplasm. This unique form of phagocytosis and digestion ("gigantophagocytosis*) is only possible in these highly specialized giant cells and explains their biological significance. It is likely that secondary lysosomes are formed in subsequent stages of digestion. The difference between our results and the experimental observations of other authors are discussed.

Bleomycin↗

Unusual obliterative disease of the hepatic veins in an infant.

Hepatic fibrosis with obliterative lesions of the small hepatic veins occurred in a three month old infant with fatal congenital leukaemia treated with cytostatic drugs. The vascular changes were characterized by an unusual, hitherto unreported angiomatoid, proliferation of the endothelium. The process is compared with the more common subendothelial-fibrous type of the "veno-occlusive disease". An etiological interpretation is difficult, possibly the process is a secondary reaction to the endothelial to a cytostatic-induced lesion with hepatic fibrosis.

Antineoplastic Agents↗

[Bleomycin lung (author's transl)].

Histological and electron-microscopic study of the lungs of 15 patients who had been treated with bleomycin for advanced squamous cell carcinoma demonstrated marked histological changes in nine. They were typical of bleomycin effects: alveolitis, intra-alveolar and interstitial oedema, pulmonary hyaline membranes, disseminated intravascular coagulation, intraalveolar and interstitial fibrosis, atelectasis, metaplasia and dysplasia of the alveolar lining cells. These lesions had a focal distribution, preferentially in the subpleural and periseptal regions. Each of these lesions alone is a non-characteristic reaction, but their combination makes it a distinct entity (bleomycin lung). Three different clinical courses were noted: (1) cases with no or little abnormality; (2) acute form during or shortly after bleomycin treatment; (3) chronic, progressive form of bleomycin lung which may end fatally as late as 1 1/2 years after bleomycin treatment had been discontinued. Squamous cell metaplasia is the most characteristic sign of bleomycin lung. It should not be confused with pulmonary metastases. To prove the diagnosis of bleomycin lung often requires systematic histological investigation. A schema of the pathogenesis of the bleomycin lung is proposed in which the formation of microthrombi plays an important part.

Aged↗

[Morphological classification of oral leukoplakia (author's transl)].

656 cases of oral leukoplakia were analysed according to macroscopic aspects, microscopic growth patterns and histologicalcytological differentiation, and the relationship to cancer of the oral cavity was studied. Homogeneous and speckled leukoplakia can be distinguished macroscopically, while flat (70%), papillary-endophytic (22%) and papillomatous-exophytic (8%) types can be distinguished by their growth pattern. Histological-cytological characteristics consist of epithelial hyperplasia (hyperkeratosis with ortho- or parakeratosis; akanthosis) and epithelial dysplasia (dyskeratosis, basal-cell hyperplasia, loss of polar arrangement of the basal cells, cell polymorphism, increased mitosis rate). No or little dysplasia was demonstrated in 74% of leukoplakias, moderate in 17% and marked in 6%. Carcinoma-in-situ, defined as high-grade dysplasia with additional loss of epithelial layering, was found in 3%. Precancerous leukoplakia (in almost 10% of cases, counting high-grade dysplasias and carcinoma-in-situ) must be delineated as a special group. Numerous correlations were found between dysplastic leukoplakias and oral cavity cancer as regards localisation, age and sex distribution. In the various leukoplakia forms there was an increased incidence of marked stroma reactions and of Candida colonisation with increased degrees of dysplasia.

Adolescent↗

Vascular lesions following perfusion with bleomycin. Electron-microscopic observations.

During intra-arterial perfusion therapy of oral squamous cell carcinomas with bleomycin, circumscribed necrotic areas in the perfused region are observed in a few cases. These are usually located in the acral regions. As the cause, a lesion of the blood vessels with formation of microthrombosis could be demonstrated. Electron-microscopic observations of the blood vessels in five bleomycin-perfused tumor areas demonstrated lesions of the endothelium characterized by swelling of the cells, formation of intracytoplasmatic vacuoles and villous projections into the lumen of the vessel. In arterioles, separation of the endothelium from the underlying tissue, swollen smooth muscle cells and destruction of elastic lamellae were found. These were the pacemakers for the formation of thrombosis. A negative influence of the vascular lesions on the cytostatic effect on the tumor is likely. Vascular lesions also constitute one of the initial factors for the development of the bleomycin-induced lung lesion (bleomycin lung).

Bleomycin↗

[Intraarterial bleomycin therapy on squamous cell carcinomas of the oral cavity. Clinico-pathological investigations (author's transl)].

The mode of action of bleomycin after intraarterial perfusion in 53 patients with advanced squamous cell carcinoma of the oral cavity is reported on the basis of clinical results and pathologico-anatomic findings. In 29 out of 32 cases not previously treated a clinically complete remission could be achieved by primary chemotherapy. In 8 cases these findings were histomorphologically confirmed and 7 patients have shown a persistant remission for 9 to 61 months. The chances of success are much less favorable in the treatment of recurrences. No clinical advantages were observed when combining bleomycin with other chemotherapeutics.

Antineoplastic Agents↗

[Obliterative disease of liver veins: clinical, diagnostic, therapeutic and pathogenetic aspects of Budd-Chiari syndrome (author's transl)].

Both external and internal factors have to be thought of as causes of obliterative disease of liver veins. Pathogenetically, thrombosis or proliferative vascular disease (endophlebitis hepatica obliterans) may affect either large veins (with occlusion of the ostia) or small ones. Veno-occlusive disease, caused by pyrrolizidine derivatives, is a special form. Injection of contrast medium to the inferior vena cava and (or) the liver veins is the most important diagnostic method. In two personal cases there was secondary occlusion of the liver veins as a result of IVC thrombosis, while in a third case there was non-thrombotic proliferative disease of the wall of the small hepatic veins, closely similar to veno-occlusive disease. In a 19-year-old girl in whom thrombosis of the vena cava (with signs of liver-vein occlusion) occurred after pregnancy, revascularisation was achieved by fibrinolytic treatment.

Adult↗

[Formation of giant cells in oral squamous cell carcinoma during bleomycin treatment: enzymehistochemical, electronmicroscopic and ultrahistochemical investigations (author's transl)].

During treatment of keratinizing squamous cell carcinomas with bleomycin tumor cells are devitalized by keratinization, while simple necrosis plays a minor role. Connected with this process is a marked resorptive granulomatous inflammation with numerous macrophages which is followed by a fibrous organization. In the border region of the keratinized tumor areas many multinucleated giant cells appear. The nature of these giant cells was the subject of controversy. Enzyme histochemical, electronmicroscopic, and ultrahistochemical investigations in three cases of advanced squamous cell carcinoma of the oral cavity prove that the giant cells which are formed during bleomycin treatment are not multinucleated tumor cells, but multinucleated macrophages. The enzymatic pattern is similar to macrophages with a high content of acid phosphatase and aminopeptidase. The ultrastructure of the giant cells is characterized by lysosomes with acid phosphatase activity, pinocytotic vesicles, and cytoplasmic projections on the cell surface with signs of macroendocytosis. The tumor cells show an epithelial differentiation with desmosomes, tonofibrils, and keratohyaline granula. The giant cells are formed by fusion of mononucleated (monocytogenic) macrophages. The fusions seem to be related to the functional status of the cells. It is possible, that the macrophages and the giant cells have an additional immunologic function. This is suggested by the frequent association of giant cells with lymphocytes. The importance of these facts for the evaluation of the action of bleomycin and the consequences for its therapeutic use are discussed. A combination with methods causing a dedifferentiation of the tumor or suppression of the immunologic defense seems to be problematic.

Acid Phosphatase↗

[The Verner-Morrison syndrome. The clinical picture and pathologic anatomy].

The Verner-Morrison Syndrome is a clinically defined entity caused by an islet cell tumor of the pancreas. More than 60 cases have been described so long. The syndrome is characterized by diarrhea, hypokalemia and hypochlorhydria. In addition to a diabetic disposition, raised calcium levels and skin alterations may be present. The diagnosis is a clinical one. A pancreatic tumor should be searched for and removed. Morphologically a benign and a maligne islet cell tumor or a diffuse hyperplasia of the islets of Langerhans can be found. Until now identification of the tumor cells has not been possible. There seems no doubt that the tumor cells produce a peptide hormone. Secretin, gastric inhibitory polypeptide, vasoactive intestinal polypeptide and combinations of hormones are discussed. The results are contradictory. Theories concerning the formal and causal pathogenesis are only incomplete and unproved up to now.

Achlorhydria↗

[Diarrhea and islet cell tumor. Clinical and morphological report on 2 observations].

The combination of diarrhea with an islet cell tumor (Verner-Morrison Syndrome) is a clinical picture presenting many diagnostic problems. It is probable that larger numbers of cases will be encountered with more widespread knowledge of this disease. The clinical features and the pathologic-anatomical findings of two characteristic cases are reported and discussed.

Adenoma, Islet Cell↗

[Desmoid tumors (invasive fibromas) in the mouth and maxillofacial region (clinical aspects and pathology)].

The desmoid is the independent pathological entity of a non-metastasizing fibroma invading the local neighboring structures. It is derived from fascia, aponeuroses or tendines. In rare cases it is found in the oral and maxillofacial region. For a firm diagnosis, it is absolutely necessary to combine clinical data (location, size growth, behavior vis-a-vis adjacent structures) with pathologic-anatomic findings (invasion of the adjacent tissue, especially musculature). In this respect, examination of the marginal regions is of decisive importance. Because of the frequency of recurrences and the danger of sarcomatous degeneration, radical resection is the therapy indicated.

Adolescent↗

The effects of intra-arterial bleomycin therapy on squamous cell carcinoma of the oral cavity. Biopsy and autopsy examinations.

The results of a clinico-pathologic study of 7 cases of advanced squamous cell carcinoma of the oral cavity are presented, which were treated by intra-arterial perfusion of bleomycin. In 5 cases, no histologically vital residual tumour could be found locally after therapy. The tumour area shows advanced fibrosis, and ulcerated areas have re-epithelized. The tumour cells are devitalized by keratinisation, while simple necrosis plays a minor role. Following the keratinisation there is a marked resorptive granulomatous inflammation with giant cells typical of a foreign body reaction and fibrous organisation. The special type of reaction of the tumour cells with keratinisation seems to be important for biopsy examinations and for therapeutic considerations. It explains the therapeutic success in highly differentiated squamous cell carcinomas with a tendency for keratinisation. For the first time a "cell-specific, cytocidal" therapy seems to be possible. Previous or simultaneous therapy with methods which might cause a de-differentiation of the tumour, seems to be harmful. Also with intra-arterial perfusion the lung must be considered as the target for the most serious side effects. In one case a bleomycin-induced lesion of the lung was the cause of death, in 4 cases a bronchopneumonia. Although in all cases the therapeutic chances and the prognosis were poor, 4 patients were cured of the tumour. One patient has lived without recurrence or metastases of the tumour for 20 months.

Aged↗