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BACKGROUND: The goal of this study was to investigate late effects following stereotactic single fraction and small volume irradiation on cerebral blood flow and histologic alterations in the rat brain parenchyma. MATERIAL AND METHODS: 66 Copenhagen rats, separated into eleven groups of six animals each received single doses of 20, 30, 40, 50 and 100 Gy using a 15 MV linear accelerator. Six rats served as controls. Two cylindrical collimators of 2 mm and 3 mm aperture were used. The diameters of the spherical 80% isodose were 3.7 and 4.7 mm, respectively (Table 1). Irradiation was applied to a predefined area in the right frontal lobe. 19 months after irradiation local cerebral blood flow (LCBF) was measured by the autoradiographic method in one animal of each dose group between 20 and 50 Gy. 9 and 19 months after irradiation, half of the animals of each group were sacrificed for brain histology. All animals irradiated with 100 Gy were sacrificed 7 months after irradiation. RESULTS: An increase of local cerebral blood flow was measured in brain structures within the 80% isodose in animals irradiated with 50 Gy (Figure 3) compared to the contralateral hemisphere. Measurements close to necrotic areas showed a strong decrease of local cerebral blood flow (Figure 1). A volume increase of the irradiated hemisphere was seen after 19 months (Figure 2). The histologic examination after 19 months showed necrotic areas in the 30-50 Gy groups (Figure 4b) but not in the 20 Gy groups (Figure 4c). The animals who received 100 Gy demonstrated brain necrosis within 9 months after irradiation (Figure 4a). At both points in time the groups irradiated with the 3-mm collimator showed more pronounced histomorphologic and functional changes compared to the groups irradiated with the 2-mm collimator. CONCLUSION: Alterations of the local cerebral blood flow were measured as a late effect after single dose irradiation. The alterations of the local cerebral blood flow could be explained by the histomorphologic changes of the blood vessels. Using a semi-quantitative classification a dose, time and volume dependence for the endpoint radionecrosis was seen.

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PURPOSE: To investigate structural and functional changes in rats after focal brain irradiation by using histologic, immunohistochemical, and angiographic methods. MATERIALS AND METHODS: Sixty rats were irradiated stereotactically with photons from a 15-MeV linear accelerator. Two collimators and single doses ranging from 20 to 100 Gy were used to treat stereotactically defined areas of 3.7- and 4.7-mm cross section (80% isodose) in the right frontal lobe. The dose-response relationship for the end-point necrosis at 19 months revealed a mean tolerance dose (D50) of 34.2 Gy (standard errors: +4.1, -3.7 Gy). Histologic, immunohistochemical, and angiographic examinations were performed to evaluate delayed radiation effects. RESULTS: All animals irradiated with 100 Gy developed radiation necrosis after 9 months. Microangiography and immunohistochemical fluorescence staining of the endothelial cells revealed dose-dependent vascular dilatation and rarefaction. Animals irradiated with 20-50 Gy showed no morphologic changes after 9 months. With irradiation of 30-50 Gy, histologic vascular changes that increased with dose were found after 19 months. At that time, no changes were detected after irradiation with 20 Gy with both field sizes and after irradiation with 30 Gy and the 2-mm collimator. Radiation-induced functional disturbances of the brain vasculature could be demonstrated by extravasation of contrast medium by using a microangiographic technique. CONCLUSION: The observed effect had a definite dependence on dose, volume, and time after treatment.

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We report about a secondary malignant fibrous histiocytoma of bone which is most frequently found in distal femur. It appears as a malignant form of a giant-cell tumor after the exposure to radiation. The typical symptoms given in literature publications: pain, swelling and the pathological fracture were present. After amputation there was no metastasis for 15 months.

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Twenty-two patients with vesical urothelial carcinoma associated with prostatic carcinoma were reviewed. They represented 1.5% of the bladder and prostatic tumours treated in our department within a 12-year period from 1968 to 1979. Their management included several treatment policies, based on the separate assessment of each tumour variant. For non-infiltrating bladder tumours, transurethral tumour resection was combined with hormonal treatment, external radiotherapy or resection of the prostate depending on the stage of the prostatic tumour. Radical cystoprostatectomy was performed for two cases of infiltrating bladder tumour with well localised prostatic tumours. A conservative primary approach seems justifiable in the management of double carcinoma of the bladder and prostate. The coincidence of bladder urothelial carcinoma and prostatic carcinoma per se is not an adverse prognostic factor; prognosis is more closely related to the pathological stage and grade of the bladder tumour. Cystoprostatectomy for patients with infiltrating bladder tumours could be curative, in selected cases, for the prostatic cancer as well.

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In 95 patients with acute necrotising pancreatitis the clinical severity of the disease was compared with morphological criteria of operative specimens. In addition, various morphological phenomena, typical in acute and chronic pancreatitis, were investigated in 3 aetiologically different groups. In these groups pathohistologic alterations, associated with aetiological factors, were seen frequently. Furthermore, there was a good correlation between classifications according to gravity criteria in the assessment of the underlying disease. About 90% of cases clinically classified as acute pancreatitis proved, on the basis of the morphology, to be chronic recurrent pancreatitis. It thus follows that "genuine" acute pancreatitis is a rather rare syndrome.

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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.

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Immunohistological investigations were carried out on human colonic tissue from, I healthy mucosa, 2 slightly inflamed mucosa, 3 mucosa with ulcerative colitis, 4 mucosa with Crohn's colitis, using antibodies against immunoglobulins and complement components. All our antibodies, including F(ab')2 fragments, demonstrated a progressive increase of labelled cells from healthy mucosa through slightly inflamed mucosa to mucosa with ulcerative colitis, in contrast to a complete absence of labelled cells in cases of Crohn's disease. The results are discussed with regard to their pathogenesis and their clinical significance for the differentiation of ulcerative colitis and Crohn's colitis.

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The microcystic adenoma of the pancreas is a very rare benign pancreatic tumour. This tumour, which is usually large and grows slowly, results in displacement and compression of the adjacent organs. Angiography reveals hypervascularisation. The characteristic structure of the tumour can be recognized both in the sonogram and in the computer tomogram.

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In order to identify amyloid deposits in patients over 60 years of age (so-called senile amyloid), the following five tissues were investigated under the light and electron microscope: 1. pituitary gland, 2. pancreatic islets of Langerhans, 3. heart, 4. aorta, and 5. brain. In all an increasing incidence of amyloid deposits was found with increasing age, and in the brain a significant quantitative increase in amyloid deposits with increasing age was observed. Despite the biochemical heterogeneity of amyloid found in old age, all the deposits seen in tissues examined were morphologically similar. Typical amyloid fibrils were always found (diameter 60-100 A), and these were invariably deposited extracellularly and primarily on basement membranes. The amyloid-binding basement membranes were in most cases those of myocytic, but were also those of endothelial or epithelial cells. The almost invariable involvement of blood vessels, indicates the importance of these structures in the genesis of the various forms of senile amyloid.

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Human and experimental amyloidosis can occur either as a generalized widespread deposit of various proteins or a localized deposit. We looked for local amyloidosis caused iatrogenically under clinical and experimental conditions. Subcutaneous tissue from one diabetic patient and six Wistar rats, which had received a continuous local infusion of 1.2 iu of insulin daily for 6 weeks, was examined histologically. In all cases the development of granulation tissue around the tip of the catheter was observed. In addition, inhomogenous extracellular deposits showing green birefringence under polarized light when stained Congo red were seen. Immunohistologically, they displayed binding of anti-insulin antibody. Electron microscopy demonstrated a typical spear-like fibrillar structure with a fibril diameter of 60 to 80 A. These findings confirmed that the deposited substance was amyloid. Iatrogenically administered protein produced in vivo amyloidosis at the site of its entry. Insulin can lead to the formation of amyloid fibrils not only in vitro but also in vivo.

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Using light and electron microscopy, 65 cases of amyloid deposits in the heart were examined. Five different groups were distinguished: I. isolated atrial amyloidosis, II. senile cardiac amyloidosis, III. cardiac amyloid accompanying chronic infections and tumors, IV. cardiac amyloid accompanying plasma cell dyscrasia, V. idiopathic cardiac amyloidosis. Seen structurally, no principal differences in the precise localization of the amyloid deposits were found in any of the groups investigated. Amyloid is always deposited in the vicinity of cells with myocytic cell differentiation (i.e. the heart muscle cells, non-striated muscle cells of the vessels), whereby the relevant basement membranes serve as conductors. A systematic relationship between amyloid and the collagenous fibers of the interstitium or the tunica adventitia of the vessels could not be demonstrated, which shows the concept "pericollagen" to be inadequate for the morphological characterization of amyloid deposits in the heart. Whereas for group I a localized mechanism for the production of amyloid must be considered, in the case of groups II-V a vascular principle expression of a generalized amyloidosis seems to be the major factor. The question of the differing concentration of amyloid deposits in the heart suggests that localized factors (e.g. changes in the myocytic basement membranes) and quantitative changes of the amyloid-building proteins may also be important.

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Amyloid is a substance that has the same composition of the basic qualities even in the different patterns of amyloidosis. Electron microscopic investigations have revealed that all forms of amyloidosis do not only exhibit homogeneous basic qualities but also common principle of accumulation. This may be commented as follows: Fibrils of amyloid are always found in close connection with basement membranes or basement membrane-like substances respectively produced by cells with the property of contracting (myocytic or "myopotent' cells). Collagen fibres of different types do not display a regular relation to the substance of amyloid. The origin and development of the various forms of amyloidosis depends on the three following factors: 1. On the extent of the production of amyloidogenic proteins which may belong to different types of proteins according to the basic disease; 2. On the way of protein silting (hematogenic silting-generalized amyloidosis; local enrichment--local amyloidosis); 3. On the site of predilection of all deposits of amyloid in the areas of basement membranes or basement membrane-like substances resp. produced by cells with the properties of contracting. A new classification should be made on the basis of these principles.

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Amyloid-containing islets of Langerhans from the pancreas of 75 diabetics and one case of an amyloid-containing insulinoma were investigated. By light and electron microscopy, amyloid deposits were observed between the B cells and adjacent capillaries. The cytoplasm of B cells and extracellular amyloid display immunohistological binding of anti-insulin antibody. Correspondingly, ferritin-labeled anti-insulin antibody was found by electron microscopy on and between the amyloid fibrils. Insulin or proinsulin (or a protein closely related to insulin) thus appears to be a component of the protein which constitutes the amyloid. The molecular weight and mode of deposition of this form of amyloid are in agreement with other amyloidoses of the hormonal type (AH-type).

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After grading into 4 groups of severity the extent of amyloidosis of the islets of Langerhans was investigated in 60 patients with diabetes and in 60 without. Distinction of 3 stages of diabetes according to clinical parameters showed clear connections between the stage of diabetes and the extent of amyloidosis. Development of amyloid locally may be evidence for progressive B cell insufficiency in diabetes of adults.

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The article reports on seven patients with a histologically established chondromatosis of the joints. The aetiology, diagnosis, pathologico-anatomic findings and treatment of this rare joint disease are discussed. The case history of a patient serves to illustrate how a benign chondromatosis can undergo malignant degeneration.

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The typical criteria of the osseous liposarcoma will be discussed by means of a case report of a 69-year-old patient. The clinical symptoms as well as the macroscopic, light- and electron microscopic results justify a specification of this rare and controversially described form of a primarily malignant bone tumor.

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Lymphography has led to falsely negative or falsely positive diagnoses in 10 to 45 per cent of the cases of testicular tumor metastases reported in the literature. In our comparative study of lymphography and sonography in the preoperative staging of 29 malignant testicular tumors lymphography was accurate in 58.5 per cent of the cases, while sonography had an accuracy rate of 82.5 per cent. Sonography was superior to lymphography in the evaluation of hilar lymph node metastases and their extent, as well as for routine checkups after lymphadenectomy or irradiation.

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