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Biomedical subjects

W J Hofmann

Publications and source records attributed to W J Hofmann.

At least 73 records · Page 4Linked to original sources

Proliferative activity of neuroendocrine tumours of the gastroenteropancreatic endocrine system: DNA flow cytometric and immunohistological investigations.

The proliferative activity of 16 tumour specimens from 13 patients with neuroendocrine tumours of the gastroenteropancreatic endocrine system was studied by DNA flow cytometry and immunohistology for the nuclear Ki67 proliferation antigen. Equivalent results were obtained with both methods, which showed the proliferative activity of gastroenteropancreatic neuroendocrine tumours to be heterogeneous. In four malignant small intestinal carcinoids and one extravisceral carcinoid localised in the retroperitoneum the percentage (index) of proliferating tumour cells as measured by DNA flow cytometry ranged from 2.9 to 36.2% corresponding to low, moderate, or high proliferative activity. In four malignant pancreatic endocrine tumours and their metastases indices ranged from 8.7 to 18.3%, corresponding to low, moderate, or high proliferative activity. In four benign pancreatic endocrine tumours indices ranged from 4.3 to 7.7%, all corresponding to low proliferative activity. This heterogeneity of proliferative activity may in part explain the heterogeneous results reported of chemotherapy treatment. As chemotherapy of tumours is largely affected by favourable cell cycling kinetics, individual diagnostic investigations of the proliferative activity of these neuroendocrine tumours may be of value for identifying patients suitable for this treatment.

Adult↗

[Morphology and clinical picture of thymus carcinoid].

A large mediastinal tumour was discovered radiologically in a 50-year-old man, with at times blood-tinged sputum and dyspnoea. Parasternal needle biopsy revealed a thymic carcinoid. After surgical excision of the tumour, which had argyrophilic foci (total weight of tumour 1,605 g), histochemical analysis demonstrated neuron-specific enolase, synaptophysin and chromogranin, as well as calcitonin (as the only hormone). For the first time in a thymic carcinoid, radioimmunoassay demonstrated growth-hormone-releasing hormone (2 micrograms/g tumour tissue). Post-operative radiotherapy (total dosage 50.5 Gy) was instituted because histological examination had shown invasion of the capsule and blood vessels. There has been no local recurrence or metastases after three years.

Biopsy, Needle↗

Clinico-pathological features and surgical management of primary epithelial hepatic malignancies.

Between January 1983 and January 1990, 89 patients with primary epithelial hepatic malignancy were admitted to the Department of Surgery, University of Heidelberg, for surgical treatment. Histopathologically, tumours were hepatocellular carcinoma (HCC) 75, fimbrolamellar carcinoma (FLC) 1 and cholangiocellular carcinoma (CCC) 13. Concomitant liver cirrhosis was found in 61%. Among the cirrhotic patients, hepatitis-B infection was found in 65% and post-alcoholic cirrhosis in 30%. Pre-operative alpha-fetoprotein serum levels were elevated in 66% of the patients with HCC and none of the patients with CCC or FLC. The resectability rate was 35.9% (32/83). Twenty-six patients underwent curative resection; six were resected palliatively. In 44 patients exploratory laparotomy and biopsy only were performed. Thirteen patients remained without any surgical procedure. The hospital mortality rate after resection was 21.8%. Short-term prognosis depended predominantly on concomitant cirrhosis associated with peri-operative blood loss and extent of hepatic resection. Long-term survival rates after curative resection were 78%, 55% and 21% for 1, 3, and 5 years, respectively. Prognostic factors of long-term survival were investigated by the Kaplan-Meier method.

Adenoma, Bile Duct↗

Primary hepatic malignancies: resection or liver transplantation?

Liver transplantation in malignancies must be confined to patients with potentially curable disease. The indication is widely accepted, however, in non-resectable tumors or in patients with cirrhosis that excludes major resection. Without treatment prognosis is extremely poor in these patients. In our own experience 12 out of 13 non-cirrhotic patients with hepatocellular carcinoma (HCC) died within 9 months, and 17 out of 19 cirrhotic patients died within the first year of non-curative or explorative surgery. None of our patients with HCC in non-cirrhotic livers has lived longer than 38 months, and those with cirrhotic livers more than 61 months even after curative resection. After liver transplantation 1-year survival rate was 54% in 14 patients with primary hepatic carcinomas (12 HCC, 2 CCC). In cirrhotic patients with large or infiltrating HCC the results of resection are worse than after grafting, at least in the Western World, so liver transplantation must be taken into consideration. The lack of grafts limits treatment by transplantation in these patients. Transplantation is only exceptionally indicated for patients with metastatic liver disease.

Adenoma, Bile Duct↗

[Clinical aspects, morphology and long-term follow-up--retrospective study of 23 thymoma patients].

Twenty-three patients with a thymoma diagnosed in the period between 1967 and 1987, were investigated retrospectively. In all the patients, the major therapeutic procedure performed had been surgery. The most important factor for the prognosis proved to be the tumour stage established at surgery. In locally non-invasive thymomas, the long-term prognosis is unimpaired. In cases showing invasion of the capsule or surrounding tissue, the prognosis deteriorates markedly, in particular in thymomas in which radical surgery is not possible. For this reason, in all stages with microscopically or macroscopically recognisable invasion, local postoperative radiation treatment is recommended. The histological classification in accordance with various proposals made in the literature has no apparent prognostic value.

Follow-Up Studies↗

Immunophenotypic similarities of mediastinal clear-cell lymphoma and sinusoidal (monocytoid) B cells.

Using 14 well-defined (clustered) monoclonal antibodies (MAbs) against B-cell restricted/associated differentiation and activation (CD) antigens and 12 mediastinal clear-cell lymphomas (MCCL), 46 follicular-center-cell lymphomas (FCCL), and 20 non-neoplastic lymph nodes--including toxoplasmic and HIV-associated lymphadenitis--were immunohistochemically examined to determine the histogenesis of MCCL. Antigenically, MCCL was characterized as CD5-, CD10-, CD19+, CD20+, CD21-, CD22+, CD30-, CD37+, CDw40+, and by a frequent expression of CD11c and CD23, while other antigens were inconsistently expressed. The antigenic profiles of MCCL and FCCL showed statistically significant differences in 4/14 distinct antigens. When the neoplastic cells of both tumor groups were compared with morphologically defined normal B-cell types, the overall resemblance of their immunophenotypes was even closer between MCCL and sinusoidal (monocytoid) B cells than between FCCL and follicular-center B cells. We conclude that MCCL is a lymphoma type distinct from FCCL, most probably representing a highly malignant neoplasm corresponding to sinusoidal B-cell reaction.

Antibodies, Monoclonal↗

Isolation and characterization of cytoplasmic and nuclear particles of hepatitis B virus.

The properties of hepatitis B virus (HBV) core particles from liver tissue of two patients with acute HBV infection were investigated. Cores were isolated from cytoplasm and nuclear fractions by centrifugation and two thirds of the cores were located in the cytoplasm. In all properties examined cores isolated from the cytoplasm or nucleus were the same. The cores had a density of 1.38 g/ml and had the same DNA and protein content when analyzed by Southern blotting and by Western blotting with C-specific antisera. Cores from both subcellular fractions had endogenous polymerase activity. We conclude that core particles with identical properties are found in both the cytoplasm and nucleus of cells during acute infection.

Blotting, Southern↗

Expression of cortical and medullary thymic epithelial antigens in thymomas. An immunohistological study of 14 cases including a characterization of the lymphocytic compartment.

Four monoclonal antibodies against antigens expressed differentially by the normal thymus epithelium, which define the cortical, medullary and subcapsular compartments, were used for immunohistological characterization of the epithelial cells in 14 thymomas. Furthermore, thymoma-associated lymphocytes were studied with monoclonal antibodies directed against T-lymphocyte differentiation antigens (CD1a, CD3, T-cell antigen receptor). Only four of the 14 thymomas could be classified into either medullary or cortical type thymoma based on the immunophenotype of epithelial cells. Ten cases escaped immunophenotypical classification due to co-expression of medullary and cortical antigens by the tumour cells. This aberration from the normal phenotype might indicate the failure of differentiation of such tumours. The immunophenotype of the associated lymphocytes, on the other hand, made it possible to classify the tumours as cortical (5 cases), mixed (2) and medullary (3) thymomas. Four thymomas escaped this classification scheme due to the absence of lymphocytes (2) or to a hybrid immunophenotype (2). Nevertheless, thymocytes of cortical type clearly predominated and were seen in all thymomas with associated lymphocytes. This feature may constitute a good diagnostic tool in differential diagnosis since, in 28 mediastinal or extramediastinal metastasis of tumours not derived from thymic epithelium and associated with various numbers of lymphocytes, none of them were found to contain CD1a positive lymphocytes.

Antibodies, Monoclonal↗

[Primary carcinoid of the choledochus].

The differential diagnosis of obstructive disease processes of the common bile duct can be very difficult even when sonography, endoscopic retrograde cholangiopancreatography (ERCP) and angiography are applied. In most cases, morphological changes are due to stones or carcinoma. We report on a case of a carcinoid tumor located in the intrapancreatic part of the common bile duct. Exact localization, delineation and demonstration of the local extension of such a tumor requires at least ERCP and angiography, as these are the most efficient imaging techniques for these purposes.

Aged↗

Intra- and extrathymic B cells in physiologic and pathologic conditions. Immunohistochemical study on normal thymus and lymphofollicular hyperplasia of the thymus.

Normal thymuses and thymuses with lymphofollicular hyperplasia have been examined immunohistologically using immunoenzymatic single and double labelling methods and a panel of monoclonal antibodies against B lymphocyte differentiation antigens (CD19-, CD20-, CD21-, CD22-, CD23- and CD37ag) and human immunoglobulins (IgM, IgD) for the presence and localisation of B lymphocytes and cells expressing B cell differentiation antigens. The numerous hyperplastic lymph follicles which occur in the pathological condition of lymphofollicular hyperplasia of the thymus were found to originate in the extrathymic compartment of the interlobular septal space. This area was found to be blown up by the growing lymph follicles with exactly the same cellular composition as their counterparts in the peripheral lymphatic tissue. Some of the B lymphocytes expressing the immunophenotype of follicular mantle zone lymphocytes which were detected in the thymic medulla probably infiltrated through discontinuities of the border between the perivascular space and the thymic medulla. Apart from this primarily extrathymic B cell compartment, B lymphocytes and cells expressing B cell antigens were found within the thymus medulla of normal control thymuses of different ages from fetal to adult life. These cells were detected as a small subpopulation in normal fetal, juvenile and adult thymuses. Morphologically they could be subdivided into small, round lymphoid cells accounting for less than 1% of medullary lymphoid cells, and into a larger variant, asteroidally shaped because of short cytoplasmic processes. These asteroid cells were even more infrequent than the lymphoid variant. Immunophenotype (CD19ag+, CD20ag+, CD22ag+, CD37ag+, IgM+, IgD+) and morphology of the first cell type led to the conclusion that the lymphoid cells were in fact B lymphocytes. They were scattered throughout the medulla of fetal and juvenile and adult thymuses alike. The second, the asteroid cell type, constantly expressed CD20ag and inconstantly IgM, CD22ag and CD37ag; furthermore, CD23ag was detected in a subset of the asteroid cells either restricted to the perinuclear zone or expressed in the entire cytoplasma and on the plasma membrane. The asteroid cells were located in the corticomedullary region of the fetal thymuses but were randomly distributed with a tendency to Hassall's corpuscles in juvenile and adult thymuses. They often formed rosettes with non-B lymphocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Thymic medullary cells expressing B lymphocyte antigens.

A small subpopulation of human thymic medullary cells was found to express B cell-restricted and -associated antigens in various combinations. The cells were detected in fetal, juvenile, and adult thymi using indirect immunoenzymatic methods and monoclonal antibodies (MoAbs). Morphologically, they could be subdivided into small, round lymphoid cells, accounting for less than 1% of medullary lymphoid cells, and into a larger variant, even more infrequent in number and asteroid in shape because of short cytoplasmic processes. Immunophenotype (CD19+, CD20+, CD22+, CD37+, IgM+, IgD+) and morphology of the first cell type led to the conclusion that the lymphoid cells were B lymphocytes. The second, asteroid cell type constantly expressed CD20 and inconstantly expressed IgM, CD19, CD22, and CD37; they were often found to form rosettes with non-B lymphocytes. It can be concluded that a small number of B cells and asteroid cells of still uncertain origin, but expressing B cell-restricted antigens, are constitutive elements of the fetal and adult thymic medulla. It can be hypothesized that the asteroid cell might represent a novel type of thymic accessory cell and that the rosetting of non-B lymphocytes around this asteroid cell might simulate or in fact be the earliest B cell interaction of maturing T cells.

Adolescent↗