Pathology of hepatocellular carcinoma.
Explore the source record for details and available documents.
Carcinoma, Hepatocellular↗
Biomedical subjects
U Pfeifer
Publications and source records attributed to U Pfeifer.
Diagnostic value of a superparamagnetic iron oxide in MR imaging of chronic liver disease in an animal model.
OBJECTIVE: The enhancement characteristics and the diagnostic value of a cell-specific superparamagnetic contrast agent (NSR 0430) in different degrees of liver fibrosis and cirrhosis were experimentally studied in an animal model. MATERIALS AND METHODS: Chronic liver damage was induced in rats either by oral administration of carbon tetrachloride (CCl4) for 15 weeks (n = 37) or by oral administration of thioacetamide (TAA) in drinking water for 24-26 weeks (n = 48). Twenty-six animals served as control subjects. T1 and T2 relaxation times for the liver and the spleen were measured in vitro with a spectrometer at 40 MHz. In vivo MR imaging at 1.5 T also was performed using T2-weighted turbo spin-echo sequences before and 1 hr after administration of NSR 0430. All data were correlated with the histologic degree of liver fibrosis and cirrhosis and the amount of connective tissue in the liver, which was measured morphometrically. RESULT: CCl4 produced liver fibrosis in most of the animals, and TAA predominantly caused liver cirrhosis. NSR 0430 caused a T2 relaxation time decrease in the control animals by 49%; in the CCl4 group with light and moderate liver fibrosis, by 25%; in the CCl4 group with severe liver fibrosis or cirrhosis, by 16%; and in the TAA group with cirrhosis, by 30%. On the T2-weighted turbo spin-echo sequences, liver signal-to-noise ratios (SNRs) decreased after contrast agent administration in the control animals by 81% and 79%, depending on the TE parameter. In the CCl4 group, liver SNRs decreased by 96% and 61% in animals with light or moderate fibrosis and by 44% and 55% in animals with severe fibrosis or cirrhosis, depending on the TE parameter. In the TAA group, liver SNR decreased by 61% and 67%, depending on the TE parameter. CONCLUSION: Enhancement of the superparamagnetic contrast agent NSR 0430 is decreased in the presence of liver fibrosis and cirrhosis in an animal model. However, the reduced enhancement is not directly related to the degree of chronic liver damage, which limits the diagnostic value of superparamagnetic contrast agents in the assessment of chronic liver disease.
Animals↗
Insulinomas derived from hyperplastic intra-hepatic islet transplants.
Insulinomas were induced in a new animal model by transplanting a low number of isologous pancreatic islets via the portal vein into the livers of 66 streptozotocin-induced diabetic rats. In contrast to high-number islet transplantation, which restored normoglycemia in 25 control animals, the low-number islet transplantation was followed by persisting hyperglycemia for at least 13 months. Hyperplasia of islet cells developed in the transplanted islets as a consequence of hyperglycemia, which for the beta cells is not only a secretory but also a proliferative stimulus. Six of thirty-three animals between the 18th and the 24th month after islet transplantation changed from hyperglycemia to severe hypoglycemia, due to insulinomas that had developed in the liver from the transplanted islets. In contrast to other animal models, insulinoma development in this new model does not result from DNA damage by chemicals or radiation or from the expression of transgenes, but starts from apparently normal islets prepared from untreated isologous donors, which are exposed to an imbalance in glucose metabolism. The persistent proliferative stimulus and the metabolic alterations caused by the longstanding hyperglycemia seem to be the most relevant oncogenic factors in this model.
Animals↗
Redifferentiation therapy with retinoic acid in follicular thyroid cancer.
We report on a patient with a follicular Hurthle cell carcinoma in whom distant metastases were initially radioiodine negative or only weakly positive. Redifferentiation therapy with 13-cis retinoic acid induced a significant radioiodine uptake in metastatic tissue. Thyroglobulin (Tg) immunostaining and autoradiography of a bone metastasis in the right femur, which was initially radioiodine negative, proved Tg synthesis, combined with iodine incorporation into tumor cells. Glucose metabolism in metastases was partially increased and partially unchanged after redifferentiation therapy. The distinct increase of serum Tg after retinoic acid treatment was interpreted as a functional sign of redifferentiation.
Adenocarcinoma↗
[Weight loss, rectal bleeding, palpable pelvic tumor and space-occupying lesion of the axilla in an 82-year-old patient].
Explore the source record for details and available documents.
Aged↗
Morphological analogies of fetal prostate stroma and stromal nodules in BPH.
BACKGROUND: A "reawakening" of ontogenetic processes in the development of BPH is still in debate. Therefore, morphological analogies of fetal prostate stroma and nodular stromal proliferates in BPH were investigated. METHODS: Fetal prostates (n = 30; weeks 12-40 of gestation) and stromal nodules of benign prostatic hyperplasia (n = 375 from autopsies, n = 100 from biopsies) were investigated by histo- and immunohistochemistry with special regard to cytoskeletal (alpha-actin, desmin, myosin, and vimentin), neuronal (S-100 protein), neuroendocrine (neuron-specific enolase), leukocytic (CD3, CD20, and CD68) and vascular (CD34, BMA-120, and factor VIII) antigens. RESULTS: The developing fetal prostate stroma consists of immature mesenchymal cells up to week 17 of gestation, followed by fibroblastic and fibromuscular stromal cells up to week 25 of gestation and predominantly smooth-muscular cells until the end of gestation. Stromal nodules occur as immature mesenchymal, fibroblastic, fibromuscular, and smooth-muscular, suggestive of a maturational process. The fetal prostate stroma and the stromal nodules present, with an increasing degree of maturation, a similar vascular pattern and a similar occurrence of CD3 (T-lymphocytes), CD20 (B-lymphocytes), CD68 (macrophages), S-100, and neuron-specific enolase-positive cells. CONCLUSIONS: The data suggest that ontogenetic processes are recapitulated in the development of stromal nodules in benign prostatic hyperplasia, supporting the idea of a "re-awakening" of fetal processes in BPH.
Adult↗
[Symptoms, tumor stage and primary treatment in patients with colorectal carcinoma].
OBJECTIVE: To obtain population-related data, previously not available for Germany, regarding primary symptoms, diagnosis and treatment of patients with colorectal carcinoma. PATIENTS AND METHODS: During 1994, in the catchment area of Bonn (town of Bonn, districts of Euskirchen and Rhein-Sieg), there were 354 cases of newly diagnosed colorectal carcinoma. For all of them initial symptoms, primary diagnosis, cancer stage at time of diagnosis as well as surgical and conservative treatment were prospectively documented. By comparing entries from all relevant hospitals and doctors with those of the pathology institutes of the region, data of about 98% of all these patients were recorded. RESULTS: The average age of the patients was older (median of 69 for men, 72 for women) with more far metastases than in comparable groups reported by German university surgical departments. Only 4.6% of the group had occult blood in the stool as the only symptom. Most of the patients had local or regional metastases (T3-4: 63.9%; N1-3: 41%, respectively). Operations intended to be curative were possible in only 65.9% of the cohort. Adjuvant radiotherapy and/or chemotherapy was given to 11.7%, using current consensus recommendations.
Adenocarcinoma↗
[Septic myocardial aneurysm in mitral valve endocarditis. Clinical and pathological-anatomical findings].
HISTORY AND CLINICAL FINDINGS: A 68-year-old woman was hospitalized because of fever and tiredness for 3 months. Her general condition was clearly impaired. She had a mild fever of 38.5 degrees C and on auscultation a 3/6 systolic murmur, maximal parasternally in the 3rd intercostal space, transmitted to the apex. There were distant râles over both lungs, the neck veins were distended and there was ankle oedema. INVESTIGATIONS: C-reactive protein was raised to 17.3 mg/dl (normal up to 0.9 mg/dl), WBC count 19,300/microliter. beta-haemolysing streptococcus (S. agalactiae) was grown in the blood culture. The ECG showed sinus tachycardia (rate of 98/min) and transthoracic echocardiography demonstrated a small pericardial, enlarged ventricles, marked mitral regurgitation and a large vegetation on the posterior mitral leaflet, as well as a 3 x 4 cm mass in the posterior wall of the ventricle, originating from the posterior mitral valve ring and communicating with the vegetation on the mitral valve. The posterior mitral leaflet was perforated. TREATMENT AND COURSE: As endocarditis of the mitral valve with a complicated course was suspected-abscess of the posterior mitral valve ring and septic myocardial aneurysm with associated pericarditis and haemodynamically insignificant effusion-she was transferred to the intensive care unit where she died suddenly of circulatory arrest only 30 min after transfer. Autopsy confirmed the echocardiographic findings. CONCLUSION: Paravalvular abscess in the course of mitral valve endocarditis is rare, but should be looked for at transthoracic echocardiography so that any necessary surgical intervention can be undertaken early.
Aged↗
[Serous psammocarcinoma of the ovary. Case report and literature review].
We report a rare case of psammocarcinoma which presented as a mass in the lower abdomen of an otherwise asymptomatic woman. Ultrasonographically, the tumor showed extensive calcification and was suspected to be a myoma. DNA image cytometry and assessment of proliferative activity were performed and showed an euploid, low proliferating tumor cell population. This underlines the low malignancy of this type of carcinoma, which is comparable to that of serous borderline lesions of the ovary and explains the benign clinical course.
Calcinosis↗
Adenovirus-induced liver necrosis in a case of AIDS.
Adenovirus-induced liver necrosis is rare. Because the era of AIDS (acquired immunodeficiency syndrome) this entity was seen predominantly in infants suffering from inborn immunodeficiency syndromes or from iatrogenic immunosuppression because of bone marrow or liver transplantation. Here, we report a case of a 30-year-old woman with AIDS who developed fever and rapidly progressing liver failure. A frozen section from a needle biopsy of the liver allowed a quick diagnosis of viral liver necrosis. The light-microscopic and electron microscopic aspects were typical of adenovirus infection and should be known to the surgical pathologist. The diagnosis was confirmed by immunohistochemistry and DNA hybridization analysis.
Acquired Immunodeficiency Syndrome↗
Inhibition and restimulation by insulin of cellular autophagy in distal tubular cells of the kidney in early diabetic rats.
Cellular autophagy in the cells of distal tubular segments (DT cells) of the kidney cortex in streptozotocin-diabetic rats was evaluated by quantitative electron microscopy. Five days after streptozotocin administration, volume and numerical densities of autophagic vacuoles (AVs) in DT cells were reduced by 56 and 57%, respectively. The correction of the diabetic state by insulin injection reversed the inhibition of cellular autophagy. Volume and numerical densities of AVs increased by 97 and 53%, respectively. Endogenous insulin replacement by islet transplantation showed the same effect on cellular autophagy. Volume and numerical densities of AVs increased by 82 and 34%, respectively, as compared with sham-operated diabetic animals. The data show that, during diabetic kidney hypertrophy, the cellular autophagy is inhibited in DT cells to the same extent as in proximal tubular cells, suggesting that DT cells contribute in a balanced manner to hypertrophic growth of the kidney cortex. Similarly, DT cells are involved in the catabolic reaction, i.e., stimulation of autophagy, after metabolic correction of the diabetic state by insulin.
Animals↗
Hepatocellular neoplasms induced by low-number pancreatic islet transplants in streptozotocin diabetic rats.
We have previously demonstrated in short-term experiments that altered hepatocytes in liver acini draining the blood from intraportally transplanted pancreatic islets in streptozotocin-induced diabetic rats with mild persisting diabetes resemble those in preneoplastic foci of altered hepatocytes. We now present the results of long-term studies (up to 22 months) in this animal model. Glycogen-storing foci (which were the first parenchymal alteration observed some days after transplantation) persisted at least for 6 months, when the first mixed-cell foci and the first hepatocellular adenoma emerged. After 15 to 22 months, 86% of the animals exhibited at least one hepatocellular adenoma and four animals (19%) showed a hepatocellular carcinoma. The transplants were found in a close spatial relationship with the preneoplastic foci and the hepatocellular neoplasms. The mitotic indices, the 5-bromo-2'-desoxyuridine labeling indices and the apoptotic indices showed significant differences between the unaltered liver parenchyma, different types of preneoplastic foci, and hepatocellular neoplasms. The immunohistochemical expression of transforming growth factor-alpha increased during the stepwise development from glycogen-storing liver acini to hepatocellular carcinomas. Hepatocarcinogenesis in this new animal model is probably due to the hormonal and growth-stimulating effects of insulin secreted by the intraportally transplanted islets of Langerhans in diabetic rats.
Adenoma↗
[Insulinoma originating from transplanted pancreatic cells after low dose portal embolic islet transplantation in streptozotocin diabetic rats].
The tumorigenesis of insulinomas is unclear. Hyperglycemia has been found in many short term experiments to be one of the strongest stimuli for proliferation of the pancreatic beta-cells. After isologous islet transplantation into the livers of streptozotocin-diabetic rats it has been shown by our group that the proliferative activity of islet graft epithelial cells is strongly increased in a hyperglycemic environment (low-number islet transplantation) compared with normoglycemic conditions (high-number islet transplantation). The aim of this study was to investigate the long-term fate of these hyperproliferative islet grafts. 66 out of 91 streptozotocin-diabetic male Lewis rats persisted in a mild diabetic state after transplantation of 250-450 islets (main group), 25 animals became normoglycemic immediately after transplantation of 1000-2000 islets (control group). 5-Bromo-2'-desoxyuridine was administered prior to sacrifice. For the determination of the proliferative activity of the different cell types immunohistochemistry for insulin, glucagon and somatostatin was combined with a 5-Bromo-2'-desoxyuridine immunohistochemistry. Six animals of the main group developed insulinomas in their livers between 18 and 24 months after islet transplantation (i.e. 18% of the animals which lived more than 18 months after transplantation). The insulinomas induced severe hypoglycemia (12-36 mg/dl blood glucose), and the tumor cells showed a high proliferative activity, a positive immunoreactivity for insulin, and typical electron dense granules. The normoglycemic control group animals did not develop endocrine tumors. This study shows for the first time that insulinomas develop in transplanted islets of Langerhans under the influence of the long-term proliferative stimulus hyperglycemia.
Animals↗
Stromal nodules in benign prostatic hyperplasia.
OBJECTIVE: Stromal nodules from benign prostatic hyperplasia (BPH; n = 375 from autopsy, n = 100 from biopsy specimens) were investigated with regard to cytoskeletal components, topography, vascularization, leukocytic infiltrates, and proliferative activity. METHODS: The nature of stromal nodules was studied by histopathology and immunohistochemistry, using antibodies against alpha-actin, desmin, myosin, vimentin, BMA-120, factor VIII, CD3, CD4, CD20, CD34, CD45RO, CD68, PCNA, and MiB1. RESULTS: The findings lead to an extended classification of stromal nodules in BPH: immature mesenchymal (IM; 8.8%), fibroblastic (FB; 65.2), fibromuscular (FM; 21.6), and smooth muscular (SM; 4.4%). The different types occurred in all age decades in a similar distribution (FB > FM > IM > SM). Topographical studies (modified zonal subdivision of McNeal) revealed stromal nodules predominantly in the transitional zone (n = 286), less in the central zone (n = 78), occasionally in the peripheral zone (n = 11), and predominantly in the periurethral (n = 287) and less in the intermediate (n = 84) and subcapsular (n = 4) regions. The different types of nodules presented a distinct vascular pattern. FB, FM, and SM nodules showed significantly increased diffuse infiltrates of T lymphocytes-mainly T helper cells (mean 73%)-and an increase of B lymphocytes. Proliferative activity in the nodules was not observed. Stromal nodules were not observed in normal nonhyperplastic prostates; they only occurred in combination with hyperplastic nodular glandular proliferates. CONCLUSIONS: The findings are suggestive of a maturational sequence of stromal nodules in BPH and of a possible significance of immunocompetent cells in the development of stromal nodules and further suggest that both stroma and epithelium of the prostate respond with nodular hyperplasia to the stimulus, which causes BPH.
Adult↗
Altered liver acini induced in diabetic rats by portal vein islet isografts resemble preneoplastic hepatic foci in their enzymic pattern.
As demonstrated previously, liver acini draining the blood from intraportally transplanted pancreatic islets in streptozotocin-diabetic rats are altered in various respects. The hepatocytes in these acini store glycogen and/or fat, and they show an increase in proliferation as well as in apoptotic activity. Thus, they are phenotypically similar to carcinogen-induced preneoplastic liver foci (glycogen-storing foci and sometimes also mixed cell foci). By means of catalytic enzyme histochemistry or immunohistochemistry, we investigated the activity of key enzymes of alternative pathways of carbohydrate metabolism and some additional marker enzymes (well known from studies on preneoplastic hepatic foci) in the altered liver acini surrounding the islet isografts. In addition, the expression of glucose transporter proteins 1 and 2 (GLUT-1 and GLUT-2) were investigated immunohistochemically. The activities of hexokinase, pyruvate kinase, glyceraldehyde-3-phosphate dehydrogenase, and glucose-6-phosphate dehydrogenase were increased, whereas the activities of glycogen phosphorylase, adenylate cyclase, glucose-6-phosphatase, and membrane-bound adenosine triphosphatase were decreased in the altered liver acini. The expression of GLUT-2 was also decreased. GLUT-1 and glutathione S-transferase placental form were not expressed, and the activities of glycogen synthase and gamma-glutamyl-transferase remained unchanged. All changes of the enzyme activities were in line with the well known effects of insulin and resembled alterations characteristic of preneoplastic liver foci observed in different models of hepatocarcinogenesis. It remains to be clarified in long-term experiments whether or not these foci represent preneoplastic lesions and may proceed to neoplasia.
Animals↗
Perforation of the small intestine in a patient with disseminated Pneumocystis carinii infection in AIDS.
Perforation of the small intestine due to a segmental transmural Pneumocystis carinii infiltrate of the whole circumference was found in a surgical resection specimen as the cause of an acute abdomen in a 48-year-old heterosexual male patient suffering from acquired immunodeficiency syndrome. On autopsy, a disseminated Pneumocystis carinii infection was found involving spleen, thyroid gland and lymph nodes. The origin of this disseminated infection was a recurrent and severe Pneumocystis carinii pneumonia, which was first diagnosed two years before death and was treated with success. The hitherto unknown complication of an extrapulmonary Pneumocystis carinii infection described here extends the spectrum of lethal complications of opportunistic infections in acquired immunodeficiency syndrome.
AIDS-Related Opportunistic Infections↗
Autopsy findings in patients with human immunodeficiency virus infection with emphasis on the risk factor of hemophilia.
The autopsy findings of 80 human immunodeficiency virus (HIV)-infected adults, who died between 1982-1995, are presented with special emphasis on the risk factor of hemophilia. The study included 23 blood product recipients (hemophiliacs n = 21; non-hemophiliacs n = 2), 34 homosexuals, four intravenous drug abusers, and 19 patients with no known risk factor. Nearly all individuals (93%) showed the late stage of acquired immunodeficiency syndrome (AIDS). Blood product recipients had a significantly lower overall frequency of opportunistic infections (p < 0.05). Homosexuality was associated with the highest overall frequency of opportunistic infections and HIV-associated malignancies, such as Kaposi's sarcoma and malignant non-Hodgkin's lymphoma. Exclusive visceral involvement of Kaposi's sarcoma was frequent, and no decrease of Kaposi's sarcoma was observed during the study period. Pneumocystis infections, atypical mycobacteriosis, and non-Hodgkin's lymphoma showed a significant increase during the last five years (1991-1995) of the observation interval. Opportunistic infections and malignancies were the cause of death in approximately one-half of the patients. In blood product recipients, hepatic failure due to posthepatitic cirrhosis and hemorrhage due to hepatic failure with subsequent coagulopathy and in non-blood product recipients, bacterial bronchopneumonia, and diffuse alveolar damage were additional major causes of death. The data suggest a lower risk for HIV-infected blood product recipients, particularly hemophiliacs, to acquire opportunistic infections and malignant neoplasms.
Adult↗
Malignant mesothelioma arising from a benign mediastinal mesothelial cyst.
A 50-year-old man presented with a cervical lymph node metastasis of malignant tumor and a radiologically documented well-defined tumorous mass in the middle portion of the mediastinum. Under the presumptive diagnosis of an undifferentiated bronchogenic carcinoma, the patient underwent chemotherapy. However, the tumor did not respond to this treatment and showed further progression. The patient died four weeks after the lymph node biopsy. Autopsy revealed a well-defined cystic tumor in the mediastinum with infiltration of the pericardium. The tumor was not attached to the lungs. By histology and immunohistochemistry, a metastasizing malignant biphasic mesothelioma was diagnosed. The tumor had metastasized to intrapulmonary perivascular and peribronchiolar lymph vessels and hilar lymph nodes. Distant metastases were found in the right and left adrenal gland and in the brain. The strictly mediastinal localization and the cystic growth pattern of the tumor strongly suggest that this mesothelioma developed from a primary benign mesothelial cyst of the pericardium with secondary transformation into a malignant mesothelioma.
Humans↗