[Evaluation of endoscopic live case demonstrations--the patient's and participant's perspective]. / Beurteilung von endoskopischen Liveübertragungen aus Sicht von Patienten und Teilnehmer.

INTRODUCTION: Benefits and ethics of live demonstrations of endoscopic interventions as part of educational meetings are controversial. Of particular importance is the acceptance and satisfaction of patients treated and the opinion of the participants of the courses. METHODS: A validated questionnaire was sent to all patients who were treated in live demonstrations at the Düsseldorf International Endoscopy Symposium (DIES) in the years 2008-2014. In addition, all participants completed evaluation forms of the same events were evaluated in order to determine the benefits of live performances. The assessments were carried out with evaluations 1-6 (1=very good, 6=very poor). RESULTS: Of 174 patients, 76 written questionnaires were returned, of which 70 were evaluable (40.2%). The rate of satisfaction with the course of treatment and stay in the endoscopy department was 80.8%. The vast majority of patients (84.1%) did not feel that a wrong treatment option was chosen, and only a few (6.7%) questioned the expertise of the treating physician. 83% of respondents felt also at the nurses in good hands. For three-quarters of patients surveyed (74.3%), the quality of life has improved as a result of the measures in the live demonstrations. Of 10,004 participants of the symposia, 6770 evaluation forms were filled out. Mean scores of below 2 were rated for questions about the quality of patient care from a medical and ethical point of view as well as for questions about the learning effect through live demonstrations compared to canned videos. CONCLUSION: The vast majority of patients treated within live demonstrations as part of the DIES is satisfied with the course, treatment and patient care and outcomes. Congress participants assess the educational value of the live broadcasts as well as patient care in medical and ethical terms as good to very good.

[Interlaboratory trial 2000 " Immunohistochemistry" of the German Society for Pathology and the Professional Association of German Pathologists]. / Ringversuch 2000 "Immunhistochemie" der Deutschen Gesellschaft für Pathologie und des Berufsverbandes der Deutschen Pathologen.

Early in 2000 an interlaboratory trial on immunohistochemistry was held in Germany in which 172 pathologists took part. Each pathologist received one H&E stained and five unstained slides of five different tumors to reach a diagnosis based on immunohistochemical stains. Additionally, the diagnosis-independent staining quality was assessed by using a multi-tissue block. Altogether, 828 diagnoses were made, among which 57% (468) were correct. The individual steps of immunohistochemistry (tentative morphological diagnosis, choice of primary antibodies, technical staining quality, conclusions from the diagnosis and rendering a final diagnosis) were assessed independently. Although each of these steps was correlated to the correct final diagnosis, in the multivariate analysis only the tentative diagnosis, choice of primary antibodies and the conclusions drawn from individual stains were independent factors to reach the correct final diagnosis. In the diagnostic part of the interlaboratory trial, the technical quality of the immunostaining was not an independent variable to reach a correct diagnosis. In contrast, the results of the multi-tissue block proved that the immunohistochemical staining quality has to be standardized to reach reproducible results in defining the estrogen receptor expression as a basis for therapeutic decisions.

Quality assurance in immunohistochemistry: results of an interlaboratory trial involving 172 pathologists.

The practicability of quality assurance in immunohistochemistry and its integration into the diagnostic process were both tested in this Germany-wide interlaboratory trial. One hundred seventy-two pathologists received one hematoxylin and eosin and five unstained slides from five cases; all cases were selected by a panel because immunohistochemistry was required for their final diagnosis. Participants rendered a morphologic diagnosis and then substantiated it immunohistochemically. Stained slides and evaluation sheets were reviewed by the panel, and the diagnostic process was analyzed in individual steps: morphologic diagnosis, selection of antibodies, staining quality, interpretation of stained slides, conclusions, and final diagnosis. Diagnosis-independent immunohistochemical performance was tested using a multisample tissue block (30 samples) that was stained and evaluated for six common antigens. For individual cases, corresponding to their difficulty, 21-89% of the final diagnoses (altogether 57% from 828 diagnoses) were correct. In a statistical analysis, the tentative diagnosis, the interpretation of stains and conclusions drawn from immunohistochemistry, were independent factors in reaching the diagnosis. Sensitivity to detect estrogen receptors on the multisample tissue block was only 48%. However, 24% of the stains were interpreted as falsely negative. The low staining sensitivity was not correlated to the number of correct diagnoses. The major problem of applying immunohistochemistry in surgical pathology appears to be its integration into the diagnostic process and not the staining quality. Both future quality control projects and training will have to regard these integrative requirements. Multisample tissue blocks provide a promising tool to standardize quantitative immunohistochemical parameters, such as receptor or proliferation scores.

Fatal pneumonia in an AIDS patient coinfected with adenovirus and Pneumocystis carinii.

BACKGROUND: Adenovirus infections are common in immunocompromised hosts. However, pulmonary adenovirus infections rarely cause significant morbidity in HIV-infected patients. PATIENT: Here we describe a 27-year-old man with AIDS who presented with tachypnea, hypoxemia and an infiltrate in the upper left lobe on chest X-ray. Bronchoscopy was performed and Pneumocystis carinii was detected in bronchoalveolar lavage (BAL) fluid. Treatment with cotrimoxazole and prednisone initially resulted in improvement, but after 10 days the patient's clinical condition deteriorated rapidly and he died after 23 days due to respiratory failure. RESULTS: On autopsy histopathologic examination showed abundant "smudge cells," suggestive of adenoviral infection. Electron microscopy revealed adenovirus-like particles arrayed in a paracrystalline manner. Subsequent immunohistochemistry confirmed the extensive presence of adenovirus in addition to P. carinii. CONCLUSION: This case demonstrates a pathogenetic role for adenovirus coinfection in P. carinii pneumonia (PCP). Earlier diagnosis, e.g. by PCR analysis of the BAL fluid or transbronchial biopsy, might have led to the consideration of ribavirin treatment.

Angiotropic large-cell lymphoma presenting as pulmonary small vessel occlusive disease.

Angiotropic lymphoma (AL) is an unusual variant of extranodal lymphoma, characterized by massive proliferation of neoplastic lymphoid cells almost exclusively within blood vessels. Whereas the lymphoid origin of this disease is widely accepted it still remains unclear whether AL is a distinct entity that originates in the blood vessels or whether it represents a form of secondary intravascular dissemination of a primary solid lymphoma. The present case is unusual because death by right heart failure owing to extensive intravascular proliferation of neoplastic cells and subsequent occlusion of pulmonary blood vessels has not been described so far. In addition, the patient had suffered from a solid deposit of a large-cell B-lymphoma months before the angiotropic manifestation, suggesting that AL might develop out of more common types of non-Hodgkin's lymphomas.

[Perforation of mucocele-like transformed Hartmann stump]. / Perforation eines mucocelenartig transformierten Hartmannstumpfs.

We report an unusual complication in a 53-year-old woman following ileostomy for Crohn's disease 22 years previously. A stenosis of the distal colonic segment was the reason for the formation and subsequent rupture of a huge colonic mucocele. To our knowledge, this is the first report of a ruptured mucocele of colonic origin after ileostomy.

Hepatocellular alterations after intraportal transplantation of ovarian tissue in ovariectomized rats.

The mechanisms of hepatocarcinogenesis by certain synthetic estrogens seem to involve both nongenotoxic and indirect genotoxic effects. However, the natural estrogen estradiol did not exert any carcinogenic effects in established experimental protocols. To elucidate specific long-term effects of natural estrogens on hepatocytes, small pieces of ovarian tissue were transplanted via the portal vein into the livers of ovariectomized female rats. One week, 3 weeks, and 3 months after transplantation the transplants were found to proliferate and to secrete estradiol. Three weeks after transplantation the hepatocytes of the liver acini downstream of the stimulated transplants already showed a remarkable loss of glycogen, distinct cytoplasmic amphophilia, enlargement of their nuclei, a strong increase in the number and size of peroxisomes, an increase in proliferative activity and apoptotic elimination, and changes in the activity of certain key enzymes of energy metabolism. All hepatocellular alterations could be inhibited by the estrogen receptor antagonist toremifene and are, therefore, attributed to specific effects of estradiol produced by the transplants. The observed alterations resemble in some respects amphophilic preneoplastic liver foci, which particularly occur after long-term administration of nongenotoxic hepatocarcinogens, including the adrenal steroid hormone dehydroepiandrosterone. In a preliminary experiment three of six animals exhibited a hepatocellular carcinoma, and another animal developed a hepatocellular adenoma 18 months after intrahepatic ovarian tissue transplantation.

Multiple macroregenerative nodules in liver cirrhosis due to Budd-Chiari syndrome. Case reports and review of the literature.

Clinical, radiological, histological and immunohistochemical methods were used to define the nature of multiple rapidly growing hepatic nodules in 2 young patients with Budd-Chiari syndrome due to myeloproliferative diseases. In one patient, the arterial hyperperfusion of large nodules was demonstrated by dynamic computed tomography and angiography. The explanted livers of these patients showed multiple well-demarcated nodules up to 3 cm in diameter on the background of liver cirrhosis resulting from chronic hepatic congestion. Histologically, these nodules covered a spectrum ranging from adenoma-like lesions to nodules resembling focal nodular hyperplasia. They consisted of essentially normal hepatocytes, and variably contained fibrous septa including neoductules and large, mostly dysmorphic arteries. Sometimes, they were located close to still patent or recanalized veins. These rapidly growing hepatic nodules are best defined as macroregenerative nodules. The knowledge of this entity may help the physician to avoid misinterpretation of such nodules as carcinomas.

Breast MR imaging screening in 192 women proved or suspected to be carriers of a breast cancer susceptibility gene: preliminary results.

PURPOSE: To compare magnetic resonance (MR) imaging with conventional imaging in screening high-risk women. MATERIALS AND METHODS: This prospective trial included 192 asymptomatic and six symptomatic women who, on the basis of personal or family history or genetic analysis, were suspected or proved to carry a breast cancer susceptibility gene. RESULTS: Fifteen breast cancers were identified: nine in the 192 asymptomatic women (six in the first and three in the second screening round) and six in the symptomatic patients. Concerning the asymptomatic women, four of the nine breast cancers were detected and correctly classified with mammography and ultrasonography (US) combined; another two cancers were visible as well-circumscribed masses and were diagnosed as fibroadenomas. MR imaging allowed the correct classification and local staging of all nine cancers. In 105 asymptomatic women with validation of the 1st-year screening results, the sensitivities of mammography, US, and MR imaging were 33%, 33% (mammography and US combined, 44%), and 100%, respectively; the positive predictive values were 30%, 12%, and 64%, respectively. CONCLUSION: The accuracy of MR imaging is significantly higher than that of conventional imaging in screening high-risk women. Difficulties can be caused by an atypical manifestation of hereditary breast cancers at both conventional and MR imaging and by contrast material enhancement associated with hormonal stimulation.

Evaluation of different models of experimentally induced liver cirrhosis for MRI research with correlation to histopathologic findings.

RATIONALE AND OBJECTIVES: Three models of experimentally induced liver cirrhosis were evaluated for MRI research on chronic liver disease. The influence of different histopathologic changes in liver fibrosis and cirrhosis on relaxation times and signal intensities was studied in vitro and in vivo. METHODS: Liver fibrosis and cirrhosis in rats was induced by oral or subcutaneous administration of carbon tetrachloride (CCl4) or by thioacetamide (TAA) in drinking water. On histology, the degree of liver fibrosis and cirrhosis, fatty infiltration, iron accumulation, and inflammatory changes were measured semiquantitatively. The amount of connective tissue was quantitatively determined by morphometry. The results were correlated with T1 and T2 relaxation times and signal intensities of the liver studied in vitro by relaxometry and in vivo by MRI. RESULTS: In both groups with CCl4 administration, histology revealed different degrees of liver fibrosis and cirrhosis. Subcutaneous injection of CCl4 also resulted in increased fatty infiltration. On the contrary, TAA produced complete liver cirrhosis in all animals. Overall, there was a good correlation between the liver T2 relaxation time and the amount of connective tissue in liver fibrosis and cirrhosis. However, the degree of liver fibrosis and cirrhosis was also strongly correlated with the degree of inflammatory changes. In the group with CCl4 administration, there was a good correlation between the fatty infiltration and the T1 relaxation time, as well as with the liver signal intensity on the T1-weighted gradient echo sequence. An increased iron accumulation was also correlated with the degree of liver fibrosis/cirrhosis; however, there was no significant influence of the iron on relaxation times or signal intensities. CONCLUSIONS: The TAA model is easier to perform and more reliable in liver cirrhosis induction than the CCl4 models. Although there is a positive correlation between the T2 relaxation times and the degree of liver fibrosis/cirrhosis, this probably results from the associated inflammatory changes and is not caused by the increased amount of connective tissue.

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.

[Löffler fibroblastic endocarditis in the thrombotic stages in isolated right ventricular tissue eosinophilia]. / Endokarditis fibroplastica Löffler im thrombotischen Stadium bei isolierter rechtsventrikulärer Gewebe-Eosinophilie.

We report on a male, 31 year old, Turkish patient with an intracardiac mass in the right ventricle, reduction of performance and weight, as well as intermittent fever. No eosinophilia was documented in the peripheral blood; cardiac function was primarily normal. Besides the differential diagnosis of Löffer's endocarditis (endomyocardial fibrosis) an inflammatory disease and a malignant cardiac tumor were suggested. The diagnosis of Löffler's endocarditis could not be confirmed morphologically by echocardiography nor histologically by right ventricular biopsy. Operative removal of the mass lesion was necessary because of fast tumor progression, fulminant pulmonary embolism, and infiltration of the tricuspid valve. Only then, histologically Löffler's eosinophilic endocarditis of thrombotic stage was diagnosed. Antiphlogistic therapy with cortisone was initially performed. With a dose reduction after 6 months, a relapse of the thrombotic mass occurred. Therefore, continuous treatment with cortisone and azathioprine was induced followed by further tumor regression and further clinical stabilization since 8 months of treatment.

Nonparenchymal cells in chronically hyperinsulinemic liver acini of diabetic rats, with special regard to hepatic stellate cells.

BACKGROUND/AIMS: An increase in proliferative activity and other distinct hepatocellular alterations--resembling preneoplastic foci and progressing to hepatocellular tumors--have been shown to develop in liver acini draining the blood from islets of Langerhans, transplanted through the portal vein into the liver of streptozotocin-diabetic rats. METHODS: Altered and unaltered liver acini were investigated for possible changes in hepatic stellate cells 4-76 days after islet transplantation. RESULTS: Corresponding to a significant increase in the hepatocellular volume, the volume density of total nonparenchymal cells was significantly reduced in altered compared to unaltered liver acini. With regard to the total nonparenchymal cell volume, the hepatic stellate cell fraction was not different, whereas the fraction of Kupffer cells was significantly reduced and the fraction of sinusoidal endothelial cells was significantly increased in altered compared to unaltered liver acini, respectively. The volume density as well as the single volume of the hepatic stellate cell mitochondria increased significantly in altered compared to unaltered liver acini. Hepatic stellate cell lipid droplets did not show significant differences between altered and unaltered liver acini. In situ hybridization for hepatocyte growth factor mRNA showed no differences in intensity of the specific signals in hepatic stellate cells of altered versus unaltered liver acini. The transplanted islets were negative for hepatic growth factor mRNA. CONCLUSIONS: The results suggest that hepatic growth factor production by hepatic stellate cells or by islet cells is not relevant to hepatocellular proliferative activity in altered liver acini.

Argyrophilic nucleolar organizer region counts in squamous cell carcinomas of the head and neck after irradiation and chemotherapy.

After irradiation or chemotherapy of tumors of the head and neck, histological alterations might be difficult to assess. In 30 cases of squamous cell carcinomas of the pharynx, changes in argyrophilic nucleolar organizer region (AgNOR) counts were investigated after therapy. After treatment a significant decrease of AgNOR counts was detected (P < 0.001). No significant differences could be found between groups treated with radiotherapy, chemotherapy or a combination of radiotherapy and chemotherapy. These findings suggest that AgNOR counts might be useful to assess cytotoxic effects on a subcellular level.

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.

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.

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.