Foveolar gastric metaplasia of the duodenum: a frequent, so far neglected type of duodenal polyp.

Foveolar gastric metaplasia of the duodenum (FGM) is considered as imperfect mucosal healing in the context of H. pylori gastritis and intake of NSAIDs or ASS.  Typical endoscopic findings are redness of the mucosa, erosion/ulcer and loss of mucosal folds. During diagnostic histological examinations we observed a frequent so far not described association of FGM with endoscopically observed duodenal polyps. The archives of two institutes of pathology with high gastroenterological workload (approximately 100 000 patients per year) were investigated for an association between "duodenal polyp" and "foveolar gastric metaplasia". In Institute 1, of 481 duodenal polyps 41 % were classified as FGM, 9 % as adenoma and 2 % as heterotopic gastric mucosa. In 48 % no histological correlate was present. In Institute 2, 217 cases of FGM were diagnosed. Of these, in 69 cases the endoscopic finding was "polyp" (32 %). In the other cases, the endoscopic findings were mucosal defect (18 %), redness/inflammation (16 %), suspicion for gastric heterotopia (5 %) and scar (3 %). In 26 % of cases no pathologic endoscopic finding was reported. Both groups of patients with FGM showed a similar distribution of age ranges (24 - 83 years and 16 - 88 years), median age (62 years and 61 years, respectively) and a dominance of male sex (both 1.5:1). In conclusion, foveolar gastric metaplasia is a frequent, so far neglected correlate of endoscopically detected duodenal polyps.

Value of ultrasound in preoperative local staging in early breast cancer.

PURPOSE: The purpose of this study was to determine the precision of breast ultrasound for the measurement of breast lesions compared to the histological measurement. A number of other dependent variables were also analyzed. MATERIAL AND METHODS: 460 patients with 445 malignant lesions were examined using breast ultrasound and the lesions were measured and compared to the histologically measured size. The data was further analyzed according to histology, tumor stage, age, grading and therapy. RESULTS: Metric comparison showed good correlation between sonography and the pathologically measured size of breast lesions, especially in tumor stage T 1 and T 2 and within ductal invasive carcinomas. Higher tumor stages lead to imprecise measurements and the histological type of lobular invasive carcinoma also results in imprecise measurements. Age and grading do not influence measurement precision. CONCLUSION: Breast ultrasound allows precise measurement of breast lesions especially at lower tumor stages. The higher the tumor stage, the more imprecise the measurement becomes. Multivariate analysis shows no cross impact between tumor stage and histological type with respect to the quality of measurement.

[Predicting response to therapy in breast cancer]. / Vorhersage des Therapieansprechens beim Mammakarzinom.

Molecular staging of breast cancer with microarray technologies leads to different gene expression profiles distinguishing 4 special groups: luminal A and B subtype, HER2 subtype and basal subtype. These 4 groups show a different prognosis as well as different behaviours and responses to adjuvant therapy. The development of gene expression profiles to classify breast cancer may contribute to the targeted institution of adjuvant therapies. Especially the 21-gene recurrence score (Oncotype DX) and the 70-gene profile (Mamma-print) have become intensively examined prognostic and predictive tools. As chemotherapy is an integral component of adjuvant therapy in early breast cancer but estrogen-receptor-positive breast cancer is the most common type, patient selection for adjuvant chemotherapy is of particular interest. In instances when the benefit from chemotherapy seems modest, there is a decision making tool beside traditional histopathological parameters that might provide additional objective prognostic and predictive information. Those genomic decision making approaches may yield more rational treatment choices and may keep patients from systemic treatment modalities of lower value.

[Pathophysiology of bone metastases in urologic carcinomas]. / Pathophysiologie der Skelettmetastasierung urologischer Karzinome.

The skeletal system is the most frequent metastatic site of hematogenous spread of urologic carcinomas. Osseus metastases are classified as osteoneutral, osteolytic, osteoblastic and combinations thereof. Osteolytic metastases lead to bone resorption by activating osteoclasts, while osteoblastic metastases stimulate osteoblasts by paracrine mechanisms. The local osteoblastic effect is associated with secondary systemic bone resorption. The use of bisphosphonates is now an established supportive therapy and newer treatment strategies including targeted intervention in the pathophysiology of bone metastases and radioimmunotherapy are being applied or will be coming soon.

[Surgical management of ovarian ectopic pregnancy]. / Operative Therapie der ovariellen Gravidität--Fallbericht und Ubersicht.

Ovarian pregnancies represent a small fraction of ectopic gestations. They are especially feared due to their life-threatening intraabdominal hemorrhage. Pre- and intraoperative diagnosis is difficult. Pathogenetically ovarian pregnancy arises from the retention of a fertilized ovum in the ovary. General guidelines for the medical management are missing. In this case report, we diagnosed a subacute ruptured ovarian pregnancy during surgery and performed a partial ovarectomy via operative laparoscopy. Other therapeutic options in managing ovarian ectopic pregnancy will be discussed.

Ultrasound-guided large-core needle biopsies of breast lesions: analysis of 962 cases to determine the number of samples for reliable tumour classification.

The objective of this one-institutional study was to determine the number of large-core needle biopsies (LCNB), under three-dimensional ultrasound (3D-US) validation, that are sufficient to obtain a reliable histological diagnosis of a sonographically detectable breast lesion. Over an 28-month period, 962 sonographically guided LCNB were performed under 3D-US validation to assess 962 breast lesions. All biopsies were carried out with an automated core biopsy device fitted with 14-gauge (22 mm excursion) needles. Data of 962 biopsied breast lesions were gathered. Surgical follow-up was available for 659 lesions. Breast malignancies were diagnosed by ultrasound-guided LCNB with a sensitivity of 98.2% by performing three cores per lesion. In few cases, the open surgical specimen revealed the presence of invasive carcinomas in contrast to initial LNCB-based classification as ductal carcinomas in situ (DCIS, 11 lesions), lobular carcinoma in situ (one lesion), and atypical ductal hyperpasia (one lesion). Owing to disagreement between classification based on breast-imaging and histological findings, eight of these tumours were subsequently excised. Of the lesions that were removed at the patients' requests despite benign LCNB diagnosis, two were infiltrating carcinoma and one a DCIS. We demonstrate that three 3D-US-guided percutaneous core specimens are sufficient to achieve tissue for a reliable histological assessment of sonographically detectable breast lesions and allow the detection of malignancies with high sensitivity and low rate of false-negative diagnoses.

[Gynecological aspects of pain in the lower abdomen]. / Gynäkologische Ursachen von Unterleibsschmerzen. Die wichtigsten Differenzialdiagnosen im Uberblick.

Lower abdominal pain in women may be a manifestation of disorders of various organ systems. In addition to surgical, urological, orthopedic, neurological, and psychogenic problems, gynecological causes have a major role to play. In the absence of other confirmed causes, women with acute or chronic lower-abdominal pain must therefore be submitted to a gynecological investigation. Important components of such an investigation are clinical gynecological examination and transvaginal ultrasonography. In women of childbearing age, a pregnancy test should always be performed. For both diagnostic and therapeutic purposes, laparoscopy is constantly gaining in importance.

Measurement of hypoxia using the comet assay correlates with preirradiation microelectrode pO2 histography in R3327-AT rodent tumors.

Polarographic determination of tumor oxygenation by Eppendorf histography is currently under investigation as a possible predictor of radiotherapy outcome. Alternatively, the alkaline comet assay has been proposed as a radiobiological approach for the detection of hypoxia in clinical tumor samples. Direct comparisons of these methods are scarce. One earlier study with different murine tumors could not establish a correlation, whereas a weak correlation was reported for a variety of human tumors. Considering the different end points and spatial resolution of the two methods, a direct comparison for a single tumor entity appeared desirable. Anaplastic R3327-AT Dunning prostate tumors were grown on Copenhagen rats to volumes of 1-6 cm(3). Eppendorf histography (100-200 readings in 5 parallel tracks) for 8 different tumors revealed various degrees of oxygenation, with median pO(2) values ranging from 1.1 to 23 mmHg. Within 5 min after an acute exposure to 8 Gy (60)Co gamma rays, tumors were excised from killed animals and rapidly cooled to limit repair, and a single cell suspension was prepared for use with the comet assay. The resulting comet moment distributions did not exhibit two subpopulations (one hypoxic and the other aerobic), and a hypoxic fraction could not be calculated. Instead, the average comet moment distribution was taken as a parameter of overall strand break induction. Corresponding experiments with tumor cells grown in vitro allowed us to derive the relationship between the oxygen enhancement ratio (OER) for the average comet moment and oxygen partial pressure (Howard-Flanders and Alper formula). The validity of this relationship was inferred for cells exposed in situ, and the convolution of a pO(2) distribution with the formula of Howard-Flanders and Alper yielded an array of expected OER values for each tumor. The average expected OER correlated well with the average comet moment (r = 0.89, P < 0.01), and the in situ comet moment distributions could be predicted from the Eppendorf data when 50% repair was taken into account, assuming a 5-min damage half-life. The findings confirm the potential of interstitial polarography to reflect radiobiologically relevant intracellular oxygenation, but also underscore the confounding influence of differences in repair that may occur when cells are prepared from irradiated tissues for use with the comet assay.

The Raf-1 kinase associates with vimentin kinases and regulates the structure of vimentin filaments.

Using immobilized GST-Raf-1 as bait, we have isolated the intermediate filament protein vimentin as a Raf-1-associated protein. Vimentin coimmunoprecipitated and colocalized with Raf-1 in fibroblasts. Vimentin was not a Raf-1 substrate, but was phosphorylated by Raf-1-associated vimentin kinases. We provide evidence for at least two Raf-1-associated vimentin kinases and identified one as casein kinase 2. They are regulated by Raf-1, since the activation status of Raf-1 correlated with the phosphorylation of vimentin. Vimentin phosphorylation by Raf-1 preparations interfered with its polymerization in vitro. A subset of tryptic vimentin phosphopeptides induced by Raf-1 in vitro matched the vimentin phosphopeptides isolated from v-raf-transfected cells labeled with orthophosphoric acid, indicating that Raf-1 also induces vimentin phosphorylation in intact cells. In NIH 3T3 fibroblasts, the selective activation of an estrogen-regulated Raf-1 mutant induced a rearrangement and depolymerization of the reticular vimentin scaffold similar to the changes elicited by serum treatment. The rearrangement of the vimentin network occurred independently of the MEK/ERK pathway. These data identify a new branch point in Raf-1 signaling, which links Raf-1 to changes in the cytoskeletal architecture.

Inhibition of terminal differentiation and matrix calcification in cultured avian growth plate chondrocytes by Rous sarcoma virus transformation.

Endochondral bone formation involves the progression of epiphyseal growth plate chondrocytes through a sequence of developmental stages which include proliferation, differentiation, hypertrophy, and matrix calcification. To study this highly coordinated process, we infected growth plate chondrocytes with Rous sarcoma virus (RSV) and studied the effects of RSV transformation on cell proliferation, differentiation, matrix synthesis, and mineralization. The RSV-transformed chondrocytes exhibited a distinct bipolar, fibroblast-like morphology, while the mock-infected chondrocytes had a typical polygonal morphology. The RSV-transformed chondrocytes actively synthesized extracellular matrix proteins consisting mainly of type I collagen and fibronectin. RSV-transformed cells produced much less type X collagen than was produced by mock-transformed cells. There also was a significant reduction of proteoglycan levels secreted in both the cell-matrix layer and culture media from RSV-transformed chondrocytes. RSV-transformed chondrocytes expressed two- to- threefold more matrix metalloproteinase, while expressing only one-half to one-third of the alkaline phosphatase activity of mock infected cells. Finally, RSV-transformed chondrocytes failed to calcify the extracellular matrix, while mock-transformed cells deposited high levels of calcium and phosphate into their extracellular matrix. These results collectively indicate that RSV transformation disrupts the preprogrammed differentiation pattern of growth plate chondrocytes and inhibit chondrocyte terminal differentiation and mineralization. They also suggest that the expression of extracellular matrix proteins, type II and type X collagens, and the cartilage proteoglycans are important for chondrocyte terminal differentiation and matrix calcification.

[First annual report of practitioners of interventional cardiology in private practice in Germany. Results of procedures of left heart catheterization and coronary interventions in the year 1996]. / Erster Jahresbericht niedergelassener Invasivkardiologen in Deutschland. Ergebnisse für diagnostische Linksherzkatheteruntersuchungen und Koronarinterventionen 1996.

The German Society for Cardiac Angiography and Interventions in Private Practice has started a registry of cardiac procedures since 1996 in order to establish a standard for performance. Although quality management for the cath lab makes sense and is also legally required, there is no generally recommended infrastructure for quality assurance existing in Germany at this time. Therefore, the German Society of Cardiologists in Private Practice (BNK) initiated a project in 1994 to develop a computer program for paperless documentation of diagnostic cardiac catheterizations and coronary interventions (PTCA) using a minimal data set. In 1996, 8 private associated groups participated in this project. The (anonymous) analysis of 10,316 diagnostic cardiac catheterizations and 2597 PTCA yielded the following results: In 95% of the patients, diagnostic cardiac catheterization was performed using the femoral and in 5% the brachial/radial approach. The mean volume of administered contrast medium was 164 +/- 138 ml/patient. The mean LV-EF was greater than 50% in 58.4% of the patients and between 30% and 50% in 10.1%. Coronary artery disease was diagnosed in 69.6% of the patients and valvular/congenital heart disease in 8.5%. In 18.4% of the patients undergoing diagnostic cardiac catheterizations no significant heart disease was identified. Mortality in the cath lab as well as the rate of cerebral insults was 0.05%. In 22.9% and 19% of the patients PTCA and cardiac surgery respectively was recommended. In patients undergoing PTCA, stable angina was present in 74.4% and unstable angina in 13.1%. Of the total number of PTCA procedures, 5.8% were performed in the setting of acute myocardial infarction. The PTCA lesion success rate was 96%, the mean diameter stenosis was 81% pre and 6% post-intervention. The mortality rate at 1 month post-PTCA was 0.4%, and myocardial infarction 1.0%. An acute occlusion occurred in 1.3% of the PTCA patients; 0.6% had to be transferred for emergency bypass surgery. None of the cath labs had on-site surgery. In comparison to other registries, our data show some similarities but also some different trends. Thus, our newly developed software proved to be reliable, fast and easy to use. Participating centers receive immediate feedback regarding their position within the whole group.

Oral manifestations of HIV infection in 600 South African patients.

Oral lesions associated with HIV infection, as classified by the EC-Clearinghouse on Oral Problems related to HIV infection and the WHO Collaborating Centre on Oral manifestations of the immunodeficiency virus, were studied in 600 consecutive HIV-infected patients in Cape Town, South Africa. One or more lesions were seen in 60.4% of cases. Combined candidal lesions were evident in 37.8%, hairy leukoplakia in 19.7% and combined gingival/periodontal lesions in 8.5% of patients seen. Lesions less commonly recorded include oral ulceration (2.9%) and Kaposi's sarcoma (1.5%). The clinical range of lesions seen is similar to those reported elsewhere, but socio-cultural differences allowed no reliable comparison. More than a quarter of our patients had oral soft tissue discomfort necessitating treatment; in 3.3% these were the presenting symptom. This indicates a potential major public health concern requiring education in recognition and appropriate referral and management.

PIP: The prevalence and clinical appearance of oral manifestations of HIV were investigated in 600 consecutive HIV patients examined at health care facilities in Cape Town, South Africa, in 1993-96. At least 1 oral lesion was present in 362 patients (60.4%). 160 oral manifestations (26.7%) were symptomatic and required treatment. The majority of lesions (37.8%) were candidosis, primarily pseudomembranous and erythematous types. Oral hairy leukoplakia was present in 19.7% of patients, while HIV-related peridontal disease was noted in 8.5%. 20 HIV-positive patients (3.3%) presented with an oral manifestation of HIV infection before HIV was diagnosed. Classifications were based on guidelines developed by the EC-Clearinghouse on Oral Problems Related to HIV Infection and the World Health Organization Collaborating Center on Oral Manifestations of the Immunodeficiency Virus. These findings, which are similar to those reported in other developed and developing countries, indicate a need for education on the recognition and appropriate management and referral of oral manifestations of HIV infection.

Prevention of EGF-modulated adhesion of tumor cells to matrix proteins by specific EGF receptor inhibition.

The adhesion of tumor cells to various extracellular matrix (ECM) proteins is influenced by epidermal growth factor (EGF). Maximal effects are obtained at low EGF concentrations, at which mostly the cytoskeleton-associated high-affinity EGF receptors (EGFRs) are saturated. Tumor cells expressing EGFR either endogenously (MDA MB 231, MTLn3) or, for the human EGFR, ectopically (MTC HER1/1) in intermediate amounts exhibited, upon EGF addition, increased cellular adhesion to various ECM proteins, such as fibronectin, collagens and vitronectin. In contrast, human A431 and MDA MB 468 cells, over-expressing EGFR, demonstrated reduced attachment in similar experimental conditions. Both increased as well as reduced EGF-dependent adhesion could be blocked using either ligand-blocking monoclonal antibody 14E1 or the potent EGFR tyrosine kinase inhibitor PD 153035. Our data indicate that signals downstream of EGFR activation are responsible for the opposing effects of EGF on cellular adhesion since both can be prevented by EGFR inhibition. Thus, the integration of EGFR- and integrin-dependent signals can be different in carcinoma cell lines and might be influenced by EGFR numbers.

Metallothionein induction in calcifying growth plate cartilage chondrocytes.

Metallothionein (MT) induction was studied in mineralizing cultures of chicken growth plate chondrocytes and quantitated using a Cd-saturation assay. In serum free media, MT induction was observed for Cd concentrations of 0.1 microM and greater and at Zn concentrations of 100 microM and greater. Supplementation of culture media with cysteine and/or methionine resulted in higher levels of MT induction and reduced toxicity during Cd exposure. Maximum MT induction appeared to coincide with the earliest culture stages during which important enzymes and matrix components are being synthesized. Of non-metal MT inducers tested, sodium butyrate caused a low level induction of MT while interleukin-1 had no effect on basal MT levels. 1,25-dihydroxyvitamin D increased MT induction. The steroid hormone dexamethasone caused a reduction in basal and induced MT levels. These findings suggest that MT regulation in growth plate chondrocytes differs significantly from what is known in other cell types and that this difference may be related to the mineralization of this tissue.

TNF accelerates the S-phase of the cell cycle in tumor cells.

The reduction of glucose supply induced the killing of tumor cells by tumor necrosis factor (TNF) in vivo and in vitro. In contrast, normal cell lines were resistant to TNF regardless of the presence or absence of glucose. Epidermal growth factor (EGF) did not exert a cytotoxic effect on tumor cells in the absence of glucose. Therefore, the killing mechanism of TNF under conditions of reduced glucose supply was investigated. Flow cytometry experiments and studies of kinetics revealed that the S-phase of the cell cycle was prolonged in the absence of glucose. After TNF treatment, the S-phase was found to be shortened and the rate of 3H-thymidine incorporation into DNA was increased, whereas EGF failed to exert such an effect. DNA synthesis and entry into mitosis are known to be regulated by cyclin A. In serum-starved tumor cells (HeLa) we have observed increased cyclin A synthesis within 10 hr, in parallel with enhancement of DNA synthesis and shortening of the S-phase after TNF treatment. We conclude that, under conditions of low glucose supply, TNF can assume the role of a growth factor in transformed cells.

Glucose depletion enhances the anti-tumor effect of TNF.

Treatment of human carcinoma xenotransplants in athymic mice with recombinant human tumor necrosis factor (rh TNF) causes necrosis mainly in the central parts of the tumors, while peripheral sections remain mitotically active. As tumors are known to be supplied with adequate glucose exclusively in their periphery, the influence of the lack of glucose on the cytotoxic activity of rh TNF was studied. The absence of glucose enhanced the killing of tumor cell lines by rh TNF in tissue culture. Meth-A, a cell line known to be resistant to TNF in vitro but highly sensitive to it in vivo, was readily killed in tissue-culture medium lacking glucose. All non-transformed cell lines tested were found to be resistant to rh TNF, regardless of the presence or absence of glucose. In tumor-bearing mice a reduction of the blood glucose content augmented by insulin led to increased anti-tumor efficiency of rh TNF. The enhanced anti-tumor activity was reflected both in histological sections of the tumor xenotransplants, by extensive central necroses, and by reduction of the tumor volumes.

Medium chain length fatty acids stimulate triacylglycerol synthesis in tissue culture cells.

In the presence of undecanoic acid (C11) or lauric acid (C12) the synthesis of triacylglycerols was stimulated up to 10-fold both in tumor cell lines and in normal cell lines. Monocarboxylic acids of shorter or longer chain length either had no effect at all or were less effective. The increased triacylglycerol production was demonstrated, on the one hand, by the incorporation of radiolabeled glycerol into triacylglycerols and, on the other, by the incorporation of radiolabeled monocarboxylic acids, the incorporation of all (1-14C)-labeled monocarboxylic acids (C6, C12, C16, C18) regardless of their chain length, being preferentially enhanced by C11 and C12. C12 stimulated the de novo synthesis of triacylglycerols to such a degree that a 7-fold increase in the total amount of triacylglycerols per cell was observed during the first 10 hr of incubation. After removal of C12 from the tissue culture medium levels of triacylglycerols reach initial values again within 6 hr, indicating that the stimulatory effect of C12 is dependent on its continued presence. This led to the speculation that medium chain length monocarboxylic acids might be involved in the control of triacylglycerol synthesis.

[Indications for surgery in distal radius fractures]. / Zur Operationsindikation bei der distalen Radiusfraktur.

In this retrospective study, the results of conservative treatment of 406 fractures of the distal radius are analysed and the limitations of conservative therapy indicated. In all, 107 male patients (average age 45 years) and 299 women (average age 65 years) were examined. In only one-third of these cases were both radiographically and clinically. Of the primarily dislocated fractures, 19% healed in the correct anatomical position with satisfactory to good clinical results. Up to now, treatment of fractures of the distal radius with dorsal tilting has been regarded as a form of conservative therapy. Although certain types of fracture, in particular unstable ones, have always been regarded as cases for operative treatment, no attempt has ever been made to define the limits between conservative and operative treatment. Evaluation of the results clearly indicates that the classification according to Frykman, the one most commonly in use, cannot be used as a primary criterion for operative treatment. In the course of a meticulous statistical evaluation, we defined the radiological parameters precisely with reference to shortening, dorsal tilt and instability and drew up a classification to define the primary indications for operation in cases of fracture of the distal radius. Shortening by over 3mm, dorsal tilting by over 10 degrees, presence of a dorsal debris zone, rupture, or osseous avulsion of the radioulnar syndesmosis as a further instability factor show the limits of conservative therapy and are clear indications for operative treatment.(ABSTRACT TRUNCATED AT 250 WORDS)