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Biomedical subjects

E Bierhoff

Publications and source records attributed to E Bierhoff.

At least 19 recordsLinked to original sources

[Cutaneous lesions due to inhibition of epidermal growth factor receptor].

Malignant tumors are increasingly being treated with therapeutic agents having molecular mechanisms of action (so-called biologics). These include therapeutic agents for the blockade of epidermal growth factor receptor (EGFR). The adverse drug reaction profile associated with EGFR inhibitors is dominated by cutaneous lesions. Most common are acneiform skin reactions followed by xerosis, eczema and changes to the hair and nails. The cutaneous changes vary greatly between individuals and may be relatively insignificant. However, they may also prevent continuation of therapy. During the use of EGFR inhibitors, a correlation was observed between the severity of cutaneous changes and the effectiveness of the therapeutic agent, a finding potentially useful for individual dose adjustment.

Antibodies, Monoclonal↗

Immunohistochemical differentiation of eosinophilic heart diseases using antibodies against eosinophil activation markers.

AIMS: Eosinophilic heart syndromes are rare in Western countries and include endocarditis parietalis fibroplastica (EPF) and hypersensitivity myocarditis (HM). There are striking differences in natural history and morphological findings. Since diagnosis can be difficult when analysing small myocardial biopsies lacking the characteristic histological features, we studied a set of immunohistochemical markers in order to characterize the activation status of the infiltrating eosinophils to distinguish between these two entities. METHODS AND RESULTS: This study is based on the investigation of seven explanted hearts and one left ventricular specimen collected during implantation of a left ventricular assist device from a total of seven patients with HM. Also investigated were three right and three left ventricular specimens from five patients with EPF. We used antibodies (Ab) against EG1, and EG2, CD44, and CD69 which have been described as markers to distinguish between resting and activated eosinophils. The EG1 to EG2 ratio of eosinophils and the immunoreactivity against CD44 showed no differences between the two entities. However, eosinophils in the EPF were completely negative for CD69, whereas eosinophils reacted positively within the HM group. CONCLUSION: The immunohistochemical investigation of eosinophilic heart diseases using antibodies against CD69 can be a useful tool to distinguish between hypersensitivity myocarditis and endocarditis parietalis fibroplastica.

Aged↗

Predictive variables for the biological behaviour of basal cell carcinoma of the face: relevance of morphometry of the nuclei.

We did a morphometric analysis of 130 histological sections of basal cell carcinoma (BCC) of the face to find out whether morphometric variables in the structure of the nuclei of BCC cells could serve as predictors of the biological behaviour. We considered the following variables: maximum and minimum diameters, perimeter, nuclear area and five form factors that characterise and quantify the shape of a structure (axis ratio, shape factor, nuclear contour index, nuclear roundness and circumference ratio). We did a statistical analysis of primary and recurring tumours and four histology-based groups (multifocal superficial BCCs, nodular BCCs, sclerosing BCCs and miscellaneous forms) using a two-sided t test for independent samples. Multifocal superficial BCCs showed significantly smaller values for the directly measured variables (maximum and minimum diameters, perimeter and nuclear area). Morphometry could not distinguish between primary and recurring tumours.

Adolescent↗

p53 immunoreactivity in biopsy specimens of T1G3 transitional cell carcinoma of the bladder--a helpful parameter in guiding the decision for or against cystectomy?

The aim of this study was to determine whether p53 is helpful in making the decision to undergo cystectomy in T1, G3 transitional cell carcinoma (TCC) of the bladder, by prospectively comparing the p53 status of bladder biopsies with the histology and p53 status of the corresponding cystectomy specimens. From January 1996 to August 1997, 38 consecutive patients with T1G3 TCC at 6 different centres were enrolled into the study. Bladder biopsies and cystectomy specimens were examined with three different antibodies against p53. The p53 status of each bladder biopsy was compared with p53 status, tumour stage and grade of the cystectomy specimen. An independent evaluation of the histology and immunohistochemistry was carried out by two pathologists. 15 of 38 patients (39%) were found to have a higher tumour stage in the cystectomy specimen compared with the staging by transurethral resection of the bladder tumour (TUR-B). 3 patients did not show residual tumour in the cystectomy specimen. No differences in p53 positivity were noted between the different antibodies. 14 of 31 evaluable tumours (45%) were p53 positive at the time of the TUR-B. p53 staining of the TUR-B specimen did not correctly predict the residual tumour in the cystectomy specimen. We, therefore, concluded that compared with standard histopathology, the p53 status of the TUR-B specimen does not provide additional relevant information with regard to local tumour staging and, thus, is not helpful in making the decision for or against a cystectomy.

Adult↗

Risk factors for relapse in stage I non-seminomatous germ-cell tumors: preliminary results of the German Multicenter Trial. German Testicular Cancer Study Group.

Risk factor analysis to identify low-risk patients for occult metastatic disease (vascular invasion, percentage embryonal carcinoma, MIB-I proliferation rate) yields reliable results if performed by experts. A correct prediction is possible at the 90% level. Similar accuracy, however, may be achieved if the computed tomography (CT) staging is optimized and the evaluation performed by an experienced investigator. The combination of both methods (biological risk factor analysis and CT staging) may virtually exclude the risk of relapse in a limited number of patients. However, so far, no risk factor that is able to reliably predict occult metastatic disease or relapse in clinical state I patients has been identified in prospective trials. The preliminary results of the current German Multicenter Trial suggest an inferior value of prediction for low-risk patients if risk factor analysis and/or CT staging is performed in non-specialized centers.

Antineoplastic Combined Chemotherapy Protocols↗

Clinical course and histopathologic risk factor assessment in patients with bilateral testicular germ cell tumors.

OBJECTIVES: To determine whether the clinical course or the histopathologic risk factor assessment of the secondary tumor justifies early detection of the premalignant testis, since only 5% of contralateral testicular biopsies in the case of a testicular tumor reveal a testicular intraepithelial neoplasia (TIN). METHODS: From 1975 to 1997, 30 patients with bilateral germ cell tumors were treated; histologic and clinical data were available in all patients. In 12 patients, histopathologic re-evaluation and immunohistochemical staining of both tumors was performed for risk factor analysis. RESULTS: At the time the primary tumor was diagnosed, the mean patient age was 28 years. The metachronous secondary tumors were detected after a mean of 5.6 years. Seminoma was the predominant histologic finding in primary (53%) and secondary (56%) tumors. Eighty-three percent of patients had clinical Stage I (Lugano classification) disease at the diagnosis of the secondary tumor and 17% Stage II. Only 3 of 12 secondary tumors showed vascular invasion. The proliferation analysis (MIB-I score) showed a mean proliferation rate of only 34% within the primary and 26% within the secondary tumors. CONCLUSIONS: The results of our study show that the low clinical stage and good outcome associated with a histologic low-risk score of the secondary tumor does not mandate contralateral biopsy to detect TIN at the time of diagnosis of the first tumor.

Adult↗

[MRI diagnosis of cardiac myxomas: sequence evaluation and differential diagnosis].

PURPOSE: To evaluate native and contrast enhanced T1-weighted spin (T1-SE), cine gradient echo (Cine-GE), and T2-weighted turbo spin (T2-TSE) sequences in the diagnosis and differential diagnosis of cardiac myxomas. METHODS: 15 patients with echocardiographically suspected cardiac atrial myxomas underwent 0.5 T-MR imaging of the heart with native T1-SE, contrast-enhanced T1-SE, Cine-GE, and T2-TSE sequences. MR images were evaluated for signal intensity (SI) and lesion's conspicuity. Results were confirmed histologically (14 x) or by follow-up (1 x). RESULTS: MRI revealed myxomas in 9 patients, sarcomas in three patients, and thrombi in three patients. Lesion conspicuity was better in Cine-GE and T2-TSE compared with native and contrast-enhanced T1-SE sequences. Myxomas were characterized by an intermediate SI similar to myocardium in T1-SE, high SI similar to water in T2-TSE, and low to moderately high enhancement (range 19-75%, mean 48%). CONCLUSION: Distinct SI characteristics together with anatomical-topographical features (attachment to the interatrial septum, no infiltration of myocardium and vessels) are diagnostic for cardiac myxomas. Cine-GE and T2-TSE sequences are the sequences of choice for detection of myxomas and other atrial masses. T2-TSE and contrast-enhanced T1-weighted sequences are most useful for mass characterisation and differentiation between myxomas, malignant tumors, and thrombi.

Diagnosis, Differential↗

[Tracheal reconstruction with preserved tracheal homograft--new aspects].

BACKGROUND: The treatment of long-segment tracheal stenosis is a biological and surgical problem. The introduction of preserved allografts established new possibilities for functional tracheal reconstruction. PATIENTS AND METHODS: Since 1979 preserved allografts were used in 112 patients (including 20 children) with tracheal stenosis. Increasing knowledge in preservation, surgical treatment and pathohistology were put into practice. RESULTS: Implantation of the preserved allografts into the infrahyoid muscles proved to be advantageous. Preservation with the tutoplast method prevented the risk of viral infection, and led to faster and trouble-free post-operative healing. Pathohistological studies let to improve surgical techniques by increasing the knowledge of the nature of tracheal stenosis. CONCLUSION: Functional tracheal reconstruction for long-segment tracheal stenosis can be achieved by implantation of preserved allografts.

Adult↗

[Proliferative activity in recurrent and nonrecurrent pleomorphic adenoma of the salivary glands].

BACKGROUND: The origin of recurrences of pleomorphic adenomas after initial surgical treatment is discussed. In this study mesenchymal and epithelial tumorcomponents were immunhistochemically stained in recurrent and nonrecurrent adenoma. In addition the proliferation activity was assessed. METHODS: Twelve nonrecurrent adenomas (10 of the parotid gland, 2 of the submandibular gland) and 18 recurrent adenomas (15 of the parotid gland, 3 of the submandibular gland) were immunhistochemically stained with a MIB1 antibody against the cell proliferation associated nuclear antigen (Ki-67 antigen). The proliferation index (MIB1 positive cells per 100 cells) was calculated separately for each tumor component. RESULTS: The mean value (x) of the proliferation indices of the component with epithelial differentiation was 4.67 (recurrent group, standard deviation [SD]: 3.14) and x = 2.34 respectively (nonrecurrent group, SD = 1.83). The difference between the mean values was significant (p = 0.028). For the component with mesenchymal differentiation the values were x = 0.33 (for recurrent adenomas, SD = 0.59) and x = 0.17 (nonrecurrent adenomas, SD = 0.39) respectively. The difference was not significant. CONCLUSIONS: Proliferation activity is markedly higher in components with epithelial differentiation of recurrent adenomas compared to nonrecurrent tumors. The results demonstrate the tumor component with epithelial differentiation as a possible origin for recurrence.

Adenoma, Pleomorphic↗

[Löffler fibroblastic endocarditis in the thrombotic stages in isolated right ventricular tissue eosinophilia].

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.

Adult↗

[MRI diagnosis of right ventricular dysplasia].

PURPOSE: Right ventricular dysplasia (RVD) represents an important cause of sudden death and ventricular arrhythmias in young patients. The aim of this study was to describe diagnostic diagnostic criteria and the MR-tomographie aspects of the disease. METHODS: 34 patients with clinically suspected RVD were examined by 0.5-T MRI (cardiac-gated T1-weighted spin echo sequences and cine gradient echo sequences). RVD was confirmed in 16 patients and ruled out in 18 patients. MR images were evaluated for presence of: 1. right myocardial fatty infiltration, 2. dilatation of the right ventricle, 3. dilatation of the right ventricular outflow tract, and 4. localised right ventricular aneurysm. RESULTS: Right myocardial fatty infiltration was detected by MRI in 11 of 16 patients (69%) with RVD. Dilatation of the right ventricle was seen in 5 patients, dilatation of the right outflow tract in one patient, and localised right ventricular aneurysm in two patients with RVD. CONCLUSIONS: MRI is able to demonstrate fatty replacement of right ventricular myocardium in most cases and plays an important role in the diagnosis of RVD.

Adipose Tissue↗

Genomic deletions in the BRCA1, BRCA2 and TP53 regions associate with low expression of the estrogen receptor in sporadic breast carcinoma.

Sporadic breast carcinoma is associated with multiple genetic alterations. The clinical relevance of these alterations, however, needs further clarification. In the present study we analyzed 266 spontaneously arising breast carcinomas for allelic losses in the BRCA1 and TP53 regions on chromosome 17, the BRCA2 region on chromosome 13, the ATM (mutated in ataxia-telangiectasia) region on chromosome 11 and on the chromosomal arms 7q and 16q. In addition the following clinical and pathological parameters were evaluated: age at diagnosis, tumor size, presence or absence of regional and distant metastases, hormone-receptor status, histopathological classification and tumor grading. The analysis of genetic and clinical observations revealed significant associations: absence of expression of the estrogen receptor was linked to a high rate of allelic losses of markers in the BRCA1, TP53 and BRCA2 regions. Expression of the progesterone receptor coincided with allelic loss on the long arm of chromosome 16. High-grade malignant lesions and ductal differentiation were frequently associated with allelic losses in the proximal portion of chromosome 17q. The accumulation of multiple allelic deletions was linked to high-grade malignant tumors, to tumor size, and to loss of expression of the estrogen receptor. Our data point to a relationship between clinically relevant prognostic factors and specific genomic deletions in the BRCA1, BRCA2 and TP53 region.

Breast Neoplasms↗

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↗

MIB-1 immunohistochemistry in clinical stage I nonseminomatous testicular germ cell tumors predicts patients at low risk for metastasis.

BACKGROUND: The clinical Stage I of nonseminomatous germ cell tumors (NSGCT) is inaccurate in 30% of patients. In previous studies on tumor biologic risk factors, low tumor proliferation rates predicted a group of patients at low risk for occult metastatic disease. The goal of this study was to confirm the immunohistochemical assessment of tumor proliferation using MIB-1 (Ki-67 receptor) in a different patient cohort with different investigators to prove the method's reliability. METHODS: Orchiectomy specimens of 78 patients with clinical Stage I NSGCT (50 patients with pathologic Stage I and 28 patients with pathologic Stage II disease, all patients underwent retroperitoneal lymph node dissection) were retrospectively analyzed by histopathologic reevaluation and MIB-1 immunostaining. RESULTS: Mean MIB-1 values between the two pathologic stages differed significantly (51.5% MIB-1 positive tumors cells in pathologic Stage I and 75.1% MIB-1 positive tumor cells in pathologic Stage II disease; P = 0.02). Using a 70% cutoff value, pathologic stages were correctly classified in 69% of cases (sensitivity of 86%, specificity of 60%, negative predictive value of 88%, and positive predictive value of 55%). Compared with traditional risk factors such as percentage of embryonal carcinoma and vascular invasion, in multivariate analysis, MIB-1 was the best predictor of patients at low risk for metastasis. CONCLUSIONS: This study in a different patient population with different investigators confirmed previous results of MIB-1 staining to predict a group of patients with clinical Stage I NSGCT who were at low risk for metastasis. The method is simple and reproducible to improve risk classification in low stage testicular carcinoma. Using this technique, a group of patients at very low risk for metastasis can be identified. [See editorial counterpoint on pages 1641-5 and reply to counterpoint on page 1646, this issue.]

Antibodies, Monoclonal↗

Liver histopathology in patients with concurrent chronic hepatitis C and HIV infection.

To investigate the influence of human immunodeficiency virus (HIV) coinfection on preexisting long-term chronic C hepatitis (HCV) 68 liver biopsies from 22 HIV/HCV-coinfected, 13 HIV- and 33 HCV-monoinfected patients and 71 livers obtained at autopsy from 26 HIV/HCV-coinfected and 45 HIV-monoinfected patients were studied by histo- and immunohistochemistry. All HIV patients had reached the advanced stage of immunodeficiency (stage III CDC), except for 3 haemophilias (stage II CDC). HCV infection was associated with a higher degree of portal, periportal and lobular inflammation-regardless of whether there was concurrent HIV infection. HIV/HCV coinfection was associated with a significantly higher rate of granulocytic cholangiolitis than HCV and HIV monoinfection (P < 0.05), a histological feature uncommon in C hepatitis. In HIV/HCV coinfection cholestasis was a predominant histological feature. HCV monoinfection and HCV/HIV coinfection were associated with the highest fibrosis index. In HIV/HCV coinfection centrilobular fibrosis was significantly more marked than in HCV monoinfection (P < 0.05), suggesting an HIV-associated fibrogenic effect. Patients with chronic C hepatitis showed a significantly increased rate of posthepatitic cirrhosis compared with the patients without HCV infection (P < 0.05). At autopsy, 10 of the 20 HIV/HCV-coinfected haemophiliacs had developed cirrhosis because of chronic C hepatitis, whereas cirrhosis was found in only 2 of 6 HIV/HCV-coinfected non-haemophiliacs (1 case of chronic B and C hepatitis, and 1 case of chronic alcohol abuse). No cirrhosis was observed in the 45 autopsy patients with HIV monoinfection. The findings suggest that HIV coinfection aggravates the course of preceding long-term chronic C hepatitis by a more marked (centrilobular) fibrosis. HIV/HCV-coinfected patients are threatened by a higher rate of posthepatitic cirrhosis-particularly in multitransfused haemophiliacs-and cholestatic hepatopathy.

Adolescent↗

Association of allelic losses on human chromosomal arms 11Q and 16Q in sporadic breast cancer.

Breast-carcinoma development presumably results from multiple mutational events in tumor-associated genes. Certain results indicate that some tumor-suppressor genes may combine their pathogenetic potential to synergistically promote tumor growth. In an effort to identify such mechanisms in breast tumors, a series of 77 (group I) paired blood tumor samples from patients with sporadic mammary carcinomas was analyzed for loss of heterozygosity with 15 polymorphic markers on the chromosomal arms 7q, 11q, 13q, 16q, 17p and 17q. A significant association was observed for the combination of allelic losses on chromosomes 11q and 16q. In order to confirm these findings, we studied a second independent series of 189 breast-tumor patients (group 2) with comparable histopathological tumor stages. Group 2 was examined for the same genetic alterations using the identical set of polymorphic markers. The data from this group confirmed the detected association of loss of heterozygosity on chromosomes 11q and 16q and indicate the cooperation of putative tumor-suppressor genes on the chromosomal arms 11q and 16q in a sub-set of breast carcinomas. The regions involved harbor the candidate genes ATM (mutated in ataxiatelangiectasia) on chromosome 11q23 and UVO (uvomorulin, cadherin E) and BBCI (breast basic conserved I) on chromosome 16q22-q24.

Alleles↗

Evidence for a novel tumor suppressor gene on chromosome 15 associated with progression to a metastatic stage in breast cancer.

Loss of heterozygosity (LOH) studies have emerged as a valuable indicator for tumor suppressor genes involved in the formation or progression of carcinomas. We here present data indicating that human chromosome 15 harbours a novel putative tumor suppressor gene which appears to play a role during later stages of carcinogenesis and which may be associated with metastasis in breast cancer. In this study, 153 primary and metastatic carcinomas from 101 patients have been analysed for LOH with 13 polymorphic microsatellite markers on chromosome 15. The tumors included carcinoma of the lung in 49 patients, breast carcinoma in 29, colorectal carcinoma in nine, renal carcinoma in five, pancreatic carcinoma in five, urinary bladder carcinoma in two and prostate carcinoma and ovarial carcinoma in one patient each. LOH15 was seen in 42/99 (42%) informative patients. In metastatic tumors, LOH15 was observed in 37/68 (54%). High incidences of allelic losses were detected in metastases from lung (56%), breast (70%) and colorectal (67%) carcinomas. In carcinomas of the breast, there was a significant difference (P<0.01) in LOH15 frequencies between non-metastatic tumors (11%) and brain metastases (70%). Such a difference was not observed on the chromosomal arm 17p which yielded high proportions of LOH in both non metastatic breast tumor (73%) and breast carcinoma metastases (90%). In 16 patients, interstitial deletions could be detected. The common region of overlap extended from D15S231 to D15S641, thus mapping this putative tumor suppressor gene to chromosome 15q14. Our data indicate that a gene on chromosome 15 contributes to the pathogenesis of metastatic carcinoma.

Brain Neoplasms↗