Hospital Itzehoe

Itzehoe, Germany

Hospital Itzehoe

Itzehoe, Germany

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Nguyen R.,University of Hamburg | Nguyen R.,University of Maryland, Baltimore | Kluwe L.,University of Hamburg | Jett K.,University of British Columbia | And 4 more authors.
Clinical Genetics | Year: 2013

The aim of this study was to characterize cardiac features of patients with neurofibromatosis 1 (NF1) and large deletions of the NF1 gene region. The study participants were 16 patients with large NF1 deletions and 16 age- and sex-matched NF1 patients without such deletions. All the patients were comprehensively characterized clinically and by echocardiography. Six of 16 NF1 deletion patients but none of 16 non-deletion NF1 patients have major cardiac abnormalities (p=0.041). Congenital heart defects (CHDs) include mitral insufficiency in two patients and ventricular septal defect, aortic stenosis, and aortic insufficiency in one patient each. Three deletion patients have hypertrophic cardiomyopathy. Two patients have intracardiac tumors. NF1 patients without large deletions have increased left ventricular (LV) diastolic posterior wall thickness (p<0.001) and increased intraventricular diastolic septal thickness (p=0.001) compared with a healthy reference population without NF1, suggestive of eccentric LV hypertrophy. CHDs and other cardiovascular anomalies are more frequent among patients with large NF1 deletion and may cause serious clinical complications. Eccentric LV hypertrophy may occur in NF1 patients without whole gene deletions, but the clinical significance of this finding is uncertain. All patients with clinical suspicion for NF1 should be referred to a cardiologist for evaluation and surveillance. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Laack E.,Ambulantes Krebszentrum Hamburg | Regier M.,Diagnostic Center | Andritzky B.,University of Hamburg | Habermann C.,Diagnostic Center | And 3 more authors.
Journal of Thoracic Oncology | Year: 2011

Miliary pattern of pulmonary metastases is a rarity in patients with lung cancer. We report five cases of patients with a never-smoking adenocarcinoma of the lung with such a pattern of metastases. In the tumor cells of all five patients, epidermal growth factor receptor (EGFR) mutation gene sequencing identified a deletion in exon 19 of the EGFR gene, and all five patients had a dramatic response to EGFR tyrosine kinase inhibitors. No echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) translocation was detected. We believe that the miliary never-soking adenocarcinoma of the lung is a distinct clinically relevant subgroup of the never-smoking non-small cell lung cancer. Physician should recognize this subgroup of patients with lung cancer when facing a picture of miliary pulmonary metastases in chest x-ray or computed tomography scan in patients with a history of never smoking and consider upfront therapy with EGFR tyrosine kinase inhibitors. Copyright © 2010 by the International Association for the Study of Lung Cancer.


Heinrich S.,University of Hamburg | Heinrich S.,University of Leipzig | Deister A.,Hospital Itzehoe | Birker T.,Psychotherapy and Psychosomatic Medicine | And 6 more authors.
Psychiatry Research | Year: 2011

Assessments of service utilization is often based on self-reports. Concerns regarding the accuracy of self-reports are raised especially in mental health care. The purpose of this study was to analyze the accuracy of self-reports and calculated costs of mental health services. In a prospective cohort study in Germany, self-reports regarding psychiatric inpatient and day-care use collected by telephone interviews based on the Client Socio-Demographic and Service Receipt Inventory (CSSRI) as well as calculated costs were compared to computerized hospital records. The sample consisted of patients with mental and behavioral disorders resulting from alcohol (ICD-10 F10, n=84), schizophrenia, schizophrenic and delusional disturbances (F2, n=122) and affective disorders (F3, n=124). Agreement was assessed using the concordance correlation coefficient (CCC), mean difference (95% confidence intervals (CI)) and the 95% limits of agreement. Predictors for disagreement were derived. Overall agreement of mean total costs was excellent (CCC = 0.8432). Costs calculated based on self-reports were higher than costs calculated based on hospital records (15 EUR (95% CI -434 to 405)). Overall agreement of total costs for F2 patients was CCC = 0.8651, for F3 CCC = 0.7850 and for F10 CCC = 0.6180. Depending on type of service, measure of service utilization and costs agreement ranged from excellent to poor and varied substantially between individuals. The number of admissions documented in hospital records was significantly associated with disagreement. Telephone interviews can be an accurate data collection method for calculating mean total costs in mental health care. In the future more standardization is needed. © 2010 Elsevier Ltd.


Nguyen R.,University of Hamburg | Kluwe L.,University of Hamburg | Kluwe L.,German Cancer Research Center | Fuensterer C.,MRI Institute | And 3 more authors.
Journal of Pediatrics | Year: 2011

Objectives: To define the frequency and clinical features of plexiform neurofibromas (PN) in children with neurofibromatosis type 1. Study design: Sixty-five children received whole-body magnetic resonance imaging (MRI) and clinical-neurologic examination. Tumor sizes were calculated volumetrically with the program MedX v3.42. χ 2 test, Fisher exact test, t test, and Spearman rank correlation were used for statistical analysis. Results: Seventy-three tumors were detected in 37 of these 65 children. The mean volume of the tumors was 145.4 mL or 4.8 mL/kg body weight. Eighteen of the 73 PNs caused clinical deficits in 17 children, and the other 56 PNs in 20 children were asymptomatic. Symptomatic tumors were larger than asymptomatic ones (9.6 vs 3.3 mL/kg body weight; P =.01). However, in certain body regions, for example, the head, small tumors also caused clinical deficits. Ten of 18 children ≥11.5 years (median age of the 37 children with PNs) had symptomatic PNs compared with 7 of 19 who were <11.5 years (P =.25). Conclusion: PNs cause clinical deficits in young children. Early detection and regular MRI monitoring help to estimate growth and possible upcoming complications, and are thus beneficial for optimizing treatment and management. © 2011 Mosby Inc. All rights reserved.


Choschzick M.,University of Hamburg | Lebeau A.,University of Hamburg | Marx A.H.,University of Hamburg | Tharun L.,University of Hamburg | And 7 more authors.
Human Pathology | Year: 2010

Cell division cycle 7 is a widely expressed protein kinase implicated in cell division, cell cycle checkpoint mechanisms, and cancer progression. To determine the relationship of cell division cycle 7 protein expression with tumor phenotype, molecular features and prognosis, 2197 highly characterized breast carcinomas were analyzed on a tissue microarray. Detectable cell division cycle 7 expression was found in 1088 (57%) of breast cancer specimens and 228 (11.9%) exhibited a moderate or strong expression. High levels of cell division cycle 7 expression were significantly related to medullary histotype (P < .0001); high tumor grade (P < .0001); negative estrogen receptor status (P < .0001); high Ki67 expression level (P < .0001); p53 and p16 overexpression (P < .0001); and amplification of HER2 (P < .0001), c-myc (P < .0001), MDM2 (P = .043), CCND1 (P = .0084), and ESR1 (P = .0012) as well as with the number of amplified genes (P < .0001). There was also a tendency towards worse prognosis in cell division cycle 7 positive as compared to negative breast cancers. The relationship between cell division cycle 7 and number of amplifications was independent from tumor proliferation raising the possibility of a direct influence of cell division cycle 7 expression for amplification development. In conclusion, cell division cycle 7 is a replication associated protein with relationships to gene amplification and genomic instability in breast carcinomas. These data support the potential utility of newly developed small molecule cell division cycle 7 inhibitors as a therapeutic alternative in at least a subset of breast carcinomas. © 2010 Elsevier Inc. All rights reserved.


Choschzick M.,University of Hamburg | Lassen P.,University of Hamburg | Lebeau A.,University of Hamburg | Marx A.H.,University of Hamburg | And 7 more authors.
Modern Pathology | Year: 2010

Copy number gains involving the long arm of chromosome 8, including high-level amplifications at 8q21 and 8q24, have been frequently reported in breast cancer. Although the role of the MYC gene as the driver of the 8q24 amplicon is well established, the significance of the 8q21 amplicon is less clear. The breast cancer cell line SK-BR-3 contains three separate 8q21 amplicons, the distal two of which correspond to putative target genes TPD52 and WWP1. To understand the effect of proximal 8q21 amplification on breast cancer phenotype and patient prognosis, we analyzed 8q21 copy number changes using fluorescence in situ hybridization (FISH) in a tissue microarray containing more than 2000 breast cancers. Amplification at 8q21 was found in 3% of tumors, and was associated with medullary type (P0.03), high tumor grade (P0.0001), high Ki67 labeling index (P0.05), amplification of MYC (P0.0001), HER2, MDM2, and CCND1 (P0.05 each), as well as the total number of gene amplifications (P0.0001). 8q21 copy number gains were significantly related to unfavorable patient outcome in univariate analysis. However, multivariate Cox regression analysis did not reveal an independent prognostic value of 8q21 amplification. The position of our FISH probe and data of a previously performed high-resolution CGH study in the breast cancer cell line SK-BR-3 involve TCEB1 and TMEM70 as new possible candidate oncogenes at 8q21 in breast cancer. © 2010 USCAP, Inc. All rights reserved.


Fiege M.,Hospital Itzehoe | Weisshorn R.,Hospital Itzehoe | Kolodzie K.,Hospital Itzehoe | Wappler F.,Hospital Itzehoe | Gerbershagen M.U.,Hospital Itzehoe
Journal of Biomedicine and Biotechnology | Year: 2011

Background. Theophylline was shown to induce contracture development in porcine malignant hyperthermia (MH) susceptible (MHS) skeletal muscles in vitro. The purpose of the current study was to investigate the in vivo effects of theophylline in MHS and MH normal (MHN) swine. Methods. MH-trigger-free general anesthesia was performed in MHS and MHN swine. Theophylline was administered intravenously in cumulative doses up to 93.5mgkg1. The clinical occurrence of MH was defined by changes of central-venous pCO2, central-venous pH, and body core temperature. Results. Theophylline induced comparable clinical alterations in the anesthetized MHS and MHN swine, especially in regard to hemodynamic data. No pig developed hypermetabolism and/or MH according to defined criteria. All animals died with tachycardia followed by ventricular fibrillation. Conclusions. The cumulative theophylline doses used in this study were much higher than doses used therapeutically in humans, as demonstrated by measured blood concentrations. Theophylline is thus not a trigger of MH in genetically determined swine. Copyright © 2011 Marko Fiege et al.


Grob T.J.,University of Hamburg | Heilenkotter U.,Hospital Itzehoe | Geist S.,Hospital Pinneberg | Paluchowski P.,Hospital Pinneberg | And 7 more authors.
Breast Cancer Research and Treatment | Year: 2012

Women with triple-negative breast cancer (TNBC) do not benefit from endocrine therapy or trastuzumab. Chemotherapy is the only systemic therapy currently available. To reduce the elevated risk of disease progression in these patients, better treatment options are needed, which are less toxic and more targeted to this patient population. We performed a comprehensive analysis of potential targetable genetic aberrations affecting the receptor tyrosine kinase/RAS/MAPK pathway, which are observed at higher frequencies in adenocarcinomas of other organs. Sixty-five individual TNBCs were studied by sequence analysis for HER2 (exon 18-23), EGFR (exon 18-21), KRAS (exon 2), and BRAF (exon 15) mutations. In addition, a tissue microarray was constructed to screen for EGFR gene copy gain and EML4-ALK fusion by FISH. Triple-negative status was confirmed by immunohistochemistry and FISH on tissue microarray sections. EGFR and CK5/6 immunohistochemical analyses were performed for identification of the basal-like phenotype. In addition, mutation analysis of TP53 (exon 5-8) was included. Sequence analysis revealed HER2 gene mutation in only one patient (heterozygous missense mutation in exon 19: p.L755S). No mutations were found in EGFR, KRAS, and BRAF. High polysomy of EGFR was detected in 5 of the 62 informative cases by FISH. True EGFR gene amplification accompanied by strong membranous EGFR protein expression was observed in only one case. No rearrangement of the ALK gene was detected. Basal-like phenotype was identified in 38 of the 65 TNBCs (58.5 %). TP53 gene mutation was found in 36/63 (57.1 %) tumors. We conclude that targetable genetic aberrations in the receptor tyrosine kinase/RAS/MAPK pathway occur rarely in TNBC. © Springer Science+Business Media, LLC. 2012.


Choschzick M.,University of Hamburg | Heilenkotter U.,Hospital Itzehoe | Lebeau A.,University of Hamburg | Jaenicke F.,University of Hamburg | And 4 more authors.
Cancer Biomarkers | Year: 2010

Background: MDM2 is overexpressed and amplified in a number of malignant tumors including breast carcinomas. Cell culture experiments showed a close connection between %of MDM2 expression and estrogen receptor status in breast cancer cell lines. Only little is known about the role of MDM2 amplifications in early-stage breast carcinomas with positive estrogen receptor status. Methods: 661 highly characterized node-negative breast carcinomas with positive estrogen receptor status (ER+ early-stage breast carcinomas) were analyzed on a tissue microarray. Molecular (HER2, CCND1, MDM2, MYC, 8q21), as well as estrogen receptor expression data used in this analysis, was available from previously published studies. The primary endpoint of overall survival analysis was death after 10 years. Results: Gene amplifications were found in 194/661 (29%) ER+ early-stage breast carcinomas and 40 (7%) exhibited amplification of the MDM2 oncogene. MDM2 amplifications were significantly related to advanced tumor stage (p < 0.05) and high Ki67 expression levels (p < 0.05). There was no relationship between MDM2 copy number changes and tumor grade, estrogen receptor expression level and co-amplification of HER2, CCND1 and 8q. Tumor stage (pT1 vs pT2-pT4; HR 1.51; 95% CI 1.02-2.24; p=0.042), grading (G1-G2 vs G3; HR 2.27; 95% CI 1.51-3.43; p < 0.001), high Ki67 proliferation index (HR 2.03; 95% CI 1.31-3.15; p=0.0015), HER2 (HR 2.6; 95% CI 1.51 to 4.5; p < 0.001) and MDM2 amplification (HR 2.05, 95% CI 1.06-3.97, p =0.033) were statistically adverse prognostic risk factors in univariate Cox regression analysis. Patient age, estrogen receptor expression level, CCND1 and 8q amplification were not associated to overall survival. Multivariate Cox regression analysis of survival data included tumor stage, grading, Ki67 labeling index, HER2 and MDM2 amplification status. In this statistical model, only MDM2 amplification was an independent factor for overall patient survival in ER+ early-stage breast carcinomas (HR 2.64; 95% CI 1.32 to 5.28; p=0.006). Conclusion: The MDM2 oncogene is amplified in a substantial proportion of ER+ early-stage breast carcinomas and an independent parameter for poor patient outcome in this subgroup. The prognostic effect of MDM2 is closely connected to estrogen receptor expression of breast carcinomas. © 2010/2011 - IOS Press and the authors. All rights reserved.


PubMed | Hospital Itzehoe, Hospital Pinneberg, University of Hamburg and Hospital Elmshorn
Type: Journal Article | Journal: Oncology letters | Year: 2016

Overexpression of class III -tubulin (TUBB3), a factor that confers dynamic properties to microtubules, is a candidate biomarker for resistance to microtubule-targeting chemotherapeutics in breast and other types of solid cancer. Discrepant results from previous studies, with respect to the association of TUBB3 expression levels with breast cancer phenotype and patient prognosis, prompted the present study to investigate TUBB3 expression in a large cohort of breast cancer cases, with available clinical follow-up data. A preexisting breast cancer prognosis tissue microarray, containing a single 0.6 mm tissue core from each of 2,197 individual patients with breast cancer, was analyzed for TUBB3 expression by immunohistochemistry. The results of the present study revealed that TUBB3 expression was less frequent in lobular breast cancer cases (34%), compared with that of cancer cases of alternative histologies, including breast cancer of no special type (60%; P<0.0001). High TUBB3 positivity was associated with high tumor grade (P<0.0001), negativity for estrogen (P<0.0001) and progesterone receptors (P<0.004), as well as the presence of human epidermal growth factor 2 amplification (P<0.0001) and a triple-negative phenotype (P<0.0001). TUBB3 overexpression was additionally associated with reduced patient survival if all breast cancer cases of any histology were jointly analyzed (P=0.0088); however this link was not evident in the subset of breast cancer cases of no special type, or in a multivariate analysis including the established prognostic factors of tumor stage, grade and nodal stage. In conclusion, the present study demonstrated that TUBB3 overexpression was associated with adverse features of breast cancer, and that TUBB3 may possess a distinct role in lobular breast cancer cases, compared with alternative histological subtypes. The results of the present study do not support a clinically relevant role for TUBB3 as a prognostic marker in breast cancer.

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