Albertinen Hospital

Hamburg, Germany

Albertinen Hospital

Hamburg, Germany

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Ruf C.G.,Helmut Schmidt University | Ruf C.G.,University of Hamburg | Isbarn H.,University of Hamburg | Wagner W.,Helmut Schmidt University | And 3 more authors.
Urologic Oncology: Seminars and Original Investigations | Year: 2014

Objectives: Testicular germ cell tumors (GCTs) have their incidence peak in the third and fourth decades of life. Histologically, GCTs comprise of seminoma and nonseminoma at almost equal proportions with a slight preponderance of nonseminoma in most of the major series. Since decades, there is a shift toward decreasing age at presentation. Recently, there are suggestions of a reversal of the age trend, and also, the histologic subtype ratio appears to shift toward seminoma. We retrospectively looked to our patient populations to verify these recent trends. Methods: A total of 2,482 patients with histologically proven GCT diagnosed between 1976 and 2010 were retrospectively evaluated regarding the year of diagnosis, histology of primary tumor, and age at presentation. Patients were categorized according to the following time periods of treatment: before 1990, 1990 to 1994, 1995 to 1999, 2000 to 2004, and 2005 to 2010. Mean age and relative proportion of seminoma were compared among patient categories by employing the chi-square test and analysis of variance, respectively. Results: The mean age significantly increased from 28 to 36 years. The age difference between the 2 histologic subtypes remained constant between 6 and 8 years during the entire observation period. The relative proportion of seminoma continuously increased from 30.9% to 56% (P <0.001). Conclusion: There is evidence of a significant shift toward older age at diagnosis of GCT. In addition, the proportion of seminoma is constantly increasing at the expense of nonseminoma. The reasons for these developments are obscure. However, 2 old theories regarding the pathogenesis of GCT may receive support from our results: first, the theory of divergent pathogenetic pathways of seminoma and nonseminoma and second, the involvement of postnatal environmental factors in the pathogenesis of GCTs. © 2014 Elsevier Inc.


Dieckmann K.-P.,Albertinen Hospital | Spiekermann M.,University of Bremen | Balks T.,Albertinen Hospital | Flor I.,University of Bremen | And 3 more authors.
British Journal of Cancer | Year: 2012

Background:miRNAs are small noncoding RNA molecules that can be released into body fluids. Germ cell tumours (GCTs) overexpress miRNAs of the miR-371-3 cluster. Thus, serum levels of these miRNAs may correlate with tumour load.Methods:miRNAs of the miR-371-3 cluster were quantified in cubital vein blood samples of 20 GCT patients with clinical stage 1, and of 4 patients with advanced stages before and after treatment. In six patients testicular vein blood (TVB) was examined additionally. Seventeen healthy males served as controls. Likewise, expression of miRNAs in 15 matching tumour specimens was measured.Results:In all patients, serum levels of miRNAs 371-3 were much higher than in controls. In stage 1, levels decreased postoperatively 336.7-fold, 7.4-fold, and 7.7-fold for miRNAs 371a-3p, 372, and 373-3p, respectively (P0.01). Also, in those cases with advanced disease levels dropped to the normal range after completion of treatment. miR-371-3 levels in TVB exceeded those in peripheral blood in all cases. Expression of miR-371a-3p was also documented in tumour tissue. However, no correlation was found regarding the extent of miRNA expression in tissue and the values measured in matching serum.Conclusion:Thus, miR-371a-3p serum level appears to be a useful biomarker in GCTs. © 2012 Cancer Research UK. All rights reserved.


Frilling B.,University of Hamburg | Von Renteln-Kruse W.,University of Hamburg | Riess F.-C.,Albertinen Hospital
Cardiology | Year: 2010

Objectives: An increasing number of elderly patients develop aortic valve disease requiring surgery. Operative risk scores are currently used to identify patients at high operative risk who may benefit from interventional treatment options. The aim of this study was to analyze the predictive value of these risk scores in geriatric patients undergoing aortic valve replacement. Methods: We reviewed data of 1,245 elderly patients who underwent aortic valve replacement with or without additional bypass surgery from 2000-2007. Patient data were derived from a prospective registry at the Department of Cardiac Surgery at Albertinen-Hospital in Hamburg, Germany. Results: Hospital mortality was 2.56% in isolated valve replacement and 3.38% in patients who had additional bypass surgery (p = ns). Age >80 years (OR 1.7; 95% CI: 1.3-3.3) and renal failure (OR 1.6; 95% CI: 1.1-2.5) were significantly associated with in-hospital death. All scores overestimated operative mortality. The median logistic EuroSCORE was 11.56% (interquartile range: 7.01-18.96), median STS score 13.9% (10.3-16.2); and median Ambler score 7.2% (4.1-9.3). There was a significant correlation of the STS score with operative mortality (Spearman's rank coefficient: 0.68), but not with EuroSCORE (Spearman's rank coefficient: 0.11) or Ambler score (Spearman's rank coefficient: -0.17). Conclusion: Current risk scores overestimate operative risk in geriatric patients undergoing aortic valve replacement substantially. Of the risk scores evaluated, only STS score correlated significantly with operative mortality. Operative risk scores aimed specifically at geriatric patients may be necessary to accurately identify patients at high operative risk who benefit from non-surgical treatment options. © 2010 S. Karger AG, Basel.


Stang A.,Martin Luther University of Halle Wittenberg | Katalinic A.,University of Lübeck | Dieckmann K.-P.,Albertinen Hospital | Pritzkuleit R.,University of Lübeck | Stabenow R.,Common Cancer Registry of the Federal States of Berlin
Cancer Epidemiology | Year: 2010

Background: Currently, only 7 out of 16 Federal States of Germany provide testicular cancer incidence rates with an estimated completeness of at least 90% which complicates the regional comparison of incidence rates. The aim of this study was to provide a novel approach to estimate the testicular cancer incidence in Germany by using nationwide hospitalization data. Methods: We used the nationwide hospitalization data (DRG statistics) of the years 2005-2006 including 16,6 million hospitalizations among men. We identified incident testicular cancer cases by the combination of a diagnosis of testicular cancer and an orchiectomy during the same hospitalization and estimated the age-specific and age-standardized (World Standard Population) incidence of testicular cancer across Federal States. We also analyzed available cancer registry data from 2005 to 2006. Results: A total of 8544 hospitalizations indicated incident testicular cancer cases in 2005-2006. The nationwide crude incidence rate of testicular cancer was 10,6 per 100.000 person-years. The ratio of the number of registered cases (cancer registry) to the estimated number of cases based on the hospitalization statistics ranged between 79% and 100%. There was only little variation of the age-standardized DRG-based incidence estimates across Federal States (range: 8,2-10,6 per 100.000 person-years). Discussion: We provided testicular cancer incidence estimates for each of the 16 Federal States of Germany based on hospitalization data for the first time. The low within-population incidence variability in Germany and high between-population incidence variability in Europe may indicate that ecologic factors play a causal role in the European variation of testicular cancer. © 2009 Elsevier Ltd. All rights reserved.


Spiekermann M.,University of Bremen | Belge G.,University of Bremen | Winter N.,University of Bremen | Ikogho R.,Albertinen Hospital | And 4 more authors.
Andrology | Year: 2015

As only 60% of the patients with germ cell tumour (GCT) express the classical markers, new markers as for example microRNAs (miRNAs) are required. One promising candidate is miR-371a-3p, but data are sparse to date. We measured serum levels of miR-371a-3p in GCT patients, in controls, and in cases with other malignancies. We also assessed the expression in other body fluids and we looked to the decline of serum miR-371a-3p levels after treatment. miR-371a-3p levels were measured by quantitative polymerase chain reaction in serum samples of 25 GCT patients, 6 testicular intraepithelial neoplasia (TIN) patients, 20 healthy males and 24 non-testicular malignancies (NTMs). Testicular vein blood (TVB) was examined in five GCT patients and five controls. Five GCT patients had serial daily measurements after orchiectomy. Five seminal plasma samples, three urine specimens and one pleural effusion fluid were processed likewise. GCT patients had significantly higher miR-371a-3p serum levels than controls and NTMs. Serum levels of controls, TINs and NTMs were not significantly different. TVB samples of GCT patients had 65.4-fold higher serum levels than peripheral blood. Malignant pleural effusion fluid had extremely high levels of miR-371a-3p, seminal plasma had strongly elevated levels by comparison with serum levels of controls. In urine of GCT patients, no miR-371a-3p expression was detected. Daily measurements after orchiectomy in stage 1 patients revealed a decline by 95% within 24 h. Serum levels of miR-371a-3p appear to be a promising specific biomarker of GCTs as is suggested by high serum levels in GCT patients, the rapid return of elevated levels to normal range after treatment, the association of serum levels with tumour bulk, the non-expression in NTMs and the much higher levels of miR-371a-3p in TVB. This potential marker deserves further exploration in a large-scale clinical study. © 2014 American Society of Andrology and European Academy of Andrology.


Markowski D.N.,University of Bremen | Huhle S.,Albertinen Hospital | Nimzyk R.,University of Bremen | Stenman G.,Gothenburg University | And 2 more authors.
Genes Chromosomes and Cancer | Year: 2013

Mutations of the mediator subcomplex 12 gene (MED12) recently have been described in a large group of uterine leiomyomas (UL) but only in a single malignant uterine smooth muscle tumor. To further address the occurrence of fibroid-type MED12 mutations in smooth muscle tumors, we have analyzed samples from 34 leiomyosarcomas (LMS), 21 UL, two extrauterine leiomyomas (EL), and 10 canine genital leiomyomas for the presence of MED12 mutations of the UL-type. Interestingly, besides UL MED12 mutations were found in one uterine LMS, one EL, and two canine vaginal leiomyomas. The results confirm the occurrence of fibroid-type MED12 mutations in malignant uterine smooth muscle tumors thus suggesting a rare but existing leiomyoma-LMS sequence. In addition, for the first time MED12 mutations are reported in smooth muscle tumors in a non-primate mammalian species. © 2012 Wiley Periodicals, Inc.


Spiekermann M.,University of Bremen | Dieckmann K.P.,Albertinen Hospital | Balks T.,Albertinen Hospital | Bullerdiek J.,University of Bremen | And 2 more authors.
Anticancer Research | Year: 2015

Conclusion: Results show that qPCR can be used without endogenous control for analyzing miR-371-3 in the serum of patients with testicular cancer and male controls if the technical procedure is performed under controlled conditions.Background: Classical biomarkers α-fetoprotein, β-human chorionic gonadotropin and lactate dehydrogenase (AFP, bHCG and LDH) are elevated in only 60% of all testicular germ cell tumor (TGCT) patients. microRNAs (miRNAs) are a novel class of useful biomarkers in cancer and miRNAs of the miR-371-3 cluster were proven to be valuable markers for TGCT patients.Materials and Methods: We compared the Ct and δCt values of miR-371-3 by real time PCR (qPCR) with and without 18S rRNA for normalization. Expression of miR-371a-3p, miR-372 and miR-373-3p was measured in 25 TGCTs, 4 non-TGCTs and 17 age-matched male controls.Results: A highly positive correlation between Ct and δCt values was found in all samples. The highest correlation was found for miR-371a-3p (R2: 0.956).


Markowski D.N.,University of Bremen | Bartnitzke S.,University of Bremen | Loning T.,Albertinen Hospital | Drieschner N.,University of Bremen | And 3 more authors.
International Journal of Cancer | Year: 2012

Recurrent chromosomal alterations are found in roughly 20% of all uterine fibroids but in the majority cytogenetic changes are lacking. Recently, mutations of the gene mediator subcomplex 12 (MED12) have been detected in a majority of fibroids but no information is available whether or not they co-occur with cytogenetic subtypes as, e.g., rearrangements of the genes encoding high mobility group AT-hook (HMGA) proteins. In a total of 80 cytogenetically characterized fibroids from 50 patients, we were not only able to confirm the frequent occurrence of MED12 mutations but also to stratify two mutually exclusive pathways of leiomyomagenesis with either rearrangements of HMGA2 reflected by clonal chromosome abnormalities affecting 12q14∼15 or by mutations affecting exon 2 of MED12. On average the latter mutations were associated with a significantly smaller tumor size. However, G>A transitions of nucleotides c.130 or c.131 correlate with a significantly larger size of the fibroids compared to other MED12 mutations thus explaining the high prevalence of the former mutations among clinically detectable fibroids. Interestingly, fibroids with MED12 mutations expressed significantly higher levels of the gene encoding wingless-type MMTV integration site family, member 4 (WNT4). Based on these findings and data from the literature, we hypothesize that estrogen and the mutated MED12 cooperate in activating the Wnt pathway which in turn activates β-catenin known to cause leiomyoma-like lesions in a mouse model. The occurrence of a "fibroid-type mutation" in a rare histologic subtype of endometrial polyps suggests that this mechanism is not confined to uterine leiomyomas. Copyright © 2012 UICC.


Bijuklic K.,Medical Care Center Prof Mathey | Haselbach T.,Albertinen Heart Center | Witt J.,Albertinen Heart Center | Krause K.,Albertinen Heart Center | And 5 more authors.
JACC: Cardiovascular Interventions | Year: 2015

Objectives The purpose of this study was to analyze the effect of transcatheter aortic valve replacement (TAVR) without versus with prior balloon aortic valvuloplasty (BAV) on the risk of cerebral embolization in patients who receive a balloon-expandable valve. Background Avoiding BAV prior to TAVR may simplify the procedure, but the risk of cerebral embolization is currently unknown. Methods A total of 87 consecutive high surgical-risk patients with no contraindications for diffusion-weighted magnetic resonance imaging (DW-MRI) were enrolled. Thirty-two patients received a balloon-expandable aortic valve with and 55 patients without BAV. The incidence, number, and volume of new ischemic lesions in DW-MRI performed 2 to 7 days after TAVI were evaluated. Results Mean age (83.8 ± 5.2 years vs. 82.9 ± 6.8 years) and sex (43.8% vs. 52.7% male) of the patients with versus without BAV, respectively, as well as other demographic and hemodynamic data were not significantly different between both groups. The procedural success rate was 93.5% with and 98.2% without BAV, and procedure duration and contrast volume were significantly lower without BAV. The incidence of new cerebral ischemic lesions in the total cohort was 66.7%. Compared with patients with BAV, those without BAV had a significantly higher total volume of cerebral ischemic lesions (235.4 ± 331.4 mm3 vs. 89.5 ± 128.2 mm3; p = 0.01). Conclusions The implantation of a balloon-expandable aortic valve without versus with prior BAV, although performed with a shorter procedure time and lower contrast volume, is associated with a significantly higher volume of cerebral ischemic lesions. © 2015 American College of Cardiology Foundation.


Petry K.U.,Klinikum der Stadt Wolfsburg | Schmidt D.,Institute of Pathology | Scherbring S.,Klinikum der Stadt Wolfsburg | Luyten A.,Klinikum der Stadt Wolfsburg | And 7 more authors.
Gynecologic Oncology | Year: 2011

Objective: Testing for human papillomavirus (HPV) has been shown to increase the sensitivity and negative predictive value for detection of high-grade cervical intraepithelial neoplasia (CIN2+), either when used in conjunction with Pap cytology testing or alone. However, there is no satisfying clinical management algorithm for women testing Pap negative/HPV positive. We therefore evaluated the clinical utility of a novel dual biomarker-based approach (p16/Ki-67 Dual-stained cytology) for the identification of CIN2+ in women with Pap negative/HPV positive screening results, without the need to refer all women to immediate colposcopy. Methods: All women aged ≥ 30 enrolled during 2007/2008 into a regional prospective Pap/HPV co-testing screening pilot project and tested Pap negative, but positive for HPV (n = 425) were included in the analysis. p16/Ki-67 Dual-stained cytology was performed from residual cellular material available from the liquid-based cytology vial collected during the initial Pap/HPV co-testing screening visit. Results were correlated to the presence of CIN2+ confirmed during preliminary follow-up. Results: p16/Ki-67 Dual-stained cytology tested positive at baseline in 108 out of 425 (25.4%) Pap negative/HPV positive cases. Sensitivity of Dual-stain testing for the detection of biopsy-confirmed CIN2+ during preliminary follow-up within the group of Pap negative/HPV positive women was 91.9% for CIN2+ (34/37 cases), and 96.4% for CIN3+ (27/28 cases). Specificity was 82.1% for CIN2+ on biopsy, and 76.9% for CIN3+, respectively. Conclusions: Triaging Pap negative/HPV positive screening test results with p16/Ki-67 Dual-stained cytology may identify women with a high probability of underlying CIN2+ and may efficiently complement HPV-based screening programs to prevent cervical cancer. © 2011 Elsevier Inc.

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