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Dive into the research topics where Daniel Wittschieber is active.

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Featured researches published by Daniel Wittschieber.


International Journal of Legal Medicine | 2014

Influence of the examiner’s qualification and sources of error during stage determination of the medial clavicular epiphysis by means of computed tomography

Daniel Wittschieber; Ronald Schulz; Volker Vieth; Martin Küppers; Thomas Bajanowski; Frank Ramsthaler; Klaus Püschel; Heidi Pfeiffer; Sven Schmidt; Andreas Schmeling

Computed tomography (CT) of the medial clavicular epiphysis has been well established in forensic age estimations of living individuals undergoing criminal proceedings. The present study examines the influence of the examiner’s qualification on the determination of the clavicular ossification stage. Additionally, the most frequent sources of error made during the stage assessment process should be uncovered. To this end, thin-slice CT scans of 1,420 clavicles were evaluated by one inexperienced and two experienced examiners. The latter did the evaluations in consensus. Two classification systems, a five-stage system and a substaging system for the main stages 2 and 3, were used. Prior to three of his six assessment sessions, the inexperienced examiner was specifically taught staging of clavicles. Comparison of the examiners’ results revealed increasing inter- and intraobserver agreements with increasing state of qualification of the inexperienced examiner (from κ= 0.494 to 0.674 and from κ= 0.634 to 0.783, respectively). The attribution of a not-assessable anatomic shape variant to an ossification stage was identified as the most frequent error during stage determination (n= 349), followed by the overlooking of the epiphyseal scar defining stage 4 (n= 144). As to the clavicular substages, classifying substage 3a instead of 3b was found to be the most frequent error (n= 69). The data of this study indicate that κ values must not be considered as objective measures for inter- and intraobserver agreements. Furthermore, a high degree of specific qualification, particularly the knowledge about the diversity of anatomic shape variants, appears to be mandatory and indispensable for reliable evaluation of the medial clavicular epiphysis.


PLOS ONE | 2012

Who Is at Risk for Diagnostic Discrepancies? Comparison of Pre- and Postmortal Diagnoses in 1800 Patients of 3 Medical Decades in East and West Berlin

Daniel Wittschieber; Frederick Klauschen; Anna-Christin Kimmritz; Moritz von Winterfeld; Carsten Kamphues; Hans-Joachim Scholman; Andreas Erbersdobler; Heidi Pfeiffer; Carsten Denkert; Manfred Dietel; Wilko Weichert; Jan Budczies; Albrecht Stenzinger

Background Autopsy rates in Western countries consistently decline to an average of <5%, although clinical autopsies represent a reasonable tool for quality control in hospitals, medically and economically. Comparing pre- and postmortal diagnoses, diagnostic discrepancies as uncovered by clinical autopsies supply crucial information on how to improve clinical treatment. The study aimed at analyzing current diagnostic discrepancy rates, investigating their influencing factors and identifying risk profiles of patients that could be affected by a diagnostic discrepancy. Methods and Findings Of all adult autopsy cases of the Charité Institute of Pathology from the years 1988, 1993, 1998, 2003 and 2008, the pre- and postmortal diagnoses and all demographic data were analyzed retrospectively. Based on power analysis, 1,800 cases were randomly selected to perform discrepancy classification (class I-VI) according to modified Goldman criteria. The rate of discrepancies in major diagnoses (class I) was 10.7% (95% CI: 7.7%–14.7%) in 2008 representing a reduction by 15.1%. Subgroup analysis revealed several influencing factors to significantly correlate with the discrepancy rate. Cardiovascular diseases had the highest frequency among class-I-discrepancies. Comparing the 1988-data of East- and West-Berlin, no significant differences were found in diagnostic discrepancies despite an autopsy rate differing by nearly 50%. A risk profile analysis visualized by intuitive heatmaps revealed a significantly high discrepancy rate in patients treated in low or intermediate care units at community hospitals. In this collective, patients with genitourinary/renal or infectious diseases were at particularly high risk. Conclusions This is the current largest and most comprehensive study on diagnostic discrepancies worldwide. Our well-powered analysis revealed a significant rate of class-I-discrepancies indicating that autopsies are still of value. The identified risk profiles may aid both pathologists and clinicians to identify patients at increased risk for a discrepant diagnosis and possibly suboptimal treatment intra vitam.


Pathobiology | 2010

Gene Promoter Methylation and Its Potential Relevance in Early Prostate Cancer Diagnosis

Isabel Steiner; Klaus Jung; Philipp Schatz; Torsten Dr. Horns; Daniel Wittschieber; Michael Lein; Manfred Dietel; Andreas Erbersdobler

Aims: We investigated hypermethylation of the glutathione S-transferase pi (GSTP1), retinoic acid receptor β2 (RARβ2), adenomatous polyposis coli (APC) and paired-like homeodomain transcription factor 2 (PITX2) gene promoters which could serve as a sensitive tool to indicate a risk of prostate cancer even in histologically tumor-free tissues. Methods: Tumor tissues and non-neoplastic tissues at variable distances from the tumor foci were retrieved from 25 formalin-fixed and paraffin-embedded prostatectomy specimens and subjected to DNA extraction. The methylation levels were assessed by means of different assay technologies. Results: Significantly increased methylation levels in cancer specimens were found for all promoter regions (GSTP1: 21/25, 84%; RARβ2: 24/25, 96%; APC: 21/25, 84%; PITX2: 20/25, 80%) and in most samples containing prostatic intraepithelial neoplasia. Several samples showed increased RARβ2 and APC methylation in adjacent non-neoplastic tissue. An association between the methylation extent of GSTP1, APC and RARβ2, respectively, and primary Gleason grade was detectable. GSTP1 methylation was also associated with extraprostatic tumor extension. Conclusion: GSTP1, APC, RARβ2 and PITX2 methylation occur frequently in prostate cancer, making these markers sensitive tools for the detection of neoplastic lesions in the prostate. For RARβ2, the results suggest a kind of methylation field effect which could be helpful for the detection of prostate cancer. Larger studies are necessary to investigate a potential correlation of GSTP1, RARβ2 and APC hypermethylation with tumor aggressiveness.


Histopathology | 2012

High nuclear poly-(ADP-ribose)-polymerase expression is prognostic of improved survival in pancreatic cancer.

Frederick Klauschen; Moritz von Winterfeld; Albrecht Stenzinger; Bruno V. Sinn; Jan Budczies; Carsten Kamphues; Marcus Bahra; Daniel Wittschieber; Wilco Weichert; Jana Kaethe Striefler; Hanno Riess; Manfred Dietel; Carsten Denkert

Klauschen F, von Winterfeld M, Stenzinger A, Sinn B V, Budczies J, Kamphues C, Bahra M, Wittschieber D, Weichert W, Striefler J, Riess H, Dietel M & Denkert C 
(2012) Histopathology 61, 409–416


Pathobiology | 2011

Decreased RECK and Increased EMMPRIN expression in urothelial carcinoma of the bladder are associated with tumor aggressiveness.

Daniel Wittschieber; Albrecht Stenzinger; Frederick Klauschen; Carsten Stephan; Klaus Jung; Andreas Erbersdobler; Anja Rabien

Objective: Urothelial bladder carcinomas show a divergent biological behavior, which significantly complicates risk stratification and clinical management. The MMP repressor RECK and the MMP activator EMMPRIN regulate the invasive potential by metalloproteinase-induced stromal degradation. Data on RECK in urothelial bladder cancer are lacking and information on EMMPRIN is sparse. This study aims to investigate the expression of RECK and EMMPRIN in urothelial carcinoma of the bladder and to correlate these findings with clinicopathological parameters. Methods: Our study included 127 specimens of urothelial carcinomas derived from 103 patients who underwent either TUR-B or cystectomy. Immunohistochemical expression analysis was performed for RECK, EMMPRIN, MMP-2, MMP-9 and MMP-14. Expression levels were graded for staining intensity and correlated with pT stage and WHO tumor grade. Results: Invasive (≧pT1) as well as WHO high-grade urothelial carcinomas showed a statistically significant and stepwise downregulation of RECK (p < 0.001) and concomitant upregulation of EMMPRIN (p < 0.001) compared to non-invasive and WHO low-grade tumors. No correlation was observed for the MMPs investigated. Conclusion: Decreased RECK and increased EMMPRIN expression are associated with increasing stage and grade. Both proteins may serve as molecular marker for the distinction between potentially invasive (≧pT1) and non-invasive tumors (≤pTa).


International Journal of Legal Medicine | 2017

Systematic procedure for identifying the five main ossification stages of the medial clavicular epiphysis using computed tomography: a practical proposal for forensic age diagnostics.

Daniel Wittschieber; Ronald Schulz; Heidi Pfeiffer; Andreas Schmeling; Sven Schmidt

In forensic age estimations of living individuals, computed tomography of the clavicle is widely used for determining the age of majority. To this end, the degree of ossification of the medial clavicular epiphysis can be determined by means of two classification systems complementing each other: a 5-stage system and an additional 6-stage system that further sub-classifies the stages 2 and 3. In recent years, practical experience and new data revealed that difficulties and even wrong stage determinations may occur especially when following the short descriptions of the fundamental 5-stage system only. Based on current literature, this article provides a systematic procedure for identifying the five main ossification stages by listing important preconditions and presenting an algorithm that is comprised of four specific questions. Each question is accompanied by comprehensive and detailed descriptions which specify the criteria used for differentiation. The information is subdivided into “single-slice view” and “multi-slice view.” In addition, illustrative case examples and schematic drawings facilitate application of the procedure in forensic practice. The pitfalls associated with the criteria of stage determination will be discussed in detail. Eventually, two general rules will be inferred to assign correct ossification stages of the medial clavicular epiphysis by means of computed tomography.


International Journal of Legal Medicine | 2016

Optimising magnetic resonance imaging-based evaluation of the ossification of the medial clavicular epiphysis: a multi-centre study

Sven Schmidt; C. A. Henke; Daniel Wittschieber; Volker Vieth; Thomas Bajanowski; Frank Ramsthaler; Klaus Püschel; H. Pfeiffer; Andreas Schmeling; Ronald Schulz

Evaluation of the ossification of the medial clavicular epiphysis plays a key role in forensic age estimation, particularly in determining whether the age of 18 has been attained. A key research objective in the forensic age estimation field at present is to establish non-X-ray methods for investigating the clavicle. This paper looks at the use of magnetic resonance imaging for evaluating the developmental state of the medial clavicular epiphysis. Clavicle specimens obtained from autopsies of 125 female and 270 male subjects aged from 10 to 30 were examined using a 3-T magnetic resonance scanner. One FFE-3D-T1 gradient echo sequence and one 2D-T2 turbo spin echo sequence were acquired. In each case, two investigators undertook a consensual determination of the ossification stage of the medial clavicular epiphysis using recognised classification systems. To determine intra-observer and inter-observer agreement, 80 clavicle specimens were subjected to repeat evaluation. We present statistics relating to the ossification stages. The inclusion of established sub-stages of clavicular ossification offers an additional option for determining whether a subject has attained the age of 18 which is applicable in both sexes. For both sexes, the minimum ages for ossification stages 4 and 5 allow conclusions to be drawn about a subject’s age at a point in time lying several years in the past. Magnetic resonance imaging is a valid investigatory procedure for determining the ossification stage of the medial clavicular epiphysis. This paper makes a contribution to expanding the range of methods available for forensic age estimation.


Pathobiology | 2012

Prolyl hydroxylase domain 2 protein is a strong prognostic marker in human gastric cancer

Carsten Kamphues; Daniel Wittschieber; Frederick Klauschen; Atsuko Kasajima; Manfred Dietel; Sven-Christian Schmidt; Matthias Glanemann; Marcus Bahra; Peter Neuhaus; Wilko Weichert; Albrecht Stenzinger

Objective: According to recent research, prolyl hydroxylase domain 2 protein (PHD2) plays an important role in human carcinogenesis by inducing neovascularization and tumor growth. The aim of this study was to evaluate PHD2 expression patterns in primary gastric adenocarcinoma and to test for a potential predictive value of PHD2 expression in gastric cancer patients. Methods: In a total of 121 patients, PHD2 expression was investigated by immunohistochemistry in paraffin-embedded tissue and correlated with clinicopathological parameters and patient survival. Results: 64 of 121 gastric carcinomas (52.9%) showed PHD2 expression in tumor cell cytoplasm. In univariate analysis, PHD2-negative patients had a significantly shortened survival in comparison with PHD2-postive patients (19.5 vs. 32.7 months, p = 0.02). Independent prognostic significance could be shown in multivariate analysis for PHD2 expression (p = 0.005), age at diagnosis (p = 0.012), lymph node status (p = 0.016) and R status (p = 0.026). Conclusion: Cytoplasmic PHD2 expression has a strong impact on survival in gastric cancer patients. Therefore, PHD2 represents a useful predictive biomarker in the evaluation of high-risk patients. Furthermore, these results underline the importance of PHD2 in gastric carcinogenesis and may identify PHD2 as a putative target for future gastric cancer therapy.


Virchows Archiv | 2010

Would Virchow be a systems biologist? A discourse on the philosophy of science with implications for pathological research

Albrecht Stenzinger; Frederick Klauschen; Daniel Wittschieber; Wilko Weichert; Carsten Denkert; Manfred Dietel; Claudio Roller

Research in pathology spans from merely descriptive work to functional studies, “-omics” approaches and, more recently, systems biology. The work presented here aims at placing pathological research into an epistemological context. Aided by Rudolf Virchow, we give an overview on the philosophy of science including the Wiener Kreis, Popper, Kuhn, Fleck and Rheinberger and demonstrate their implications for routine diagnostics and science in pathology. A focus is on the fields of “-omics” and systems pathology.


Urologe A | 2010

The significance of chronic prostatitis for the etiopathology of prostate cancer

Daniel Wittschieber; S. Schenkenberg; Manfred Dietel; Andreas Erbersdobler

Although prostate cancer is of crucial impact as a common disease of men, numerous relationships remain unknown, particularly concerning its pathogenesis. A novel approach regarding the origin and development of prostate cancer is a phenomenon that has already been investigated in other human cancers: cancerogenesis due to chronic inflammation. Hence, the present review introduces the current state of research concerning the relationship between chronic prostatitis and prostate cancer. In addition to histological and biochemical features, the latest discoveries are discussed, including the relationship between the pathogenesis of prostate cancer and infection by the novel gammaretrovirus XMRV, similar to cervical cancer associated with HPV.ZusammenfassungObwohl dem Prostatakarzinom als Krankheitsbild des Mannes eine große epidemiologische Bedeutung zukommt, sind noch zahlreiche Zusammenhänge insbesondere zu seiner Pathogenese weitgehend unbekannt. Einen neuen und derzeit intensiv untersuchten Ansatz bietet ein bereits in verschiedenen anderen Organen untersuchtes Phänomen – die Kanzerogenese im Rahmen chronischer Entzündungsprozesse. Die vorliegende Übersichtsarbeit stellt den aktuellen Forschungsstand der Zusammenhänge zwischen chronischer Prostatitis und dem Prostatakarzinom vor und diskutiert hierbei neben den histologischen und biochemischen Kriterien außerdem jüngste Entdeckungen, welche die Pathogenese des Prostatakarzinoms, ähnlich dem HPV-assoziierten Zervixkarzinom, in Zusammenhang mit einer Infektion durch das neuartige Gammaretrovirus XMRV bringen.AbstractAlthough prostate cancer is of crucial impact as a common disease of men, numerous relationships remain unknown, particularly concerning its pathogenesis. A novel approach regarding the origin and development of prostate cancer is a phenomenon that has already been investigated in other human cancers: cancerogenesis due to chronic inflammation. Hence, the present review introduces the current state of research concerning the relationship between chronic prostatitis and prostate cancer. In addition to histological and biochemical features, the latest discoveries are discussed, including the relationship between the pathogenesis of prostate cancer and infection by the novel gammaretrovirus XMRV, similar to cervical cancer associated with HPV.

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Sven Schmidt

Humboldt University of Berlin

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Thomas Bajanowski

University of Duisburg-Essen

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Albrecht Stenzinger

University Hospital Heidelberg

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