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https://www.readbyqxmd.com/read/28741114/-fetal-autopsies-relic-or-still-a%C3%A2-gold-standard
#1
J Andruszkow, W Weichert, T Braunschweig, R Knüchel-Clarke, F Erlmeier
BACKGROUND: Fetal autopsy rates are decreasing in Western countries although post-mortem examinations render important information for the parents concerning the cause of abortion and risk of recurrence in future pregnancies. OBJECTIVE: The intention of the presented study was to analyze the development of fetal autopsies in Germany during the last decade and to review accessible information obtained by fetal autopsy. MATERIAL AND METHODS: Reports of fetal autopsies conducted in two German university Institutes of pathology between 2005 and 2014 were evaluated retrospectively...
July 24, 2017: Der Pathologe
https://www.readbyqxmd.com/read/28698908/-adult-autopsies-during-the-past-decade-in-germany-data-from-two-university-hospitals
#2
F Erlmeier, W Weichert, R Knüchel, J Andruszkow
BACKGROUND: The clinical autopsy is the ultimate medical service for a patient and plays a crucial role in the education of physicians and other medical personnel, as well as in the context of quality control. Nevertheless, the number of autopsies is constantly decreasing. Numerous factors, such as the personal attitude of relatives and also clarification of relatives, as well as the increasing application of imaging methods while the patient is still alive, play a central role in this decline...
July 11, 2017: Der Pathologe
https://www.readbyqxmd.com/read/28692477/r0-versus-r1-resection-matters-after-pancreaticoduodenectomy-and-less-after-distal-or-total-pancreatectomy-for-pancreatic-cancer
#3
Ihsan Ekin Demir, Carsten Jäger, A Melissa Schlitter, Björn Konukiewitz, Lynne Stecher, Stephan Schorn, Elke Tieftrunk, Florian Scheufele, Lenika Calavrezos, Rebekka Schirren, Irene Esposito, Wilko Weichert, Helmut Friess, Güralp O Ceyhan
OBJECTIVE: The aim of this study was to decipher the true importance of R0 versus R1 resection for survival in pancreatic ductal adenocarcinoma (PDAC). SUMMARY OF BACKGROUND DATA: PDAC is characterized by poor survival, even after curative resection. In many studies, R0 versus R1 does not result in different prognosis and does not affect the postoperative management. METHODS: Pubmed, Embase, and Cochrane databases were screened for prognostic studies on the association between resection status and survival...
July 7, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28682793/impact-of-pet-and-mri-threshold-based-tumor-volume-segmentation-on-patient-specific-targeted-radionuclide-therapy-dosimetry-using-clr1404
#4
Abigail E Besemer, Benjamin Titz, Joseph J Grudzinski, Jamey P Weichert, John S Kuo, H Ian Robins, Lance T Hall, Bryan P Bednarz
Variations in tumor volume segmentation methods in targeted radionuclide therapy (TRT) may lead to dosimetric uncertainties. This work investigates the impact of PET and MRI threshold-based tumor segmentation on TRT dosimetry in patients with primary and metastatic brain tumors. In this study, PET/CT images of five brain cancer patients were acquired at 6, 24, and 48 h post-injection of (124)I-CLR1404. The tumor volume was segmented using two standardized uptake value (SUV) threshold levels, two tumor-to-background ratio (TBR) threshold levels, and a T1 Gadolinium-enhanced MRI threshold...
July 6, 2017: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/28675161/structural-insights-into-the-mechanism-of-the-membrane-integral-n-acyltransferase-step-in-bacterial-lipoprotein-synthesis
#5
Maciej Wiktor, Dietmar Weichert, Nicole Howe, Chia-Ying Huang, Vincent Olieric, Coilín Boland, Jonathan Bailey, Lutz Vogeley, Phillip J Stansfeld, Nienke Buddelmeijer, Meitian Wang, Martin Caffrey
Lipoproteins serve essential roles in the bacterial cell envelope. The posttranslational modification pathway leading to lipoprotein synthesis involves three enzymes. All are potential targets for the development of new antibiotics. Here we report the crystal structure of the last enzyme in the pathway, apolipoprotein N-acyltransferase, Lnt, responsible for adding a third acyl chain to the lipoprotein's invariant diacylated N-terminal cysteine. Structures of Lnt from Pseudomonas aeruginosa and Escherichia coli have been solved; they are remarkably similar...
July 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28657901/increased-intraepithelial-cd3-t-lymphocytes-and-high-pd-l1-expression-on-tumor-cells-are-associated-with-a-favorable-prognosis-in-esophageal-squamous-cell-carcinoma-and-allow-prognostic-immunogenic-subgrouping
#6
Moritz Jesinghaus, Katja Steiger, Julia Slotta-Huspenina, Enken Drecoll, Nicole Pfarr, Petra Meyer, Björn Konukiewitz, Marcus Bettstetter, Kathrin Wieczorek, Katja Ott, Markus Feith, Rupert Langer, Wilko Weichert, Katja Specht, Melanie Boxberg
Esophageal squamous cell carcinoma (ESCC) is the most common esophageal cancer associated with poor prognosis and additional therapeutic strategies must be implemented to optimize ESCC treatment. Meanwhile, the important biologic role and potential prognostic and therapeutic implications of a tumors immunologic microenvironment (IM) have been recognized in various cancers.In order to investigate the contexture and the prognostic relevance of the IM in ESCC, we immunohistochemically evaluated the extent of overall/intraepithelial TILs (CD3+/CD8+) and of PD-1 / PD-L1 expression in a cohort of 125 therapy-naive ESCCs, additionally assessing PD-L1 copy number status via fluorescence in-situ hybridization...
June 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28648701/universal-genomic-testing-the-next-step-in-oncological-decision-making-or-a-dead-end-street
#7
Julian Walter Holch, Klaus Hans Metzeler, Andreas Jung, Kristina Riedmann, Philipp Jakob Jost, Wilko Weichert, Thomas Kirchner, Volker Heinemann, Christoph Benedikt Westphalen
The concept of 'personalised medicine' aims at allocating patients to different treatment options based on individual characteristics to optimise treatment benefit and side effects. In oncology, personalised treatments coupled to biomarkers have led to the approval of targeted agents with high anti-tumour activity. However, these therapies are often limited to narrow, molecularly defined subsets of patients with a specific morphomolecular tumour profile. Recently, it became obvious that the same molecular alteration might drive oncogenesis in many different tumours, and it might be beneficial to target the alteration in a histology informed but entity-overarching way...
June 22, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28642333/patients-and-providers-perceptions-of-the-preventability-of-hospital-readmission-a-prospective-observational-study-in-four-european-countries
#8
Louise S van Galen, Mikkel Brabrand, Tim Cooksley, Peter M van de Ven, Hanneke Merten, Ralph Kl So, Loes van Hooff, Harm R Haak, Rachel M Kidney, Christian H Nickel, John Ty Soong, Immo Weichert, Mark Hh Kramer, Christian P Subbe, Prabath Wb Nanayakkara
OBJECTIVES: Because of fundamental differences in healthcare systems, US readmission data cannot be extrapolated to the European setting: To investigate the opinions of readmitted patients, their carers, nurses and physicians on predictability and preventability of readmissions and using majority consensus to determine contributing factors that could potentially foresee (preventable) readmissions. DESIGN: Prospective observational study. Readmitted patients, their carers, and treating professionals were surveyed during readmission to assess the discharge process and the predictability and preventability of the readmission...
June 22, 2017: BMJ Quality & Safety
https://www.readbyqxmd.com/read/28639280/mutational-profiles-of-brenner-tumors-show-distinctive-features-uncoupling-urothelial-carcinomas-and-ovarian-carcinoma-with-transitional-cell-histology
#9
Nicole Pfarr, Silvia Darb-Esfahani, Jonas Leichsenring, Eliane Taube, Melanie Boxberg, Ioana Braicu, Moritz Jesinghaus, Roland Penzel, Volker Endris, Aurelia Noske, Wilko Weichert, Peter Schirmacher, Carsten Denkert, Albrecht Stenzinger
Brenner tumors (BT) are rare ovarian tumors encompassing benign, borderline and malignant variants. While the histopathology of BTs and their clinical course is well described, little is known about the underlying genetic defects. We employed targeted next generation sequencing to analyze the mutational landscape in a cohort of 23 BT cases (17 benign, 2 borderline, 4 malignant) and 3 ovarian carcinomas with transitional cell histology (TCC). Copy number variations (CNV) were validated by fluorescence in-situ hybridization (FISH) and quantitative PCR-based copy number assays...
June 22, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28634753/fetal-cephaloceles-prenatal-diagnosis-and-course-of-pregnancy-in-65-consecutive-cases
#10
Jan Weichert, Friederike Hoellen, Martin Krapp, Ute Germer, Roland Axt-Fliedner, Andrea Kempe, Annegret Geipel, Christoph Berg, Ulrich Gembruch
PURPOSE: To scrutinize the characteristics of all cases with antenatally established diagnosis of cephalocele in two tertiary referral centers. METHODS: We retrospectively reviewed 65 cases diagnosed with cephaloceles and tabulated sonographic findings and autopsy recordings as well as medical charts of all survivors in terms of clinical outcome. RESULTS: The case notes of 65 fetuses were available for final analysis. Gestational age (GA) at diagnosis ranged from 10...
June 20, 2017: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/28627323/perspective-of-%C3%AE-v%C3%AE-6-integrin-imaging-for-clinical-management-of-pancreatic-carcinoma-and-its-precursor-lesions
#11
Katja Steiger, Anna-Melissa Schlitter, Wilko Weichert, Irene Esposito, Hans-Jürgen Wester, Johannes Notni
ß6-integrin immunohistochemistry analysis of a large number of pancreatic ductal adenocarcinoma (PDAC, 383 primary tumors, 7 lymph node, and 8 distant metastases) and 34 pancreatic intraepithelial neoplasia (PanIN) specimens revealed a high prevalence of αvß6-integrin expression in PDAC primaries (88%) and in almost all metastases, as well as in PanIN (57%). These findings underscore the high potential of a novel αvß6-integrin targeting positron emission tomography (PET) radiopharmaceutical, Ga-68-Avebehexin, for early diagnosis of pancreatic cancer...
January 1, 2017: Molecular Imaging
https://www.readbyqxmd.com/read/28597939/precision-oncology-based-on-omics-data-the-nct-heidelberg-experience
#12
Peter Horak, Barbara Klink, Christoph Heining, Stefan Gröschel, Barbara Hutter, Martina Fröhlich, Sebastian Uhrig, Daniel Hübschmann, Matthias Schlesner, Roland Eils, Daniela Richter, Katrin Pfütze, Christina Geörg, Bettina Meißburger, Stephan Wolf, Angela Schulz, Roland Penzel, Esther Herpel, Martina Kirchner, Amelie Lier, Volker Endris, Stephan Singer, Peter Schirmacher, Wilko Weichert, Albrecht Stenzinger, Richard F Schlenk, Evelin Schröck, Benedikt Brors, Christof von Kalle, Hanno Glimm, Stefan Fröhling
Precision oncology implies the ability to predict which patients will likely respond to specific cancer therapies based on increasingly accurate, high-resolution molecular diagnostics as well as the functional and mechanistic understanding of individual tumors. While molecular stratification of patients can be achieved through different means, a promising approach is next-generation sequencing of tumor DNA and RNA, which can reveal genomic alterations that have immediate clinical implications. Furthermore, certain genetic alterations are shared across multiple histologic entities, raising the fundamental question of whether tumors should be treated by molecular profile and not tissue of origin...
June 9, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28579623/reference-curve-for-the-mean-uterine-artery-pulsatility-index-in-singleton-pregnancies
#13
Alexander Weichert, Andreas Hagen, Michael Tchirikov, Ilka B Fuchs, Wolfgang Henrich, Michael Entezami
INTRODUCTION: Doppler sonography of the uterine artery (UA) is done to monitor pregnancies, because the detected flow patterns are useful to draw inferences about possible disorders of trophoblast invasion. Increased resistance in the UA is associated with an increased risk of preeclampsia and/or intrauterine growth restriction (IUGR) and perinatal mortality. In the absence of standardized figures, the normal ranges of the various available reference curves sometimes differ quite substantially from one another...
May 2017: Geburtshilfe und Frauenheilkunde
https://www.readbyqxmd.com/read/28572216/genetic-subclone-architecture-of-tumor-clone-initiating-cells-in-colorectal-cancer
#14
Klara M Giessler, Kortine Kleinheinz, Daniel Huebschmann, Gnana Prakash Balasubramanian, Taronish D Dubash, Sebastian M Dieter, Christine Siegl, Friederike Herbst, Sarah Weber, Christopher M Hoffmann, Raffaele Fronza, Ivo Buchhalter, Nagarajan Paramasivam, Roland Eils, Manfred Schmidt, Christof von Kalle, Martin Schneider, Alexis Ulrich, Claudia Scholl, Stefan Fröhling, Wilko Weichert, Benedikt Brors, Matthias Schlesner, Claudia R Ball, Hanno Glimm
A hierarchically organized cell compartment drives colorectal cancer (CRC) progression. Genetic barcoding allows monitoring of the clonal output of tumorigenic cells without prospective isolation. In this study, we asked whether tumor clone-initiating cells (TcICs) were genetically heterogeneous and whether differences in self-renewal and activation reflected differential kinetics among individual subclones or functional hierarchies within subclones. Monitoring genomic subclone kinetics in three patient tumors and corresponding serial xenografts and spheroids by high-coverage whole-genome sequencing, clustering of genetic aberrations, subclone combinatorics, and mutational signature analysis revealed at least two to four genetic subclones per sample...
July 3, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28569765/corrigendum-small-genomic-insertions-form-enhancers-that-misregulate-oncogenes
#15
Brian J Abraham, Denes Hnisz, Abraham S Weintraub, Nicholas Kwiatkowski, Charles H Li, Zhaodong Li, Nina Weichert-Leahey, Sunniyat Rahman, Yu Liu, Julia Etchin, Benshang Li, Shuhong Shen, Tong Ihn Lee, Jinghui Zhang, A Thomas Look, Marc R Mansour, Richard A Young
This corrects the article DOI: 10.1038/ncomms14385.
June 1, 2017: Nature Communications
https://www.readbyqxmd.com/read/28557978/prevalence-of-somatic-mitochondrial-mutations-and-spatial-distribution-of-mitochondria-in-non-small-cell-lung-cancer
#16
Daniel Kazdal, Alexander Harms, Volker Endris, Roland Penzel, Mark Kriegsmann, Florian Eichhorn, Thomas Muley, Albrecht Stenzinger, Nicole Pfarr, Wilko Weichert, Arne Warth
BACKGROUND: Mitochondria are considered relevant players in many tumour entities and first data indicate beneficial effects of mitochondria-targeted antioxidants in both cancer prevention and anticancer therapies. To further dissect the potential roles of mitochondria in NSCLC we comprehensively analysed somatic mitochondrial mutations, determined the spatial distribution of mitochondrial DNA within complete tumour sections and investigated the mitochondrial load in a large-scale approach...
July 11, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28526679/succession-of-transiently-active-tumor-initiating-cell-clones-in-human-pancreatic-cancer-xenografts
#17
Claudia R Ball, Felix Oppel, Karl Roland Ehrenberg, Taronish D Dubash, Sebastian M Dieter, Christopher M Hoffmann, Ulrich Abel, Friederike Herbst, Moritz Koch, Jens Werner, Frank Bergmann, Naveed Ishaque, Manfred Schmidt, Christof von Kalle, Claudia Scholl, Stefan Fröhling, Benedikt Brors, Wilko Weichert, Jürgen Weitz, Hanno Glimm
Although tumor-initiating cell (TIC) self-renewal has been postulated to be essential in progression and metastasis formation of human pancreatic adenocarcinoma (PDAC), clonal dynamics of TICs within PDAC tumors are yet unknown. Here, we show that long-term progression of PDAC in serial xenotransplantation is driven by a succession of transiently active TICs producing tumor cells in temporally restricted bursts. Clonal tracking of individual, genetically marked TICs revealed that individual tumors are generated by distinct sets of TICs with very little overlap between subsequent xenograft generations...
July 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28505009/a-novel-grading-system-based-on-tumor-budding-and-cell-nest-size-is-a-strong-predictor-of-patient-outcome-in-esophageal-squamous-cell-carcinoma
#18
Moritz Jesinghaus, Melanie Boxberg, Björn Konukiewitz, Julia Slotta-Huspenina, Anna M Schlitter, Katja Steiger, Katja Specht, Kathrin Wieczorek, Arne Warth, Thomas Schmidt, Arndt Hartmann, Ihsan E Demir, Markus Feith, Katja Ott, Wilko Weichert
The determination of prognosis in patients with esophageal squamous cell carcinoma (ESCC) is primarily based on staging according to the TNM-classification, whereas conventional grading is of minor clinical importance because of its deficiencies in prognostic patient stratification. Recently, a novel, highly prognostic grading scheme based on budding activity and cell nest size has been proposed for squamous cell carcinoma (SCC) of both pulmonary as well as oral origin. In order to investigate the utility and transferability of this approach to ESCC, we evaluated budding activity and cell nest size, as well as other histomorphologic characteristics, in a cohort of 135 primarily resected tumors and correlated the results with clinicopathologic and outcome parameters...
August 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28504689/molecular-signaling-in-multiple-myeloma-association-of-ras-raf-mutations-and-mek-erk-pathway-activation
#19
J Xu, N Pfarr, V Endris, E K Mai, N H Md Hanafiah, N Lehners, R Penzel, W Weichert, A D Ho, P Schirmacher, H Goldschmidt, M Andrulis, M S Raab
Multiple myeloma (MM) is a plasma cell malignancy that is still considered to be incurable in most cases. A dominant mutation cluster has been identified in RAS/RAF genes, emphasizing the potential significance of RAS/RAF/MEK/ERK signaling as a therapeutic target. As yet, however, the clinical relevance of this finding is unclear as clinical responses to MEK inhibition in RAS-mutant MM have been mixed. We therefore assessed RAS/RAF mutation status and MEK/ERK pathway activation by both targeted sequencing and phospho-ERK immunohistochemistry in 180 tissue biopsies from 103 patients with newly diagnosed MM (NDMM) and 77 patients with relapsed/refractory MM (rrMM)...
May 15, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28462862/high-prevalence-of-incidental-and-symptomatic-venous-thromboembolic-events-in-patients-with-advanced-pancreatic-cancer-under-palliative-chemotherapy-a-retrospective-cohort-study
#20
Anne Katrin Berger, Hans Martin Singh, Wiebke Werft, Alexander Muckenhuber, Martin R Sprick, Andreas Trumpp, Wilko Weichert, Dirk Jäger, Christoph Springfeld
OBJECTIVES: Pancreatic cancer patients are at high risk for venous thromboembolic events (VTEs), and chemotherapy is a known additional risk factor. In this context, there is a controversial discussion whether prophylactic anticoagulation should be offered to all outpatients receiving chemotherapy. METHODS: In this retrospective study, we analyzed incidental and symptomatic VTEs in 150 pancreatic cancer patients receiving either gemcitabine-based chemotherapy or chemotherapy according to the FOLFIRINOX protocol...
April 22, 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
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