Publications by authors named "Horst D"

Necrosis in postoperative histology has been reported as being specific for adrenocortical carcinoma (ACC) compared to adenoma. We therefore retrospectively analyzed the diagnostic accuracy of the finding of necrosis in preoperative cross-sectional imaging and postoperative histology as a marker for ACC in our patient cohort. Among the 411 adrenalectomies in 396 patients performed between 2008 and April 2022, 30 cases of ACC (7.

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Background: The PanaMa trial aimed to compare the efficacy of 5-fluorouracil and folinic acid (FU/FA) ± panitumumab maintenance in untreated wild-type metastatic colorectal cancer (mCRC) patients.

Methods: In this final phase 2 trial analysis, adult mCRC patients responding to six cycles of FU/FA, oxaliplatin and panitumumab were randomized (1:1, open-label) to maintenance of either FU/FA + panitumumab or FU/FA alone. The primary endpoint was superiority of progression-free survival of maintenance (PFS; time from random assignment to progression/death) in favour of FU/FA + panitumumab.

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Purpose: Placental alkaline phosphatase (PLAP) is a protein with a poorly understood function that is normally only expressed in the placenta. In cancer, PLAP expression is a hallmark of germ cell neoplasms, but it can also occur in urothelial carcinoma. To evaluate the potential clinical significance of PLAP expression in bladder cancer, METHODS: PLAP protein was analyzed by immunohistochemistry in more than 2500 urothelial bladder carcinomas in a tissue microarray format.

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Homozygous 9p21 deletions usually result in a complete loss of S-methyl-5'-thioadenosine phosphorylase (MTAP) expression visualizable by immunohistochemistry (IHC). MTAP deficiency has been proposed as a marker for predicting targeted treatment response. A tissue microarray including 2,710 urothelial bladder carcinomas were analyzed for 9p21 deletion by fluorescence in situ hybridization and MTAP expression by IHC.

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Background: Distinguishing donor- vs. recipient-derived myelodysplastic neoplasm (MDS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is challenging and has direct therapeutical implications.

Methods: Here, we took a translational approach that we used in addition to conventional diagnostic techniques to resolve the origin of MDS in a 38-year-old patient with acquired aplastic anemia and evolving MDS after first allo-HSCT.

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  • This study focuses on the role of Thyroid Transcription Factor-1 (TTF-1) in lung adenocarcinoma (LUAD) brain metastases, specifically its predictive value and relationship with patient outcomes.
  • Researchers analyzed data from 245 patients who had brain metastases, looking at factors like tumor volume and survival rates based on TTF-1 expression status.
  • Results indicate that TTF-1 negative patients had larger tumors, higher proliferation rates, and worse survival outcomes, suggesting that TTF-1 negativity signifies a more aggressive form of the disease, warranting further study on its underlying mechanisms.
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We present the rare case of a 51-year-old male diagnosed with a solitary fibrous tumor (SFT) of the prostate, along with a concurrent low-grade prostate adenocarcinoma (Gleason score 3 + 3, Grade Group 1). The diagnosis was confirmed by positive immunohistochemical markers, including CD34, BCL2, and STAT6, and molecular analysis showing a NAB2-STAT6 fusion. Following successful surgical management and the simultaneous diagnosis of a pulmonary relapse from a prior thyroid carcinoma, the patient remains under clinical surveillance.

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Objective: There is a shortage of established prognostic biomarkers in bladder cancer. One candidate is tumour protein 63 (p63), a transcription factor of the p53 gene family that is expressed in the normal urothelium. Recently proposed RNA expression-based molecular classifiers of bladder cancer identified high p63 expression as a component of a basal/squamous subtype linked to poor patient prognosis.

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Background: We have recently constructed a DNA methylation classifier that can discriminate between pancreatic ductal adenocarcinoma (PAAD) liver metastasis and intrahepatic cholangiocarcinoma (iCCA) with high accuracy (PAAD-iCCA-Classifier). PAAD is one of the leading causes of cancer of unknown primary and diagnosis is based on exclusion of other malignancies. Therefore, our focus was to investigate whether the PAAD-iCCA-Classifier can be used to diagnose PAAD metastases from other sites.

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GPA33 is a promising surface antigen for targeted therapy in colorectal cancer (CRC). It is expressed almost exclusively in CRC and intestinal epithelia. However, previous clinical studies have not achieved expected response rates.

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Aim: To identify patient-reported complaints affecting quality of life in Crohn's disease patients with a perianal fistula, and to compare differences between subgroups.

Method: A questionnaire was distributed to 1667 patients from the Dutch Crohn's and Colitis Patients' organization, those patients with Crohn's disease and perianal fistula were included. Patients were asked to report (using free text) their most important fistula-related complaints affecting their quality of life.

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Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to the global pandemic of Coronavirus Disease (2019) (COVID-19), underscoring the urgency for effective antiviral drugs. Despite the development of different vaccination strategies, the search for specific antiviral compounds remains crucial. Here, we combine machine learning (ML) techniques with in vitro validation to efficiently identify potential antiviral compounds.

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17p13 deletions including TP53 and other genes represent a common cause for reduced/lost p53 function in tumor cells. In this study, we analyzed the impact of 17p13 (TP53) deletions and p53 expression on tumor aggressiveness and patient prognosis in urothelial carcinoma. The 17p13 copy number status was analyzed by fluorescence in situ hybridization (FISH) on more than 2700 urothelial bladder carcinomas in a tissue microarray format.

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  • Whole Exome Sequencing (WES) is a powerful tool in cancer diagnostics that allows for comprehensive analysis of genes, improving the detection of complex biomarkers compared to traditional panel-based methods.
  • A study analyzing tissue specimens across 21 NGS centers showed that, although there was a 76% agreement in somatic variant calling, refining filtering criteria improved this to 88%, highlighting the importance of filter settings in variant detection.
  • The reliability of detecting specific genomic changes (like CNAs and complex biomarkers) varied among labs, emphasizing the need for improved bioinformatics processes and collaborative testing to minimize discrepancies in future analyses.
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Therapy-related acute myeloid leukemia (t-AML) often exhibits adverse (genetic) features. There is ongoing discussion on the impact of t-AML on long-term outcome in AML. Therefore, we retrospectively analyzed clinical and biological characteristics of 1133 AML patients (225 t-AML patients and 908 de novo AML patients) with a median follow-up of 81.

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Single-cell analyses can be confounded by assigning unrelated groups of cells to common developmental trajectories. For instance, cancer cells and admixed normal epithelial cells could adopt similar cell states thus complicating analyses of their developmental potential. Here, we develop and benchmark CCISM (for Cancer Cell Identification using Somatic Mutations) to exploit genomic single nucleotide variants for the disambiguation of cancer cells from genomically normal non-cancer cells in single-cell data.

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Objectives: Carcinoembryonic antigen (CEA) is a cell surface glycoprotein that represents a promising therapeutic target. Serum measurement of shedded CEA can be utilized for monitoring of cancer patients.

Material And Methods: To evaluate the potential clinical significance of CEA expression in urothelial bladder neoplasms, CEA was analysed by immunohistochemistry in more than 2500 urothelial bladder carcinomas in a tissue microarray format.

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  • Researchers discovered that 4-octyl itaconate (4-OI) can enhance the effects of an oncolytic virus, VSVΔ51, in resistant cancer cells and models, leading to better treatment outcomes.
  • The mechanism involves 4-OI suppressing antiviral immunity in cancer cells by modifying specific proteins, which suggests that combining metabolite-derived drugs with oncolytic viruses could significantly improve cancer treatment.
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  • A study examined variations in treatment outcomes and costs of inflammatory bowel disease (IBD) across 8 hospitals in the Netherlands, focusing on how these differences can inform quality and cost improvements in care.
  • The study included 1010 patients and found that while clinicians reported high remission rates (83%), patient-reported rates were significantly lower (40%), indicating discrepancies in perceived outcomes.
  • Most variations in treatment outcomes and costs were linked to individual patient factors rather than the hospitals themselves, suggesting that future efforts should concentrate on enhancing patient-level care rather than evaluating hospitals based on these variations.
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Background: A high level of PD-L1 expression is the most relevant predictive parameter for response to immune checkpoint inhibitor (CPI) therapy in urinary bladder cancer. Existing data on the relationship between PD-L1 expression and the natural course of disease are controversial and sparse.

Methods: To expand our understanding of the relationship between PD-L1 expression and parameters of cancer aggressiveness, PD-L1 was analyzed on tissue microarrays containing 2710 urothelial bladder carcinomas including 512 patients with follow-up data who underwent radical cystectomy and follow-up therapies in the pre-immune checkpoint inhibitor therapy era.

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Background: Tumor embolism is a very rare primary manifestation of cancers and the diagnosis is challenging, especially if located in the pulmonary arteries, where it can mimic nonmalignant pulmonary embolism. Intimal sarcoma is one of the least commonly reported primary tumors of vessels with only a few cases reported worldwide. A typical location of this malignancy is the pulmonary artery.

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Programmed cell death ligand 1 (PDL1), as an important biomarker, is quantified by immunohistochemistry (IHC) with few established histopathological patterns. Deep learning aids in histopathological assessment, yet heterogeneity and lacking spatially resolved annotations challenge precise analysis. Here, we present a weakly supervised learning approach using bulk RNA sequencing for PDL1 expression prediction from hematoxylin and eosin (H&E) slides.

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  • PARP inhibitors have shown effectiveness in treating ovarian cancer, particularly benefiting patients with homologous recombination deficiency (HRD), and various assays can be used to assess these biomarkers.
  • The study compares the performance of multiple molecular assays for genomic instability (GI) against the standard Myriad myChoice assay using DNA from high-grade serous ovarian cancer (HGSOC) samples.
  • Results indicate high concordance between different assays for assessing GI, supporting their use in clinical settings for HRD evaluation, which aligns with European Medicines Agency guidelines for PARP inhibitor treatment.
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Background: In-hospital consultation is essential for patient care. We previously proposed a framework of seven specific consultation types to classify consult requests to improve communication, workflow, and provider satisfaction.

Methods: This multimethods study's aim was to evaluate the applicability of the consult classification framework to real internal medicine (IM) consults.

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