Publications by authors named "Alphonse Charbel"

Article Synopsis
  • - KAT6B/A::KANSL1 gene fusion tumours display similarities with endometrial stromal and smooth muscle tumours, causing debate over their classification as a unique tumour type or variants of existing ones.
  • - Analysis of DNA methylation and genetic variations revealed a distinct subgroup of these tumours that presented with less aggressive histological features, while others exhibited high-grade characteristics linked to poorer clinical outcomes.
  • - The study indicates that KAT6B/A::KANSL1 uterine sarcomas are distinct molecular entities, with significant differences in prognosis, suggesting they should be classified separately from other uterine tumours.
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Article Synopsis
  • People with primary sclerosing cholangitis (PSC) are at a significant risk of developing biliary tract cancer (BTC), and this study used whole-exome sequencing to analyze the genetic changes in BTC associated with PSC.
  • The researchers identified 53 candidate cancer genes, including some that had not been previously linked to BTC, while also recognizing genes known to be involved in other cancers.
  • Their findings reveal specific and common genetic alterations that could improve understanding of BTC development in PSC, paving the way for personalized treatment strategies.
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Aims: Intrahepatic cholangiocarcinoma (iCCA) is a diagnosis of exclusion that can pose a challenge to the pathologist despite thorough clinical workup. Although several immunohistochemical markers have been proposed for iCCA, none of them reached clinical practice. We here assessed the combined usage of two promising diagnostic approaches, albumin in situ hybridisation (Alb-ISH) and C reactive protein (CRP) immunohistochemistry, for distinguishing iCCA from other adenocarcinoma primaries.

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Article Synopsis
  • The study introduces HEPNET, a deep learning model designed to accurately distinguish between intrahepatic cholangiocarcinoma and colorectal liver metastasis using H&E-stained whole-slide images.
  • HEPNET was trained on a large dataset from 456 patients and demonstrated high accuracy, achieving 96.5% on an internal test set and 98.1% on an external validation set, outperforming experienced pathology experts.
  • The model aims to improve routine pathology practices by providing a reliable diagnostic tool, potentially streamlining the diagnostic process in pathology laboratories.
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Background: Intraductal papillary neoplasms (IPN) and biliary epithelial neoplasia (BilIN) are well-defined precursor lesions of biliary tract carcinoma (BTC). The aim of this study was to provide a comprehensive characterisation of the inflammatory microenvironment in BTC precursor lesions.

Methods: Immunohistochemistry was employed to assess tumour-infiltrating immune cells in tissue samples from patients, for whom precursor lesions were identified alongside invasive BTC.

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Liver cancers, which are mostly hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), are very aggressive tumors with poor prognosis. Therapeutic options with curative intent are largely limited to surgery and available systemic therapies show limited benefit. Signal transducer and activator of transcription 1 (STAT1) and 3 (STAT3) are key transcription factors activated by pro-inflammatory cytokines such as interferon-γ (IFN-γ) and interleukin-6 (IL-6).

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Cholangiocarcinoma (CCA) is a heterogeneous malignancy with a dismal prognosis. Therapeutic options are largely limited to surgery and conventional chemotherapy offers limited benefit. As immunotherapy has proven highly effective in various cancer types, we have undertaken a quantitative immunohistopathological assessment of immune cells expressing the immunoinhibitory T cell immune response cDNA 7 receptor (TIRC7), an emerging immunoinhibitory receptor, in a cohort of 135 CCA patients.

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Inhibition of the programmed cell death protein-1/ligand-1 (PD-1/PD-L1) axis has opened a new era in the treatment of solid cancers. However, there is no data on the expression and relevance of PD-L1 in Western gallbladder cancer (GBC). We assessed PD-L1 immunohistochemically in 131 GBC patients as Tumor Proportion Score (TPS), Immune Cell Score (IC) and Combined Positivity Score (CPS).

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