Vascular intrusion is a mimic of true vascular invasion in large bowel adenomatous polyps.

Aims: 'Vascular intrusion' is a proposed but poorly recognised phenomenon of colorectal adenomas whereby dysplastic epithelium is forced into blood vessels. This study aimed to validate its existence and to characterise histological features that distinguish it from true vascular invasion.

Methods And Results: Three gastrointestinal pathologists independently assessed 38 colorectal polyps showing possible vascular intrusion as two cohorts.

Results of a modified Delphi consensus on the optimal testing pathway for oesophago-gastric cancer care in the UK.

Objective: To develop expert consensus on the optimal testing pathway for oesophago-gastric (OG) cancer care.

Methods And Analysis: The process followed a modified Delphi methodology to develop consensus on the optimal testing pathway for OG cancer care. In November 2023, a review of available literature on the topic of OG cancer was conducted.

Low-coverage whole genome sequencing of low-grade dysplasia strongly predicts advanced neoplasia risk in ulcerative colitis.

Background: The risk of developing advanced neoplasia (AN; colorectal cancer and/or high-grade dysplasia) in ulcerative colitis (UC) patients with a low-grade dysplasia (LGD) lesion is variable and difficult to predict. This is a major challenge for effective clinical management.

Objective: We aimed to provide accurate AN risk stratification in UC patients with LGD.

A constitutive interferon-high immunophenotype defines response to immunotherapy in colorectal cancer.

Fewer than 50% of metastatic deficient mismatch repair (dMMR) colorectal cancer (CRC) patients respond to immune checkpoint inhibition (ICI). Identifying and expanding this patient population remains a pressing clinical need. Here, we report that an interferon-high immunophenotype locally enriched in cytotoxic lymphocytes and antigen-presenting macrophages is required for response.

Context-dependent effects of CDKN2A and other 9p21 gene losses during the evolution of esophageal cancer.

CDKN2A is a tumor suppressor located in chromosome 9p21 and frequently lost in Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). How CDKN2A and other 9p21 gene co-deletions affect EAC evolution remains understudied. We explored the effects of 9p21 loss in EACs and cancer progressor and non-progressor BEs with matched genomic, transcriptomic and clinical data.

to: Breast implant-associated Epstein-Barr virus-positive large B-cell lymphomas: a report of three cases.

In reference to our paper published in the August issue 2020 of Haematologica,1 the sentence "funded by the European Union Next Generation EU, funds that finance the actions of the Recovery and Resilience Mechanism (RRM)" in the Funding was missing. We need to add it to justify the project. So the Funding paragraph should read as follows: Funding: this work was supported by grants from the Instituto de Salud Carlos III (ISCIII) of the Spanish Ministry of Economy and Competence, co-funded by European Union (FEDER) (ERDF/ESF, "A way to make Europe"/"Investing in your future" (MINECO, ISCIII) funded by the European Union Next Generation EU, funds that finance the actions of the Recovery and Resilience Mechanism (RRM) (Plan Nacional I+D+I: PI17/02172, PI21/01724, 15826/004, 41163/005 and PMP21/00015), AECC, the Madrid Autonomous Community and STARTUP2020/L2566.

System transferability of Raman-based oesophageal tissue classification using modern machine learning to support multi-centre clinical diagnostics.

Background: The clinical potential of Raman spectroscopy is well established but has yet to become established in routine oncology workflows. One barrier slowing clinical adoption is a lack of evidence demonstrating that data taken on one spectrometer transfers across to data taken on another spectrometer to provide consistent diagnoses.

Methods: We investigated multi-centre transferability using human oesophageal tissue.

The MondoA-dependent TXNIP/GDF15 axis predicts oxaliplatin response in colorectal adenocarcinomas.

Chemotherapy, the standard of care treatment for cancer patients with advanced disease, has been increasingly recognized to activate host immune responses to produce durable outcomes. Here, in colorectal adenocarcinoma (CRC) we identify oxaliplatin-induced Thioredoxin-Interacting Protein (TXNIP), a MondoA-dependent tumor suppressor gene, as a negative regulator of Growth/Differentiation Factor 15 (GDF15). GDF15 is a negative prognostic factor in CRC and promotes the differentiation of regulatory T cells (Tregs), which inhibit CD8 T-cell activation.

Homopolymer switches mediate adaptive mutability in mismatch repair-deficient colorectal cancer.

Mismatch repair (MMR)-deficient cancer evolves through the stepwise erosion of coding homopolymers in target genes. Curiously, the MMR genes MutS homolog 6 (MSH6) and MutS homolog 3 (MSH3) also contain coding homopolymers, and these are frequent mutational targets in MMR-deficient cancers. The impact of incremental MMR mutations on MMR-deficient cancer evolution is unknown.

Multivariable prognostic modelling to improve prediction of colorectal cancer recurrence: the PROSPeCT trial.

Objective: Improving prognostication to direct personalised therapy remains an unmet need. This study prospectively investigated promising CT, genetic, and immunohistochemical markers to improve the prediction of colorectal cancer recurrence.

Material And Methods: This multicentre trial (ISRCTN 95037515) recruited patients with primary colorectal cancer undergoing CT staging from 13 hospitals.

[F]FDG PET/CT Signal Correlates with Neoangiogenesis Markers in Patients with Fibrotic Interstitial Lung Disease Who Underwent Lung Biopsy: Implication for the Use of PET/CT in Diffuse Lung Diseases.

The use of [F]FDG PET/CT as a biomarker in diffuse lung diseases is increasingly recognized. We investigated the correlation between [F]FDG uptake with histologic markers on lung biopsy of patients with fibrotic interstitial lung disease (fILD). We recruited 18 patients with fILD awaiting lung biopsy for [F]FDG PET/CT.

FUME-TCRseq Enables Sensitive and Accurate Sequencing of the T-cell Receptor from Limited Input of Degraded RNA.

Unlabelled: Genomic analysis of the T-cell receptor (TCR) reveals the strength, breadth, and clonal dynamics of the adaptive immune response to pathogens or cancer. The diversity of the TCR repertoire, however, means that sequencing is technically challenging, particularly for samples with low-quality, degraded nucleic acids. Here, we developed and validated FUME-TCRseq, a robust and sensitive RNA-based TCR sequencing methodology that is suitable for formalin-fixed paraffin-embedded samples and low amounts of input material.

Epigenome and early selection determine the tumour-immune evolutionary trajectory of colorectal cancer.

Immune system control is a major hurdle that cancer evolution must circumvent. The relative timing and evolutionary dynamics of subclones that have escaped immune control remain incompletely characterized, and how immune-mediated selection shapes the epigenome has received little attention. Here, we infer the genome- and epigenome-driven evolutionary dynamics of tumour-immune coevolution within primary colorectal cancers (CRCs).

Poor Diagnostic Reproducibility in the Identification of Nonconventional Dysplasia in Colitis Impacts the Application of Histologic Stratification Tools.

Due to their increased cancer risk, patients with longstanding inflammatory bowel disease are offered endoscopic surveillance with concomitant histopathologic assessments, aimed at identifying dysplasia as a precursor lesion of colitis-associated colorectal cancer. However, this strategy is beset with difficulties and limitations. Recently, a novel classification criterion for colitis-associated low-grade dysplasia has been proposed, and an association between nonconventional dysplasia and progression was reported, suggesting the possibility of histology-based stratification of patients with colitis-associated lesions.

Self-supervised deep learning for highly efficient spatial immunophenotyping.

Background: Efficient biomarker discovery and clinical translation depend on the fast and accurate analytical output from crucial technologies such as multiplex imaging. However, reliable cell classification often requires extensive annotations. Label-efficient strategies are urgently needed to reveal diverse cell distribution and spatial interactions in large-scale multiplex datasets.

Limited efficacy of APRIL CAR in patients with multiple myeloma indicate challenges in the use of natural ligands for CAR T-cell therapy.

Background: We used a proliferating ligand (APRIL) to construct a ligand-based third generation chimeric antigen receptor (CAR) able to target two myeloma antigens, B-cell maturation antigen (BCMA) and transmembrane activator and CAML interactor.

Methods: The APRIL CAR was evaluated in a Phase 1 clinical trial (NCT03287804, AUTO2) in patients with relapsed, refractory multiple myeloma. Eleven patients received 13 doses, the first 15×10 CARs, and subsequent patients received 75,225,600 and 900×10 CARs in a 3+3 escalation design.

Identification of vulnerable carotid plaque with histologically validated CT-derived plaque maps.

Objectives: Ruptured carotid plaque causes stroke, but differentiating rupture-prone necrotic core from fibrous tissue with CT is limited by overlap of X-ray attenuation. We investigated the ability of CT-derived plaque maps created from ratios of plaque/contrast attenuation to identify histologically proven vulnerable plaques.

Methods: Seventy patients underwent carotid CT angiography and carotid endarterectomy.

Deep Learning Applied to Raman Spectroscopy for the Detection of Microsatellite Instability/MMR Deficient Colorectal Cancer.

Defective DNA mismatch repair is one pathogenic pathway to colorectal cancer. It is characterised by microsatellite instability which provides a molecular biomarker for its detection. Clinical guidelines for universal testing of this biomarker are not met due to resource limitations; thus, there is interest in developing novel methods for its detection.