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Impact of the COVID-19 pandemic in the early-onset colorectal cancer

The COVID19 pandemic has affected the spectrum of cancer care worldwide. Early onset colorectal cancer (EOCRC) is defined as diagnosis below the age of 50. Patients with EOCRC faced multiple challenges during the COVID19 pandemic and in some institutions it jeopardized cancer diagnosis and care delivery. Our study aims to identify the clinicopathological features and outcomes of patients with EOCRC in our Centre during the first wave of the pandemic in comparison with the same period in 2019 and 2021.

Patients with EOCRC visited for the first time at Vall d'Hebron University Hospital in Spain from the 1st March to 31st August of 2019, 2020 and 2021 were included in the analysis. 177 patients with EOCRC were visited for the first time between 2019 and 2021, of which 90 patients met the inclusion criteria (2019: 30 patients, 2020: 29 patients, 2021: 31 patients). Neither differences in frequency nor in stage at diagnosis or at first visit during the given periods were observed. Of note, indication of systemic therapy in the adjuvant or metastatic setting was not altered. Days to treatment initiation and enrollment in clinical trials in this subpopulation was not affected due to the COVID-19 outbreak.

Team OPTIMISTICC
Journal Translational Oncology
Authors Iosune Baraibar et al
DATE 05 April 2023
A common cancer at an uncommon age

Early-onset colorectal cancer (EOCRC), also called young-onset colorectal cancer, is defined as CRC diagnosed in individuals aged less than 50 years. EOCRC is increasing globally and anticipated to become the leading cause of cancer death in individuals aged 20 to 49 in the US by 2030 (1). Since the 1990s, the age-adjusted incidence of EOCRC has risen at an alarming rate of 2 to 4% per year in many countries, with even sharper increases in individuals younger than 30 years (1). This is despite a reduction in overall CRC incidence that is likely attributable to improved screening and prevention in older individuals. The exact reasons and pathophysiology behind the rising incidence of EOCRC remain unknown. Currently, only limited studies exist and they have focused on single aspects of EOCRC etiology. A multidisciplinary path forward is needed to expand the understanding of this increasingly prevalent problem.

Team OPTIMISTICC
Journal Science Magazine
Authors Marios Giannakis, Kimmie Ng
DATE 16 March 2023
Epithelial-Stromal Interactions in Barrett’s Esophagus Modeled in Human Organ Chips

Barrett’s esophagus (BE) is an adaptive response of the lower esophagus to recurring exposure to gastroesophageal reflux that leads to intestinal metaplasia and/or gastric metaplasia depending on the specific criteria in each country.1 The tissue microenvironment and local resident fibroblasts are critically involved in tissue homeostasis and repair processes2; however, the involvement of stromal-derived fibroblasts in BE and, in particular, their involvement in rare instances of metaplastic transformation and progression to esophageal adenocarcinoma (EAC) are poorly understood. To examine this, we have leveraged a human organ-on-a-chip (Organ Chip) microfluidic culture methodology3 to construct tissue recombinant models containing esophageal epithelial cells isolated from organoids derived from multiple BE patients (Figure A1A and B and Table) interfaced with fibroblasts isolated from normal esophagus or from metaplastic, dysplastic, or cancerous regions of the same esophagus that was surgically resected from an EAC patient. Flow cytometric analysis confirmed that 80–95% of the stromal cells isolated from each of these regions stained positively for 2 different known fibroblast markers (CD90 and CD73), and that were regional differences as well as some interpatient variability in the expression of fibroblast surface markers, including CD36, podoplanin, platelet-derived growth factor-α, and platelet-derived growth factor-β (Figure A2A and B). Interestingly, this analysis also revealed that fibroblasts from a healthy, disease-free esophagus exhibited a distinct phenotype that those from adjacent normal-appearing regions from EAC patients. In contrast to a past in vitro BE modeling study,4 all cell derivatives used in these chips were not genetically manipulated and their growth conditions were designed to retain the natural self-renewing property of the BE tissue which is believed to arise from esophageal or gastric glandular epithelium,5,6,7 rather than using conditions optimized for growth of normal squamous epithelium. This is the first time, to our knowledge, that it has been possible to analyze in vitro the heterogeneous responses of BE epithelium to coculture with stromal cells from different regions of the same organ from the same patient that exhibit differences in disease phenotype in vivo.

Team STORMing Cancer
Journal Gastro Hep Advances
Authors Elee Shimshoni et al
DATE 08 March 2023
Analysis of an Indian colorectal cancer microbiome faecal collection demonstrates universal cancer-associated patterns, but…

It is increasingly being recognised that changes in the gut microbiome have either a causative or associative relationship with colorectal cancer (CRC). However, most of this research has been carried out in a small number of developed countries with high CRC incidence. It is unknown if lower incidence countries such as India have similar microbial associations.

Having previously established protocols to facilitate microbiome research in regions with developing research infrastructure, we have now collected and sequenced microbial samples from a larger cohort study of 46 Indian CRC patients and 43 healthy volunteers.

When comparing to previous global collections, these samples resemble other Asian samples, with relatively high levels of Prevotella. Predicting cancer status between cohorts shows good concordance. When compared to a previous collection of Indian CRC patients, there was similar concordance, despite different sequencing technologies between cohorts.

These results show that there does seem to be a global CRC microbiome, and that some inference between studies is reasonable. However, we also demonstrate that there is definite regional variation, with more similarities between location-matched comparisons. This emphasises the importance of developing protocols and advancing infrastructure to allow as many countries as possible to contribute to microbiome studies of their own populations.

Team OPTIMISTICC
Journal BMC Microbiology
Authors Mayilvahanan Bose & Ramakrishan Ayloor Seshadri
DATE 02 March 2023
Characterizing prophages in the genus Fusobacterium

Objectives: We set out to identify and characterize prophages within genomes of published Fusobacterium strains, and to develop qPCR-based methods to characterize intra- and extra-cellular induction of prophage replication in a variety of environmental contexts. Methods: Various in silico tools were used to predict prophage presence across 105 Fusobacterium spp. Genomes. Using the example of the model pathogen, Fusobacterium nucleatum subsp. animalis strain 7-1, qPCR was used with DNase I treatment to determine induction of its 3 predicted prophages ɸFunu1, ɸFunu2, and ɸFunu3, across several conditions. Results: 116 predicted prophage sequences were found and analyzed. An emerging association between the phylogenetic history of a Fusobacterium prophage and that of its host was detected, as was the presence of genes encoding putative host fitness factors (e.g. ADP-ribosyltransferases) in distinct subclusters of prophage genomes. For strain 7-1, a pattern of expression for ɸFunu1, ɸFunu2, and ɸFunu3 was established indicating that ɸFunu1 and ɸFunu2 are capable of spontaneous induction. I Salt and mitomycin C exposure were able to promote induction of ɸFunu2. A range of other biologically relevant stressors, including exposure to pH, mucin and human cytokines showed no or minimal induction of these same prophages. ɸFunu3 induction was not detected under tested conditions. Conclusion: The heterogeneity of Fusobacterium strains is matched by their prophages. While the role of Fusobacterium prophages in host pathogenicity remains unclear, this work provides the first overview of clustered prophage distribution among this enigmatic genus and describes an effective assay for quantifying mixed samples of prophages that cannot be detected by plaque assay.

Team OPTIMISTICC
Journal Anaerobe
Authors Jacob Wilde, Emma Allen-Vercoe
DATE 15 February 2023