Background The incidence of colorectal cancer (CRC) is increasing in developing countries, yet limited research on the CRC- associated microbiota has been conducted in these areas, in part due to scarce resources, facilities, and the difficulty of fresh or frozen stool storage/transport. Here, we aimed (1) to establish a broad representation of diverse developing countries (Argentina, Chile, India, and Vietnam); (2) to validate a ‘resource-light’ sample-collection protocol translatable in these settings using guaiac faecal occult blood test (gFOBT) cards stored and, importantly, shipped internationally at room temperature; (3) to perform initial profiling of the collective CRC-associated microbiome of these developing countries; and (4) to compare this quantitatively with established CRC biomarkers from developed countries. Methods We assessed the effect of international storage and transport at room temperature by replicating gFOBT from five UK volunteers, storing two in the UK, and sending replicates to institutes in the four countries. Next, to determine the effect of prolonged UK storage, DNA extraction replicates for a subset of samples were performed up to 252 days apart. To profile the CRC-associated microbiome of developing countries, gFOBT were collected from 41 treatment-naïve CRC patients and 40 non-CRC controls from across the four institutes, and V4 16S rRNA gene sequencing was performed. Finally, we constructed a random forest (RF) model that was trained and tested against existing datasets from developed countries. Results The microbiome was stably assayed when samples were stored/transported at room temperature and after prolonged UK storage. Large-scale microbiome structure was separated by country and continent, with a smaller effect from CRC. Importantly, the RF model performed similarly to models trained using external datasets and identified similar taxa of importance (Parvimonas, Peptostreptococcus, Fusobacterium, Alistipes, and Escherichia). Conclusions This study demonstrates that gFOBT, stored and transported at room temperature, represents a suitable method of faecal sample collection for amplicon-based microbiome biomarkers in developing countries and suggests a CRC-faecal microbiome association that is consistent between developed and developing countries.
BACKGROUNDThe aim of the study is to investigate the prognostic role of pre-treatment of markers of the systemic inflammatory response (neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and albumin) in patients with oropharyngeal carcinoma treated with chemoradiotherapy.METHODSA total of 251 patients with oropharyngeal squamous cell cancer treated with chemoradiotherapy between 2004 and 2010 were retrospectively identified. NLR, PLR, and albumin were recorded from baseline blood parameters. NLR threshold of >5 and PLR thresholds of ≤150, >150 and ≤300, and >300 were used for analysis.RESULTSMedian follow-up was 46 months (range 9–98). The 3 year overall survival, local control, regional control, and distant control were 70%, 85%, 87%, and 87%, respectively. On multivariate analysis, locoregional control was associated with T stage (HR 3.3 (95% CI 1.5–6.9), P = 0.002) and NLR (HR 2.1 (95% CI 1.1–3.9), P = 0.023). Overall survival was associated with T stage (HR 2.47 (95% CI 1.45–4.2), P = 0.001) and grade (HR 0.61 (95% CI 0.38–0.99), P = 0.048). PLR and albumin were not significantly associated with disease outcomes or survival.CONCLUSIONSThe NLR is an independent prognostic factor for locoregional control in oropharyngeal cancer treated with chemoradiotherapy.
The evolution of cellular pathology as a specialty has always been driven by technological developments and the clinical relevance of incorporating novel investigations into diagnostic practice. In recent years, the molecular characterisation of cancer has become of crucial relevance in patient treatment both for predictive testing and subclassification of certain tumours. Much of this has become possible due to the availability of next-generation sequencing technologies and the whole-genome sequencing of tumours is now being rolled out into clinical practice in England via the 100 000 Genome Project. The effective integration of cellular pathology reporting and genomic characterisation is crucial to ensure the morphological and genomic data are interpreted in the relevant context, though despite this, in many UK centres molecular testing is entirely detached from cellular pathology departments. The CM-Path initiative recognises there is a genomics knowledge and skills gap within cellular pathology that needs to be bridged through an upskilling of the current workforce and a redesign of pathology training. Bridging this gap will allow the development of an integrated ‘morphomolecular pathology’ specialty, which can maintain the relevance of cellular pathology at the centre of cancer patient management and allow the pathology community to continue to be a major influence in cancer discovery as well as playing a driving role in the delivery of precision medicine approaches. Here, several alternative models of pathology training, designed to address this challenge, are presented and appraised.
To assess the utility of microbiome profiles for national-scale colorectal cancer (CRC) screening, we assessed 2,252 routinely processed NHS Bowel Cancer Screening Programme guaiac faecal occult blood test (gFOBT) samples. We generated four microbiome-based random forest classification models, each showing potential to improve accuracy.Two distinguished either CRC or neoplasm (CRC or adenoma) from gFOBT blood-negative samples (equivalent to firsttier screening). Two distinguished CRC or neoplasm from samples that had tested positive for blood by gFOBT, with participants referred for colonoscopy, but at colonoscopy no-lesion was found (second-tier screening to rule out gFOBT false positives). Each model remained robust to validation and when restricted to fifteen taxa, raising the possibility of an inexpensive qPCR-test. The models performed favourably compared with existing microbiome studies, FIT and Cologuard. These results suggest that microbiome analysis could be integrated into national CRC screening to improve accuracy and reduce the number of unnecessary screening colonoscopies.
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