Preoperative Localization in Colonic Surgery (PLoCoS Study): a multicentric experience on behalf of the Italian Society of Colorectal Surgery (SICCR)

The aim of this prospective multicentric study was to compare the accurate colonic lesion localization ratio between CT and colonoscopy in comparison with surgery. All consecutive patients from 1st January to 31st December 2019 with a histologically confirmed diagnosis of dysplastic adenoma or adenocarcinoma with planned elective, curative colonic resection who underwent both colonoscopy and CT scans were included. Each patient underwent conventional colonoscopy and CT to stage the tumour, and the localization results of each procedure were registered. CT and colonoscopic localization were compared with surgical localization, adopted as the reference. Our analysis included 745 patients from 23 centres. After comparing the accuracy of colonoscopy and CT (for visible lesions) in localizing colonic lesions, no significant differences were found between the two preoperative tools (510/661 vs 499/661 correctly localized lesions, p = 0.518). Furthermore, after analysing only the patients who underwent complete colonoscopy and had a visible lesion on CT, no significant difference was observed between conventional colonoscopy and CT (331/427 vs 340/427, p = 0.505). Considering the intraoperative localization results as a reference, a comparison between colonoscopy and CT showed that colonoscopy significantly failed to correctly locate the lesions localized in the descending colon (17/32 vs 26/32, p = 0.031). We did not identify an advantage in using CT to localize colonic tumours. In this setting, colonoscopy should be considered the reference to properly localize lesions; however, to better identify lesions in the descending colon, CT could be considered a valuable tool to improve the accuracy of lesion localization.

EP.WE.330The role of computerized tomography scan in 2 week wait colorectal pathway during COVID-19 pandemic

Aims The standard way to investigate patients referred on the two week wait colorectal cancer (2WW) pathway is to do a colonoscopy when patients are deemed fit. Due to limited endoscopy services during the COVID-19 lockdown period, we performed computerized tomography scan of thorax, abdomen and pelvis (CT TAP) for all fast-track colorectal referrals in addition to colonoscopy when service restarted. The aim of this study is to assess the benefit of CT scan in this group of patients. Methods All 2WW patients referred to our district general hospital from April 1, 2020 to July 31, 2020 were included in the study. The data were collected retrospectively from GP referral forms and the electronic patient records. Patient demographics, presenting complaints, investigations, diagnosis and treatment were recorded. Results A total of 658 patients were included in the study. The commonest presenting complaint was change in bowel habit (62.5%). A total of 414 colonoscopies, 347 CT TAP, 89 flexible sigmoidoscopies and 37 CT colonography were performed. 194 patients had both CT TAP and colonoscopy and another 32 patients had both CT TAP and flexible sigmoidoscopy showing that 34% of patients had both CT TAP and endoscopy. 41 patients were diagnosed with colorectal malignancy (6.2%) and 120 had polyps (18%). CT TAP missed 3 colorectal cancers but picked up 28 patients (4.3%) diagnosed with extra-colonic tumours. Conclusions Colonoscopy remains the gold standard for investigating colorectal cancer. However, CT scan have their value in diagnosing extra-colonic tumours in this specific group of patients.

Oncogenic BRAF, unrestrained by TGFβ-receptor signalling, drives right-sided colonic tumorigenesis

Right-sided (proximal) colorectal cancer (CRC) has a poor prognosis and a distinct mutational profile, characterized by oncogenic BRAF mutations and aberrations in mismatch repair and TGFβ signalling. Here, we describe a mouse model of right-sided colon cancer driven by oncogenic BRAF and loss of epithelial TGFβ-receptor signalling. The proximal colonic tumours that develop in this model exhibit a foetal-like progenitor phenotype (Ly6a/Sca1+) and, importantly, lack expression of Lgr5 and its associated intestinal stem cell signature. These features are recapitulated in human BRAF-mutant, right-sided CRCs and represent fundamental differences between left- and right-sided disease. Microbial-driven inflammation supports the initiation and progression of these tumours with foetal-like characteristics, consistent with their predilection for the microbe-rich right colon and their antibiotic sensitivity. While MAPK-pathway activating mutations drive this foetal-like signature via ERK-dependent activation of the transcriptional coactivator YAP, the same foetal-like transcriptional programs are also initiated by inflammation in a MAPK-independent manner. Importantly, in both contexts, epithelial TGFβ-receptor signalling is instrumental in suppressing the tumorigenic potential of these foetal-like progenitor cells.

Emu Oil And Grape Seed Extract Reduce Tumour Burden And Disease Parameters In Murine Colitis-Associated Colorectal Cancer

Ulcerative colitis (UC) is an incurable condition whereby patients are at an increased risk of developing colorectal cancer (CRC). We aimed to investigate the combination of Emu Oil and grape seed extract (GSE) in an azoxymethane (AOM)/dextran sulphate sodium (DSS) model of colitis-associated CRC (CA-CRC). C57BL/6 mice (n=10/group) were injected i.p. with saline or AOM (7.4mg/kg) and underwent three DSS/water cycles. Mice were orally-gavaged thrice weekly with water (80μL), EO (80μL), GSE (80μL; 400mg/kg) or combined EO/GSE (160μL). Mice were euthanized on day 63. AOM/DSS induced significant bodyweight loss (max -21%) and increased DAI (max +83%) throughout the trial (p<0.05). EO (max -53%), GSE (max -51%) and EO/GSE (max -71%) reduced DAI scores in AOM/DSS mice in all DSS cycles (p<0.05). EO/GSE-treatment in AOM/DSS mice resulted in further DAI reduction compared to EO (max -62%) and GSE (max -71%) alone (p<0.05). AOM/DSS mice presented with severe colonoscopically-assessed colitis at all time-points, which was reduced by EO, GSE and EO/GSE (p<0.05). EO, GSE and EO/GSE reduced the number of colonic tumours compared to AOM/DSS controls (p<0.05). Myeloperoxidase (acute inflammation) and FITC-dextran levels (intestinal permeability) were increased in AOM/DSS controls (p<0.05). EO (-58%) and EO/GSE (-77%) reduced FITC-dextran compared to AOM/DSS controls (p<0.05), with no effect on MPO. Histologically-assessed severity scores were increased in the distal colon of AOM/DSS mice compared to saline (p<0.05), with no effect observed following treatment. The combination of EO and GSE improved clinical indicators and reduced colonic tumours in AOM/DSS treated mice, suggesting potential in CA-CRC management

The oral microbiota in colorectal cancer is distinctive and predictive

Background and aimsMicrobiota alterations are linked with colorectal cancer (CRC) and notably higher abundance of putative oral bacteria on colonic tumours. However, it is not known if colonic mucosa-associated taxa are indeed orally derived, if such cases are a distinct subset of patients or if the oral microbiome is generally suitable for screening for CRC.MethodsWe profiled the microbiota in oral swabs, colonic mucosae and stool from individuals with CRC (99 subjects), colorectal polyps (32) or controls (103).ResultsSeveral oral taxa were differentially abundant in CRC compared with controls, for example, Streptococcus and Prevotellas pp. A classification model of oral swab microbiota distinguished individuals with CRC or polyps from controls (sensitivity: 53% (CRC)/67% (polyps); specificity: 96%). Combining the data from faecal microbiota and oral swab microbiota increased the sensitivity of this model to 76% (CRC)/88% (polyps). We detected similar bacterial networks in colonic microbiota and oral microbiota datasets comprising putative oral biofilm forming bacteria. While these taxa were more abundant in CRC, core networks between pathogenic, CRC-associated oral bacteria such as Peptostreptococcus, Parvimonas and Fusobacterium were also detected in healthy controls. High abundance of Lachnospiraceae was negatively associated with the colonisation of colonic tissue with oral-like bacterial networks suggesting a protective role for certain microbiota types against CRC, possibly by conferring colonisation resistance to CRC-associated oral taxa and possibly mediated through habitual diet.ConclusionThe heterogeneity of CRC may relate to microbiota types that either predispose or provide resistance to the disease, and profiling the oral microbiome may offer an alternative screen for detecting CRC.