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Background: Post-colonoscopy colorectal cancers (PCCRCs) pose a challenge in clinical practice. PCCRCs occur due to a combination of procedural and biological causes. Specific features of lesions may contribute for this. In a nested case-control study, we compared clinical and molecular features of PCCRCs and detected CRCs (DCRCs). Methods: PCCRCs were defined according to the WEO 2018 classification, as cancers occurring after a complete index colonoscopy, which excluded CRC. CRCs in patients without colonoscopy or with colonoscopy >10 years before were defined as DCRCs. Whole genome chromosomal copy number changes and mutation status of genes commonly affected in CRC (including APC, KRAS, BRAF, FBXW7, PIK3CA, NRAS, SMAD4 and TP53) were examined by low-coverage WGS and targeted sequencing, respectively. MSI and CIMP status were also determined. Results: In total, 122 PCCRCs and 98 DCRCs with high quality DNA were examined. PCCRCs were more often located proximally in the colon (p<0.001), non-polypoid appearing (p=0.004), early stage (p=0.009), and poorly differentiated (p=0.006). PCCRCs showed similar patterns of DNA copy number changes typical of CRC, although significantly less 18q loss (FDR <0.2), compared to DCRCs. No significant differences in mutations were detected between PCCRCs and DCRCs. PCCRCs were more commonly CIMP-high (p=0.014) and MSI (p=0.029). After correction for tumour location, the only molecular difference between PCCRCs and DCRCs that remained significant was less frequent loss of 18q chromosome in PCCRCs (p=0.005). Conclusion: Although PCCRCs show molecular characteristics that are common to the canonical CIN, MSI and hypermethylation pathways, molecular features associated with the sessile serrated lesions (SSLs) and non-polypoid colorectal neoplasms (CRNs) are more commonly seen in PCCRCs than in DCRCs. This and the clinical features observed in PCCRCs support the hypothesis that sessile serrated lesions and non-polypoid CRNs are contributors to the development of these cancers. In order to further reduce the occurrence of PCCRCs, the focus should be directed at improving the detection, determination and endoscopic removal of these non-polypoid CRN and SSLs. Clinical Trial Registration: NTR3093 in the Dutch trial register (www.trialregister.nl)
Background: Post-colonoscopy colorectal cancers (PCCRCs) pose a challenge in clinical practice. PCCRCs occur due to a combination of procedural and biological causes. Specific features of lesions may contribute for this. In a nested case-control study, we compared clinical and molecular features of PCCRCs and detected CRCs (DCRCs). Methods: PCCRCs were defined according to the WEO 2018 classification, as cancers occurring after a complete index colonoscopy, which excluded CRC. CRCs in patients without colonoscopy or with colonoscopy >10 years before were defined as DCRCs. Whole genome chromosomal copy number changes and mutation status of genes commonly affected in CRC (including APC, KRAS, BRAF, FBXW7, PIK3CA, NRAS, SMAD4 and TP53) were examined by low-coverage WGS and targeted sequencing, respectively. MSI and CIMP status were also determined. Results: In total, 122 PCCRCs and 98 DCRCs with high quality DNA were examined. PCCRCs were more often located proximally in the colon (p<0.001), non-polypoid appearing (p=0.004), early stage (p=0.009), and poorly differentiated (p=0.006). PCCRCs showed similar patterns of DNA copy number changes typical of CRC, although significantly less 18q loss (FDR <0.2), compared to DCRCs. No significant differences in mutations were detected between PCCRCs and DCRCs. PCCRCs were more commonly CIMP-high (p=0.014) and MSI (p=0.029). After correction for tumour location, the only molecular difference between PCCRCs and DCRCs that remained significant was less frequent loss of 18q chromosome in PCCRCs (p=0.005). Conclusion: Although PCCRCs show molecular characteristics that are common to the canonical CIN, MSI and hypermethylation pathways, molecular features associated with the sessile serrated lesions (SSLs) and non-polypoid colorectal neoplasms (CRNs) are more commonly seen in PCCRCs than in DCRCs. This and the clinical features observed in PCCRCs support the hypothesis that sessile serrated lesions and non-polypoid CRNs are contributors to the development of these cancers. In order to further reduce the occurrence of PCCRCs, the focus should be directed at improving the detection, determination and endoscopic removal of these non-polypoid CRN and SSLs. Clinical Trial Registration: NTR3093 in the Dutch trial register (www.trialregister.nl)
Background The oropharyngeal dysphagia is an underestimated symptom with various causes in the geriatric population. Clinical presentation is often insidious and dysphagia symptoms are seldomly mentioned by elderly patients although causing many life-threatening complications. The aim of this work was to introduce an easy applicable tool to be used by the caregivers and general practitioners for screening of dysphagia in geriatrics for early detection of at risk individuals. Methods A sample of 200 Egyptian Arabic-speaking elderly patients (65 years or older) not complaining of dysphagia was recruited from nursing homes in Greater Cairo Area. They or their caregivers completed the designed screening tool, including; the designed questionnaires of dysphagia manifestations and eating habits. General, oral motor and bedside evaluation were also performed. In addition to filling in the EAT10 questionnaire and FEES that was performed for only suspected cases for the purpose of validation of the screening tool. Results The dysphagia manifestations questionnaire was significantly correlated with EAT 10 with p value of 0.001. It was correlated in some of its aspects with FEES showing quite reliability with p values’ range between 0.012 and 0.044. The Questionnaire of eating habits reliability of r- value of 0.568 slightly exceeding EAT10 reliability of r -value of 0.721 in the subjects under study. The cutoff point of total score of the dysphagia manifestations was > 5, with a sensitivity of 17.65% & a specificity of 94.20%. The cutoff point of total score of the bedside evaluation was ≤ 1 with a sensitivity of 66.9% & a specificity of 56.9%. Conclusion the use of this easy applicable screening tool managed to suspect and later on diagnose cases with oropharyngeal dysphagia in non-complaining aging subjects.
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