In Reply We greatly appreciate the letter by Wong and Wong, which addresses important issues with relevant implications for clinical practice and preventive health policies.
Incidence of right-sided colon cancers has been progressively increasing over recent decades.1 This is probably the result of both a true increase in the incidence of ascending colon and cecal cancers and increased screening by flexible sigmoidoscopy with removal of precancerous lesions in the left colon.2 Moreover, colonoscopy is more effective in preventing left-sided as compared with right-sided colorectal cancers because of obvious limitations of the examination quality including a more difficult visualization or preparation for proximal colon lesions. However, intrinsic biologic differences such as BRAF mutations, high microsatellite instability, and CpG island methylation more properly distinguish proximal from distal cancers and may explain their worse overall prognosis, as we suggested in our work.3 Tumors arising on the right side of the colon, in fact, follow different molecular pathways of oncogenesis. To this regard, the serrated pathway has been increasingly acknowledged as one of the peculiar mechanisms of cancerogenesis for right-sided colon cancers. Indeed, serrated adenomas are more commonly found in tumors originating proximally to splenic flexure, frequently carry BRAF mutations, and typically lack classic dysplasia.2 Besides having a higher potential to develop colorectal cancers,4 these lesions are challenging for endoscopists because they are flatter and more difficult to visualize or to remove.
Tomasello G, Petrelli F, Barni S. Risk of Primary Tumor Sidedness as a Criterion for Screening, Diagnostic Colonoscopy, and Surveillance Intervals—Reply. JAMA Oncol. Published online June 22, 2017. doi:10.1001/jamaoncol.2017.1516