One Colon Lumen but Two Organs

摘要: The colon is a remarkable organ in that it manages the final products of digestion after nutrient assimilation, and packages as waste to expel. has highest bacterial load any organ, with commensal bacteria occupying niche prevents noncommensal organisms from expanding, some producing vitamins can be utilized. It colon, its local environmental influences on intrinsic stem cells an individual’s genetic background, makes this third most common site for cancer men or women second cause deaths overall.1 Because risk cancer, early detection key, are screened according latest guidelines detect cancers precursor lesion, adenoma, hopes reducing incidence intervene save lives.2 relatively high population led development multiple tests either adenomas and/or each having variable sensitivities specificities.2 Colonoscopy particular been advocated because relative sensitivity, diagnostic therapeutic capabilities both cancer. Although gold standard colonic neoplasia detection, colonoscopy miss lesions may related endoscopist’s expertise thoroughness,3 although other factors biology growth characteristics occur within colon. Fundamentally, 1 but develops 2 different embryonic areas primitive gut: midgut, which gives rise small intestine through proximal two thirds transverse hindgut, distal upper anal canal.4 Functionally, absorbs remaining water incoming digestive contents utilizing effective haustral shuttling, whereas remainder utilizes peristalsis primary motility characteristic, lubricates becomes more solid while progressing toward rectum. right “sees” bile acids metabolites have escaped intestine’s reuptake detoxifying mechanisms, form before action metabolites. Genetic profiling normal left confirm major differences between sites endodermally derived organ: There >165 genes showing >2-fold 49 >3-fold gene expression adult human colon.5 The likewise differs by colon. As we age, left-to-right shift ensues seventh eighth decades life.6 Females likely develop males cancers,4 suggesting possibility hormonal incidence. African Americans higher prevalence >9 mm proximally compared Caucasians, cancers.7,8 Adjuvant neoadjuvant treatment based site, rectal being treated at earlier stages (stage II) addition radiation chemotherapy, stage III no radiation.9 Treatment responses indicate biological behavior site-specific cancers.10 Morphologic observed Laterally spreading tumors, type superficial “flat” neoplasm, commonly found difficult without enhanced endoscopic methods.11 These much contain than their polypoid counterparts,11 lack exophytic attributed KRAS mutation.12 Microsatellite instability (MSI), seen up 20% sporadic prevalent cancers, caused hypermethylation DNA mismatch repair hMLH1 (through CpG island methylator phenotype [CIMP] pathway), these tumors mutated V600E BRAF mutation.10,13 Sessile serrated associated progress right-sided mutation, often manifest MSI methylation hMLH1, strongly mutations drive morphologically low profile located tumors.13 All morphogenetic findings unified defining pathogenic pathway One ascertained clinical consequence presence CIMP patient’s predicts improved survival response 5-fluorouracil–based chemotherapy.14–16 Detection polyps appears endoscopist dependent,17 screening increases interval during surveillance.18 Are there mortality site? best evidence suggests is.19,20 At worst, does not improve cancers,19 best, improves markedly lesser extent cancers.20 Perhaps should considered organs matching origin, varying approaches morphologic, genetic, racial, gender, lesions. Akin unseen moisture road freezes, neoplastic “black ice” Strategies better recognize (eg, optical, dye based, etc) need pursued broader fashion apparently identify lesions, order make impact par beneficial effect left-sided