External Validation of the Endoscopic Features of Sessile Serrated Adenomas in Expert and Trainee Colonoscopists.
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ABSTRACT: Background/aims
It is unclear whether the endoscopic features of sessile serrated adenomas (SSAs) would be useful to trainee colonoscopists to predict SSA. Therefore, the present study aimed to identify features that expert and trainee colonoscopists can use to independently and reliably predict SSA by using high-resolution white-light endoscopy.Methods
Endoscopic images of 81 polyps (39 SSAs, 22 hyperplastic polyps, and 20 tubular adenomas) from 43 patients were retrospectively evaluated by 10 colonoscopists (four experts and six trainees). Eight endoscopic features of SSAs were assessed for each polyp.Results
According to multivariable analysis, a mucous cap (odds ratio [OR], 10.44; 95% confidence interval [CI], 5.72 to 19.07), indistinctive borders (OR, 4.21; 95% CI, 2.74 to 7.16), dark spots (OR, 3.64; 95% CI, 1.89 to 7.00), and cloud-like surface (OR, 2.43; 95% CI, 1.27 to 4.668) were independent predictors of SSAs. Among these, a mucous cap, indistinctive borders, and cloud-like surface showed moderate interobserver agreement (mean ? >0.40) among experts and trainees. When ?1 of the three predictors was observed, the sensitivity and specificity for diagnosing SSAs were 79.0% and 81.4%, respectively.Conclusions
Colonoscopy trainees and experts can use several specific endoscopic features to independently and reliably predict SSAs.
SUBMITTER: Yang HJ
PROVIDER: S-EPMC5475520 | biostudies-literature | 2017 May
REPOSITORIES: biostudies-literature
Publications
External Validation of the Endoscopic Features of Sessile Serrated Adenomas in Expert and Trainee Colonoscopists.
Yang Hyo-Joon HJ Lee Jeong In JI Park Soo-Kyung SK Jung Yoon Suk YS Sohn Jin Hee JH Choi Kyu Yong KY Park Dong Il DI
Clinical endoscopy 20160913 3
<h4>Background/aims</h4>It is unclear whether the endoscopic features of sessile serrated adenomas (SSAs) would be useful to trainee colonoscopists to predict SSA. Therefore, the present study aimed to identify features that expert and trainee colonoscopists can use to independently and reliably predict SSA by using high-resolution white-light endoscopy.<h4>Methods</h4>Endoscopic images of 81 polyps (39 SSAs, 22 hyperplastic polyps, and 20 tubular adenomas) from 43 patients were retrospectively ...[more]
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Project description:BackgroundSessile serrated adenomas (SSAs) are common polyps which give rise to 20-30% of colorectal cancer (CRC). SSAs display clinicopathologic features which present challenges in surveillance, including overrepresentation in young patients, proclivity for the proximal colon and rarity of histologic dysplasia (referred to then as SSAs with dysplasia, SSADs). Once dysplasia develops, there is rapid progression to CRC, even at a small size. There is therefore a clinical need to separate the "advanced" SSAs at high risk of progression to SSAD and cancer from ordinary SSAs. Since SSAs are known to accumulate methylation over time prior to the development of dysplasia, SSAD backgrounds (the remnant SSA present within an SSAD) likely harbour additional methylation events compared with ordinary SSAs. We therefore performed MethyLight and comprehensive methylation array (Illumina MethylationEPIC) on 40 SSAD backgrounds and 40 matched ordinary SSAs, and compared the methylation results with CRC methylation, CRC expression and immunohistochemical data.ResultsSSAD backgrounds demonstrated significant hypermethylation of CpG islands compared with ordinary SSAs, and the proportion of hypermethylated probes decreased progressively in the shore, shelf and open sea regions. Hypomethylation occurred in concert with hypermethylation, which showed a reverse pattern, increasing progressively away from the island regions. These methylation changes were also identified in BRAF-mutant hypermethylated CRCs. When compared with CRC expression data, SV2B, MLH1/EPM2AIP1, C16orf62, RCOR3, BAIAP3, OGDHL, HDHD3 and ATP1B2 demonstrated both promoter hypermethylation and decreased expression. Although SSAD backgrounds were histologically indistinguishable from ordinary SSAs, MLH1 methylation was detectable via MethyLight in 62.9% of SSAD backgrounds, and focal immunohistochemical MLH1 loss was seen in 52.5% of SSAD backgrounds.ConclusionsSignificant hyper- and hypomethylation events occur during SSA progression well before the development of histologically identifiable changes. Methylation is a heterogeneous process within individual SSAs, as typified by MLH1, where both MLH1 methylation and focal immunohistochemical MLH1 loss can be seen in the absence of dysplasia. This heterogeneity is likely a generalised phenomenon and should be taken into account in future methylation-based studies and the development of clinical methylation panels.
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Project description:Background & aimsMany cancers in the proximal colon develop via from sessile serrated adenomas (SSAs), which have flat, subtle features that are difficult to detect with conventional white-light colonoscopy. Many SSA cells have the V600E mutation in BRAF. We investigated whether this feature could be used with imaging methods to detect SSAs in patients.MethodsWe used phage display to identify a peptide that binds specifically to SSAs, using subtractive hybridization with HT29 colorectal cancer cells containing the V600E mutation in BRAF and Hs738.St/Int cells as a control. Binding of fluorescently labeled peptide to colorectal cancer cells was evaluated with confocal fluorescence microscopy. Rats received intra-colonic 0.0086 mg/kg, 0.026 mg/kg, or 0.86 mg/kg peptide or vehicle and morbidity, mortality, and injury were monitored twice daily to assess toxicity. In the clinical safety study, fluorescently labeled peptide was topically administered, using a spray catheter, to the proximal colon of 25 subjects undergoing routine outpatient colonoscopies (3 subjects were given 2.25 μmol/L and 22 patients were given 76.4 μmol/L). We performed blood cell count, chemistry, liver function, and urine analyses approximately 24 hours after peptide administration. In the clinical imaging study, 38 subjects undergoing routine outpatient colonoscopies, at high risk for colorectal cancer, or with a suspected unresected proximal colonic polyp, were first evaluated by white-light endoscopy to identify suspicious regions. The fluorescently labeled peptide (76.4 μmol/L) was administered topically to proximal colon, unbound peptide was washed away, and white-light, reflectance, and fluorescence videos were recorded digitally. Fluorescence intensities of SSAs were compared with those of normal colonic mucosa. Endoscopists resected identified lesions, which were analyzed histologically by gastrointestinal pathologists (reference standard). We also analyzed the ability of the peptide to identify SSAs vs adenomas, hyperplastic polyps, and normal colonic mucosa in specimens obtained from the tissue bank at the University of Michigan.ResultsWe identified the peptide sequence KCCFPAQ and measured an apparent dissociation constant of Kd = 72 nM and an apparent association time constant of K = 0.174 min-1 (5.76 minutes). During fluorescence imaging of patients during endoscopy, regions of SSA had 2.43-fold higher mean fluorescence intensity than that for normal colonic mucosa. Fluorescence labeling distinguished SSAs from normal colonic mucosa with 89% sensitivity and 92% specificity. The peptide had no observed toxic effects in animals or patients. In the analysis of ex vivo specimens, peptide bound to SSAs had significantly higher mean fluorescence intensity than to hyperplastic polyps.ConclusionsWe have identified a fluorescently labeled peptide that has no observed toxic effects in animals or humans and can be used for wide-field imaging of lesions in the proximal colon. It distinguishes SSAs from normal colonic mucosa with 89% sensitivity and 92% specificity. This targeted imaging method might be used in early detection of premalignant serrated lesions during routine colonoscopies. ClinicalTrials.gov ID: NCT02156557.
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