Sessile Serrated Adenomas/polyps Research Articles

Annexin A10 Expression in Hyperplastic Polyp, Sessile Serrated Adenoma Polyp and Conventional Adenoma

Annexin A10 Expression in Hyperplastic Polyp, Sessile Serrated Adenoma Polyp and Conventional Adenoma

Endoscopic diagnosis of sessile serrated adenoma/polyp with and without dysplasia/carcinoma.

Sessile serrated adenoma/polyps (SSA/Ps) are early precursor lesions in the serrated neoplasia pathway, which results in colorectal carcinomas with BRAF mutations, methylation for DNA repair genes, a CpG island methylator phenotype, and high levels of microsatellite instability. Some of these lesions can rapidly become dysplastic or invasive carcinomas that exhibit high lymphatic invasion and lymph node metastasis potentials. Detecting serrated lesions, including SSA/Ps with and without dysplasia/carcinoma, is critical, but SSA/Ps can be difficult to detect, are inconsistently identified by endoscopists and pathologists, and are often incompletely resected. Therefore, SSA/Ps are considered to be major contributors to “interval cancers”. If colonoscopists can identify the specific endoscopic characteristics of SSA/Ps, their detection and the effectiveness of colonoscopy may improve. Here, the endoscopic features of SSA/Ps with and without dysplasia/carcinoma, including the characteristics determined using magnifying endoscopy, are reviewed in the context of previous reports. Endoscopically, these subtle polyps are like hyperplastic polyps, because they are slightly elevated and pale. Unlike hyperplastic polyps, SSA/Ps are usually larger than 5 mm, frequently covered by a thin layer called the ‘‘mucus cap’’, and are more commonly located in the proximal colon. Magnifying narrow-band imaging findings, which include dark spots inside the crypts and varicose microvascular vessels, in addition to the type II-open pit patterns detected using magnifying chromoendoscopy, effectively differentiate SSA/Ps from hyperplastic polyps. The lesions’ endoscopic characteristics, which include their (semi)pedunculated morphologies, double elevations, central depressions, and reddishness, and the use of magnifying endoscopy, might help to detect dysplasia/carcinoma within SSA/Ps. Greater awareness may promote further research into improving the detection, identification, and complete resection rates of SSA/Ps with and without dysplasia/carcinoma and reduce the interval cancer rates.

Reappraisal of the genetic heterogeneity of sessile serrated adenoma/polyp

Sessile serrated adenoma/polyp (SSA/P) is regarded as a genetically homogeneous entity, with most lesions harbouring the BRAF V600E mutation. The present study aimed to reappraise the genetic heterogeneity of SSA/Ps and its clinicopathological significance. We performed next-generation sequencing of 272 SSA/Ps without dysplasia and evaluated morphological and molecular features associated with the respective genotypes. BRAF V600E, BRAF non-V600E, KRAS and NRAS mutations were found in 223 (82.0%), three (1.2%), 28 (10.3%) and one lesion (0.4%), respectively. Notably, all lesions with BRAF non-V600E mutations had either KRAS or NRAS mutations concurrently. Twenty SSA/Ps (7.4%) were negative for these mutations. KRAS-mutated SSA/Ps were located more often in the distal colon (42%) compared to those with the BRAF V600E mutation (14%). Histologically, minimally serrated crypts and goblet cell-rich crypts were more common in KRAS-mutated and mutation-negative SSA/Ps. However, in most instances, SSA/Ps lacking the BRAF V600E mutation were indistinguishable morphologically from those with the BRAF V600E mutation. MUC5AC and MUC6 expression was common regardless of the mutation status, but more extensive in SSA/Ps with the BRAF V600E mutation. CpG island methylator phenotype-high was more frequent in SSA/Ps with the BRAF V600E mutation (60%), followed by mutation-negative SSA/Ps (40%) and KRAS-mutated SSA/Ps (16%). The present study confirmed the common presence of the BRAF V600E mutation in SSA/Ps, but also demonstrated a degree of molecular heterogeneity of SSA/Ps. SSA/Ps with and without the BRAF V600E mutation showed slightly different but overlapping histological and molecular features.

Additional Thirty Seconds Observation with Linked Color Imaging Improves Detection of Missed Polyps in the Right-Sided Colon.

Background and Aims Missed polyps are a pitfall of colonoscopy. In this study, we analyzed the efficacy of an additional 30 seconds observation using linked color imaging (LCI) for detecting adenoma and sessile serrated adenoma/polyp (SSA/P). Materials and Methods We enrolled patients undergoing colonoscopy from February to October 2017 in two institutions. In all patients, the cecum and ascending colon were observed with white light imaging (WLI) first. The colonoscope was inserted again, and the cecum and ascending colon were observed for an additional 30 seconds using either LCI or WLI. The method for the 30 sec observation was to insufflate the cecum and ascending colon sufficiently and observe them in a distant view, because the length of the second observation was determined to be precisely 30 sec. For the second observation, LCI was performed for the first 65 patients and WLI for the next 65. Adenoma and SSA/P detection rate (ASDR) in the second observation were examined in both groups. According to a pilot study, the sample size was estimated 65. Results In the first observation, ASDR were 30.7% in the LCI group and 32.2% in the WLI group (p = 0.85). For the second observation, 13 polyps were detected in the LCI group and 5 polyps in the WLI group (p = 0.04). Additionally, ASDR for the second observation were 18.5% and 6.1%, respectively (p = 0.03). There were no significant differences between the LCI and WLI groups with respect to morphology (ratio of polypoid) (38.5% versus 60.0%, p = 0.52) and histology (ratio of adenoma) (92.3% versus 100.0%, p = 0.91). Total adenoma and SSA/P number were 48 in the LCI group and 36 in the WLI group (p = 0.02). Conclusion The 30 seconds additional observation with LCI improved the detection of adenoma and SSA/P in the right-sided colon.

Molecular Profiling Based on KRAS/BRAF Mutation, Methylation, and Microsatellite Statuses in Serrated Lesions

AimThe aim of your study is to characterize serrated lesions according to their molecular patterns, specifically BRAF/KRAS mutation, methylation, and microsatellite statuses. We evaluated the molecular patterns of 163 serrated lesions, including 37 microvesicular hyperplastic polyps, 73 sessile serrated adenomas/polyps (SSA/Ps), 31 traditional serrated adenomas, and 22 SSA/Ps with cytological dysplasia/adenocarcinoma.MethodsMutations in BRAF (V600E)/KRAS (exon 2) and microsatellite status [microsatellite stability (MSS) vs. MSI] were examined using a pyrosequencer and the PCR-based microsatellite method, respectively. DNA methylation status was classified as low (LME), intermediate (IME), or high methylation epigenotype (HME) according to a PCR-based two-step method. In addition, mucin and annexin A10 expression was examined. Finally, we performed a hierarchical clustering analysis of the BRAF/KRAS mutation, DNA methylation, and microsatellite statuses.ResultsThe molecular patterns observed in the serrated lesions could be divided into five subgroups: lesions characterized by (1) BRAF mutation, HME, and MSI; (2) BRAF mutation, HME, and MSS; (3) BRAF mutation, LME/IME, and MSS; (4) no BRAF/KRAS mutations, LME/IME, and MSS; and (5) KRAS mutation, LME/IME, and MSS. In addition, we demonstrated that these observed molecular patterns help identify the associations of the molecular patterns and markers (i.e., mucin and annexin A10) with the clinicopathological findings, including histological features and histological diagnosis.ConclusionsWe suggest that the identified molecular patterns play an important role in the pathway of serrated lesion development.

Mo1667 WATER EXCHANGE ALONE (WE) AND WATER EXCHANGE WITH CHROMOENDOSCOPY (CWE) SIGNIFICANTLY ENHANCED DETECTION OF PROXIMAL COLON SESSILE SERRATED LESIONS (SSLS) COMPARED WITH AIR INSUFFLATION (AI) IN A RCT

Proximal colon hyperplastic polyps (HP), with a different pathology compared to distal HP, are more closely related to sessile serrated adenoma/polyps (SSA/P) (CGH 2013;11:760). Collectively proximal sessile serrated lesions (SSLs: SSA/P and HP) are linked to proximal colon cancers through a different pathway than conventional adenoma-carcinoma sequence. Predominantly flat, proximal SSLs are more difficult to identify by endoscopy with AI; and as missed lesions, are believed to contribute to interval cancers in the proximal colon. We completed a RCT (NCT01607255) comparing sedated screening colonoscopy performed with chromoendoscopy and water exchange (CWE), water exchange alone (WE) and air insufflation (AI). In a 2017 ACG late breaking abstract we reported that there were no differences in patient demographics (age and BMI), cecal intubation success rate, overall and proximal colon adenoma detection rate (ADR) (primary outcome) amongst groups. Overall and proximal colon ADR were >60% and >50%, respectively, confirming high quality examinations. We have now completed further analysis of the secondary outcome of proximal colon SSLs and procedural variables. 480 patients were randomized to sedated screening colonoscopy performed with CWE (160), WE (161) and AI (159) method. AI was performed with conventional air insufflation. WE was performed with air button turned off and water was infused/suctioned (exchanged) to facilitate scope insertion until cecal intubation. Air insufflation was used on withdrawal to facilitate removal of lesions. CWE used a dilute (0.008%) solution of indigo carmine and the method was otherwise same as WE. Polyps were removed using biopsy forceps, cold or hot snares. Table 1 shows the proximal colon SSLs detection rate was significantly higher for CWE and WE than AI (26.3%, 23.6% and 11.3%, respectively, p=0.002). Compared to AI, insertion time was not prolonged, withdrawal time was shorter, and withdrawal bowel prep score was significantly better, with WE. Single operator and subjects limited to Veterans; SSLs are only surrogate markers of, and not interval cancers. Use of WE or CWE significantly and equally improved detection of SSLs in the proximal colon compared to AI. Since missed proximal colon SSLs may account for proximal colon interval cancers developed through an alternative pathway (DCR 2009;52:1535), the enhanced detection of proximal colon SSLs could reduce risks of interval cancers (AJG 2012;107:1315-30). Without prolonging insertion time, with shorter withdrawal time and significantly better withdrawal bowel prep score, WE alone is sufficient to produce a significant improvement in proximal colon SSLs compared to AI. WE could improve clinical outcome by reducing interval cancers. The prevention of interval cancers by WE deserves to be studied.Tabled 1Table 1. Comparison of proximal SSLs detection rateProcedure characteristicsOverall p-valuesTukey adjusted p-values for pairwise [email protected]CWE (N=160)WE (N=161)AI (N=159)CWE vs WECWE vs AIWE vs AICecal intubation time (SD) min.13.3 (7.8)12.0 (6.3)12.2 (7.8).22**nsnsnsWithdrawal time (SD) min. with adenoma26.2 (8.6)20.2 (8.6)21.8 (10.2)<.001**<.001.003.52Volume water infused for procedure (SD) ml655.5 (513.6)614.0 (478.9)479.2 (457.5).004**.08<.001<.001Overall preparation in2.45 (0.29)2.49 (0.24)2.48 (0.27).41**nsnsnsOverall preparation out#3.33 (0.39)3.48 (0.34)3.22 (0.36)<.001**<.001.03<.001Proximal colon SSLs (HP/ SSA/P) detection rate (%)26.323.611.3.002.58<.001.004CWE=chromoendoscopy + water exchange; WE=water exchange; AI=air insufflation; SSLs=sessile serrated lesions (sessile serrated adenoma/polyp + hyperplastic polyps); Proximal colon: splenic flexure to cecum; SD=standard deviation.*Chi square test and **Wilcoxon rank sum test, p<0.05 is significant; ns=not significant @ only pairwise comparisons for tests for which the omnibus test was significant are required. Open table in a new tab

Sa1051 FREQUENCY OF RIGHT-SIDED PRECANCEROUS POLYPS REMAINS HIGH DESPITE ABSENCE OF POLYPS IN THE LEFT COLON

Flexible sigmoidoscopy has become an important tool for colorectal cancer screening but unfortunately lacks visualization of more proximal colonic lesions. Colorectal lesions found during flexible sigmoidoscopy may warrant further proximal colonic lesion investigation. There however is limited research on the frequency of right-sided precancerous polyps in the absence of polyps in the left colon. Assess the likelihood of finding a polyp, adenoma or sessile serrated adenoma/polyp (SSA/P) in the right colon when no polyps are seen within the left colon. Colonoscopy quality data was collected prospectively at our single tertiary referral center from June 2012 to Nov 2017 using Qualoscopy (Docbot, Inc.). We included all colonoscopies for patients of all ages. We compared detection rates of polyps (PDR), adenomas (ADR) and sessile serrated adenomas/polyps (SSADR/SSPDR) with the left colon (rectum to splenic flexure) and right colon (transverse colon to cecum). 2777 colonoscopies met our inclusion criteria. 49% of patients were male and 51% were female. Mean age was 58.1 years, average Boston prep scores was 7.9 out of 10 and average cecal intubation rate was 98%. Table 1 shows the detection rates and mean number of polyps, adenomas, SSAs and SSPs within the right colon. The ‘Independent of Left Colon Findings’ row shows right colon detection rates that are independent of lesions within the left colon. The ‘No Polyps’ row shows these same values when no polyp was found within the left colon. The ‘Adenoma’ row shows these same values when at least 1 adenoma was found in the left colon. The ‘Sessile Serrated Polyp’ row shows these same values when at least 1 SSA or 1 hyperplastic polyp was found in the left colon. The PDR, ADR and SSADR in the right colon when no polyp was found within the left colon were, 0.33%, 0.22% and 0.058%, respectively. Table 1 also shows the rates of PDR, ADR and SSADR/P are higher when an adenoma or SSP was found within the left colon. Our data demonstrate a higher detection rate of polyps, adenomas and SSA/Ps in the right colon if an adenoma or SSP is found within the left colon. More importantly and interestingly, our data also reveals the absence of polyps in the left colon does not reliably predict the rate of precancerous polyps in the right colon. High PDR, ADR and SSADR within the right colon despite an absence of polyps in the left colon suggest that limited colonoscopies such as flexible sigmoidoscopies may miss many significant precancerous lesions more proximally.Tabled 1Detection Rates within the Right ColonRIGHT COLONLEFT COLONColonoscopiesPDRADRSSADRSSPDRMean Polyps PPMean Adenomas PPMean SSAs PPMean SSPs PPIndependent of Left Colon Findings27770.440.290.08N/A2.201.941.51N/ANo Polyps17010.330.220.0580.630.380.075Adenoma5470.640.490.121.621.080.20Sessile Serrated Polyp5360.620.39N/A0.291.570.76N/A0.55PDR-polyp detection rate, ADR-adenoma detection rate, SSADR -sessile serrated adenoma detection rate, SSPDR – sessile serrated polyp detection rate (SSADR + hyperplastic polyp detection rate), PP - per procedure, SSA -sessile serrated adenoma, SSP – sessile serrated polyp Open table in a new tab PDR-polyp detection rate, ADR-adenoma detection rate, SSADR -sessile serrated adenoma detection rate, SSPDR – sessile serrated polyp detection rate (SSADR + hyperplastic polyp detection rate), PP - per procedure, SSA -sessile serrated adenoma, SSP – sessile serrated polyp

Clinicopathological features of advanced colorectal serrated lesions: A single‐center study in China

A growing body of evidence indicates that patients with colorectal serrated lesions, especially advanced serrated lesions (ASLs), are at risk of subsequent malignancy. This study aimed to analyze the clinicopathological features of ASLs and the association between ASLs and synchronous advanced colorectal neoplasia (sACN) in a single center of China. A retrospective cross-sectional study of consecutive symptomatic patients and healthy individuals who underwent colonoscopy between January 2010 and March 2016 was performed. Clinicopathological characteritics of the patients with ASLs were documented from the colonoscopy database. Colorectal serrated lesions were pathologically confirmed in 277 (N = 38 981, 0.7%) cases. Among them, 156 (56.3%) were found to have ASLs, with a total of 161 lesions including 71 sessile serrated adenoma/polyps (SSA/P) and 90 traditional serrated adenomas (TSAs). There were no differences in age and gender between the ASL and non-ASL patients. Among the 161 ASLs, 29 (18.0%) were ≥10 mm in diameter. Compared with non-ASLs, ASLs appeared more in the proximal colon (P = 0.007). Flat and subpedunculated lesions were more commonly found in the ASL group compared with the non-ASL group. Nearly all ASLs (160/161) had dysplasia. Moreover, 16 sACN lesions were found in 156 ASL patients, and large diameter (≥10 mm) might be a significant risk factor for sACN (odds ratio 4.35, 95% confidence interval 1.467-12.894, P < 0.05). ASLs are more likely to occur in the proximal colon, and mainly present as flat and sub-pedunculated types. Large ASLs are significantly associated with sACN.

Endoscopic analysis of colorectal serrated lesions with cancer.

Serrated lesions, including hyperplastic polyps (HPs), traditional serrated adenomas (TSAs) and sessile serrated adenomas/polyps (SSA/Ps), are important contributors to colorectal carcinogenesis. The aim of the present study was to analyze the potential of conventional endoscopy and advanced endoscopic imaging techniques to delineate the characteristic features of serrated lesions with cancer. The present study was a retrospective analysis of the data of 168 patients who had undergone colonoscopy, and a total of 228 serrated lesions (77 HPs, 58 TSAs, 84 SSA/Ps, 9 SSA/P plus TSAs) have been identified in these patients. A cancer component was identified in 2.6% of HPs, 13.8% of TSAs and 10.7% of SSA/Ps, but none of SSA/P plus TSAs. Compared with the lesions without cancer, the lesions with cancer exhibited a larger size (HP, TSA and SSA/P), a reddish appearance (SSA/P), a two-tier raised appearance (HP and SSA/P), a central depression (HP, TSA and SSA/P), the type V pit pattern (HP, TSA and SSA/P), and/or the type III capillary pattern (TSA and SSA/P). Deep invasion was identified in 50.0% of HPs, 12.5% of TSAs and 55.6% of SSA/Ps with cancer. The Ki-67 proliferative zone was distributed diffusely within the area of the cancer, but partially within the non-cancer area of HPs, TSAs and SSA/Ps. The lesion types were also analyzed on the basis of mucin phenotype. The present study suggested that a detailed endoscopic analysis of serrated lesions with cancer is useful for delineating characteristic features, and the analysis aids treatment selection.

Clinical and endoscopic evaluations of sessile serrated adenoma/polyps with cytological dysplasia.

Although sessile serrated adenoma/polyps (SSA/Ps) are considered to be premalignant lesions and rapidly progress to carcinomas after they develop cytological dysplasia (CD), a treatment strategy for SSA/Ps in Asian countries is still being debated and has not yet been established. The present study aimed to propose a treatment strategy for SSA/Ps. Histopathological data of patients, who underwent colonoscopy at our center between January 2011 and December 2016, were reviewed. Data of patients with ≥1 SSA/P were retrieved, and clinicopathological characteristics were retrospectively analyzed. A total of 281 patients with 326 SSA/Ps, including 258 patients who had 300 SSA/Ps without CD (SSA/Ps-CD[-]) and 23 patients who had 26 SSA/Ps with CD (SSA/Ps-CD[+]), were evaluated in this study. Although SSA/Ps-CD(+) were often found in older female patients and in the proximal colon, there were no significant differences between SSA/Ps-CD(-) and SSA/Ps-CD(+). Endoscopic morphological findings, such as large or small nodules on the surface and partial protrusion of the lesions, were significantly more common in SSA/Ps-CD(+) than in SSA/Ps-CD(-). Although the diagnostic ability of nodule/protrusion in lesions to predict CD within SSA/Ps was very high with an accuracy of 93.9% and a negative predictive value of 95.4%, sensitivity was low at 46.2%. SSA/Ps-CD(+) were significantly larger than SSA/Ps-CD(-), and the rate of CD within SSA/Ps significantly increased with lesion size (≤5mm, 0%; 6-9mm, 6.0%; ≥10mm, 13.6%). The study proposes removing all SSA/Ps ≥6mm in order to remove high-risk SSA/Ps-CD(+), with high sensitivity.

Development and endoscopic appearance of colorectal tumors are characterized by the expression profiles of miRNAs.

Accumulating data indicates that certain microRNAs (miRNAs or miRs) are differently expressed in samples of tumors and paired non-tumorous samples taken from the same patients with colorectal tumors. We previously reported to clarify the relationship between the expression of the miRNAs and the endoscopic morphological appearance of the colorectal tumors. In this report, we focused on colorectal adenoma (tubular or tubulovillous adenoma), or tubular early carcinoma or type 2 adenocarcinoma, familial adenomatous polyposis (FAP), ulcerative colitis-associated tumor (UCAT), and sessile serrated adenoma/polyp (SSA/P). We tried to clarify the relationship between the expression of the miRNAs and the colorectal tumor development. The expression levels of miR-143, -145, and -34a were reduced in most of the polypoid and FAP tumors compared with those in the flat elevated, UCAT, SSA/P ones. In type 2 adenocarcinomas, the expression profile of these miRNAs was similar to those of the polypoid and FAP tumors. The expression levels of miR-7 and -21 were up-regulated in non-granular type of laterally spreading tumor, UCAT, and SSA/P compared with those in polypoid and FAP tumors. These findings indicated that the expression of onco-related miRNAs was closely associated with the development and endoscopic appearance of colorectal tumors.

Analysis of endoscopic features for colorectal sessile serrated adenoma/polyp

Objective To evaluate the endoscopic features of colorectal sessile serrated adenoma/polyp(SSA/P). Methods The data of 109 cases of SSA/P and 218 cases of polyps randomly selected in Xijing Hospital from January 2014 to December 2016 were collected. The endoscopic features of SSA/P and polyps were compared, and the risk factors of occurrence and cancerization of SSA/P were analyzed. Results The mean age of patients in the SSA/P group was older than that of polyps group (P=0.011). The distribution of lesions was no significant difference between the two groups (P=0.092). The gross type of SSA/P was mainly type Ⅰ and Ⅱ, while polyps were more in type Ⅰ (P=0.036). According to the pit pattern of Kudo, type Ⅱ was more in SSA/P, but types Ⅰ and Ⅱ were more in polyps (P=0.004). For capillary pattern comparison, type Ⅱ was more in SSA/P, but type Ⅰ was more in polyps (P≤0.000 1). For surface morphological features comparison, the SSA/P group was more likely to be observed the mucous cap (P=0.002) and blood vessel thickening (P=0. 004). On pathologic diagnosis, the SSA/P group was more susceptible to atypia and carcinogenesis (P=0.001). Higher microvascular morphological classification, being mucous cap, and blood vessel thickening were risk factors of atypia and carcinogenesis of SSA/P. Conclusion There were significant differences between SSA/P and polyps on lesion location, pit pattern, capillary pattern, surface structure characteristics, and risk factors of atypia and carcinogenesis. Key words: Colorectal neoplasms; Adenomatous polyps; Endoscopy

Subtypes of the Type II Pit Pattern Reflect Distinct Molecular Subclasses in the Serrated Neoplastic Pathway.

Colorectal serrated lesions (SLs) are important premalignant lesions whose clinical and biological features are not fully understood. We aimed to establish accurate colonoscopic diagnosis and treatment of SLs through evaluation of associations among the morphological, pathological, and molecular characteristics of SLs. A total of 388 premalignant and 18 malignant colorectal lesions were studied. Using magnifying colonoscopy, microsurface structures were assessed based on Kudo's pit pattern classification system, and the Type II pit pattern was subcategorized into classical Type II, Type II-Open (Type II-O) and Type II-Long (Type II-L). BRAF/KRAS mutations and DNA methylation of CpG island methylator phenotype (CIMP) markers (MINT1, -2, -12, -31, p16, and MLH1) were analyzed through pyrosequencing. Type II-O was tightly associated with sessile serrated adenoma/polyps (SSA/Ps) with BRAF mutation and CIMP-high. Most lesions with simple Type II or Type II-L were hyperplastic polyps, while mixtures of Type II or Type II-L plus more advanced pit patterns (III/IV) were characteristic of traditional serrated adenomas (TSAs). Type II-positive TSAs frequently exhibited BRAF mutation and CIMP-low, while Type II-L-positive TSAs were tightly associated with KRAS mutation and CIMP-low. Analysis of lesions containing both premalignant and cancerous components suggested Type II-L-positive TSAs may develop into KRAS-mutated/CIMP-low/microsatellite stable cancers, while Type II-O-positive SSA/Ps develop into BRAF-mutated/CIMP-high/microsatellite unstable cancers. These results suggest that Type II subtypes reflect distinct molecular subclasses in the serrated neoplasia pathway and that they could be useful hallmarks for identifying SLs at high risk of developing into CRC.

Linked color imaging enhances endoscopic detection of sessile serrated adenoma/polyps.

Background and study aims Although new image-enhanced endoscopy (IEE) technologies such as blue laser imaging (BLI), BLI-bright, and linked color imaging (LCI) have been developed, their utility for the detection of sessile serrated adenoma/polyps (SSA/Ps) is still unclear. This study aimed to evaluate the utility of BLI, BLI-bright, and LCI for SSA/P detection in still image examinations and in a prospective randomized controlled trial (RCT). Patients and methods A group of 6 expert and non-expert endoscopists read 200 endoscopic still images containing SSA/P lesions using white light image (WLI), BLI, BLI-bright, and LCI. Color differences were calculated using the color space method. A prospective RCT of tandem colonoscopy with WLI and LCI was performed. Patients with SSA/P and those with a history of SSA/P that had been endoscopically removed were enrolled and randomly allocated to WLI-LCI or LCI-WLI groups. Additional endoscopic detection rates for SSA/P were compared between the 2 groups. Results LCI showed the highest SSA/P detection rate among the 4 modes for both expert and non-expert endoscopists. The detection rate with LCI for the 6 expert endoscopists (mean 98.3 ± standard deviation 2.0 %) was significantly higher than that with WLI (86.7 ± 6.0 %, P < 0.01). Likewise, the detection rate with LCI for the 6 non-expert endoscopists (92.3 ± 2.9 %) was significantly higher than that with WLI (72.7 ± 11.5 %, P < 0.01). The color difference of SSA/P with LCI was the highest among the 4 modes, and was significantly higher than with WLI (median 15.9, (interquartile range 13.7 – 20.6) vs. 10.2, (7.6 – 14.2); P < 0.0001). In the RCT, a total of 44 patients (WLI-LCI 22 vs. LCI-WLI 22) underwent colonoscopy. The additional detection rate for SSA/P in the second inspection in the WLI-LCI group (21.6 %, 8/37) was significantly higher than in the LCI-WLI group (3.2 %, 1/31; P = 0.02). The small, flat, non-mucus and isochromatic SSA/Ps in the transverse colon were detected more frequently in the second inspection with LCI. Conclusions LCI was the most sensitive mode for SSA/P detection among WLI, BLI, BLI-bright, and LCI in the still image examinations. Our RCT strongly suggests that LCI is superior to conventional WLI for SSA/P detection during colonoscopy. UMIN000017599.

Clinical Effectiveness of Submucosal Injection with Indigo Carmine Mixed Solution for Colon Endoscopic Mucosal Resection.

Submucosal injection with indigo carmine mixed solution can improve the delineation of colorectal neoplasia during endoscopic mucosal resection (EMR). Thus, the aim of this study was to evaluate the efficacy of submucosal injection with indigo carmine mixed solution during EMR of colorectal neoplasia. This was a prospective, randomized, controlled study of a total of 212 neoplastic colon polyps (5-20mm) subjected to EMR in a single tertiary university hospital. The patients were randomized into two groups according to whether or not indigo carmine mixed solution was used, and the complete resection rate (CRR) after EMR was evaluated. A total of 212 neoplastic polyps (normal saline group, 115; indigo carmine group, 97) were successfully removed by EMR. There was no significant difference in the CRR (92.8 vs. 89.6%, p=0.414) or macroscopic delineation (86.0 vs. 93.8%, p=0.118) between the two groups. In a separate analysis of sessile serrated adenomas/polyps (SSAs/Ps), macroscopic delineation was better in the indigo carmine group than the normal saline group (87.5 vs. 53.8%), albeit not significantly (p=0.103). In univariate analyses, the CRR was significantly related to polyp location, polyp morphology, macroscopic delineation, and pathologic findings. In a multiple logistic regression analysis, macroscopic delineation (odds ratio (OR),7.616, p=0.001) and polyp pathology (OR, 8.621; p<0.001) were significantly associated with the CRR. Submucosal injection with indigo carmine mixed solution did not improve the CRR or macroscopic delineation of EMR of colorectal neoplasias.

Adjunctive use of chromoendoscopy may improve the diagnostic performance of narrow-band imaging for small sessile serrated adenoma/polyp.

Endoscopic diagnosis of sessile serrated adenoma/polyp (SSA/P) is challenging because of their subtle appearance. Narrow-band imaging (NBI) is useful for diagnosis, but its utility with concurrent chromoendoscopy (CE), especially to detect small SSA/P, is unproven. This prospective study enrolled 367 consecutive patients who underwent screening colonoscopy with the finding of serrated polyps. Patients were divided into derivation and validation cohorts: Diagnostic criteria using different endoscopic modalities were generated by regression analysis in the derivation cohort and were validated in the validation cohort for sensitivity, specificity, and accuracy. There were 180 patients with 119 SSA/P and 147 hyperplastic polyps (HP) in the derivation cohort and 187 patients with 177 SSA/P and 125 HP in the validation cohort. With white-light endoscopy plus NBI, mucus cap, surface grooves, and expanded crypt were most associated with SSA/P. With white-light endoscopy plus CE, II-O pit pattern, mucus cap, and superficial telangiectasia were most associated with SSA/P. With the combined use of these three modalities, II-O pit pattern, mucus cap, and surface grooves were most associated with SSA/P. For large serrated polyp, NBI in combination with CE had a better accuracy than NBI alone (91% vs 86%, P=0.025) to distinguish SSA/P from HP. CE alone had a better accuracy than NBI alone for distinguishing small SSA/P from small HP (85% vs 72%, P<0.0001). Compared with NBI alone, adjunctive use of CE can improve the diagnostic accuracy for distinguishing SSA/P from HP, especially for small SSA/P.

Clinical, Histologic, and Immunophenotypic Features of Serrated Polyps in Patients With Inflammatory Bowel Disease.

BackgroundColorectal serrated polyps (SP), which include hyperplastic polyps (HP), sessile serrated adenomas/polyps (SSA/P), and traditional serrated adenomas, are not uncommon and have been implicated to play a role in the pathogenesis in a subset of sporadic colorectal carcinomas; however, their significance in patients with prolonged inflammatory bowel disease (IBD) remains unclear.MethodsWe retrospectively studied the clinicopathologic features, BRAF and β-catenin immunohistochemistry staining patterns in 36 SPs from 28 patients with IBD compared with 40 SPs in patients without IBD.ResultsEleven SSA/Ps and 25 HPs from IBD and site-matched controls were included. SSA/Ps in the study group were slightly more commonly seen in males (55% vs. 41%, P = 0.7) and older patients (55.2 vs. 47.8 years, P = 0.2) compared to patients with HP. They were moderately larger (7.13 mm vs. 4.83 mm, P = 0.14) and more likely located on the right (63.6% vs. 32%, P = 0.46). Smaller percentage of SSA/Ps showed BRAF staining compared to controls (55.6% vs. 73.3%, P = 0.41) and HPs showed similar features (52.0% vs. 54.2%, P = 1). β-catenin was negative in all cases. During follow-up, only one patient in the SSA/P group developed carcinoma 42 months after at the same site and two developed adenoma-like low-grade dysplasia but no patients with HPs had such findings.ConclusionsOur findings show that SPs in IBD share similar clinicodemographic and immunophenotypical features with sporadic SPs. However, patients with SSA/Ps may have a slight increase in risk of developing dysplasia compared to patients with HPs in IBD.

Potential Red-Flag Identification of Colorectal Adenomas with Wide-Field Fluorescence Molecular Endoscopy.

Adenoma miss rates in colonoscopy are unacceptably high, especially for sessile serrated adenomas / polyps (SSA/Ps) and in high-risk populations, such as patients with Lynch syndrome. Detection rates may be improved by fluorescence molecular endoscopy (FME), which allows morphological visualization of lesions with high-definition white-light imaging as well as fluorescence-guided identification of lesions with a specific molecular marker. In a clinical proof-of-principal study, we investigated FME for colorectal adenoma detection, using a fluorescently labelled antibody (bevacizumab-800CW) against vascular endothelial growth factor A (VEGFA), which is highly upregulated in colorectal adenomas.Methods: Patients with familial adenomatous polyposis (n = 17), received an intravenous injection with 4.5, 10 or 25 mg of bevacizumab-800CW. Three days later, they received NIR-FME.Results: VEGFA-targeted NIR-FME detected colorectal adenomas at all doses. Best results were achieved in the highest (25 mg) cohort, which even detected small adenomas (<3 mm). Spectroscopy analyses of freshly excised specimen demonstrated the highest adenoma-to-normal ratio of 1.84 for the 25 mg cohort, with a calculated median tracer concentration in adenomas of 6.43 nmol/mL. Ex vivo signal analyses demonstrated NIR fluorescence within the dysplastic areas of the adenomas.Conclusion: These results suggest that NIR-FME is clinically feasible as a real-time, red-flag technique for detection of colorectal adenomas.

Epigenetic silencing of SMOC1 in traditional serrated adenoma and colorectal cancer.

Colorectal sessile serrated adenoma/polyps (SSA/Ps) are well-known precursors of colorectal cancer (CRC) characterized by BRAF mutation and microsatellite instability. By contrast, the molecular characteristics of traditional serrated adenoma (TSAs) are not fully understood. We analyzed genome-wide DNA methylation in TSAs having both protruding and flat components. We identified 11 genes, including SMOC1, methylation of which progressively increased during the development of TSAs. SMOC1 was prevalently methylated in TSAs, but was rarely methylated in SSA/Ps (p < 0.001). RT-PCR and immunohistochemistry revealed that SMOC1 was expressed in normal colon and SSA/Ps, but its expression was decreased in TSAs. Ectopic expression of SMOC1 suppressed proliferation, colony formation and in vivo tumor formation by CRC cells. Analysis of colorectal lesions (n = 847) revealed that SMOC1 is frequently methylated in TSAs, high-grade adenomas and CRCs. Among these, SMOC1 methylation was strongly associated with KRAS mutation and CpG island methylator phenotype (CIMP)-low. These results demonstrate that epigenetic silencing of SMOC1 is associated with TSA development but is rarely observed in SSA/Ps. SMOC1 expression could thus be a diagnostic marker of serrated lesions, and SMOC1 methylation could play a role in neoplastic pathways in TSAs and conventional adenomas.

Increased Risk for Colon Polyps in Patients with Reflux Disease.

Previous studies have found an increased risk for colonic neoplasm in patients with Barrett's esophagus. It is unknown whether such risk applies similarly to other types of gastroesophageal reflux disease (GERD). To test whether GERD represents a risk factor for the occurrence of colon polyps. The Miraca Life Sciences Database is a large national electronic repository of histopathologic records of patients distributed throughout the entire USA. A case-control study evaluated whether presence of (1) Barrett's metaplasia, (2) erosive esophagitis on endoscopy or histologic signs of reflux esophagitis, (3) clinical diagnosis of GERD, (4) any type of GERD affected the occurrence hyperplastic polyps (HP), sessile serrated adenomas/polyps (SSA/P), or tubular adenomas (TA) among 228,506 subjects undergoing bidirectional endoscopy. Multivariate logistic regression analyses were used to calculate odds ratios and their 95% confidence intervals for the risk of HP, TA or SSA/P associated with various types of GERD and adjusted for age, sex, and presence of H. pylori. The analysis revealed positive associations between GERD and all types of colon polyps. These associations applied similarly to HP (1.47, 1.44-1.50), TA (1.30, 1.27-1.32), and SSA/P (1.52, 1.46-1.58). They also applied to different forms of GERD, showing a trend toward stronger associations, that is higher odds ratios, with Barrett's metaplasia or erosive esophagitis than clinical diagnosis of GERD. All types of GERD represent a risk factor for the occurrence of different colon polyps, such as HP, TA, or SSA/P.