Sessile Serrated Adenomas/polyps Research Articles

Clinical and Biological Features of Interval Colorectal Cancer.

Interval colorectal cancer (I-CRC) is defined as a CRC diagnosed within 60 months after a negative colonoscopy, taking into account that 5 years is the “mean sojourn time.” It is important to prevent the development of interval cancer. The development of interval colon cancer is associated with female sex, old age, family history of CRC, comorbidities, diverticulosis, and the skill of the endoscopist. During carcinogenesis, sessile serrated adenomas/polyps (SSA/Ps) share many genomic and colonic site characteristics with I-CRCs. The clinical and biological features of I-CRC should be elucidated to prevent the development of interval colon cancer.

Hyper-Methylated Loci Persisting from Sessile Serrated Polyps to Serrated Cancers.

Although serrated polyps were historically considered to pose little risk, it is now understood that progression down the serrated pathway could account for as many as 15%–35% of colorectal cancers. The sessile serrated adenoma/polyp (SSA/P) is the most prevalent pre-invasive serrated lesion. Our objective was to identify the CpG loci that are persistently hyper-methylated during serrated carcinogenesis, from the early SSA/P lesion through the later cancer phases of neoplasia development. We queried the loci hyper-methylated in serrated cancers within our right-sided SSA/Ps from the New Hampshire Colonoscopy Registry, using the Illumina Infinium Human Methylation 450 k panel to comprehensively assess the DNA methylation status. We identified CpG loci and regions consistently hyper-methylated throughout the serrated carcinogenesis spectrum, in both our SSA/P specimens and in serrated cancers. Hyper-methylated CpG loci included the known the tumor suppressor gene RET (p = 5.72 × 10−10), as well as loci in differentially methylated regions for GSG1L, MIR4493, NTNG1, MCIDAS, ZNF568, and RERG. The hyper-methylated loci that we identified help characterize the biology of SSA/P development, and could be useful as therapeutic targets, or for future identification of patients who may benefit from shorter surveillance intervals.

Distinctive crypt shape in a sessile serrated adenoma/polyp: Distribution of Ki67-, p16INK4a-, WNT5A-positive cells and intraepithelial lymphocytes.

Serrated lesions in the colorectum are currently predominantly classified as hyperplastic polyps (HPs), sessile serrated adenomas/polyps (SSA/Ps), and traditional serrated adenomas (TSAs) according to their morphology. However, the histological morphology and the molecular changes in the serrated lesions are still unclear. We performed immunohistochemistry for Ki67, p16INK4a, and WNT5A in human HPs (n=22), SSA/Ps (n=41), and TSAs (n=19). The distribution of Ki67 and p16INK4a positive cells in TSAs was different from that in HPs and SSA/Ps. Co-expression of Ki67 and P16INK4a was infrequent in HPs and SSA/Ps; p16INK4a-positive cells were found in the crypt cleft and stromal WNT5A-positive stromal cells were localized near the cleft in SSA/Ps, while intraepithelial lymphocytes (IELs) in SSA/Ps were more abundant than HPs. In conclusion, our study provides evidence that HPs branch because of the increase in and patchy distribution of senescent and proliferative cells, with increased and misdistributed stromal and inflammatory cells, which might contribute to creation of L- and/or T-shaped crypts, which are of distinctive shapes in SSA/Ps. Our findings may facilitate better understanding and therapy in the serrated lesions.

Clinicopathological characteristics of serrated polyps as precursors to colorectal cancer: Current status and management.

Serrated polyps have long been thought to lack malignant potential in the human colorectum. However, identification of the serrated pathway to colorectal cancer based on molecular biology has improved our understanding of the pathogenesis of colorectal cancers. Accordingly, serrated polyps such as traditional serrated adenoma and sessile serrated adenoma/polyps (SSA/P) are now considered to be precursor lesions of the serrated pathway. Recently, serrated polyps were classified into three subtypes, consisting of hyperplastic polyp, SSA/P, and traditional serrated adenoma, according to the World Health Organization classification. It has been suggested that SSA/P in the proximal colon are a precursor lesion of pathogenesis of colorectal cancer and are characterized by BRAF mutation and a CpG island methylator phenotype with or without microsatellite instability. However, SSA/P is more challenging to detect by colonoscopy and is likely to account for some interval cancers, particularly in the proximal colon because it presents flat or sessile, isochroous appearance, and occasionally has a mucous cap. Furthermore, the possibility has been raised that pathologists misclassify SSA/P as hyperplastic polyp. It is important for gastroenterologists to recognize the endoscopic features of serrated polyps to facilitate their detection and removal and also to establish postpolypectomy surveillance guidelines. In this review, we discuss the recent classification of serrated polyps; the molecular characteristics of the serrated pathway; appropriate diagnostic methods using endoscopy, including a new image-enhanced endoscopic technique; and management of these lesions.

Providing data for serrated polyp detection rate benchmarks: an analysis of the New Hampshire Colonoscopy Registry

Similar to achieving adenoma detection rate (ADR) benchmarks to prevent colorectal cancer (CRC), achieving adequate serrated polyp detection rates (SDRs) may be essential to the prevention of CRC associated with the serrated pathway. Previous studies have been based on data from high-volume endoscopists at single academic centers. Based on a hypothesis that ADR is correlated with SDR, we stratified a large, diverse group of endoscopists (n= 77 practicing at 28 centers) into high performers and low performers, based on ADR, to provide data for corresponding target SDR benchmarks. By using colonoscopies in adults aged≥50 years (4/09-12/14), we stratified endoscopists by high and low ADRs (<15%, 15%-<25%, 25%-<35%,≥35%) to determine corresponding SDRs by using 2 SDR measures, for screening and surveillance colonoscopies separately: (1) Clinically significant SDR (CSSDR), meaning colonoscopies with any sessile serrated adenoma/polyp (SSA/P), traditional serrated adenoma (TSA), or hyperplastic polyp (HP) >1 cm anywhere in the colon or HP >5mm in the proximal colon only divided by the total number of screening and surveillance colonoscopies, respectively. (2) Proximal SDR (PSDR) meaning colonoscopies with any serrated polyp (SSA/P, HP, TSA) of any size proximal to the sigmoid colon divided by the total number of screening and surveillance colonoscopies, respectively. A total of 45,996 (29,960 screening) colonoscopies by 77 endoscopists (28 facilities) were included. Moderately strong positive correlation coefficients were observed for screening ADR/CSSDR (P= .69) and ADR/PSDR (P= .79) and a strong positive correlation (P= .82) for CSSDR/PSDR (P< .0001 for all) was observed. For ADR≥25%, endoscopists' median (interquartile range) screening CSSDR was 6.8% (4.3%-8.6%) and PSDR was 10.8% (8.6%-16.1%). Derived from ADR, the primary colonoscopy quality indicator, our results suggest potential SDR benchmarks (CSSDR= 7% and PSDR= 11%) that may guide adequate serrated polyp detection. Because CSSDR and PSDR are strongly correlated, endoscopists could use the simpler PSDR calculation to assess quality.

Prevalence and Anatomic Distribution of Serrated and Adenomatous Lesions in Patients with Inflammatory Bowel Disease.

Background. Sessile serrated adenomas/polyps (SSA/Ps) and traditional serrated adenomas (TSAs) have not been well characterized in patients with inflammatory bowel disease (IBD). This study assesses the prevalence and anatomic distribution of SSA/Ps, TSAs, and conventional adenomas/dysplasia (Ad/Ds) in IBD patients. Methods. IBD patients with serrated, adenomatous, or hyperplastic lesions between 2005 and 2009 were identified in the regional tertiary-care hospital database. Clinicopathological information was reviewed and the histology of biopsies was reevaluated. Results. Ninety-six Ad/Ds, 25 SSA/Ps, and 4 TSAs were identified in 83 patients. Compared to Ad/Ds, serrated lesions were more prevalent in females (p = 0.046). The prevalence of Ad/Ds was 4.95%, SSA/Ps was 1.39%, and TSAs was 0.31%. No relationship was identified between lesion type and IBD type. Comparing all IBD patients, the distribution of lesion types was significantly different (p = 0.02) with Ad/Ds more common distally, SSA/Ps more common proximally, and TSAs evenly distributed. Among Crohn's disease (CD) patients, a similar distribution difference was noted (p < 0.001). However, ulcerative colitis (UC) patients had a uniform distribution of lesion types (p = 0.320). Conclusions. IBD patients have a lower prevalence of premalignant lesions compared to the general population, and the anatomic distribution of lesions differed between CD and UC patients. These findings may indicate an interaction between lesion and IBD pathogenesis with potential clinical implications.

MicroRNA Signatures of Colonic Polyps on Screening and Histology.

Colorectal cancer and adenoma adjacent to cancer exhibit distinct microRNA (miRNA) alterations in an apparent mucosa-to-adenocarcinoma sequence. The pattern of microRNAs in screen-detected polyps in relation to histologic features and cancer risk has not been investigated. miRNA expression analysis was performed on normal mucosa (NM), hyperplastic polyps (HP), tubular adenomas (TA), tubulovillous adenomas or high-grade dysplasia (TVHG), and serrated polyps [sessile serrated adenoma/polyps (SSA/P) and traditional serrated adenomas (TSA)] in biopsy specimens from 109 patients undergoing screening/surveillance colonoscopy. Generalized linear models were used to identify differentially expressed miRNAs by histologic type and logistic regression to identify miRNA predictors of histopathology. False discovery rate (FDR) was used to control for multiple comparisons. We identified 99 miRNAs differing in at least one of five histopathologic groups (FDR ≤0.05). In a comparison of HPNM versus TVHG, the top most upregulated and downregulated miRNAs in HPNM included miR-145, -143, -107, -194, and -26a (upregulated), and miR-663, -1268, -320b, -1275, and -320b (downregulated; FDR P < 0.05). miR-145 and -619 showed high accuracy to discriminate low- from high-risk polyps without serrated histology (TVHG vs. HPNM + TA; CI, 95.6%), whereas miR-124, -143, and -30a showed high accuracy of separating high-risk polyps (TVHG + TSA) from low-risk polyps (HPNM + TA + SSA/P; CI, 96.0%). For TSAs, miR-125b and -199a were uniquely downregulated relative to HPNMs, and miR-335, -222, and -214 discriminated between non-serrated and serrated histology. Our data support the presence of colorectal cancer-associated miRNA alterations in screen-detected adenomas that may be useful for risk stratification for surveillance interval planning. Cancer Prev Res; 9(12); 942-9. ©2016 AACR.

Serrated polyps and their association with synchronous advanced colorectal neoplasia

Abstract Introduction Large serrated polyps (SP), proximal SP, SP with dysplasia and the presence of multiple sessile serrated adenomas/polyps (SSA/P), which we refer to as SP with increased risk of metachronous lesions (SPIRML), have been associated with an increased risk of advanced colon lesions on follow-up. It is unclear, however, whether SPIRML are also associated with an increased risk of synchronous advanced colorectal neoplasia (ACN). Aim The aim of this study was to estimate the prevalence of SPIRML and to evaluate the association between SPIRML and synchronous ACN. Methods A cross-sectional population-based study in all patients (1538) with histological diagnosis of SP obtained from colonoscopies, sigmoidoscopies and colonic surgery performed in Navarra Health Service hospitals (Spain) in 2011. Demographic parameters and synchronous colonic lesions (adenomas, advanced adenomas [AA] and ACN) were analysed. Results One fourth of the sample (384 patients) presented SPIRML. These were older patients, with a slight predominance of women, and with no differences in body mass index (BMI) compared to patients without SPIRML. In the univariate analysis, patients with SPIRML showed an increased risk of adenoma, AA and ACN. In the multivariate analysis, the SPIRML group had a higher risk of synchronous AA and ACN (odds ratio [OR]: 2.38 [1.77–3.21] and OR: 2.29 [1.72–3.05], respectively); in the case of ACN, this risk was statistically significant in both locations (proximal or distal), with OR slightly higher for the proximal location. Different subtypes of SPIRML had a higher risk of AA and synchronous NA. Conclusion SPIRML were common in patients with SP, and their presence was associated with an increased risk of synchronous ACN.

Detection Rate, Distribution, Clinical and Pathological Features of Colorectal Serrated Polyps

Background:Colorectal serrated polyp is considered as histologically heterogeneous lesions with malignant potential in western countries. However, few Asian studies have investigated the comprehensive clinical features of serrated polyps in symptomatic populations. The aim of the study was to evaluate the features of colorectal serrated polyps in a Chinese symptomatic population.Methods:Data from all consecutive symptomatic patients were documented from a large colonoscopy database and were analyzed. Chi-square test or Fisher's exact test and logistic regression analysis were used for the data processing.Results:A total of 9191 (31.7%) patients were detected with at least one colorectal polyp. The prevalence of serrated polyps was 0.53% (153/28,981). The proportions of hyperplastic polyp (HP), sessile serrated adenoma/polyp (SSA/P), and traditional serrated adenoma (TSA) of all serrated polyps were 41.2%, 7.2%, and 51.6%, respectively, which showed a lower proportion of HP and SSA/P and a higher proportion of TSA. Serrated polyps appeared more in males and elder patients while there was no significant difference in the subtype distribution in gender and age. The proportions of large and proximal serrated polyps were 13.7% (21/153) and 46.4% (71/153), respectively. In total, 98.9% (89/90) serrated adenomas were found with dysplasia. Moreover, 14 patients with serrated polyps were found with synchronous advanced colorectal neoplasia, and large serrated polyps (LSPs) (odds ratio: 3.446, 95% confidence interval: 1.010–11.750, P < 0.05), especially large HPs, might have an association with synchronous advanced neoplasia (AN).Conclusions:The overall detection rate of colorectal serrated polyps in Chinese symptomatic patient population was low, and distribution pattern of three subtypes is different from previous reports. Moreover, LSPs, especially large HPs, might be associated with an increased risk of synchronous AN.

Prevalence of sessile serrated adenoma/polyp in hyperplastic-appearing diminutive rectosigmoid polyps

The American Society for Gastrointestinal Endoscopy recommends that distal colon hyperplastic lesions can be left in place without resection if adenomatous histology can be excluded with >90% negative predictive value. However, some lesions could be sessile serrated adenomas/polyps (SSA/Ps), which is also precancerous. The aim of this study was to describe the prevalence of SSA/Ps in hyperplastic-appearing diminutive rectosigmoid polyps. We prospectively placed 513 consecutive diminutive rectosigmoid polyps that appeared hyperplastic to an expert endoscopist in individual bottles for pathologic. Each polyp was examined by 3 expert GI pathologists. The prevalence of SSA/P in the study polyps ranged from .6% to 2.1%. The lowest negative predictive value found by the endoscopist for the combination of adenomas plus SSA/Ps was 96.7%. The prevalence of SSA/Ps in diminutive rectosigmoid hyperplastic-appearing polyps is very low. These results support the safety and feasibility of a "do not resect" policy for diminutive hyperplastic-appearing rectosigmoid polyps.

Gastric Proteins MUC5AC and TFF1 as Potential Diagnostic Markers of Colonic Sessile Serrated Adenomas/Polyps.

Objectives: A subset of colon cancers originates from sessile serrated adenomas/polyps (SSA/Ps). Our goal was to identify markers for SSA/Ps that could aid in distinguishing them from hyperplastic polyps (HPs). Methods: We performed immunostaining for gastric proteins MUC5AC and TFF1 in formalin-fixed, paraffin-embedded (FFPE) samples of HPs (n = 47), SSA/Ps (n = 37), and normal colon (n = 30). Results: Control mucosa expressed only trace amounts of MUC5AC and TFF1. HPs exhibited an 11.3- and 11.4-fold increase in MUC5AC and TFF1 expression confined to the upper segments of the crypts near the luminal surface of the polyps. SSA/Ps displayed on average 1.6-fold (MUC5AC, P < .008) and 1.4-fold (TFF1, P < .03) higher signal intensity for these markers than HPs, with a dramatic coexpression of MUC5AC and TFF1 typically occupying the entire length of the crypt. Immunoperoxidase results were similar to immunofluorescence staining for both MUC5AC and TFF1. Conclusions: Our results suggest that the analysis of expression of MUC5AC and TFF1 may be useful for differentiating SSA/Ps from HPs. We also suggest the possibility that crypt morphology may be at least partly due to overproduction of highly viscous gastric mucins and that these proteins may play a role in the serrated pathway to colon carcinogenesis.

Clinicopathological Features of Sessile Serrated Polyp/Adenoma: Improving Serration Detection to Adjust Interval Follow-up Colonoscopy

Introduction: The majority of colorectal cancers (CRCs) develop through the adenoma-carcinoma sequence, while 15-20% develop via the serrated neoplasia pathway. Sessile Serrated Adenoma/Polyp (SSA/P) is more difficult to detect during colonoscopy, leading to a disproportionate contribution to interval carcinoma (CRCs diagnosed within 6-36 months of colonoscopy). These polyps lead to cancer faster than conventional adenomas. In order to better define patients at risk for these lesions, we performed a retrospective study to evaluate clinicopathological features of patients diagnosed with SSA/P. Methods: We reviewed the pathology reports of patients at Howard University Hospital from 2010-2015. We identified 5,900 patients with polyps, of whom 312 (5.3%) were diagnosed with SSA/P. We presented the frequency of gender, age groups, anatomic location, clinical symptoms and reason for colonoscopy in SSA/P patients. Results: We identified 312 cases with SSA/P. The incidence of SSA/P over that 5-year period was 5.3%. 198/312 (63.4%) patients had 2 or more polyps. 54.5% of the patients diagnosed with SSA/P were females. 70.5% of patients were 50-64 years of age and 18% were older than 65. SSA/P lesions' locations were as follows: rectal -32.1%; rectosigmoid -18.6%; sigmoid - 16.8%; Ascending Colon - 13.2 %; Descending Colon - 7.1%. Reasons for colonoscopy were as follows: Screening - 43.6 %; GI bleeding - 15.1%; Abdominal Pain - 13.1%; Change in Bowel Habits - 10.2%. Conclusion: Our results show that there is a slightly increased predominance of SSA/P occurrence in females. The most common age range for an SSA/P diagnosis is from 50 to 64 years. This age range is younger in comparison to patients with conventional adenomas. We also found that SSA/P was predominantly distal (rectal, rectosigmoid, sigmoid) whereas previous literature reports a proximal location for SSA/P. Most patients in our study were diagnosed in screening colonoscopies; however, other patients presented with symptoms such as GI bleeding, abdominal pain, or change in bowel habits.Figure 1Figure 2Figure 3

Small Non-coding RNA Transcriptome in Sessile Serrated Colon Polyps

Introduction: Serrated colon polyps are found in 15-20% of patients undergoing screening colonoscopy and may account for up to a third of all colorectal cancers (CRC). Sessile serrated adenomas/polyps (SSA/Ps) have a high risk for development into CRC. However, the molecular biology of serrated pathway to cancer is poorly understood. We describe multiple unique non-coding RNA differentially expressed in SSA/Ps and provide an insight into the potential pathways to serrated carcinoma. Methods: Small RNA sequencing was performed on 66 colon RNA samples including 13 SSA/P's, 9 Hyperplastic polyps, 7 Adenomas, 22 uninvolved colon and 15 control colon. The small (< 200 bases) RNA transcriptome of SSA/Ps and other polyp types were characterized to identify unique non-coding RNA expression in SSA/Ps. Gene targets for each of our differentially expressed microRNAs (miRNAs) were identified using multiple miRNA databases. Results: We found 104 small RNAs including 53 miRNA, 46 small nucleolar RNA and 5 nuclear RNA differentially expressed (Fold change >1.5, False discovery rate MIR31) was most differentially expressed (>6 fold) followed by MIR135B expression (>4-fold) in SSA/Ps. MIR378A was downregulated by twofold in SSA/Ps. We identified 14 gene targets for MIR378A that were statistically overexpressed in miRNA sequencing data, four of which are involved in insulin growth factor signaling. Conclusion: We describe a comprehensive analysis of the small non-coding RNA transcriptome in SSA/Ps and HPs. Increased expression of MIR31 has beendescribed in SSA/Ps and our data is consistent with recent studies. MIR135B overexpression and its role in the APC/Wnt pathway has been described in CRC and our study suggests disruption of Wnt signaling possibly playing a role in the serrated pathway. MIR378A is a tumor suppressor gene and we present the first evidence of decreased expression of MIR378A in SSA/Ps. 4 of the 14 MIR378A gene targets identified in our study are important in insulin growth factor signaling pathway which may be contributing to serrated cancer development. Our data provides insights into small RNA expression unique to SSA/Ps and potential oncological pathways which may help understand the molecular biology of progression of SSA/Ps into CRC.

Mucins and associated O-glycans based immunoprofile for stratification of colorectal polyps: clinical implication for improved colon surveillance.

Sessile serrated adenoma/polyps (SSA/P) are premalignant lesions of colorectal cancer that are difficult to distinguish histologically from hyperplastic polyps (HP) of minimal to no malignant potential. Specific markers for differentiating SSA/P from HP can aid clinicians for optimizing colon surveillance intervals. The present study investigates the potential of mucins and associated O-glycans to distinguish SSA/P from HP. Expression of colonic mucins (MUC1, MUC4, MUC17, MUC2, and MUC5AC) and O-glycans [Sialyl LewisA (CA19-9) and Tn/Sialyl-Tn on MUC1] were analyzed in HP (n=33), SSA/P (n=39), and tubular adenoma (TA) (n=36) samples by immunohistochemistry. A significantly reduced expression of MUC4 (p=0.0066), elevated expression of MUC17 (p=0.0002), and MUC5AC (p<0.0001) was observed in SSA/P cases in comparison to HP cases. Interestingly, significantly higher number of SSA/P cases (p<0.0001) exhibited MUC5AC expression in the goblet cells as well as filled the crypt lumen compared to only goblet cells in majority of the HP cases. Improved diagnostic potential was revealed by multivariate logistic regression analysis where combinatorial panel of MUC5AC/MUC17 discriminated SSA/P from HP (SN/SP=85/82%). Finally, the decision tree model based marker panel (CA19-9/MUC17/MUC5AC) predicted HP, SSA/P and TA with SN/SP of 58%/95%, 79%/90% and 97%/83%, respectively. Overall, the mucin and associated O-glycan based panel defined in the present study could aid in discriminating SSA/P from HP to devise better colon surveillance strategies.

Distinct endoscopic characteristics of sessile serrated adenoma/polyp with and without dysplasia/carcinoma

Sessile serrated adenoma/polyp (SSA/P) is a colorectal polyp that has malignant potential. However, the dysplastic components within an SSA/P can be difficult to detect. This study aimed to clarify the endoscopic characteristics of SSA/P with advanced histology. We examined 462 endoscopically or surgically resected lesions that were pathologically diagnosed as SSA/P, including 414 without and 41 with cytologic dysplasia, and 7 with invasive carcinoma. We retrospectively studied the clinicopathologic and endoscopic characteristics and performed pit pattern analysis. A stepwise increase in the size of the SSA/P series was identified along with their dysplastic progression, although 19 of 48 (39.6%) SSA/Ps with dysplasia/carcinoma were≤10mm in size. Most lesions were covered with a mucus cap. Macroscopically, (semi)pedunculated morphology, double elevation, central depression, and reddishness were found more frequently in SSA/P with cytologic dysplasia and invasive carcinoma ([semi]pedunculated morphology, 17.1%/28.6%; double elevation, 63.4%/57.1%; central depression, 9.8%/28.6%; reddishness, 39.0%/85.7%) than in those without dysplasia (4.6%, 4.6%, 3.9%, and 3.4%, respectively). Furthermore, the presence of at least 1 of these 4 markers had high sensitivity (91.7%) for identifying the dysplasia/carcinoma within a SSA/P, with a specificity of 85.3%. In the pit pattern analysis, all SSA/Ps without dysplasia exhibited type II pit pattern only, whereas 94.4% of SSA/Ps with dysplasia/carcinoma showed type II in addition to type IIIL, IV, VI, or VN pit patterns. In an SSA/P series, endoscopic characteristics, including (semi)pedunculated morphology, double elevation, central depression, and reddishness, in addition to the use of magnifying endoscopy, may be useful to accurately diagnose advanced histology within an SSA/P.

Confocal laser endomicroscopy features of sessile serrated adenomas/polyps.

Sessile serrated adenomas/polyps (SSA/Ps) are difficult to differentiate from non-neoplastic tissue on white-light endoscopy. Confocal laser endomicroscopy (CLE) provides subcellular imaging and real-time "optical biopsy". The aim of this study was to prospectively describe CLE features of SSA/Ps. Consecutive patients with SSA/Ps were prospectively evaluated with probe-based CLE imaging. CLE images and polyp histology were independently reviewed by three endoscopists and an expert gastrointestinal (GI) pathologist. Distinguishing CLE features of SSA/Ps were identified in conjunction with pathologic correlation. In total, 260 CLE images were generated from nine SSA/Ps evaluated in seven patients. Four consensus CLE features of SSA/P were identified: (1) a mucus cap with a bright, cloud-like appearance; (2) thin, branching crypts; (3) increased number of goblet cells and microvesicular mucin-containing cells; and (4) architectural disarray, with dystrophic goblet cells and lack of regular circular crypts. This is a novel description of characteristic CLE features of SSA/Ps. The four features we identified are easy to detect and may allow for CLE to serve as a diagnostic modality.

Diagnosis of sessile serrated adenomas/polyps with image-enhanced endoscopy: a systematic review and meta-analysis.

Distinguishing sessile serrated adenomas/polyps (SSA/Ps) from non-neoplastic tissue may be challenging when white-light endoscopy (WLE) is used. Image-enhanced endoscopy (IEE) has shown accuracy in differentiating adenomas from hyperplastic polyps. The aim of this systematic review and meta-analysis was to evaluate the utility of IEE in diagnosis of SSA/Ps. Studies were eligible if: they included patients undergoing colonoscopy with an endoscopy-based image-enhancement modality; endoscopic diagnoses, including SSA/P, were based on the appearance of polyps at IEE; and the corresponding histologic diagnoses of polyps were provided. The primary outcome was sensitivity of IEE for SSA/Ps differentiated from non-neoplastic lesions (primary convention) and differentiated from all non-SSA/P lesions, including adenomas (secondary convention). 13 studies met inclusion criteria. Sensitivity ranged from 38 % to 100 % but sensitivity ≥ 90 % was seen in 4 of 10 narrow band imaging (NBI) or magnification-NBI studies. Pooled sensitivities for discriminating SSA/Ps from non-neoplastic lesions were 80 % for magnification-NBI, 60 % for NBI, 49 % for autofluorescence, and 47 % for flexible spectral imaging color enhancement. In head-to-head comparisons with WLE, NBI (89 % vs. 75 %) and magnification-NBI (78 % vs. 63 %) demonstrated significantly greater sensitivity, while autofluorescence imaging (56 % vs. 66 %), flexible spectral imaging color enhancement (100 % vs. 100 %), and high-resolution endomicroscopy (88 % vs. 100 %) did not. IEE currently cannot be recommended as a diagnostic tool for SSA/P. While NBI studies showed promise, more IEE studies employing validated SSA/P criteria in well-defined polyp populations are needed. IEE studies assessing SSA/P detection rates at colonoscopy are also needed.

Clinicopathologic Features of Inverted Serrated Lesions of the Large Bowel

Background/Aims: Serrated lesions (SLs) of the large bowel occasionally manifest as inverted growths with endophytic expansion within the muscularis mucosa. The aims of this investigation were to investigate the incidence of inverted SLs (ISLs) among SLs and to describe the clinicopathologic features. Methods: We reviewed the colonoscopy records from 2006 to 2014 at our institution and identified cases of endoscopically or surgically resected SLs, including hyperplastic polyps (HPs), sessile serrated adenomas/polyps (SSA/Ps) and traditional serrated adenomas (TSAs). The incidence of ISLs among the SLs and their colonoscopic findings were investigated retrospectively. Results: There were 35 HPs in 30 patients, 80 SSA/Ps in 65 patients and 70 TSAs in 65 patients. The incidence of ISLs was significantly higher among SSA/Ps (8.8%) and HPs (5.7%) than among TSAs (0%; p = 0.04). A predominant right-sided location, a flat-elevated configuration with a central depression and round-open pit pattern or expanded crypt openings were characteristic of ISLs of the SSA/P type. Conclusions: Right-sided flat lesions with a central depression and round or expanded crypts are indicative of ISLs of the SSA/P type.

Su1699 An Investigation of Diagnostic Endoscopy of Sessile Serrated Adenoma / Polyp (SSA/P): How to Skillfully Perform Diagnostic Endoscopy

Su1699 An Investigation of Diagnostic Endoscopy of Sessile Serrated Adenoma / Polyp (SSA/P): How to Skillfully Perform Diagnostic Endoscopy

Role of Fusobacteria in the serrated pathway of colorectal carcinogenesis.

Fusobacteria are associated with colorectal cancer (CRC) and are amplified during colorectal carcinogenesis. Compared to the adenoma-carcinoma sequence of carcinogenesis, serrated neoplasm has distinct clinical features and a different molecular background. We aimed to compare the gut microbiome between tubular adenoma (TA) and sessile serrated adenoma/polyp (SSA/P). Patients with TA, SSA/P, or CRC were recruited. Three pieces of colorectal mucosal tissue were obtained from each patient by endoscopic biopsy. 16S rRNA gene pyrosequencing and phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) were performed. Among 26 enrolled patients, 8, 10, and 8 had TA, SSA/P, and CRC, respectively. The relative abundance of Fusobacteria did not differ significantly between the TA and SSA/P groups (4.3% and 1.9%, P = 0.739) but was higher in the CRC group (33.8%) than in the TA or SSA/P group, respectively (TA vs. CRC, P = 0.002, false discovery rate [FDR] = 0.023; SSA/P vs. CRC, P < 0.001, FDR = 0.001). PICRUSt revealed that most functions in the TA metagenome were similar to those in the SSA/P metagenome. The gut microbiome, including relative abundance of Fusobacteria, did not differ between TA and SSA/P, suggesting that Fusobacteria may contribute to both the serrated pathway and the adenoma-carcinoma sequence.