Sessile Serrated Adenomas Research Articles

Efficacy of cold piecemeal EMR of medium to large adenomas compared with sessile serrated lesions

There is growing evidence for the role of cold piecemeal endoscopic mucosal resection (C-EMR) in the treatment of colorectal lesions ≥10mm. However, it is unclear if it is equally efficacious for all histologic subtypes and sizes. This retrospective study compares the efficacy and safety of C-EMR in the resection of medium (10-19mm) and large (≥20mm) serrated and adenomatous lesions. A retrospective analysis was performed of Paris IIa colonic lesions resected utilising a C-EMR technique over a 3.5 year period at our center. C-EMR was performed for 242 lesions in 151 patients. Lesion size ranged between 10mm to 50mm, with median size of 20mm. Ninety-five polyps were adenomatous, with 147 sessile serrated lesions (SSLs). At six month surveillance colonoscopy, the combined recurrence rate was 6.2%. Adenomas ≥20mm demonstrated a higher rate of recurrence (16.1%) compared to large SSLs (4.1%), medium adenomas (3.0%), and medium SSLs (1.4%). There were no adverse events reported following C-EMR. C-EMR seems to be less effective for the resection of large adenomas when compared to medium adenomas or large SSLs. C-EMR is equally safe for all lesion size and histology.

Colonoscopy quality measures and adherence to follow-up guidelines among endoscopists participating in a U.S. endoscopy registry

Colonoscopy screening can substantially reduce colorectal cancer incidence and mortality. Colonoscopies may achieve maximum benefit when they are performed with high quality and accompanied by follow-up recommendations that adhere to clinical guidelines. This study aimed to determine to what extent endoscopists met targets for colonoscopy quality from 2016 through 2019 (the most recent years prior to the COVID-19 pandemic). We examined measures of colonoscopy quality and recommended follow-up intervals in the GI Quality Improvement Consortium, a large nationwide endoscopy registry. The analysis included over 2.5 million outpatient screening colonoscopies in average risk adults aged 50-75 years. At least 90% of endoscopists met performance targets for adequate bowel preparation, cecal intubation rate, and adenoma detection rate. However, nonadherence to guidelines for follow-up intervals was common. For patients with no colonoscopy findings, 12.0% received a follow-up interval recommendation of ≤5 years instead of the guideline-recommended 10 years. For patients with 1-2 small tubular adenomas, 13.5% received a follow-up interval recommendation of ≤3 years instead of the guideline-recommended 5-10 years. For patients with small sessile serrated polyps, 30.7% received a follow-up interval recommendation of ≤3 years instead of the guideline-recommended 5 years. Some patients with higher risk findings received a follow-up interval recommendation of ≥5 years instead of the guideline-recommended 3 years, including 18.2% of patients with advanced serrated lesions. Additional attention may be needed to achieve more consistent adherence to guidelines for colonoscopy follow-up recommendations.

Different modifiable risk factors for the development of non-advanced adenoma, advanced adenomatous lesion, and sessile serrated lesions, on screening colonoscopy

The development of premalignant colorectal polyps is significantly influenced by various lifestyle and modifiable risk factors. In our study, we used a large cohort of 9025 patients, who underwent screening colonoscopies at a university hospital, to assess the risk factors associated with the development of three different colorectal cancer precursor lesions: non-advanced adenomas (NAs), advanced adenomatous lesions (ADLs), and sessile serrated lesions (SSLs). Among the participants, 3641 had NAs, 836 had ADLs, and 533 had SSLs. We identified obesity, current smoking, and appendicular skeletal muscle mass as modifiable lifestyle risk factors that increase the development of NAs and ADLs (all P < 0.05). Furthermore, we found a positive correlation between the degree of obesity and an increased risk of developing NAs and ADLs (all P for trend < 0.001), while non-smoking was associated with a decreased risk (P for trend < 0.001 and 0.003, respectively). Smoking was the only modifiable risk factor for developing SSLs (adjusted odds ratio [aOR] 1.58; 95% confidence interval [CI] 1.20–2.07), and the risk was even higher in patients with metabolic syndrome (aOR 1.71; 95% CI 1.05–2.77). Addressing modifiable lifestyle factors such as smoking and obesity could play an important role in reducing the risk of both non-advanced and advanced adenomatous lesions. Smoking cessation is especially important as it is a significant modifiable risk factor for sessile serrated lesions.

Current Trends in the Management of a Complex Polyp: Endoscopy versus Surgery

AbstractMany colorectal cancers arise from either adenomatous polyps or sessile serrated lesions. However, due to the implementation of screening guidelines at the age of 45 years and the ability to perform therapeutic endoscopic polyp resections, the incidence and mortality of colorectal cancer has been decreasing in the United States. Polyps can be distinguished not only by pathology, but characterized by their complexity depending on the size, location, and morphology. Historically, polyps that were endoscopically more challenging to resect were referred for surgical resection. However, due to rapid advancement in endoscopic techniques and availability of tools, many of these complex polyps can be safely and effectively resected endoscopically. In this section, we review the different methods and potential challenges associated with endoscopic resection techniques including endoscopic mucosal resection, endoscopic submucosal dissection, or endoscopic full-thickness resection of a complex polyp.

Usefulness of magnifying endoscopy for diagnosis of sessile serrated lesion with dysplasia or carcinoma: Large retrospective study.

Background and study aims Sessile serrated lesions (SSLs) are precursor lesions in the serrated neoplasia pathway that lead to invasive carcinoma from dysplasia arising from SSLs. This study aimed to elucidate the clinicopathological and endoscopic features of SSLs with and without dysplasia or carcinoma. Patients and methods We reviewed the clinicopathological and endoscopic data from all colorectal lesions pathologically diagnosed as SSLs at Juntendo University Hospital, Tokyo, Japan, between 2011 and 2022. In addition to conventional endoscopic findings, we retrospectively evaluated magnifying endoscopic findings with narrow-band imaging (NBI) or blue laser imaging (BLI) using the Japan NBI Expert Team system and analyzed pit patterns using magnified chromoendoscopic images. Results Of the 2,132 SSLs, 92.5%, 4.7%, 1.8%, and 0.9% had no dysplasia, low-grade dysplasia, high-grade dysplasia, and submucosal invasive carcinoma, respectively. Older age, the proximal colon, and larger lesions were more frequently associated with SSLs with dysplasia or carcinoma. However, 41.3% of the SSLs with dysplasia or carcinoma were ≤ 10 mm in size. Endoscopic findings, such as (semi)pedunculated morphology, double elevation, central depression, and reddishness, were frequently found in SSLs with dysplasia or carcinoma. Furthermore, magnifying endoscopy using NBI or BLI and magnifying chromoendoscopy showed high sensitivity, specificity, and accuracy for diagnosing dysplasia or carcinoma within SSLs. Conclusions SSLs with and without dysplasia or carcinoma exhibit distinct clinicopathological and endoscopic features. In an SSL series, conventional endoscopic characteristics in addition to use of magnifying endoscopy may be useful for accurately diagnosing advanced histology within an SSL.

Clinical and endoscopic characteristics of colorectal sessile serrated lesions with or without dysplasia/carcinoma: A systematic review and meta-analysis.

We aimed to compare the clinical and endoscopic characteristics of sessile serrated lesions (SSLs) with dysplasia/carcinoma (SSLD/Cs) and SSLs without dysplasia in this systematic review and meta-analysis. MEDLINE, EMBASE, and Cochrane Library databases and Clinicaltrials.gov were searched for relevant studies published up to August 28, 2023. The primary outcome was lesion size in SSLD/Cs and SSLs without dysplasia. The secondary outcomes included risk of dysplasia/carcinoma, morphology (classified based on the Paris classification), and lesion features such as mucus cap and nodules/protrusions in the two groups. Thirteen studies with 14 381 patients were included. The proportion of SSLD/Cs ≥10 mm was significantly higher than that of SSLs without dysplasia (odds ratio [OR] 3.82, 95% confidence interval [CI] 1.21-12.02, p = 0.02). There was no significant difference in the risk of dysplasia/carcinoma between the proximal (OR 0.80, 95% CI 0.57-1.14) and distal colon (OR 1.25, 95% CI 0.88-1.77, p = 0.21). The 0-Ip (OR 2.47, 95% CI 1.50-4.09) and 0-IIa + Is (OR 10.38, 95% CI 3.08-34.98) morphologies were more prevalent among SSLD/Cs, whereas the 0-IIa morphology (OR 0.38, 95% CI 0.22-0.65) was more prevalent among SSLs without dysplasia (all p < 0.001). Furthermore, mucus cap (OR 0.61, 95% CI 0.42-0.89, p = 0.01) was more common among SSLs without dysplasia, whereas nodules/protrusions (OR 7.80, 95% CI 3.07-19.85, p < 0.001) were more common in SSLD/Cs. SSLs >10 mm, 0-Ip or 0-IIa + Is morphologies, and those with nodules/protrusions are significantly associated with dysplasia/carcinoma.

Analysis of Immunohistochemical Expression of BRAF (V600E) Mutation in Serrated Colorectal Polyps: A Study from Tertiary Hospital in Oman.

Colorectal cancer (CRC) is considered one of the most common cancers in the world. Serrated polyps were found to be precursor lesions for CRC. BRAF mutation (V600E) has been strongly linked to the development of these lesions. No previous study concerning BRAF immunohistochemical expression in serrated polyps- was done in Oman. The primary objective of our study was to assess the prevalence of BRAF (V600E) mutation in serrated colorectal polyps in the Omani population. The secondary objectives were to assess the prevalence of serrated polyps and their characteristic features: type, site and size as well as the relationship between BRAF (V600E) mutation and polyp type, site and size. Ninety-one hyperplastic polyps (HP) (76.5%), 24 sessile serrated lesions (SSL) (20.2%) and 4 cases of tubular adenomas with low grade dysplasia (3.4%) were studied for BRAF (V600E) immunohistochemical expression. No case of traditional serrated adenoma (TSA) was present. Control cases of craniopharyngioma and papillary thyroid carcinoma were included. BRAF (V600E) IHC was positive in 63 of the HP polyps (69.2%), 13 SSLs (54.2%) and none of the adenomatous polyps. The majority of positive polyps (75.0%) were ≤5 mm in size, 17.9% were 5-10 mm and 7.1% were ≥10 mm in size. The majority of BRAF (V600E) positive polyps (68.1 %) were in the distal colon and 31.9 % were in the proximal colon. The majority of positive cases for BRAF (V600E) were showing multiple polyps (61.8 %). None of the tubular adenomas showed any BRAF (V600E) positivity. Serrated polyps are now well known for their potential to develop CRC. Immunohistochemistry is an easy and reproducible way to detect BRAF (V600E) mutation. Our study showed there is high prevalence (64.3%) of BRAF mutation in serrated polyps in the Omani population. The majority of these polyps- were HP and SSL; and ≤5 mm in size and located in the distal colon.

Patient and procedural factors associated with true histology rates in patients undergoing colonoscopy with computer-aided detection of polyps

Computer-aided detection (CADe) devices have been shown to increase adenoma detection rates and adenomas per colonoscopy compared to standard colonoscopies. Questions remain about whether CADe colonoscopies are mainly increasing the detection of small, nonneoplastic lesions or if they are detecting more pathologically meaningful polyps. In this analysis, we compare the true histology rate (defined as polyps with confirmation of clinically relevant histopathology) of CADe-identified polyps with polyps identified during standard colonoscopies. Using data from the SKOUT trial, we compared the true histology rate (THR) between CADe and standard colonoscopies. We also conducted a subgroup analysis by patient, procedural, and endoscopist factors. To account for multiple testing of comparisons, we used the false discovery rate. A total of 1423 participants were included (CADe, n= 714; standard, n= 709). Overall, THR was similar between the CADe and standard colonoscopy arms for adenomas, sessile serrated lesions, and large hyperplastic polyps. Higher THR with CADe colonoscopy was observed in some subgroups for adenomas. Endoscopists with 11 to 20 years of experience and procedures occurring after 12 pm had significantly higher adenoma THRs in the CADe cohort. Patients younger than 65 years, male patients, and procedures with a withdrawal time of≥8 minutes had borderline significance in the CADe device adenoma THR subgroup. CADe colonoscopies may hold the key to improving endoscopic quality measures, provided that the polyps identified by the CADe device are those of clinical relevance. Although the benefit and significance in the CADe group were demonstrated in this analysis, further research is warranted to ensure that the true histology is maintained when applied in real-world applications.

A computer-aided detection system in the everyday setting of diagnostic, screening, and surveillance colonoscopy: an international, randomized trial.

Computer-aided detection (CADe) has been developed to improve detection during colonoscopy. After initial reports of high efficacy, there has been an increasing recognition of variability in the effectiveness of CADe systems. The aim of this study was to evaluate a CADe system in a varied colonoscopy population. A multicenter, randomized trial was conducted at seven hospitals (both university and non-university) in Europe and Canada. Participants referred for diagnostic, non-immunochemical fecal occult blood test (iFOBT) screening, or surveillance colonoscopy were randomized (1:1) to undergo CADe-assisted or conventional colonoscopy by experienced endoscopists. Participants with insufficient bowel preparation were excluded from the analysis. The primary outcome was adenoma detection rate (ADR). Secondary outcomes included adenomas per colonoscopy (APC) and sessile serrated lesions (SSLs) per colonoscopy. 581 participants were enrolled, of whom 497 were included in the final analysis: 250 in the CADe arm and 247 in the conventional colonoscopy arm. The indication was surveillance in 202/497 colonoscopies (40.6 %), diagnostic in 199/497 (40.0 %), and non-iFOBT screening in 96/497 (19.3 %). Overall, ADR (38.4 % vs. 37.7 %; P = 0.43) and APC (0.66 vs. 0.66; P = 0.97) were similar between CADe and conventional colonoscopy. SSLs per colonoscopy was increased (0.30 vs. 0.19; P = 0.049) in the CADe arm vs. the conventional colonoscopy arm. In this study conducted by experienced endoscopists, CADe did not result in a statistically significant increase in ADR. However, the ADR of our control group substantially surpassed our sample size assumptions, increasing the risk of an underpowered trial.

Polyp size is associated with colorectal cancer death across histologic polyp subtypes: a retrospective study of a screening colonoscopy registry.

Surveillance colonoscopy after polyps have been detected at screening aims to reduce the risk for subsequent colorectal cancer, so-called post-colonoscopy colorectal cancer (PCCRC). Inconsistencies exist as to whether the risk should be stratified by histologic subtype. We aimed to compare the risk for PCCRC mortality in screening participants with sessile serrated lesions (SSLs)/traditional serrated adenomas (TSAs), hyperplastic polyps (HPPs), or conventional adenomas. Screening colonoscopy registry data were linked to death registry data between 2010 and 2022. We assessed the association of PCCRC death after a diagnosis of SSL/TSA, conventional adenoma, or HPP by Cox regression, and stratified by polyp size ≥10 and <10 mm. 383,801 participants were included in the analysis. There were 1490 HPPs ≥10 mm (2.6%), compared with 1853 SSL/TSAs (19.6%) and 10,960 conventional adenomas (12.9%). When adjusted for polyp location, the association of polyp size ≥10 mm with PCCRC death was of similar magnitude in participants with conventional adenomas (hazard ratio [HR] 3.68, 95%CI 2.49-5.44), SSL/TSAs (HR 2.55, 95%CI 1.13-5.72), and HPPs (HR 5.01, 95%CI 2.45-10.22). Participants with HPPs mostly died of tumors in the distal colon (54.1%; n = 20), while participants with SSL/TSAs more frequently died of proximal tumors (33.3%; n = 3). Across all histologic types, participants with polyps ≥10 mm had at least a two-fold increase in the likelihood of PCCRC death compared with those with polyps <10 mm. These data suggest that size, rather than histologic subtype, should be a determinant for risk stratification after screening colonoscopy.

Predictors for dMMR colorectal cancer in patients with serrated lesions and polyps – A register-based cohort study

BackgroundSerrated lesions and polyps (SP) are precursors of up to 30 % of colorectal cancers (CRC) through the serrated pathway. This often entails early BRAF mutations and MLH1 hypermethylation leading to mismatch repair deficient (dMMR) CRC. We investigated predictors of dMMR CRC among patients with co-occurrence of CRC and SP to increase our knowledge on the serrated pathway. MethodsWe used data from The Danish Pathology Registry and Danish Colorectal Cancer Groups Database from the period 2010–2021 to investigate risk factors for development of dMMR CRC. We used logistic regression models to identify difference in risk factors of developing dMMR CRC in comparison to CRC with proficient MMR (pMMR). ResultsWe included 3273 patients with a median age of 70.7 years [64.3,76.4] of which 1850 (56.5 %) were male. dMMR CRC was present in 592 patients (18.1 %), with loss of MLH1/PMS2 being most common. The risk of dMMR CRC was significantly higher in females OR 3.47 [2.87;4.20]. When adjusting for age, SP subtype, conventional adenomas (CA), anatomical location and lifestyle factors, female sex remained the strongest predictor OR 2.84 [2.27;3.56]. The presence of sessile serrated lesions with or without dysplasia was related to higher risk OR 1.60 [1.11;2.31] and OR 1.42 [1.11;1.82] respectively, while conventional adenomas constituted a lower risk OR 0.68 [0.55;0.84]. ConclusionIn conclusion we found several predictors of whom female sex had the strongest correlation with dMMR CRC in patients with SP.

Sessile serrated lesion prevalence and factors associated with their detection: a post-hoc analysis of a multinational randomized controlled trial from Asia.

Sessile serrated lesions (SSLs) are associated with an increased risk of colorectal cancer. Data on the prevalence of SSLs in Asia are limited. We performed this study to estimate the prevalence of SSLs in Asia and to explore endoscopic factors that are associated with SSL detection. This is a post-hoc analysis of a multicenter randomized controlled trial from four Asian countries/regions that compared adenoma detection rates using linked-color imaging (LCI) and white-light imaging. Colonoscopies were performed in an average-risk population for screening, diagnostic examination, or polyp surveillance. Patients with SSLs were compared against those without SSLs to evaluate for possible predictors of SSL detection using Firth's logistic regression. 2898 participants (mean age 64.5 years) were included in the analysis. The estimated prevalence of SSLs was 4.0% (95%CI 3.4%-4.8%), with no sex or age group differences. On multivariable analysis, use of LCI (adjusted odds ratio [aOR] 1.63, 95%CI 1.10-2.41), experienced endoscopists (aOR 1.94, 95%CI 1.25-3.00), use of transparent cap (aOR 1.75, 95%CI 1.09-2.81), and longer withdrawal time (aOR 1.06, 95%CI 1.03-1.10) were independently associated with SSL detection. Synchronous adenoma detection (aOR 1.89, 95%CI 1.20-2.99) was also predictive of SSL detection. The prevalence of SSLs in Asia is 4.0%. Use of LCI or a transparent cap, greater endoscopist experience, and longer withdrawal time were all associated with increased SSL detection.

Identification of Early Events in Serrated Pathway Colorectal Tumorigenesis by Using Digital Spatial Profiling.

The colorectal serrated pathway involves precursor lesions known as sessile serrated lesions (SSL) and traditional serrated adenomas (TSA). Mutations in BRAF or KRAS are crucial early events in this pathway. Additional genetic and epigenetic changes contribute to the progression of these lesions into high-grade lesions and, eventually, invasive carcinoma. We employed digital spatial profiling to investigate the transcriptional changes associated with SSL and TSA. The genes identified are confirmed by immunohistochemical (IHC) staining. Colorectal cancer (CRC) cell lines with CEACAM6 overexpression and knockdown were established to study the roles of CEACAM6 on tumorigenesis of CRC. Ten genes were upregulated in SSL and TSA, and seven were upregulated in both types of lesions. IHC staining confirmed overexpression of CEACAM6, LCN2, KRT19, and lysozyme in SSL and TSA. CEACAM6 expression is an early event in the serrated pathway but a late event in the conventional pathway. Using cell line models, we confirmed that CEACAM6 promotes CRC cells' proliferation, migration, and invasion abilities. These results highlight that the transcriptional changes in the early stages of tumorigenesis exhibit relative uniformity. Identifying these early events may hold significant promise in elucidating the mechanisms behind tumor initiation.

Endoscopic characteristics and performance ofWASP classification in the diagnosis of colorectal sessile-serrated lesions in Vietnamese patients.

Sessile-serrated lesions (SSLs) are challenging to detect due to their typically subtle appearance. The Workgroup serrAted polypS and Polyposis (WASP) classification was developed to diagnose SSLs endoscopically. This study aimed to evaluate the endoscopic characteristics of SSLs and the performance of the WASP classification in the Vietnamese population. This cross-sectional study was carried out on patients with lower gastrointestinal symptoms who underwent colonoscopy at a Vietnamese tertiary hospital. Univariate and multivariate analyses were performed to identify endoscopic features associated with SSLs. The performance of the WASP classification for diagnosing SSLs was assessed, and SSLs were diagnosed according to the 2019 World Health Organization (WHO) criteria. There were 2489 patients, with a mean age of 52.1 ± 13.1 years and a female-to-male ratio of 1:1.1. A total of 121 specimens from 105 patients were diagnosed with SSLs. According to multivariate analysis, the endoscopic features significantly associated with SSLs were proximal location (odds ratio [OR]: 2.351; 95% confidence interval [CI]: 1.475-3.746), size >5 mm (OR: 2.447; 95% CI: 1.551-3.862), flat morphology (OR: 2.781; 95% CI: 1.533-5.044), irregular shape (OR: 4.516; 95% CI: 2.173-9.388), varicose microvascular vessels (OR: 5.030; 95% CI: 2.657-9.522), and dark spots inside the crypts (OR: 5.955; 95% CI: 3.291-10.776). The accuracy of the WASP classification for diagnosing SSLs was 94.0% (95% CI: 92.8%-95.0%). Proximal location, size >5 mm, flat morphology, irregular shape, varicose microvascular vessels, and dark spots inside the crypts were significantly associated with SSLs. The WASP classification had high accuracy in the diagnosis of SSLs.

Serrated polyposis syndrome: defining the epidemiology and predicting the risk of dysplasia.

Serrated polyposis syndrome is the most common polyposis syndrome that has neoplastic potential. However, the natural history, genetic basis, and risk of dysplasia and neoplasia of serrated polyposis syndrome are incompletely understood. The objective of this study is to define the epidemiology of serrated polyposis syndrome. Using this data, we aim to evaluate candidate variables for predicting the risk of dysplasia and neoplasia in sessile serrated lesions found in serrated polyposis syndrome patients. Finally, we aim to use this data to create and evaluate clinical prediction models for accuracy in predicting dysplastic sessile serrated lesions in serrated polyposis syndrome patients. This was a regional Australian single-centre retrospective cohort study. Data was prospectively collected data from the clinical record database of a regional Australian gastroenterology practice. All patients undergoing colonoscopy at Port Macquarie Gastroenterology between January 2015 and September 2021 were screened for this study. Collected data included patient demographic, endoscopic, and histopathological findings. Clinical and endoscopic multivariate logistic regression models were created to predict dysplastic sessile serrated lesions. Model performance was examined using the area under the receiver operating curve. In total 8401 patients underwent a colonoscopy procedure during the study period. Serrated polyposis syndrome was diagnosed in 247, representing a prevalence of 2.94% (mean age 67.15 years, 62.75% female). Logistic regression identified; older age at serrated polyposis syndrome diagnosis, a personal history of colorectal cancer, size of the largest sessile serrated lesions removed, and total sessile serrated lesions count as predictors of dysplastic sessile serrated lesions. The clinical and endoscopic model had an area under the receiver operating curve of 0.75. Serrated polyposis syndrome is more common than previously described. The clinical and endoscopic variables identified in logistic regression have acceptable accuracy in predicting the risk of dysplasia, however other populations need to be studied to achieve generalisability and improve model performance.

Association of Endoscopist Colonoscopy Quality Measures With Follow-Up Colonoscopy Outcomes After Positive Stool Tests (Multitarget Stool DNA or Fecal Immunochemical Test): Retrospective Cross-Sectional Analysis of Data From the New Hampshire Colonoscopy Registry.

Negative colonoscopies following positive stool tests could result from stool test characteristics or from the quality of endoscopist performance. We used New Hampshire Colonoscopy Registry data to examine the association between endoscopist detection rates and polyp yield in colonoscopies performed for positive fecal immunochemical test (FIT) or multitarget stool DNA (mt-sDNA) test to evaluate the degree to which positive stool tests followed by negative colonoscopy ("false positives") vary with endoscopist quality. In addition, we investigated the frequency of significant polyps in the subgroup of highest quality colonoscopies following positive stool tests. We compared the frequencies of negative colonoscopies and of specific polyps following positive stool tests across quartiles of endoscopist adenoma detection rate (ADR) and clinically significant serrated polyp detection rate (CSSDR). Our sample included 864 mt-sDNA+ and 497 FIT+ patients. We found a significantly lower frequency of negative colonoscopies following positive stool tests among endoscopists with higher ADR and CSSDR, particularly in the 2 highest quartiles. In addition, detection of any adenoma after a positive stool test for endoscopists in the fourth ADR quartile was 63.3% (FIT+) and 62.8% (mt-sDNA+). Among endoscopists in the fourth CSSDR quartile, sessile serrated lesions were found in 29.2% of examinations following a positive mt-sDNA and in 13.5% following FIT+ examinations. The frequency of negative colonoscopies after positive stool tests was significantly higher in examinations performed by endoscopists with low ADR and CSSDR. Our results also suggest a benchmark target of at least 40% for ADR in patients with mt-sDNA+ or FIT+ tests and 20% for sessile serrated lesions in mt-sDNA+ patients.

A survey of current practices in post-polypectomy surveillance in Korea.

We investigated the clinical practice patterns of post-polypectomy colonoscopic surveillance among Korean endoscopists. In a web-based survey conducted between September and November 2021, participants were asked about their preferred surveillance intervals and the patient age at which surveillance was discontinued. Adherence to the recent guidelines of the U.S. Multi-Society Task Force on Colorectal Cancer (USMSTF) was also analyzed. In total, 196 endoscopists completed the survey. The most preferred first surveillance intervals were: a 5-year interval after the removal of 1-2 tubular adenomas < 10 mm; a 3-year interval after the removal of 3-10 tubular adenomas < 10 mm, adenomas ≥ 10 mm, tubulovillous or villous adenomas, ≤ 20 hyperplastic polyps < 10 mm, 1-4 sessile serrated lesions (SSLs) < 10 mm, hyperplastic polyps or SSLs ≥ 10 mm, and traditional serrated adenomas; and a 1-year interval after the removal of adenomas with highgrade dysplasia, >10 adenomas, 5-10 SSLs, and SSLs with dysplasia. In piecemeal resections of large polyps ( > 20 mm), surveillance colonoscopy was mostly preferred after 1 year for adenomas and 6 months for SSLs. The mean USMSTF guideline adherence rate was 30.7%. The largest proportion of respondents (40.8%-55.1%) discontinued the surveillance at the patient age of 80-84 years. A significant discrepancy was observed between the preferred post-polypectomy surveillance intervals and recent international guidelines. Individualized measures are required to increase adherence to the guidelines.

Analysis of the Characteristics of Coexisting Lesions in Colorectal Cancer Patients in an International Study: A Subgroup Analysis of the ATLAS Trial

Introduction: We investigated coexisting lesion types in patients with invasive colorectal cancer (CRC) in a multinational study for comprehending the adenoma-carcinoma and serrated pathway about the development of CRC. Methods: We retrospectively reviewed 3,050 patients enrolled in the international randomized controlled trial (ATLAS study) to evaluate the colorectal polyp detection performance of image-enhanced endoscopy in 11 institutions in four Asian countries/regions. In the current study, as a subgroup analysis of the ATLAS study, 92 CRC patients were extracted and compared to 2,958 patients without CRC to examine the effects of age, sex, and coexisting lesion types (high-grade adenoma [HGA], low-grade adenoma with villous component [LGAV], 10 adenomas, adenoma ≥10 mm, sessile serrated lesions [SSLs], and SSLs with dysplasia [SSLD]). Additional analyses of coexisting lesion types were performed according to sex and location of CRC (right- or left-sided). Results: A multivariate analysis showed that HGA (odds ratio [95% confidence interval] 4.29 [2.16–8.18]; p < 0.01), LGAV (3.02 [1.16–7.83], p = 0.02), and age (1.04 [1.01–1.06], p = 0.01) were independently associated with CRC. According to sex, the coexisting lesion types significantly associated with CRC were LGAV (5.58 [1.94–16.0], p < 0.01) and HGA (4.46 [1.95–10.20], p < 0.01) in males and HGA (4.82 [1.47–15.80], p < 0.01) in females. Regarding the location of CRC, SSLD (21.9 [1.31–365.0], p = 0.03) was significant for right-sided CRC, and HGA (5.22 [2.39–11.4], p < 0.01) and LGAV (3.46 [1.13–10.6], p = 0.02) were significant for left-sided CRC. Conclusions: The significant coexisting lesions in CRC differed according to sex and location. These findings may contribute to comprehending the pathogenesis of CRC.

Evaluation of EGFR and COX pathway inhibition in human colon organoids of serrated polyposis and other hereditary cancer syndromes.

Serrated polyposis syndrome (SPS) presents with multiple sessile serrated lesions (SSL) in the large intestine and confers increased colorectal cancer (CRC) risk. However, the etiology of SPS is not known. SSL-derived organoids have not been previously studied but may help provide insights into SPS pathogenesis and identify novel biomarkers and chemopreventive strategies. This study examined effects of EGFR and COX pathway inhibition in organoid cultures derived from uninvolved colon and polyps of SPS patients. We also compared with organoids representing the hereditary gastrointestinal syndromes, Familial Adenomatous Polyposis (FAP) and Lynch syndrome (LS). Eighteen total organoid colon cultures were generated from uninvolved colon and polyps in SPS, FAP, LS, and non-syndromic screening colonoscopy patients. BRAF and KRAS mutation status was determined for each culture. Erlotinib (EGFR inhibitor) and sulindac (COX inhibitor) were applied individually and in combination. A 44-target gene custom mRNA panel (including WNT and COX pathway genes) and a 798-gene microRNA gene panel were used to quantitate organoid RNA expression by NanoString analysis. Erlotinib treatment significantly decreased levels of mRNAs associated with WNT and MAPK kinase signaling in organoids from uninvolved colon from all four patient categories and from all SSL and adenomatous polyps. Sulindac did not change the mRNA profile in any culture. Our findings suggest that EGFR inhibitors may contribute to the chemopreventive treatment of SSLs. These findings may also facilitate clinical trial design using these agents in SPS patients. Differentially expressed genes identified in our study (MYC, FOSL1, EGR1, IL33, LGR5 and FOXQ1) may be used to identify other new molecular targets for chemoprevention of SSLs.

Linked color imaging improves colorectal lesion detection especially for low performance endoscopists: An international trial in Asia.

Linked color imaging (LCI) is an image-enhanced endoscopy technique that accentuates the color difference between red and white, potentially improving the adenoma detection rate (ADR). However, it remains unclear whether LCI performance in detecting colorectal lesions differs based on endoscopists' experience levels. We aimed to evaluate the differences in LCI efficacy based on the experience levels of endoscopists by conducting an exploratory analysis. In this post hoc analysis of an international randomized controlled trial comparing the detection of adenoma and other lesions using colonoscopy with LCI and high-definition white light imaging (WLI), we included patients from 11 institutions across four countries/regions: Japan, Thailand, Taiwan, and Singapore. We retrospectively reviewed differences in the lesion detection of LCI according to endoscopists' colonoscopy history or ADR. We included 1692 and 1138 patients who underwent colonoscopies performed by 54 experts (experience of ≥5000 colonoscopies) and by 43 non-experts (experience of <5000 colonoscopies), respectively. Both expert and non-expert groups showed a significant improvement in ADR with LCI compared to WLI (expert, 61.7% vs 46.4%; P<0.001; non-expert, 56.6% vs 46.4%; P<0.001). LCI had no effect on sessile serrated lesion detection rate in non-experts (3.1% vs 2.5%; P=0.518). LCI significantly improved detection rates in endoscopists with relatively low detection performance, defined as an ADR<50%. This exploratory study analyzed data from a previous trial and revealed that LCI is useful for both experts and non-experts and is even more beneficial for endoscopists with relatively low detection performance using WLI.