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The serrated pathway to colorectal cancers (CRCs) is a significant pathway encompassing five distinct types of lesions, namely hyperplastic polyps (HPs), sessile serrated lesions (SSLs), sessile serrated lesions with dysplasia (SSL-Ds), traditional serrated adenomas (TSAs), and serrated adenoma unclassified. In contrast to the conventional adenoma-carcinoma pathway, the serrated pathway primarily involves two mechanisms: BRAF/KRAS mutations and CpG island methylator phenotype (CIMP). HPs are the most prevalent non-malignant lesions, while SSLs play a crucial role as precursors to CRCs, On the other hand, traditional serrated adenomas (TSAs) are the least frequently encountered subtype, also serving as precursors to CRCs. It is crucial to differentiate these lesions based on their unique morphological characteristics observed in histology and colonoscopy, as the identification and management of these serrated lesions significantly impact colorectal cancer screening programs. The management of these lesions necessitates the crucial steps of removing premalignant lesions and implementing regular surveillance. This article provides a comprehensive summary of the epidemiology, histologic features, molecular features, and detection methods for various serrated polyps, along with recommendations for their management and surveillance. [ABSTRACT FROM AUTHOR]

Up to 30% of colorectal cancers (CRCs) develop from sessile serrated lesions (SSLs). Within the serrated neoplasia pathway, at least two principally distinct oncogenetic routes exist generating microsatellite‐stable and microsatellite‐instable CRCs, respectively. Aberrant DNA methylation (DNAm) is found early in the serrated pathway and might play a role in both oncogenetic routes. We studied a cohort of 23 SSLs with a small focus (<10 mm) of dysplasia or cancer, 10 of which were MLH1 deficient and 13 MLH1 proficient. By comparing, for each SSL, the methylation status of (1) the region of dysplasia or cancer (SSL‐D), (2) the nondysplastic SSL (SSL), and (3) adjacent normal mucosa, differentially methylated probes (DMPs) and regions (DMRs) were assessed both genome‐wide as well as in a tumor‐suppressor gene‐focused approach. By comparing DNAm of MLH1‐deficient SSL‐Ds with their corresponding SSLs, we identified five DMRs, including those annotating for PRDM2 and, not unexpectedly, MLH1. PRDM2 gene promotor methylation was associated with MLH1 expression status, as it was largely hypermethylated in MLH1‐deficient SSL‐Ds and hypomethylated in MLH1‐proficient SSL‐Ds. Significantly increased DNAm levels of PRDM2 and MLH1, in particular at 'critical' MLH1 probe sites, were to some extent already visible in SSLs as compared to normal mucosa (p = 0.02, p = 0.01, p < 0.0001, respectively). No DMRs, nor DMPs, were identified for SSLs destined to evolve into MLH1‐proficient SSL‐Ds. Our data indicate that, within both arms of the serrated CRC pathway, the majority of the epigenetic alterations are introduced early during SSL formation. Promoter hypermethylation of PRDM2 and MLH1 on the other hand specifically initiates in SSLs destined to transform into MLH1‐deficient CRCs suggesting that the fate of SSLs may not necessarily result from a stochastic process but possibly is already imprinted and predisposed. [ABSTRACT FROM AUTHOR]

Abstract Up to 30% of colorectal cancers (CRCs) develop from sessile serrated lesions (SSLs). Within the serrated neoplasia pathway, at least two principally distinct oncogenetic routes exist generating microsatellite‐stable and microsatellite‐instable CRCs, respectively. Aberrant DNA methylation (DNAm) is found early in the serrated pathway and might play a role in both oncogenetic routes. We studied a cohort of 23 SSLs with a small focus (

Background/Aims Some sessile serrated lesions (SSLs) progress into dysplasia and colorectal cancer, however, the clinical and endoscopic characteristics of SSLs with dysplasia remain to be determined. In this study, we elucidated these characteristics in SSLs with dysplasia/carcinoma, compared with those of SSLs without dysplasia. Methods We retrospectively collected the clinical, endoscopic, and pathological data of 254 SSLs from 216 patients endoscopically resected between January 2009 and December 2020. Results All SSLs included 179 without dysplasia and 75 with dysplasia/carcinoma, including 55 with low-grade dysplasia, 10 with high-grade dysplasia, and 10 with submucosal cancer. In clinical characteristics, SSLs with dysplasia/carcinoma were significantly associated with advanced age, metabolic diseases, and high-risk adenomas. In endoscopic characteristics, SSLs with dysplasia/carcinoma were significantly associated with the distal colon, large size, polypoid morphology, surface-changes, no mucus cap, and narrow-band imaging international colorectal endoscopic classification (NICE) type 2/3. In the multivariate analysis, high-risk adenomas (odds ratio [OR], 2.98; p = 0.01), large size (OR, 1.18; p < 0.01), depression (OR, 11.74; p = 0.03), and NICE type 2/3 (OR, 14.97; p < 0.01) were significantly associated with SSLs with dysplasia/carcinoma. Conclusions SSLs had a higher risk of dysplasia in the distal colon than in the proximal colon. SSLs with large size, depression, and adenomatous surface-patterns, as well as those in patients with high-risk adenomas, increased the risk of dysplasia/carcinoma. This suggests that the clinical and endoscopic characteristics can aid in the diagnosis and management of SSLs with dysplasia/carcinoma.

BackgroundA low adenoma detection rate (ADR) increases risks of interval cancers (ICs). Proximal colon flat polyps, e.g. serrated lesions (SLs), are difficult to find. Missed proximal colon flat lesions likely contribute to IC.AimsWe compared chromoendoscopy with water exchange (CWE), water exchange (WE) and air insufflation (AI) in detecting adenomas in screening colonoscopy.MethodsAfter split-dose preparation, 480 veterans were randomized to AI, WE and CWE.ResultsPrimary outcome of proximal ADR (55.6% vs 53.4% vs 52.2%, respectively) were similar in all groups. Adenoma per colonoscopy (APC) and adenoma per positive colonoscopy (APPC) were comparable. Detection rate of proximal colon SLs was significantly higher for CWE and WE than AI (26.3%, 23.6% and 11.3%, respectively, p = 0.002). Limitations: single operator; SLs only surrogate markers of but not IC.ConclusionsWhen an endoscopist achieves high-quality AI examinations with overall ADR twice (61.6%) the recommended standard (30%), use of WE and CWE does not produce further improvement in proximal or overall ADR. Comparable APC and APPC confirm equivalent withdrawal inspection techniques. WE alone is sufficient to significantly improve detection of proximal SLs. The impact of increased detection of proximal SLs by WE on prevention of IC deserves to be studied. This study is registered at ClinicalTrial.gov (NCT#01607255).

Background/aims: Growing recognition identifies sessile serrated lesions (SSL) as colorectal cancer (CRC) precursors. However, the SSL detection rate remains debatable and lacks a definitive consensus. Additionally, understanding the influencing factors in SSL development is limited. We aim to retrospectively analyze the true prevalence and risk factors of SSL in China., Materials and Methods: This retrospective study collected medical data from patients who underwent colonoscopy at the Endoscopy Center of Shanghai East Hospital affiliated with Tongji University between March 1, 2019 and February 28, 2022. Data were sourced through the electronic medical record system and included information such as age, sex, lesion location, number, and pathology. This study predominantly focused on the detection rate and the clinical and endoscopic features of SSL., Results: Of 72 287 colonoscopies in 3 years, 3905 cases were histologically confirmed as SSL. Among them, 2290 (58.6%) were male, and 1615 (41.4%) were female. The overall SSL detection rate was 5.40%, slightly surpassing Asian/Chinese averages but lower than Western rates. Males had a higher SSL detection rate (6.1%) than females (4.6%). Univariate analysis revealed a significant association between SSL with dysplasia/adenocarcinoma (SSL-D/AD) and obesity (Body Mass Index, BMI ≥ 24), CRC family history, and hypertension. After multivariable logistic regression, only obesity (BMI ≥ 24) remained a statistically significant independent risk factor for SSL-D/AD., Conclusions: The SSL detection rate at our center is 5.4% and increases with age. Males have a significantly higher detection rate than females. Our findings suggest that endoscopists should consider risk factors for SSL-D/AD, such as obesity, CRC family history, and hypertension.

Over the last decade, our knowledge of colorectal serrated polyps and lesions has significantly improved due to numerous studies on this group of precursor lesions. Serrated lesions were misleading as benign before 2010, but they are currently reclassified as precancerous lesions that contribute to 30% of colorectal cancer through the serrated neoplasia pathway. The World Health Organization updated the classification for serrated lesions and polyps of the colon and rectum in 2019, which is more concise and applicable in daily practice. The responsible authors prescribe that "colorectal serrated lesions and polyps are characterized by a serrated (sawtooth or stellate) architecture of the epithelium." From a clinical standpoint, sessile serrated lesion (SSL) and SSL with dysplasia (SSLD) are the two most significant entities. Despite these advancements, the precise diagnosis of SSL and SSLD based mainly on histopathology remains challenging due to various difficulties. This review describes the nomenclature and the terminology of colorectal serrated polyps and lesions and highlights the diagnostic criteria and obstacles encountered in the histopathological diagnosis of SSL and SSLD., Competing Interests: Conflict-of-interest statement: The authors have disclosed that they have no significant relationships with or financial interest in any commercial companies mentioned in this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction. Polypectomy has been shown to reduce the incidence of colorectal cancer. The ESGE guidelines from 2017 recommends that cold snare polypectomy should be used for removal of the diminutive polyps, smaller than 5 mm and also for sessile polyps 6 - 9 mm in size. This recommendation is based on lower complication rates and higher complete resections. Objectives. The goal of the study is to establish if the cold snare polypectomy is safe in removing the polyps smaller than 1 cm. Methods. The patients with polyps detected at colonoscopy between 2020-2022 years in the Gastroenterology Clinic from the Emergency Hospital, Targu-Mures entered this study. Results. From the total number of the polyps (753), 623 (82,73%) were adenoma and 130 (17,26%) were sessile. From the last group 83 were hyperplastic polyps, 35 sessile serrated lesions (SSL) and 12 traditional serrated adenomas (TSA). The hyperplastic polyps and 75% of the SSA were resected with cold snare, being less than 1cm. There were no bleedings and no complications. The rest of the SSL were resected by hot snare, with no complications either. Conclusions. Cold snare polypectomy is safe in serrated lesions less than 1 cm. There are recently published studies that demonstrated that cold snare polypectomy is safe also in SSA larger than 1 cm, however this has to be further established in the future guidelines. [ABSTRACT FROM AUTHOR]

Background: Sessile serrated lesions (SSLs) are often missed on colonoscopy, and studies have shown this to be an essential cause of interstitial colorectal cancer. The SSLs with dysplasia (SSL-D + ), in particular, have a faster rate of carcinogenesis than conventional tubular adenomas. Therefore, there is a clinical need for some endoscopic features with independent diagnostic value for SSL-D + s to assist endoscopists in making immediate diagnoses, thus improving the quality of endoscopic examination and treatment., Aim: To compare the characteristics of SSLs, including those with and without dysplasia (SSL-D + and SSL-D - ), based on white light and image-enhanced endoscopy, to achieve an immediate differential diagnosis for endoscopists., Methods: From January 2017 to February 2023, cases of colorectal SSLs confirmed by colonoscopy and histopathology at the Gastrointestinal Endoscopy Center of Beijing Tsinghua Changgung Hospital were collected. The general, endoscopic, and histopathological data were reviewed and analyzed to determine the diagnostic utility. Univariate analysis was used to find potential diagnostic factors, and then multivariate regression analysis was performed to derive endoscopic features with independent diagnostic values for the SSL-D + ., Results: A total of 228 patients with 253 lesions were collected as a result. There were 225 cases of colorectal SSL-D - s and 28 cases of SSL-D + s. Compared to the colorectal SSL-D - , the SSL-D + was more common in the right colon ( P = 0.027) with complex patterns of depression, nodule, and elevation based on cloud-like surfaces ( P = 0.003), reddish ( P < 0.001), microvascular varicose ( P < 0.001), and mixed type (Pit II, II-O, IIIL, IV) of crypt opening based on Pit II-O ( P < 0.001). Multifactorial logistic regression analysis indicated that lesions had a reddish color [odds ratio (OR) = 18.705, 95% confidence interval (CI): 3.684-94.974], microvascular varicose (OR = 6.768, 95%CI: 1.717-26.677), and mixed pattern of crypt opening (OR = 20.704, 95%CI: 2.955-145.086) as the independent predictors for SSL-D + s., Conclusion: The endoscopic feature that has independent diagnostic value for SSL-D + is a reddish color, microvascular varicose, and mixed pattern of crypt openings., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Transfer RNA (tRNA)-derived small RNAs (tsRNAs) are small fragments that form when tRNAs severe. tRNA halves (tiRNAs), a subcategory of tsRNA, are involved in the oncogenic processes of many tumors. However, their specific role in sessile serrated lesions (SSLs), a precancerous lesion often observed in the colon, has not yet been elucidated., Aim: To identify SSL-related tiRNAs and their potential role in the development of SSLs and serrated pathway of colorectal cancer (CRC)., Methods: Small-RNA sequencing was conducted in paired SSLs and their adjacent normal control (NC) tissues. The expression levels of five SSL-related tiRNAs were validated by q-polymerase chain reaction. Cell counting kit-8 and wound healing assays were performed to detect cell proliferation and migration. The target genes and sites of tiRNA-1:33-Pro-TGG-1 (5'tiRNA-Pro-TGG) were predicted by TargetScan and miRanda algorithms. Metabolism-associated and immune-related pathways were analyzed by single-sample gene set enrichment analysis. Functional analyses were performed to establish the roles of 5'tiRNA-Pro-TGG based on the target genes., Results: In total, we found 52 upregulated tsRNAs and 28 downregulated tsRNAs in SSLs compared to NC. The expression levels of tiRNA-1:33-Gly-CCC-2, tiRNA-1:33-Pro-TGG-1, and tiRNA-1:34-Thr-TGT-4-M2 5'tiRNAs were higher in SSLs than those in NC, while that of 5'tiRNA-Pro-TGG was associated with the size of SSLs. It was demonstrated that 5'tiRNA-Pro-TGG promoted cell proliferation and migration of RKO cell in vitro . Then, heparanase 2 ( HPSE2 ) was identified as a potential target gene of 5'tiRNA-Pro-TGG. Its lower expression was associated with a worse prognosis in CRC. Further, lower expression of HPSE2 was observed in SSLs compared to normal controls or conventional adenomas and in BRAF -mutant CRC compared to BRAF -wild CRC. Bioinformatics analyses revealed that its low expression was associated with a low interferon γ response and also with many metabolic pathways such as riboflavin, retinol, and cytochrome p450 drug metabolism pathways., Conclusion: tiRNAs may profoundly impact the development of SSLs. 5'tiRNA-Pro-TGG potentially promotes the progression of serrated pathway CRC through metabolic and immune pathways by interacting with HPSE2 and regulating its expression in SSLs and BRAF -mutant CRC. In the future, it may be possible to use tiRNAs as novel biomarkers for early diagnosis of SSLs and as potential therapeutic targets in serrated pathway of CRC., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Along with the discovery and refinement of serrated pathways, the World Health Organization amended the classification of digestive system tumors in 2019, recommending the renaming of sessile serrated adenomas/polyps to sessile serrated lesions (SSLs). Given the particularity of the endoscopic appearance of SSLs, it could easily be overlooked and missed in colonoscopy screening, which is crucial for the occurrence of interval colorectal cancer. Existing literature has found that adequate bowel preparation, reasonable withdrawal time, and awareness of colorectal SSLs have improved the quality and accuracy of detection. More particularly, with the continuous advancement and development of endoscopy technology, equipment, and accessories, a potent auxiliary tool is provided for accurate observation and immediate diagnosis of SSLs. High-definition white light endoscopy, chromoendoscopy, and magnifying endoscopy have distinct roles in the detection of colorectal SSLs and are valuable in identifying the size, shape, character, risk degree, and potential malignant tendency. This article delves into the relevant factors influencing the detection rate of colorectal SSLs, reviews its characteristics under various endoscopic techniques, and expects to attract the attention of colonoscopists., Competing Interests: Conflict-of-interest statement: All authors declare that there is no conflict-of-interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Serrated polyp associated colorectal cancer (CRC) develops from an alternative mechanism of colorectal carcinogenesis and accounts for 10-15% of all CRC. Serrated polyposis syndrome (SPS) occurs infrequently and is characterized by the occurrence of multiple serrated polyps (hyperplastic polyps, sessile serrated lesions and traditional serrated adenomas) throughout the colon and/or rectum and has been strongly associated with development of CRC. However, SPS is frequently unrecognized, due to application failure of the WHO criteria regarding diagnosis and/or missed serrated polyps during endoscopy. The management of SPS requires surveillance at regular intervals and removal of large serrated polyps. Endoscopic resection suitability and technique depends on lesion size and the endoscopist's experience. In this manuscript, we present an update regarding SPS epidemiology, molecular characteristics, management, surveillance strategies and endoscopic resection techniques., Competing Interests: None., (AJTR Copyright © 2021.)

Background and Aim: Cold snare polypectomy (CSP) is growing in popularity due to its safety and convenience. Its indication is benign tumours such as adenoma and sessile serrated lesions (SSLs) <10 mm in size. CSP for SSLs ≥10 mm in size has not been well examined. In this study, we aimed the feasibility of this treatment regarding therapeutic results and local recurrence., Methods: This was a single-centre retrospective cohort study. We reviewed SSLs with or without dysplasia of 10-20 mm that were resected by CSP from 2014 to 2020. All tumours were diagnosed endoscopically as SSLs without dysplasia before CSP with the help of magnifying narrow band imaging or blue laser imaging. We analysed the lesion characteristics, en bloc resection, histopathological diagnosis, adverse events and local recurrence. We analysed risk factors for recurrence, comparing recurrent lesions to non-recurrent lesions. We also compared risk factors for lesions 10-14 mm in size to those for lesions 15-20 mm in size., Results: We analysed 160 lesions in 100 patients (M age  ± SD = 67.7 ± 10.1 years). The polyp size (M ± SD) was 11.8 ± 2.8 mm, and the en bloc resection rate was 60.0% (96 cases). The rates of massive perioperative haemorrhage, postoperative haemorrhage and perforation were 1.3%, 0% and 0%, respectively. Regarding histopathological diagnosis, two (1.2%) cases showed SSLs with high-grade dysplasia. The recurrence rate in 101 lesions with a median follow-up period of 18 months (interquartile range 12-24 months) was 5.0%. There were no significant risk factors such as tumour size, location, morphology and so on in terms of recurrence. All recurrent cases could be resected by repeat CSP. The recurrence rates of lesions 10-14 mm in size and 15-20 mm in size were 4.7% and 6.3%, respectively (p = 0.713)., Conclusion: CSP of SSLs ≥10 mm in size according to magnifying endoscopic diagnosis was safe and promising, but the rate of recurrence was slightly high, meaning that close follow-up is required., (© 2020 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.)

In the last two decades, the vision of a unique carcinogenesis model for colorectal carcinoma (CRC) has completely changed. In addition to the adenoma to carcinoma transition, colorectal carcinogenesis can also occur via the serrated pathway. Small non-coding RNA, known as microRNAs (miRNAs), were also shown to be involved in progression towards malignancy. Furthermore, increased expression of certain miRNAs in premalignant sessile serrated lesions (SSLs) was found, emphasizing their role in the serrated pathway progression towards colon cancer. Since miRNAs function as post-transcriptional gene regulators, they have enormous potential to be used as useful biomarkers for CRC and screening in patients with SSLs particularly. In this review, we have summarized the most relevant information about the specific role of miRNAs and their relevant signaling pathways among different serrated lesions and polyps as well as in serrated adenocarcinoma. Additional focus is put on the correlation between gut immunity and miRNA expression in the serrated pathway, which remains unstudied., Competing Interests: Conflict-of-interest statement: Authors declare no conflict of interests for this article., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)