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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.)

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.)

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.)