Prevalence, risk factors, and BRAF mutation of colorectal sessile serrated lesions among Vietnamese patients

BACKGROUND Sessile serrated lesions(SSLs)are considered precancerous colorectal lesions that should be detected and removed to prevent colorectal cancer.Previous studies in Vietnam mainly investigated the adenoma pathway,with limited data on the serrated pathway.AIM To evaluate the prevalence,risk factors,and BRAF mutations of SSLs in the Vietnamese population.METHODS This is a cross-sectional study conducted on patients with lower gastrointestinal symptoms who underwent colonoscopy at a tertiary hospital in Vietnam.SSLs were diagnosed on histopathology according to the 2019 World Health Organi-zation classification.BRAF mutation analysis was performed using the Sanger DNA sequencing method.The multivariate logistic regression model was used to determine SSL-associated factors.RESULTS There were 2489 patients,with a mean age of 52.1±13.1 and a female-to-male ratio of 1:1.1.The prevalence of SSLs was 4.2%[95%confidence interval(CI):3.5-5.1].In the multivariate analysis,factors significantly associated with SSLs were age≥40[odds ratio(OR):3.303;95%CI:1.607-6.790],male sex(OR:2.032;95%CI:1.204-3.429),diabetes mellitus(OR:2.721;95%CI:1.551-4.772),and hypertension(OR:1.650,95%CI:1.045-2.605).The rate of BRAF mutations in SSLs was 35.5%.CONCLUSION The prevalence of SSLs was 4.2%.BRAF mutations were present in one-third of SSLs.Significant risk factors for SSLs included age≥40,male sex,diabetes mellitus,and hypertension.

Superficial Serrated Adenoma (SuSA): A New Subtype of Serrated Lesions

Superficial serrated adenoma (SuSA) is a new subtype of serrated lesions proposed in recent years, most of which are located in the sigmoid colon or rectum, with typical mixed adenoma and serrated pathological features, and its molecular features are high frequency of KRAS mutation and RSPO fusion or overexpression. At present, it is believed that SuSA has two subtypes: traditional serrated adenoma (TSA)-associated SuSA and isolated SuSA. Solitary SuSA showed faded pedicle-free protuberant lesions under endoscope and lobulated, pp (pit pattern) classification was type II and type IIIH, TSA-associated SuSA showed double-layer eminence, SuSA part showed white flat eminence, pp classification showed type II and IIIH, TSA part showed red tone high eminence, pp was IVH type. SuSA can develop into colorectal cancer through the evolution of TSA, and it can also directly develop into MSS colorectal cancer. In view of the superficial understanding of SuSA and the lack of a complete description of SuSA, this paper review the research progress of SuSA at home and abroad from the origin, endoscope features, histopathological features, molecular biology, differential diagnosis and treatment of SuSA, in order to better promote the understanding and clinical diagnosis of lesions.

5’tiRNA-Pro-TGG,a novel tRNA halve,promotes oncogenesis in sessile serrated lesions and serrated pathway of colorectal cancer

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-M25′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′tiRNAPro-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 interferonγresponse 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.

Current progress on the endoscopic features of colorectal sessile serrated lesions

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.Highdefinition 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.

Endoscopic diagnosis for colorectal sessile serrated lesions

BACKGROUND Hyperplastic polyps are considered non-neoplastic, whereas sessile serrated lesions(SSLs) are precursors of cancer via the ‘‘serrated neoplastic pathway’’. The clinical features of SSLs are tumor size(> 5 mm), location in the proximal colon, coverage with abundant mucus called the ‘‘mucus cap’’, indistinct borders, and a cloud-like surface. The features in magnifying narrow-band imaging are varicose microvascular vessels and expanded crypt openings. However, accurate diagnosis is often difficult.AIM To develop a diagnostic score system for SSLs.METHODS We retrospectively reviewed consecutive patients who underwent endoscopic resection during colonoscopy at the Toyoshima endoscopy clinic. We collected data on serrated polyps diagnosed by endoscopic or pathological examination. The significant factors for the diagnosis of SSLs were assessed using logistic regression analysis. Each item that was significant in multivariate analysis was assigned 1 point, with the sum of these points defined as the endoscopic SSL diagnosis score. The optimal cut-off value of the endoscopic SSL diagnosis score was determined by receiver-operating characteristic curve analysis.RESULTS Among 1288 polyps that were endoscopically removed, we analyzed 232 diagnosed as serrated polyps by endoscopic or pathological examination. In the univariate analysis, the location(proximal colon), size(> 5 mm), mucus cap, indistinct borders, cloud-like surface, and varicose microvascular vessels were significantly associated with the diagnosis of SSLs. In the multivariate analysis, size(> 5 mm;P = 0.033), mucus cap(P = 0.005), and indistinct borders(P = 0.033) were independently associated with the diagnosis of SSLs. Size > 5 mm, mucus cap, and indistinct borders were assigned 1 point each and the sum of these points was defined as the endoscopic SSL diagnosis score. The receiver-operating characteristic curve analysis showed an optimal cut-off score of 3, which predicted pathological SSLs with 75% sensitivity, 80% specificity, and 78.4% accuracy. The pathological SSL rate for an endoscopic SSL diagnosis score of 3 was significantly higher than that for an endoscopic SSL diagnosis score of 0, 1, or 2(P < 0.001).CONCLUSION Size > 5 mm, mucus cap, and indistinct borders were significant endoscopic features for the diagnosis of SSLs. Serrated polyps with these three features should be removed during colonoscopy.

Serrated lesions:A challenging enemy

The serrated pathway accounts for 30%-35%of colorectal cancer(CRC).Unlike hyperplastic polyps,both sessile serrated lesions(SSLs)and traditional serrated adenomas are premalignant lesions,yet SSLs are considered to be the principal serrated precursor of CRCs.Serrated lesions represent a challenge in detection,classification,and removal–contributing to post-colonoscopy cancer.Therefore,it is of the utmost importance to characterize these lesions properly to ensure complete removal.A retrospective cohort study developed a diagnostic scoring system for SSLs to facilitate their detection endoscopically and subsequent removal.From the study,it can be ascertained that both indistinct border and mucus cap are essential in both recognizing and diagnosing serrated lesions.The proximal colon poses technical challenges for some endoscopists,which is why high-quality colonoscopy plays such an important role.The indistinct border of some SSLs poses another challenge due to difficult complete resection.Overall,it is imperative that gastroenterologists use the key features of mucus cap,indistinct borders,and size of at least five millimeters along with a high-quality colonoscopy and a good bowel preparation to improve the SSL detection rate.

Usefulness of analyzing endoscopic features in identifying the colorectal serrated sessile lesions with and without dysplasia

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.

Precision in detecting colon lesions:A key to effective screening policy but will it improve overall outcomes?

Colonoscopy is the gold standard for the screening and diagnosis of colorectal cancer,resulting in a decrease in the incidence and mortality of colon cancer.However,it has a 21%rate of missed polyps.Several strategies have been devised to increase polyp detection rates and improve their characterization and delimi-tation.These include chromoendoscopy(CE),the use of other devices such as Endo cuffs,and major advances in endoscopic equipment[high definition,magnification,narrow band imaging,i-scan,flexible spectral imaging color enhancement,texture and color enhancement imaging(TXI),etc.].In the retrospective study by Hiramatsu et al,they compared white-light imaging with CE,TXI,and CE+TXI to determine which of these strategies allows for better definition and delimitation of polyps.They concluded that employing CE associated with TXI stands out as the most effective method to utilize.It remains to be demonstrated whether these results are extrapolatable to other types of virtual CE.Additionally,further investigation is needed in order to ascertain whether this strategy could lead to a reduction in the recurrence of excised lesions and potentially lower the occurrence of interval cancer.

Serrated polyps of the colon and rectum:Remove or not?

In recent years,the serrated neoplasia pathway where serrated polyps arise as a colorectal cancer has gained considerable attention as a new carcinogenic pathway.Colorectal serrated polyps are histopathologically classified into hyperplastic polyps(HPs),sessile serrated lesions,and traditional serrated adenomas;in the serrated neoplasia pathway,the latter two are considered to be premalignant.In western countries,all colorectal polyps,including serrated polyps,apart from diminutive rectosigmoid HPs are removed.However,in Asian countries,the treatment strategy for colorectal serrated polyps has remained unestablished.Therefore,in this review,we described the clinicopathological features of colorectal serrated polyps and proposed to remove HPs and sessile serrated lesions≥6 mm in size,and traditional serrated adenomas of any size.

What could microRNA expression tell us more about colorectal serrated pathway carcinogenesis?

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.

Clinical predictors for sessile serrated polyposis syndrome:A case control study

AIM To compared individuals with serrated polyposis syndrome (SPS) to those with sessile serrated adenoma (SSA) and adenomas in the setting of endoscopists with high adenoma detection rates at a secondary and tertiary academic centre.METHODS Retrospectively we collated the clinical,endoscopic and histological features of all patients with SPS at St Vincent's public and private hospital in the last 3 years.Patients were identified by searching through 2 pathology databases.Variables explored included smoking status,symptoms,and family history of concurrent colorectal cancer,number and location of polyps.Patients with SPS were matched to two cohorts (1) patients with SSA not meeting World Health Organization (WHO) criteria for SPS over 3 years; and (2) patients with exclusively adenomas.The control cases were also matched according to gender and endoscopist.Adenoma detection rates ranged from 25% to 40%.RESULTS Forty patients with SPS were identified and matched with 40 patients in each control group.In total 15452 colonoscopies were performed over the study period which amounts to a prevalence of 1: 384 patients (0.26%) with SPS.Fourteen patients (35%) required more than 1 year to accumulate enough polyps to reach WHO criteria for SPS.The diagnosis of SPS was largely incidental and 5% SPS patients were diagnosed with colorectal cancer over 3 years.The chance of detecting a meta-synchronous adenoma was similar in those with SPS(42%) and those with SSA(55%),P = 0.49.The majority of patients(75%) meeting criteria for SPS were women.The mean age of those with SPS (45 years) was significantly lower than both cohorts with SSA(57 years) and adenomas(63 years),P = 0.01.On univariate analysis cigarette exposure,firstdegree family history of colorectal cancer and a high BMI weren't significantly more associated with SPS compared to patients with SSA or patients with adenomas.However,patients with SPS (97%) and patients with SSAs not meeting SPS criteria(98%) were significantly more likely to be Caucasian compared to patients with adenomas (79%),P = 0.01.CONCLUSION The prevalence of SPS in our study was 0.26%.The vast majority of patients diagnosed with SPS were women.As a group,they were significantly younger compared to patients with SSA not meeting WHO criteria and patients with adenomatous polyps by more than a decade.Patients with SPS were no more likely to have a first degree relative with colorectal cancer or smoking history than the other two groups.Patients with serrated polyps were more likely to be Caucasian than patients with adenomas.

Improved visibility of colorectal tumor by texture and color enhancement imaging with indigo carmine

BACKGROUND Accurate diagnosis and early resection of colorectal polyps are important to prevent the occurrence of colorectal cancer.However,technical factors and morphological factors of polyps itself can lead to missed diagnoses.Imageenhanced endoscopy and chromoendoscopy(CE)have been developed to facilitate an accurate diagnosis.There have been no reports on visibility using a combination of texture and color enhancement imaging(TXI)and CE for colorectal tumors.AIM To investigate the visibility of margins and surfaces with the combination of TXI and CE for colorectal lesions.METHODS This retrospective study included patients who underwent lower gastrointestinal endoscopy at the Toyoshima Endoscopy Clinic.We extracted polyps that were resected and diagnosed as adenomas or serrated polyps(hyperplastic polyps and sessile serrated lesions)from our endoscopic database.An expert endoscopist performed the lower gastrointestinal endoscopies and observed the lesion using white light imaging(WLI),TXI,CE,and TXI+CE modalities.Indigo carmine dye was used for CE.Three expert endoscopists rated the visibility of the margin and surface patterns in four ranks,from 1 to 4.The primary outcomes were the average visibility scores for the margin and surface patterns based on the WLI,TXI,CE,and TXI+CE observations.Visibility scores between the four modalities were compared by the Kruskal-Wallis and Dunn tests.RESULTS A total of 48 patients with 81 polyps were assessed.The histological subtypes included 50 tubular adenomas,16 hyperplastic polyps,and 15 sessile serrated lesions.The visibility scores for the margins based on WLI,TXI,CE,and TXI+CE were 2.44±0.93,2.90±0.93,3.37±0.74,and 3.75±0.49,respectively.The visibility scores for the surface based on WLI,TXI,CE,and TXI+CE were 2.25±0.80,2.84±0.84,3.12±0.72,and 3.51±0.60,respectively.The visibility scores for the detection and surface on TXI were significantly lower than that on CE but higher than that on WLI(P<0.001).The visibility scores for the margin and surface on TXI+CE were significantly higher than those on CE(P<0.001).In the sub-analysis of adenomas,the visibility for the margin and surface on TXI+CE was significantly better than that on WLI,TXI,and CE(P<0.001).In the sub-analysis of serrated polyps,the visibility for the margin and surface on TXI+CE was also significantly better than that on WLI,TXI,and CE(P<0.001).CONCLUSION TXI+CE enhanced the visibility of the margin and surface compared to WLI,TXI,and CE for colorectal lesions.

Artificial intelligence fails to improve colonoscopy quality:A single centre retrospective cohort study

BACKGROUND Limited data currently exists on the clinical utility of Artificial Intelligence Assisted Colonoscopy(AIAC)outside of clinical trials.AIM To evaluate the impact of AIAC on key markers of colonoscopy quality compared to conventional colonoscopy(CC).METHODS This single-centre retrospective observational cohort study included all patients undergoing colonoscopy at a secondary centre in Brisbane,Australia.CC outcomes between October 2021 and October 2022 were compared with AIAC outcomes after the introduction of the Olympus Endo-AID module from October 2022 to January 2023.Endoscopists who conducted over 50 procedures before and after AIAC introduction were included.Procedures for surveillance of inflammatory bowel disease were excluded.Patient demographics,proceduralist specialisation,indication for colonoscopy,and colonoscopy quality metrics were collected.Adenoma detection rate(ADR)and sessile serrated lesion detection rate(SSLDR)were calculated for both AIAC and CC.RESULTS The study included 746 AIAC procedures and 2162 CC procedures performed by seven endoscopists.Baseline patient demographics were similar,with median age of 60 years with a slight female predominance(52.1%).Procedure indications,bowel preparation quality,and caecal intubation rates were comparable between groups.AIAC had a slightly longer withdrawal time compared to CC,but the difference was not statistically significant.The introduction of AIAC did not significantly change ADR(52.1%for AIAC vs 52.6%for CC,P=0.91)or SSLDR(17.4%for AIAC vs 18.1%for CC,P=0.44).CONCLUSION The implementation of AIAC failed to improve key markers of colonoscopy quality,including ADR,SSLDR and withdrawal time.Further research is required to assess the utility and cost-efficiency of AIAC for high performing endoscopists.