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Traditional serrated adenoma. This polyp is composed of villiform projections of hypereosinophilic cells with small oval-shaped nuclei oriented basally along the basement membrane. The cells are growing in a hyperserrated luminal contour. Multiple ectopic crypts are present. These are composed of crypts oriented perpendicular to the long axis of the villi. Overall, goblet cells are decreased in number.

Traditional serrated adenoma. This polyp is composed of villiform projections of hypereosinophilic cells with small oval-shaped nuclei oriented basally along the basement membrane. The cells are growing in a hyperserrated luminal contour. Multiple ectopic crypts are present. These are composed of crypts oriented perpendicular to the long axis of the villi. Overall, goblet cells are decreased in number.

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Serrated lesions of the colorectum are the precursors of perhaps one-third of colorectal cancers (CRCs). Cancers arising in serrated lesions are usually in the proximal colon, and account for a disproportionate fraction of cancer identified after colonoscopy. We sought to provide guidance for the clinical management of serrated colorectal lesions b...

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... TSAs often show a complex and distorted tubulovillous or villous ("filiform") configuration (Figure 3). In many cases, the villi are elongated with bulbous tips, and have been termed filiform TSAs (26). ...

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... Clinically significant serrated polyps (SSPs) were defined as any sessile serrated polyp/adenoma, traditional serrated polyp, hyperplastic polyps ≥ 1 cm anywhere in the colon, or hyperplastic polyp ≥ 5 mm located proximally to the sigmoid colon. We chose this definition based on the expert consensus on serrated polyp by Rex et al. [13], which recommended shorter screening intervals for any hyperplastic polyp > 5 mm located proximally to the sigmoid colon. ...
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Background and aims Polyps histology and diameter up to 1 cm determine whether a patient needs a colonoscopy after 3 years or less, or far ahead. Endoscopists’ and pathologists’ size estimations can be imprecise. Our aim was to assess endoscopist ability to correctly recommend surveillance colonoscopies for patients with polyps around the 10 mm threshold, based on its endoscopic sizing and optical diagnosis by NBI. Methods NBI-assisted diagnosis and endoscopist estimation of polyp size were compared with reference standard, considering this as the post resection polyp measurements by the nurse assistant and the pathologic results, in a prospective, multicenter, real life study, that recruited adults undergoing colonoscopy in five hospitals. By comparing the endoscopic and pathologist size estimation, with polyps’ measurement after resection, and optical and histological diagnoses in patients with polyps between 5 and 15 mm, sensitivity was assessed at the patient level by means of two characteristics: the presence of adenoma, and the surveillance interval. Surveillance intervals were established by the endoscopist, based on optical diagnosis, and by another gastroenterologist, grounded on the pathologic report. Determinants of accuracy were explored at the polyp level. Results 532 polyps were resected in 451 patients. Size estimation was more precise for the endoscopist. Endoscopist sensitivity for the presence of adenoma or carcinoma was 98.7%. Considering the presence of high-grade dysplasia or cancer, sensitivity was 82.6% for the endoscopic optical diagnosis. Sensitivity for a correct 3-year surveillance interval was 91.5%, specificity 82.3%, with a PPV of 93.2% and NPV of 78.5% for the endoscopist. 6.51% of patients would have had their follow-up colonoscopy delayed, whereas 22 (4.8%) would have it been performed earlier, had endoscopist recommendations been followed. Conclusion Our study observes that NBI optical diagnosis can be recommended in routine practice to establish surveillance intervals for polyps between 5 and 15 mm. Clinical Trials Registration Number: NCT04232176
... Interestingly, the rate of serrated adenomas did not significantly differ (P = 0.32) between patients age > 50 (11.7%) and patients age 45-49 (10.1%) [5], suggesting surveillance colonoscopy in younger patients found to have serrated lesions may be warranted as one-third of colorectal cancer percussor lesion are found to serrated adenomas [12]. ...
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Purpose of review We aimed to determine whether young-onset adenomas increased the risk for colorectal cancer by determining the adenoma prevalence, risk factors associated with young-onset adenomas, as well as the need for surveillance colonoscopies in the young-adult population (age < 50). Recent findings By examining multiple meta-analyses and systematic review studies, we determined that while adenoma rates are lower in young adults (age < 45) compared to those > age 50, subsets of young adults are at higher risk of adenoma formation and therefore may have increased colorectal cancer risk. Therefore, surveillance colonoscopy may be beneficial for patients aged 40–49 years of age to reduce colorectal cancer risk, particularly in young-adult patients presenting with concerning symptoms, such as bright red blood per rectum, those found to have high-risk advanced adenomas, and those with risk factors associated with higher adenoma detection rates including diabetes, male gender, and metabolic syndrome. Summary Young adults found to have adenomas may warrant both close surveillance with colonoscopy as well as hereditary cancer risk assessment and genetic testing to identify underlying hereditary cancer syndromes.
... WHO requires the presence of at least 3 crypts with minimum 2 crypts showing one or more of the features mentioned above, while the American gastroenterology association criteria involves the presence of a single crypt with the mentioned characteristic changes. 18 Adenoma-carcinoma sequence is commonly known to explain the pathway of molecular changes. Ultimately, it leads to the malignant transformation of an adenoma. ...
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Colorectal cancer (CRC) is the second most deadly cancer affecting globally. Although most CRCs seen in young adults are sporadic, hereditary cancer syndromes should be considered as an essential factor. Screening for colorectal cancer aids in the early detection and treatment of early-stage CRC; which reduces mortality rates. This review article aimed to present neoplastic and non-neoplastic polyps and their management from a surgeon's perspective while describing screening protocols in high-risk groups. It also highlighted the etiology, clinical features, diagnosis and management of adenomatous polyps and hereditary bowel cancer syndromes like Peutz-Jeghers syndrome (PJS), juvenile polyposis syndrome (JPS), Cowden syndrome (CS), Lynch syndrome (LS) and familial adenomatous polyposis (FAP). The article summarized the importance of these syndromes as a risk factor in colorectal cancer and identifies these as high-risk group patients in colorectal screening protocols. A summary of the management of these risk factors has been described from a surgeon's point of view.
... Among those classifications, HP accounts for the majority of serrated lesions, followed by SSA and SSP, whereas TSA is the least common [3]. Previously, serrated lesions were mainly considered to be HPs and were not considered malignant; however, in recent years, serrated lesions characterized by a saw-toothed appearance were found to have malignant potential and heterogeneity compared to other polyps [4,5]. ...
Article
The serrated pathway is important in the development of colorectal cancer; currently, knowledge about the lipid metabolism profiles of serrated lesions is limited. Clinical characteristics were compared via Pearson's chi-squared test, nonparametric Kruskal-Wallis test and ANOVA. For some missing values, the MCAR test and multiple imputations were performed. Compared to patients with HP, the rates of younger patients (<50) and male patients with SSA or SSP were increased (P<0.05). Additionally, the BMI index and triglyceride levels were increased in patients with SSA or SSP. Inversely, patients with SSA/P had lower levels of HDL (P<0.05). Interestingly, the value of uric acid and tumor size in SSA/P patients tended to be greater than those in HP patients, and the ratio of patients who smoked was also increased. Other characteristics, such as LDL, ALB, γ-GT, and the N/L ratio, were similar among the subtypes of serrated lesions. Analysis of GEO data (GSE43841) showed that 9 genes were associated with lipid metabolism, including ADRB3, DEGS2, PRKACB, SLC44A1, and CA4. PRKACB was downregulated in SSA/P tissue compared to HP tissue samples from the GSE76987 dataset and our hospital. In conclusion, compared to benign HP, lower HDL levels and higher triglyceride levels tended to occur in CRC precursor SSA/P lesions, and these factors may be associated with metabolic genomic markers, such as PRKACB.
... [26][27][28][29][30][31] Our transcriptome analysis showed that some of them, including BRAF and APC, were mildly decreased, but direct Sanger sequencing of the BRAF gene showed a mutation rate (BRAF V600E) of 25%, which was less than that previously reported. 4,32 We also found that CDX2 showed the lowest expression ratio in tumor tissues compared with normal tissues, which was verified by immunohistochemical staining. ...
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The objective of this study was to elucidate the molecular background of sessile serrated adenoma/polyp (SSA/P) endoscopically resected with comprehensive gene expression analysis. Gene expression profiling was performed for 10 tumor‐normal pairs of SSA/P. Cluster analysis, gene set enrichment analysis (GSEA), and consensus molecular subtype (CMS) classification of colorectal cancer (CRC) were applied to our transcriptome analysis. Unsupervised cluster analysis showed that the gene expression profile of SSA/Ps is different from that of adjacent normal epithelial cells, even in the very early stage of tumorigenesis. According to the CMS classification, our microarray data indicated that SSA/Ps were classified as CMS1. GSEA demonstrated a strong association between SSA/P and microsatellite instability‐high (MSI‐H) CRC (p < 10−5). Transcriptome analysis of five MSI‐related genes (MSH2, MSH6, MLH1, PMS1, and PMS2) and five CRC‐related genes (BRAF, KRAS, APC, TP53, and CDX2) showed that CDX2 expression was most severely decreased in SSA/P. Immunohistochemical staining confirmed that CDX2 protein was reduced compared with the surrounding mucosa. Direct sequencing of the BRAF gene showed that the BRAF V600E mutation was detected in only nine of 36 cases. In a mouse model, BRAF, APC, or CDX2 deficiency indicated that the gene expression pattern with loss of CDX2 is more similar to our SSA/Ps compared with those induced by BRAF or APC mutation. Transcriptome analysis of SSA/Ps showed characteristic gene expression with a strong resemblance to MSI‐H CRC. Downregulation of CDX2 expression is an essential molecular mechanism involved in the initial stage of SSA/P tumorigenesis. (UMIN000027365). SSA/Ps showed characteristic gene expression with a strong resemblance to microsatellite instability‐high colorectal cancer. And the downregulation of CDX2 expression is an essential molecular mechanism involved in the initial stage of SSA/P tumorigenesis.
... Moreover, it is well known that leptin's physiological mechanism of action is exerted throughout its receptor (LEPR), which is expressed in CRC [60], i.e., higher leptin serum levels [61]. Interestingly, the associations between LEP and LEPR gene variants and CRC are still contradictory [62,63], with mutation gain being a crucial factor enabling the genetic process of CRC [64]. ...
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Obesity and colorectal cancer (CRC) are among the leading diseases causing deaths in the world, showing a complex multifactorial pathology. Obesity is considered a risk factor in CRC development through inflammation, metabolic, and signaling processes. Leptin is one of the most important adipokines related to obesity and an important proinflammatory marker, mainly expressed in adipose tissue, with many genetic variation profiles, many related influencing factors, and various functions that have been ascribed but not yet fully understood and elucidated, the most important ones being related to energy metabolism, as well as endocrine and immune systems. Aberrant signaling and genetic variations of leptin are correlated with obesity and CRC, with the genetic causality showing both inherited and acquired events, in addition to lifestyle and environmental risk factors; these might also be related to specific pathogenic pathways at different time points. Moreover, mutation gain is a crucial factor enabling the genetic process of CRC. Currently, the inconsistent and insufficient data related to leptin’s relationship with obesity and CRC indicate the necessity of further related studies. This review summarizes the current knowledge on leptin genetics and its potential relationship with the main pathogenic pathways of obesity and CRC, in an attempt to understand the molecular mechanisms of these associations, in the context of inconsistent and contradictory data. The understanding of these mechanisms linking obesity and CRC could help to develop novel therapeutic targets and prevention strategies, resulting in a better prognosis and management of these diseases.
... Since serrated colorectal lesions were recognized as premalignant lesions leading CRC, in addition to the conventional morphologic adenoma-carcinoma sequence a n morphologic pathway, the so-called "serrated neoplasia pathway", was described. past decades, researchers tried to understand the molecular basis of this new pathw able to convert normal mucosa in a serrated colorectal lesion and then in CRC [64][65][66][67][68]. the molecular level, CRCs arising from serrated lesions originate via two different m lecular pathways, namely sporadic MSI and CpG island methylator phenotype (CIM the latter being considered as the major mechanism that drives the serrated pathw toward CRC [69]. Unlike CRCs arising through the adenoma-carcinoma pathw APC-inactivating mutations are rarely shown in the serrated neoplasia pathway. ...
... Since serrated colorectal lesions were recognized as premalignant lesions leading to CRC, in addition to the conventional morphologic adenoma-carcinoma sequence a new morphologic pathway, the so-called "serrated neoplasia pathway", was described. In past decades, researchers tried to understand the molecular basis of this new pathway able to convert normal mucosa in a serrated colorectal lesion and then in CRC [64][65][66][67][68]. At the molecular level, CRCs arising from serrated lesions originate via two different molecular pathways, namely sporadic MSI and CpG island methylator phenotype (CIMP), the latter being considered as the major mechanism that drives the serrated pathway toward CRC [69]. ...
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Until 2010, colorectal serrated lesions were generally considered as harmless lesions and reported as hyperplastic polyps (HPs) by pathologists and gastroenterologists. However, recent evidence showed that they may bear the potential to develop into colorectal carcinoma (CRC). Therefore, the World Health Organization (WHO) classification has identified four categories of serrated lesions: hyperplastic polyps (HPs), sessile serrated lesions (SSLs), traditional serrated adenoma (TSAs) and unclassified serrated adenomas. SSLs with dysplasia and TSAs are the most common precursors of CRC. CRCs arising from serrated lesions originate via two different molecular pathways, namely sporadic microsatellite instability (MSI) and the CpG island methylator phenotype (CIMP), the latter being considered as the major mechanism that drives the serrated pathway towards CRC. Unlike CRCs arising through the adenoma–carcinoma pathway, APC-inactivating mutations are rarely shown in the serrated neoplasia pathway.
... We sought to determine the effectiveness of a simple, low-cost intervention of displaying polyp detection posters aimed at improving detection of SSLs and AN, which are challenging to de-tect as they occur on the right side, are flat or sessile, and in the case of SSLs, often have irregular borders and an overlaying mucosa cap [9]. Detecting these lesions requires rigorous withdrawal technique and high vigilance for looking for them. ...
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Background and study aims Colonoscopy is effective in reducing the incidence of colorectal cancer, but interval cancers remain a concern and their occurrence mainly is thought to be due to poor detection of sessile serrated lesions (SSLs) and advanced neoplasia (AN). Currently there are no low-cost, easy-to-implement tools to improve detection of difficult-to-detect polyps. Our aims were to compare the detection rate for SSLs and AN between two groups of endoscopists at a large community practice, one of which received an intervention of a polyp detection poster displayed over the monitor in their endoscopy suite for 6 months. We compared preintervention and post-intervention detection rates in the intervention and control groups. Methods This was a convenience case control quality improvement project. For 6 months, a 2’ × 3’ poster of pictures of SSLs and advanced neoplasia was displayed over the monitor for 44 endoscopist in a large community gastroenterology practice in the Minneapolis/St.Paul area, while another 44 physicians performed colonoscopy in the usual fashion without the poster. The endpoints were improvement in detection rates for SSLs and AN preintervention and post-intervention between the control and intervention groups. Results During the study, 88 endoscopists performed 54,861 colonoscopies. At least one adenoma was detected in 41.3 % of patients, one or more SSLs in 11.4 %, and AN in 10.6 %. During the intervention period, the SSL detection rates were 10.9 % and 12.3 % for the control and intervention groups and for AN, the detection rates were 10.4 % and 10.75 % for the two groups, respectively. Exposure to the polyp detection poster significantly changed SSL detection for the intervention group relative to the control group (likelihood ratio test P
... Several longitudinal studies have investigated the relationship between the future risks of colorectal neoplasms and the clinicopathological characteristics of SPs, such as histology, size, anatomic location, or numbers (5)(6)(7). Evidence indicates that the detection of large SPs at the first endoscopy is more likely to have metachronous advanced neoplasms than those with no SPs (8), and it is an independent risk factor for subsequent CRC even with stronger association than that for advanced adenomas (9,10). Cross-sectional reports have also substantially manifested that over-representation of malignancy hallmarks in SPs including BRAF mutation, MLH1 methylation, MUC5AC demethylation, and CIMP proposes possibly higher risks of CRC compared to conventional adenomas (11)(12)(13). ...
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Background Follow-up guidelines for serrated polyps (SPs) are mainly based on factors such as histology and size with limited evidence. The underlying genomic mechanism of SPs in relation to recurrence risks is utterly unknown.Methods We applied targeted next-generation sequencing (NGS) approach on two groups of SPs [polyp-relapsed SPs (PRSPs) vs. polyp-free SPs (PFSPs)] based on the surveillance outcomes to compare differences of DNA variants in 71 colorectal cancer-associated genes. A multicenter validation cohort was established longitudinally from 2016 to 2019 to confirm the relevant results.ResultsAmong the 96 NGS samples, at least one mutant after filtration was detected in 90 samples (94%). Molecular profiling presented BRAF, KRAS, and APC as top 3 mutated genes. FBXW7, MSH2, and ERBB2 might be recurrence-relevant, while DMD, BRCA1, and BRCA2 might be negatively correlated with recurrence. Notably, ERBB2 mutants (R678Q and V842I) (n = 5) had higher risks of polyp recurrence than the wild types (n = 85), with a median polyp-free interval of 15 months compared to 26 months [P < 0.001; hazard ratio (HR) = 4.9; 95% confidence interval (CI) = 1.9–12.8]. Furthermore, a multicenter cohort composed by 321 SPs verified that ERBB2-mutated SPs had increased risks of polyp recurrence (P < 0.001; HR = 3.7; 95% CI = 2.3–6.0) and advanced neoplastic lesion (ANL) recurrence (P < 0.001; HR = 10.0; 95% CI = 2.7–36.9) compared with wild-type SPs, respectively.Conclusions Our results are emphasizing that SP individuals with ERBB2 mutants are at higher risks of subsequent colorectal neoplasms. ERBB2 mutants might work as facilitated markers for prediction of high-risk SPs and might implicate a potential mechanism in the serrated pathway to colorectal carcinoma (CRC).
... SSLs are frequently found in the right colon, where bowel preparation may be poorer. They mostly appear as flat lesions with indistinct borders and are often concealed by a mucous cap or fecal debris [7,8]. SSLs are frequently missed and resected incompletely [9]; the incomplete resection rate during hot snare polypectomy is almost four times higher than that of conventional adenomas (31.0% vs. 7.2%) [10]. ...
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Background and aims Sessile serrated lesions (SSLs) are more prone to incomplete resection than conventional adenomas. This study evaluated whether circumferential submucosal incision prior to endoscopic mucosal resection (CSI-EMR) can increase the rate of complete and en bloc resections of colorectal lesions with endoscopic features of SSL. Methods Retrospective analyses and propensity score matching were performed for the resection of colorectal lesions ≥ 10 mm with endoscopic features of SSL. Results After 1:1 ratio matching, 127 lesions in the CSI-EMR group and 127 in the EMR group were selected for analysis. The median size of the lesions was 15 mm (IQR 12–16) in both groups. There was no significant difference in either the complete resection rate or en bloc resection rate between CSI-EMR and EMR groups (96.9% vs. 92.9%, P = 0.155; 92.1% vs. 89.0%, P = 0.391). By contrast, the R0 resection rate was significantly higher in the CSI-EMR group than in the EMR group (89.8% vs. 59.8%, P < 0.001). The median procedure time was significantly longer in the CSI-EMR group than in the EMR group (6.28 min vs. 2.55 min, P < 0.001), whereas there was no significant difference between the two groups in the incidence of adverse events or recurrence rate. Multivariate analysis showed that CSI-EMR was the only factor significantly associated with R0 resection (P < 0.001). Conclusions For colorectal lesions with endoscopic features of SSL, CSI-EMR does not increase the complete or en bloc resection rate, but does increase the R0 resection rate. The procedure time is longer for CSI-EMR than EMR. The association of CSI-EMR with R0 resection and non-recurrence should be further evaluated.