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Objective: 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. Methods: 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. Results: 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. Conclusion: SSLs >10 mm, 0‐Ip or 0‐IIa + Is morphologies, and those with nodules/protrusions are significantly associated with dysplasia/carcinoma. [ABSTRACT FROM AUTHOR]

Serrated polyps are considered the precursor lesions of colorectal cancer through the serrated pathway. In the present study, we aimed to evaluate and discuss the clinical and endoscopic characteristics and management of serrated polyps. The data of 220 cases with serrated polyps between September 2018 and November 2021 in Shenzhen People's Hospital were retrospectively analyzed. Of all these cases, 32 were hyperplastic polyps, 36 were traditional serrated adenomas, 126 were sessile serrated lesions, 25 were SSLs with dysplasia, and one was an unclassified serrated adenoma. Although most patients were males aged ≥50 years and most serrated polyps were located in the distal colon and rectum with a size of 6–10 mm and the shape of type 0-Is, there was no significant difference (P > 0.05). Serrated polyps of ≤5 mm in size and type 0-IIa were mostly removed by cold biopsy forceps. Cold snare polypectomy was primarily used for those of 6–10 mm in size. Endoscopic mucosal resection was used for those of 6–20 mm, and endoscopic submucosal dissection was used for those of ≥20 mm (P < 0.05). All complications occurred in SSL patients with or without dysplasia (P < 0.05). Clinical and endoscopic characteristics were beneficial for distinguishing and diagnosing serrated polyps. In addition, management options were crucial to prevent recurrence and progression. However, the detection rate of serrated polyps was relatively low. Therefore, prospective multicenter studies with large samples are necessary to better assess colorectal serrated polyps. [ABSTRACT FROM AUTHOR]

Abstract Objectives This study aimed to extract endoscopic findings for diagnosing colorectal neoplasia associated with sessile serrated lesions (SSLs), which are of significant interest. Methods To compare the magnifying narrow‐band imaging (NBI) findings with microscopic morphology, we classified SSLs into two groups: Group A SSLs included the majority of uniform SSLs and any dysplasia other than that classified as group B SSLs. Group B SSLs included SSLs with intramucosal and invasive carcinoma. We also quantitatively assessed visible vessels using ImageJ software. Results This study included 47 patients with 50 group B SSLs who underwent endoscopic resection between 2012 and 2020. The results were retrospectively compared with those of 237 patients with 311 group A SSLs that underwent endoscopic resection. Using conventional white‐light endoscopy, significantly more group B SSLs had uneven shapes and some reddening compared to group A SSLs. The diagnostic odds ratios for group B SSLs were as follows: lesions with a diameter ≥10 mm, 9.76; uneven shape, 3.79; reddening, 15.46; and visible vessels with NBI, 11.32. Regarding visible vessels with NBI, the specificity and diagnostic accuracy for group B SSLs were 94.9% and 93.1%, respectively. The percentage of the vascular tonal area of NBI images was significantly larger for group B SSLs than for group A SSLs (3.97% vs. 0.29%; p < 0.01). Conclusions SSLs with reddening and/or a diameter ≥10 mm are suspected to contain cancerous components. Moreover, visible vessels observed using magnifying NBI can serve as objective indicators for diagnosing SSLs with cancerous components with a high degree of accuracy.

Abstract 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

The 2019 World Health Organization (WHO) Classification of Tumours of the Digestive System (5th edition) introduced the term "sessile serrated lesion" (SSL) to replace the term "sessile serrated adenoma/polyp" (SSA/P). SSLs are early precursor lesions in the serrated neoplasia pathway that result in colorectal carcinomas with BRAF mutations, methylation for DNA repair genes, a CpG island methylator phenotype, and high levels of microsatellite instability. Some of these lesions can rapidly become dysplastic or invasive carcinomas that exhibit high lymphatic invasion and lymph node metastasis potential. The 2019 WHO classification noted that dysplasia arising in an SSL most likely is an advanced polyp, regardless of the morphologic grade of the dysplasia. Detecting SSLs with or without dysplasia is critical; however, detection of SSLs is challenging, and their identification by endoscopists and pathologists is inconsistent. Furthermore, indications for their endoscopic treatment have not been established. Moreover, SSLs are considered to contribute to the development of post‐colonoscopy colorectal cancers. Herein, the clinicopathological and endoscopic characteristics of SSLs, including features determined using white light and image‐enhanced endoscopy, therapeutic indications, therapeutic methods, and surveillance are reviewed based on the literature. This information may lead to more intensive research to improve detection, diagnosis, and rates of complete resection of these lesions and reduce post‐colonoscopy colorectal cancer rates. [ABSTRACT FROM AUTHOR]

ObjectiveVitamin D consumption and circulating 25(OH)D level are associated with decreased risk of colorectal cancer (CRC) and colorectal adenoma (CRA), but few studies have assessed their relationship with the incidence and recurrence of CRC precursors. Therefore, we performed this meta-analysis to further evaluate the association.MethodsWe searched PubMed, Web of Science, Scopus and Embase databases in English until August 2021. Studies evaluating the association of vitamin D intake and circulating 25(OH)D level with risk of CRC precursors were included. A random-effects model was used to pool the risk estimates.ResultsA total of 48 studies were selected for inclusion. The CRC precursors incidence was negatively correlated with total vitamin D intake (RR = 0.84 95%CI: 0.80–0.88) and circulating 25(OH)D level (RR = 0.79 95%CI: 0.67–0.92). However, vitamin D intake and circulating 25(OH)D level did not show significant effects on the risk of CRC precursors recurrence. For dose-response analysis, evidence of a linear association was found between CRC precursors incidence and circulating 25(OH)D level, and the risk decreased by 14% per 10 ng/ml increment of circulating 25(OH)D level (RR = 0.86 95% CI: 0.75–0.99).ConclusionVitamin D intake and circulating 25(OH)D level can play an effective role in reducing the risk of incidence of CRC precursors. However, they have not prevented the recurrence of CRC precursors.

Abstract Background The histological discrimination of hyperplastic polyps from sessile serrated lesions can be difficult. Sessile serrated lesions and hyperplastic polyps are types of serrated polyps which confer different malignancy risks, and surveillance intervals, and are sometimes difficult to discriminate. Our aim was to reclassify previously diagnosed hyperplastic polyps as sessile serrated lesions or confirmed hyperplastic polyps, using additional serial sections. Methods Clinicopathological data for all colorectal hyperplastic polyps diagnosed in 2016 and 2017 was collected. The slides were reviewed and classified as hyperplastic polyps, sessile serrated lesion, or other, using current World Health Organization criteria. Eight additional serial sections were performed for the confirmed hyperplastic polyp group and reviewed. Results Of an initial 147 hyperplastic polyps from 93 patients, 9 (6.1%) were classified as sessile serrated lesions, 103 as hyperplastic polyps, and 35 as other. Of the 103 confirmed hyperplastic polyps, 7 (6.8%) were proximal, and 8 (7.8%) had a largest fragment size of ≥5 mm and

Abstract Background Little is known about the natural history of serrated polyps (SPs), partly due to the lack of large-scale epidemiologic data. In this study, we examined the validity of SP identification according to SNOMED (Systematised Nomenclature of Medicine) codes and free text from colorectal histopathology reports. Methods Through the ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) study, we retrieved data on SPs from all pathology departments in Sweden in 2015–2017 by using SNOMED codes and free-text search in colorectal histopathology reports. Randomly selected individuals with a histopathology report of SPs were validated against patient charts using a structured, retrospective review. Results SPs were confirmed in 101/106 individuals with a histopathology report of SPs, yielding a positive predictive value (PPV) of 95% (95%CI = 89–98%). By year of diagnosis, the PPV was 89% (95%CI = 69–97%), 96% (95%CI = 81–99%) and 97% (95%CI = 89–99%) for individuals diagnosed before 2001 (n = 19), between 2001 and 2010 (n = 26) and after 2010 (n = 61), respectively. According to search method, the PPV for individuals identified by SNOMED codes was 100% (95%CI = 93–100%), and 93% (95%CI = 86–97%) using free-text search. Recorded location (colon vs. rectum) was correct in 94% of all SP histopathology reports (95%CI = 84–98%) identified by SNOMED codes. Individuals with SPs were classified into hyperplastic polyps (n = 34; 32%), traditional serrated adenomas (n = 3; 3%), sessile serrated adenomas/polyps (SSA/Ps) (n = 70; 66%), unspecified SPs (n = 3, 3%), and false positive SPs (n = 5, 5%). For individuals identified by SNOMED codes, SSA/Ps were confirmed in 49/52 individuals, resulting in a PPV of 94% (95%CI: 84–98%). In total, 57% had ≥2 polyps (1: n = 44, 2–3: n = 33 and ≥ 4: n = 27). Some 46% of SPs (n = 71) originated from the proximal colon and 24% were ≥ 10 mm in size (n = 37). Heredity for colorectal cancer, intestinal polyposis syndromes, or both was reported in seven individuals (7%). Common comorbidities included diverticulosis (n = 45, 42%), colorectal cancer (n = 19, 18%), and inflammatory bowel disease (n = 10, 9%). Conclusion Colorectal histopathology reports are a reliable data source to identify individuals with SPs.

Background/Aims: Sessile serrated adenomas/polyps (SSA/Ps) are a putative precursor lesion of colon cancer. Although the relevance of DNA hypermethylation in the SSA/P-cancer sequence is well documented, the role of DNA hypomethylation is unknown. We investigated the biological relevance of DNA hypomethylation in the SSA/P-cancer sequence by using 3-dimensional organoids of SSA/P. Methods: We first analyzed hypomethylated genes using datasets from our previous DNA methylation array analysis on 7 SSA/P and 2 cancer in SSA/P specimens. Expression levels of hypomethylated genes in SSA/P specimens were determined by RT-PCR and immunohistochemistry. We established 3-dimensional SSA/P organoids and performed knockdown experiments using a lentiviral shRNA vector. DNA hypomethylation at CpG sites of the gene was quantitated by MassARRAY analysis. Results: The mean number of hypomethylated genes in SSA/P and cancer in SSA/P was 41.6 ± 27.5 and 214 ± 19.8, respectively, showing a stepwise increment in hypomethylation during the SSA/P-cancer sequence. S100P, S100α2, PKP3, and MUC2 were most commonly hypomethylated in SSA/P specimens. The mRNA and protein expression levels of S100P, S100α2, and MUC2 were significantly elevated in SSA/P compared with normal colon tissues, as revealed by RT-PCR and immunohistochemistry, respectively. Among these, mRNA and protein levels were highest for S100P. Knockdown of the S100P gene using a lentiviral shRNA vector in 3-dimensional SSA/P organoids inhibited cell growth by >50% (p < 0.01). The mean diameter of SSA/P organoids with S100P gene knockdown was significantly smaller compared with control organoids. MassARRAY analysis of DNA hypomethylation in the S100P gene revealed significant hypomethylation at specific CpG sites in intron 1, exon 1, and the 5′-flanking promoter region. Conclusion: These results suggest that DNA hypomethylation, including S100P hypomethylation, is supposedly associated with the SSA/P-cancer sequence. S100P overexpression via DNA hypomethylation plays an important role in promoting cell growth in the SSA/P-cancer sequence. [ABSTRACT FROM AUTHOR]

Background: The histological discrimination of hyperplastic polyps from sessile serrated lesions can be difficult. Sessile serrated lesions and hyperplastic polyps are types of serrated polyps which confer different malignancy risks, and surveillance intervals, and are sometimes difficult to discriminate. Our aim was to reclassify previously diagnosed hyperplastic polyps as sessile serrated lesions or confirmed hyperplastic polyps, using additional serial sections. Methods: Clinicopathological data for all colorectal hyperplastic polyps diagnosed in 2016 and 2017 was collected. The slides were reviewed and classified as hyperplastic polyps, sessile serrated lesion, or other, using current World Health Organization criteria. Eight additional serial sections were performed for the confirmed hyperplastic polyp group and reviewed. Results: Of an initial 147 hyperplastic polyps from 93 patients, 9 (6.1%) were classified as sessile serrated lesions, 103 as hyperplastic polyps, and 35 as other. Of the 103 confirmed hyperplastic polyps, 7 (6.8%) were proximal, and 8 (7.8%) had a largest fragment size of ≥5 mm and < 10 mm. After 8 additional serial sections, 11 (10.7%) were reclassified as sessile serrated lesions. They were all less than 5 mm and represented 14.3% of proximal polyps and 10.4% of distal polyps. An average of 3.6 serial sections were required for a change in diagnosis. Conclusion: Histopathological distinction between hyperplastic polyps and sessile serrated lesions remains a challenge. This study has uncovered a potential role for the use of additional serial sections in the morphological reappraisal of small hyperplastic polyps, especially when proximally located. [ABSTRACT FROM AUTHOR]

Sessile serrated adenomas/polyps (SSA/Ps) are the putative precursors of the ~20% of colon cancers with the CpG island methylator phenotype (CIMP). To investigate the epigenetic phenotype of these precancers, we prospectively collected fresh-tissue samples of 17 SSA/Ps and 15 conventional adenomas (cADNs), each with a matched sample of normal mucosa. Their DNA was subjected to bisulfite next-generation sequencing to assess methylation levels at ~2.7 million CpGs located predominantly in gene regulatory regions and spanning 80.5Mb; RNA was sequenced to define the samples’ transcriptomes. Compared with normal mucosa, SSA/Ps and cADNs exhibited markedly remodeled methylomes. In cADNs, hypomethylated regions were far more numerous (18,417 vs 4288 in SSA/Ps) and rarely affected CpG islands/shores. SSA/Ps seemed to have escaped this wave of demethylation. Cytosine hypermethylation in SSA/Ps was more pervasive (hypermethylated regions: 22,147 vs 15,965 in cADNs; hypermethylated genes: 4938 vs 3443 in cADNs) and more extensive (region for region), and it occurred mainly within CpG islands and shores. Given its resemblance to the CIMP typical of SSA/Ps' putative descendant colon cancers, we refer to the SSA/P methylation phenotype as proto-CIMP. Verification studies of six hypermethylated regions in an independent series of precancers demonstrated DNA methylation markers’ high potential for predicting the diagnosis of SSA/Ps and cADNs. Surprisingly, proto-CIMP in SSA/Ps was associated with upregulated gene expression; downregulation was more common in cADNs. In conclusion, the epigenetic landscape of SSA/Ps differs markedly from that of cADNs. These differences are a potentially rich source of novel tissue-based and noninvasive biomarkers.

Abstract Background Colorectal sessile serrated adenoma/polyps (SSA/Ps) are considered early precursor lesions in the serrated neoplasia pathway. Recent studies have shown associations of SSA/Ps with lost MLH1 expression, a CpG island methylator phenotype, and BRAF mutations. However, the molecular biological features of SSA/Ps with early neoplastic progression have not yet been fully elucidated, owing to the rarity of cases of SSA/P with advanced histology such as cytologic dysplasia or invasive carcinoma. In this study, we aimed to elucidate the molecular biological features of SSA/Ps with dysplasia/carcinoma, representing relatively early stages of the serrated neoplasia pathway. Methods We performed immunostaining for β-catenin, MLH1, and mucins (e.g., MUC2, MUC5AC, MUC6, and CD10); targeted next-generation sequencing; and microsatellite instability (MSI) testing in 8 SSA/P lesions comprised of 4 SSA/Ps with high-grade dysplasia and 4 SSA/Ps with submucosal carcinoma. Results Lost MLH1 expression was found in 5 cases. All lesions studied were positive for nuclear β-catenin expression. Regarding phenotypic mucin expression, all lesions were positive for MUC2, but negative for CD10. MUC5AC and MUC6 positivity was observed in 7 cases. Genetically, the most frequently mutated gene was BRAF (7 cases), and other mutations were detected in FBXW7 (3 cases); TP53 (2 cases), and KIT, PTEN, SMAD4, and SMARCB1 (1 case each). Furthermore, 4 of 8 lesions were MSI-high and the remaining 4 lesions were microsatellite-stable (MSS). Interestingly, all 4 MSI-high lesions displayed MLH1 loss, 3 of which harbored a FBXW7 mutation, but not a TP53 mutation. However, 2 MSS lesions harbored a TP53 mutation, although none harbored a FBXW7 mutation. Conclusions SSA/Ps with dysplasia/carcinoma frequently harbored BRAF mutations. Activation of the WNT/β-catenin signaling pathway may facilitate the development of dysplasia in SSA/Ps and progression to carcinoma. Furthermore, our results suggested that these lesions might be associated with both MSI-high and MSS colorectal cancer, which might be distinguished by distinct molecular biological features such as lost MLH1 expression, FBXW7 mutations, and TP53 mutations.

In a 64-year-old woman, we identified a flat, elevated lesion that was located at the caecum and was composed of 3 different areas (areas A, B, and C). We diagnosed it as “carcinoma with sessile serrated adenoma/polyp (SSA/P)” histologically. Although area A was diagnosed as classical SSA/P, area B was regarded as a high-grade SSA/P. In contrast, area C showed a differentiated-type adenocarcinoma that invaded the submucosa. The patient had a recurrence of cancer 1.5 years after endoscopic resection. Overexpression of TP53 was detected in area C. Although BRAF mutation was detected in all areas, CpG island methylator phenotype-high cancer was found only in area C. The genomic phenotype of the cancerous tissue was classified as microsatellite stable (MLH1 gene not methylated). In the present case, we showed that a lesion with genetic alterations based on the histological sequence SSA/P → high-grade SSA/P → cancer in SSA/P and an alternative serrated pathway may exhibit aggressive behavior.

Purpose: The sessile serrated adenoma/polyp detection rate (SSA/PDR) among different colonoscopy indications from daily practice has not been fully understood. This study aimed to evaluate the detection and clinical characteristics of serrated polyps and conventional adenomas between outpatient department (OPD) and physical checkup unit (PCU) patients receiving colonoscopy. Methods: The data for this retrospective study were collected between 2016 and 2017 at Kaohsiung Veterans General Hospital in Taiwan. A total of 7047 individuals were included, and information on polyp and adenoma detection was extracted from the colonoscopy reports. Results: The adenoma detection rate, the SSA/PDR, and the detection rate of traditional serrated adenoma (TSA) were 32.2%, 0.60%, and 0.50%, respectively. Risk analysis revealed no significant difference (p = 0.095) in SSA/PDR between individuals < 50 years and ≥ 50 years, and no trend of increased SSA/PDR as age increased was observed (p = 0.320). SSA/P and TSA had higher risks for synchronous advanced neoplasia than conventional adenoma, but with proximal hyperplastic polyps lower (p < 0.001, respectively). No significant difference of SSA/PDR between OPD and PCU patients was observed (p = 1.000); however, the age of SSA/P was significantly older in OPD than in PCU patients (p = 0.048). Conclusion: The detection rates of CA and TSA were associated with age groups; however, SSA/PDR was insignificantly higher among individuals aged < 50 years than those with other age groups. In addition, SSA/PDR between OPD and PCU patients was not significantly found in daily practice of colonoscopies. [ABSTRACT FROM AUTHOR]

Based on the concept of the adenoma‐carcinoma sequence, most colorectal cancers are considered to arise from conventional adenomas. However, recent studies suggested that a subset of colorectal cancers develop through the serrated neoplastic pathway. It has also been documented that serrated polyps can rapidly transform into invasive cancers even when they are small in size. We now describe a case of a sessile serrated adenoma/polyp which had been followed up for 4 years but eventually showed rapid transformation into an advanced cancer accompanied by a remarkable morphological change within only 13 months. Retrospective genetic and epigenetic analyses showed microsatellite instability, CpG island methylator phenotype‐positive, and BRAF mutation in the lesion, suggesting the tumor had developed through the serrated neoplastic pathway. This case may provide valuable information about the natural history of sessile serrated adenoma/polyps which eventually progress to advanced cancers. [ABSTRACT FROM AUTHOR]

Aim: Compromise of the gastric acid barrier may facilitate bacterial invasion of the lower intestinal tract and promote the development of colonic neoplasia. Our study aimed to test the associations between histopathological abnormalities of the upper and lower gastrointestinal tract in patients undergoing bidirectional endoscopy. Method: The Inform Diagnostics database is a national electronic repository of histopathological records of patients distributed throughout the USA. A case–control study of 302 061 patients, 163 168 of whom had colonic polyps, evaluated whether the occurrence of colonic polyps was influenced by the presence of the following gastro‐oesophageal diagnoses: gastric Helicobacter pylori infection, gastric intestinal metaplasia, fundic gland polyps and gastric hyperplastic polyps. The influence of individual diagnoses on the occurrence of colonic polyps was expressed as odds ratios with their 95% confidence intervals. Results: The odds ratio for tubular adenomas being associated with gastric H. pylori was 1.53 (1.49–1.58), with intestinal metaplasia 1.65 (1.59–1.71), with fundic gland polyps 1.49 (1.45–1.54) and with gastric hyperplastic polyps 1.85 (1.75–1.96). The odds ratio for sessile serrated polyps being associated with gastric H. pylori was 1.03 (0.96–1.10), with intestinal metaplasia 1.21 (1.13–1.30), with fundic gland polyps 1.79 (1.69–1.89) and with gastric hyperplastic polyps 1.52 (1.35–1.71. Conclusion: A diminished gastric acid barrier function, which occurs in various upper gastrointestinal diseases associated with lowered gastric acid output, may promote the development of colonic neoplasia. [ABSTRACT FROM AUTHOR]

Purpose: BRAF mutation and DNA hypermethylation have linked sessile serrated adenomas/polyps (SSA/Ps) to serrated colorectal cancer (CRC) in cross-sectional studies, but they have not been evaluated in a longitudinal study. We aimed to evaluate the associations between molecular markers of serrated polyps and subsequent advanced colorectal neoplasia. Methods: Study subjects included Kaiser Permanente Washington members aged 20–75 years who received an index colonoscopy between 1/1/1998 and 12/31/2007 and had hyperplastic polyps (HPs) or SSA/Ps according to study pathology review. Polyps from index colonoscopies were removed and assayed for BRAF mutation, CpG island methylator phenotype (CIMP), and MLH1 methylation. Pathology reports and biopsies from the subsequent lower gastrointestinal endoscopy through 1/1/2013 were reviewed for advanced colorectal neoplasia. We identified additional incident CRC cases through linkage to the Seattle-Puget Sound Surveillance Epidemiology and End Results registry. We used generalized estimating equations to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) for subsequent advanced colorectal neoplasia, comparing index serrated polyps with different molecular markers. Results: We included 553 individuals with index serrated polyps (420 HPs and 133 SSA/Ps) and 795 subsequent endoscopies. The prevalence of BRAF-mutant, CIMP-high, and MLH1-methylated serrated polyps were 51%, 4%, and 2%, respectively. BRAF and CIMP were not associated with subsequent advanced colorectal neoplasia. MLH1-methylated SSP/As were significantly more likely to have subsequent advanced neoplasia (OR = 4.66, 95% CI 1.06–20.51). Conclusion: Our results suggest that BRAF-mutant and CIMP-high serrated polyps are not associated with subsequent advanced colorectal neoplasia. Among SSA/Ps, MLH1 methylation may be an important marker to identify high-risk CRC precursors. [ABSTRACT FROM AUTHOR]

Background: The efficacy of second-generation PillCam -COLON2 capsule endoscopy (CCE2) in detecting colorectal superficial lesions remains unclear. Objective: We sought to determine the diagnostic yield of CCE2 in the detection of colorectal superficial lesions. Methods: We performed CCE2 in 60 consecutive patients between April 2011 and -December 2017. Lesions ≥6 mm in size were detected in 34 patients (25 males, average age: 60.5 years). We performed endoscopic resection and histopathological analysis of all resected lesions within 3 months after CCE2. We considered the optical colonoscopy (OC) findings as the gold standard and evaluated CCE2 sensitivity. Results: Sixty-seven lesions (≥6 mm) were detected via OC, with 27 colorectal superficial lesions and 40 protruded lesions. CCE2 sensitivity for ≥6-mm-sized, superficial, and protruded lesions was 84, 78, and 88%, respectively. No significant intergroup differences were observed. CCE2 false-negative colorectal superficial lesions accounted for 31% of right-sided colon lesions and 50% of sessile serrated adenomas/polyps (SSA/Ps). The CCE2 false-negative protruded lesions accounted for 17% of right-sided colon lesions. Conclusion: CCE2 sensitivities for colorectal superficial and protruded lesions were not significantly different. However, flat-type SSA/Ps in the right colon, especially when the transit time is fast, have a risk of demonstrating CCE2 false-negative results. [ABSTRACT FROM AUTHOR]

Background: Little is known about the natural history of serrated polyps (SPs), partly due to the lack of large-scale epidemiologic data. In this study, we examined the validity of SP identification according to SNOMED (Systematised Nomenclature of Medicine) codes and free text from colorectal histopathology reports.Methods: Through the ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) study, we retrieved data on SPs from all pathology departments in Sweden in 2015-2017 by using SNOMED codes and free-text search in colorectal histopathology reports. Randomly selected individuals with a histopathology report of SPs were validated against patient charts using a structured, retrospective review.Results: SPs were confirmed in 101/106 individuals with a histopathology report of SPs, yielding a positive predictive value (PPV) of 95% (95%CI = 89-98%). By year of diagnosis, the PPV was 89% (95%CI = 69-97%), 96% (95%CI = 81-99%) and 97% (95%CI = 89-99%) for individuals diagnosed before 2001 (n = 19), between 2001 and 2010 (n = 26) and after 2010 (n = 61), respectively. According to search method, the PPV for individuals identified by SNOMED codes was 100% (95%CI = 93-100%), and 93% (95%CI = 86-97%) using free-text search. Recorded location (colon vs. rectum) was correct in 94% of all SP histopathology reports (95%CI = 84-98%) identified by SNOMED codes. Individuals with SPs were classified into hyperplastic polyps (n = 34; 32%), traditional serrated adenomas (n = 3; 3%), sessile serrated adenomas/polyps (SSA/Ps) (n = 70; 66%), unspecified SPs (n = 3, 3%), and false positive SPs (n = 5, 5%). For individuals identified by SNOMED codes, SSA/Ps were confirmed in 49/52 individuals, resulting in a PPV of 94% (95%CI: 84-98%). In total, 57% had ≥2 polyps (1: n = 44, 2-3: n = 33 and ≥ 4: n = 27). Some 46% of SPs (n = 71) originated from the proximal colon and 24% were ≥ 10 mm in size (n = 37). Heredity for colorectal cancer, intestinal polyposis syndromes, or both was reported in seven individuals (7%). Common comorbidities included diverticulosis (n = 45, 42%), colorectal cancer (n = 19, 18%), and inflammatory bowel disease (n = 10, 9%).Conclusion: Colorectal histopathology reports are a reliable data source to identify individuals with SPs. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to extract endoscopic findings for diagnosing colorectal neoplasia associated with sessile serrated lesions (SSLs), which are of significant interest., Methods: To compare the magnifying narrow-band imaging (NBI) findings with microscopic morphology, we classified SSLs into two groups: Group A SSLs included the majority of uniform SSLs and any dysplasia other than that classified as group B SSLs. Group B SSLs included SSLs with intramucosal and invasive carcinoma. We also quantitatively assessed visible vessels using ImageJ software., Results: This study included 47 patients with 50 group B SSLs who underwent endoscopic resection between 2012 and 2020. The results were retrospectively compared with those of 237 patients with 311 group A SSLs that underwent endoscopic resection. Using conventional white-light endoscopy, significantly more group B SSLs had uneven shapes and some reddening compared to group A SSLs. The diagnostic odds ratios for group B SSLs were as follows: lesions with a diameter ≥10 mm, 9.76; uneven shape, 3.79; reddening, 15.46; and visible vessels with NBI, 11.32. Regarding visible vessels with NBI, the specificity and diagnostic accuracy for group B SSLs were 94.9% and 93.1%, respectively. The percentage of the vascular tonal area of NBI images was significantly larger for group B SSLs than for group A SSLs (3.97% vs. 0.29%; p < 0.01)., Conclusions: SSLs with reddening and/or a diameter ≥10 mm are suspected to contain cancerous components. Moreover, visible vessels observed using magnifying NBI can serve as objective indicators for diagnosing SSLs with cancerous components with a high degree of accuracy., Competing Interests: None., (© 2023 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Sessile serrated adenoma/polyps (SSA/Ps) are early precursor lesions in the serrated neoplasia pathway, which results in BRAF‐mutated colorectal carcinomas with not only high levels of microsatellite instability but also microsatellite stable. SSA/Ps with advanced histology, including cytological dysplasia or minimally invasive carcinomas, are important lesions because SSA/Ps are considered major contributors to "interval cancers" and these lesions can rapidly become dysplastic or invasive carcinomas. Clinicopathologically, SSA/Ps with dysplasia or invasive carcinoma were associated with advanced age, female sex, and proximal colon. Although SSA/Ps with submucosal invasive carcinoma were smaller and invaded less deeply into the submucosal layer than conventional tubular adenomas with submucosal invasive carcinoma, SSA/Ps with submucosal invasive carcinoma frequently had a mucinous component and exhibited a higher potential for lymphatic invasion and lymph node metastasis. In an SSA/P series, endoscopic characteristics, including (semi)pedunculated morphology, double elevation, central depression, and reddishness, may help accurately diagnose SSA/Ps with advanced histology. Removal of SSA/Ps with dysplasia or invasive carcinoma was recommended. Endoscopic treatment such as endoscopic mucosal resection or endoscopic submucosal dissection is useful for those lesions. However, surgical resection with lymph node dissection might be indicated when SSA/Ps with invasive carcinoma are endoscopically suspected, because these have the high risk of lymph node metastasis. Greater awareness may promote further research into improving the detection, recognition, and complete resection rates of SSA/Ps with dysplasia or invasive carcinoma and reduce the interval cancer rates. [ABSTRACT FROM AUTHOR]

Background The Aspirin/Folate Polyp Prevention Study previously found folic acid increased risk of advanced and multiple colorectal adenomas during a surveillance colonoscopy interval starting about 3 y after randomization. Objective We conducted secondary analyses to evaluate folic acid effects with additional follow-up after treatment was stopped. Methods In total, 1021 participants recently diagnosed with colorectal adenomas were randomly assigned to 1 mg/d of folic acid (n  = 516) or placebo (n  = 505), with or without aspirin, beginning 6 July 1994. The original 3-y treatment period was extended into a subsequent colonoscopy interval, but eventually stopped prematurely on 1 October 2004. With additional post-treatment follow-up, a total of 663 participants who extended treatment completed a second colonoscopic surveillance interval after the initial 3-y follow-up. In addition, 490 participants provided information regarding a subsequent surveillance colonoscopy occurring before completion of follow-up on 31 May 2012, including 325 who had agreed to extended treatment. Study endpoints included conventional adenomas, sessile serrated adenomas/polyps (SSA/Ps), or colorectal cancer, and RRs with 95% CIs were adjusted for baseline characteristics associated with availability of follow-up. Results Among those who extended treatment, any colorectal neoplasia was found in 118 (36%) participants assigned to placebo and 146 (43%) assigned to folic acid during the second surveillance interval (RR: 1.21; 95% CI: 0.99, 1.47; P  = 0.06). Increased risk of SSA/P with extended folic acid supplementation was statistically significant during the second surveillance interval (RR: 1.94; 95% CI: 1.02, 3.68; P  = 0.04). There was no evidence of post-treatment effects for any colorectal neoplasia (RR: 1.01; 95% CI: 0.80, 1.28; P  = 0.94), and the post-treatment effect for SSA/P was no longer statistically significant (RR: 1.38; 95% CI: 0.59, 3.19; P  = 0.46). Conclusions Delayed treatment effects were not observed, but folic acid may increase SSA/P risk. This trial was registered at clinicaltrials.gov as NCT00272324. [ABSTRACT FROM AUTHOR]

Aims: Dysplasia in colonic sessile serrated adenomas (SSAs)/sessile serrated polyps often shows loss of MLH1 expression as determined with immunohistochemistry, but the significance of loss of MLH1 expression in non‐dysplastic crypts in these polyps is less well studied. The purpose of this study was to evaluate the prevalence of loss of MLH1 expression in non‐dysplastic crypts in SSAs, and to evaluate its significance with regard to progression of these polyps. Methods and results: Four hundred SSAs, including 158 SSAs without dysplasia, 219 SSAs with dysplasia (SSAD), and 23 SSAs with invasive adenocarcinoma (SSAC), were evaluated immunohistochemically for loss of MLH1 expression in both non‐dysplastic and dysplastic portions of the polyps. Seventy‐one of 400 (18%) SSAs showed loss of MLH1 expression in non‐dysplastic crypts. The prevalence of MLH1‐deficient non‐dysplastic crypts was higher in polyps with dysplasia or carcinoma (7%, 22%, and 52% in SSAs, SSADs, and SSACs, respectively; P < 0.0001). When SSAs with MLH1‐deficient dysplasia and those with MLH‐1‐proficient dysplasia were compared, those with MLH1‐deficient dysplasia were more likely to have MLH1‐deficient non‐dysplastic crypts (66% versus 8.1%, P < 0.0001) and a greater number of discrete foci (3.6 foci versus 1.1 foci, P = 0.008). Also, non‐dysplastic crypts with loss of MLH1 expression were more likely to be contiguous with the dysplasia when the dysplasia also showed loss of MLH1 expression (26% versus 0%, P = 0.02). Conclusions: Our results suggest that loss of MLH1 expression in non‐dysplastic crypts in SSAs precedes the development of MLH1‐deficient dysplasia and adenocarcinoma, and may be a biomarker of an advanced serrated polyp even in the absence of dysplasia. [ABSTRACT FROM AUTHOR]

Purpose: Colorectal cancer (CRC) screening guidelines recommend increased surveillance of individuals with sessile serrated adenomas/polyps (SSA/Ps), but there is uncertainty about the risk associated with SSA/Ps. We aimed to determine the association between SSA/Ps and subsequent advanced colorectal neoplasia.Methods: This case-control study included Kaiser Permanente Washington (KPWA) members who received an index colonoscopy between 1/1/1998 and 12/31/2007, and had hyperplastic polyps (HPs) or SSA/Ps but no conventional adenomas according to study pathologist histologic review. Subsequent pathology reports and biopsies through 1/1/2013 were reviewed for advanced colorectal neoplasia. We linked to the Seattle-Puget Sound Surveillance Epidemiology and End Results (SEER) registry to identify additional CRC cases. We used generalized estimating equations with a logit link to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for advanced colorectal neoplasia, comparing those with SSA/Ps to those with HPs.Results: There were 161 individuals with index SSA/Ps, 548 with HPs, and 918 subsequent endoscopies included in analyses. Of those with index SSA/Ps, 19 had subsequent advanced colorectal neoplasia; 39 with HPs had subsequent advanced colorectal neoplasia. Compared to those with HPs, those with SSA/Ps were not statistically significantly more likely to have subsequent advanced colorectal neoplasia (adjusted OR 1.79; CI 0.98-3.28). Polyp size ≥ 10 mm, right colon location, and the presence of multiple serrated polyps were also not associated with advanced colorectal neoplasia.Conclusions: Our results suggest that there is not a strong association between SSA/Ps and subsequent advanced colorectal neoplasia during the 5 years following SSA/P removal. [ABSTRACT FROM AUTHOR]

Abstract Colorectal cancer (CRC) is a heterogeneous group of diseases both from the morphological and molecular point of view. The sessile serrated adenoma/polyp (SSA/P) has been proposed as the precursor lesion of CRCs characterized by CpG island methylator phenotype (CIMP), DNA mismatch repair (MMR) system deficiency, and BRAF gene mutations. However, no study so far investigated the molecular landscape of "sessile serrated" adenoma to carcinoma transition in early CRCs. Six formalin-fixed paraffin-embedded CRCs developed within SSA/P were profiled for the immunohistochemical expression of MMR proteins (MLH1, MSH2, MSH6, PMS2, and Ep-CAM), p16, and β-catenin. DNA was extracted from the two components of each sample, after microdissection, and characterized for CIMP status and by applying a custom hotspot multigene mutational profiling of 164 hotspot regions of eleven CRC-associated genes (AKT1, APC, BRAF, CTNNB1, KIT, KRAS, NRAS, PDGFRA, PIK3CA, PTEN , and TP53). Five out of the six CRCs shared the same molecular profile (i.e. CIMP positive, MSI status, and BRAF mutation) with their SSA/P components. One out of five CRCs was also APC mutated, whereas another one showed an additional TP53 mutation. The remaining case was CIMP negative and MMR proficient in both the components, harbored a BRAF mutation in the SSA/P counterpart, whereas the CRC one was APC and TP53 mutated and showed p16 and β-catenin dysregulation. This study provides the molecular evidence that SSA/P, even without cytological dysplasia, is a precursor lesion of CRC and that conventional CRC might arise from mixed polyp. [ABSTRACT FROM AUTHOR]

Background and Objective: Colorectal serrated polyp is considered as histologically heterogeneous lesions with malignant potential. The aim of the study was to evaluate the endoscopic, clinic and pathologic characteristics of colorectal serrated polyps. Methods: The endoscopic, clinic and pathologic characteristics of 52 cases with colorectal serrated polyps between January 2014 and May 2018 in our hospital were analyzed. retrospectively. Results: The prevalence of serrated polyps was 0.39% (52/13,346). The proportions of hyperplastic polyp (HP), sessile serrated adenoma/polyp (SSA/P), and traditional serrated adenoma (TSA) of all serrated polyps were 61.5%, 17.3%, and 21.2%, respectively, which showed a lower proportion of TSA and SSA/P and a higher proportion of HP. Conclusions: The overall detection rate of colorectal serrated polyps was relatively low, and it is necessary to discriminate between SSAPs and HPs during endoscopic examination because of the malignant potential. [ABSTRACT FROM AUTHOR]

Background: Colorectal serrated polyp is considered as histologically heterogeneous lesions with malignant potential in western countries. However, few Asian studies have investigated the comprehensive clinical features of serrated polyps in symptomatic populations. The aim of the study was to evaluate the features of colorectal serrated polyps in a Chinese symptomatic population. Methods: Data from all consecutive symptomatic patients were documented from a large colonoscopy database and were analyzed. Chi-square test or Fisher′s exact test and logistic regression analysis were used for the data processing. Results: A total of 9191 (31.7%) patients were detected with at least one colorectal polyp. The prevalence of serrated polyps was 0.53% (153/28,981). The proportions of hyperplastic polyp (HP), sessile serrated adenoma/polyp (SSA/P), and traditional serrated adenoma (TSA) of all serrated polyps were 41.2%, 7.2%, and 51.6%, respectively, which showed a lower proportion of HP and SSA/P and a higher proportion of TSA. Serrated polyps appeared more in males and elder patients while there was no significant difference in the subtype distribution in gender and age. The proportions of large and proximal serrated polyps were 13.7% (21/153) and 46.4% (71/153), respectively. In total, 98.9% (89/90) serrated adenomas were found with dysplasia. Moreover, 14 patients with serrated polyps were found with synchronous advanced colorectal neoplasia, and large serrated polyps (LSPs) (odds ratio: 3.446, 95% confidence interval: 1.010-11.750, P < 0.05), especially large HPs, might have an association with synchronous advanced neoplasia (AN). Conclusions: The overall detection rate of colorectal serrated polyps in Chinese symptomatic patient population was low, and distribution pattern of three subtypes is different from previous reports. Moreover, LSPs, especially large HPs, might be associated with an increased risk of synchronous AN.

Aims: Sessile serrated adenoma/polyp (SSA/P) is regarded as a genetically homogeneous entity, with most lesions harbouring the BRAF V600E mutation. The present study aimed to reappraise the genetic heterogeneity of SSA/Ps and its clinicopathological significance. Methods and results: We performed next‐generation sequencing of 272 SSA/Ps without dysplasia and evaluated morphological and molecular features associated with the respective genotypes. BRAF V600E, BRAF non‐V600E, KRAS and NRAS mutations were found in 223 (82.0%), three (1.2%), 28 (10.3%) and one lesion (0.4%), respectively. Notably, all lesions with BRAF non‐V600E mutations had either KRAS or NRAS mutations concurrently. Twenty SSA/Ps (7.4%) were negative for these mutations. KRAS‐mutated SSA/Ps were located more often in the distal colon (42%) compared to those with the BRAF V600E mutation (14%). Histologically, minimally serrated crypts and goblet cell‐rich crypts were more common in KRAS‐mutated and mutation‐negative SSA/Ps. However, in most instances, SSA/Ps lacking the BRAF V600E mutation were indistinguishable morphologically from those with the BRAF V600E mutation. MUC5AC and MUC6 expression was common regardless of the mutation status, but more extensive in SSA/Ps with the BRAF V600E mutation. CpG island methylator phenotype‐high was more frequent in SSA/Ps with the BRAF V600E mutation (60%), followed by mutation‐negative SSA/Ps (40%) and KRAS‐mutated SSA/Ps (16%). Conclusions: The present study confirmed the common presence of the BRAF V600E mutation in SSA/Ps, but also demonstrated a degree of molecular heterogeneity of SSA/Ps. SSA/Ps with and without the BRAF V600E mutation showed slightly different but overlapping histological and molecular features. [ABSTRACT FROM AUTHOR]

Sessile serrated adenomas/polyps (SSA/Ps) are the putative precursors of the ~20% of colon cancers with the CpG island methylator phenotype (CIMP). To investigate the epigenetic phenotype of these precancers, we prospectively collected fresh-tissue samples of 17 SSA/Ps and 15 conventional adenomas (cADNs), each with a matched sample of normal mucosa. Their DNA was subjected to bisulfite next-generation sequencing to assess methylation levels at ~2.7 million CpGs located predominantly in gene regulatory regions and spanning 80.5Mb; RNA was sequenced to define the samples' transcriptomes. Compared with normal mucosa, SSA/Ps and cADNs exhibited markedly remodeled methylomes. In cADNs, hypomethylated regions were far more numerous (18,417 vs 4288 in SSA/Ps) and rarely affected CpG islands/shores. SSA/Ps seemed to have escaped this wave of demethylation. Cytosine hypermethylation in SSA/Ps was more pervasive (hypermethylated regions: 22,147 vs 15,965 in cADNs; hypermethylated genes: 4938 vs 3443 in cADNs) and more extensive (region for region), and it occurred mainly within CpG islands and shores. Given its resemblance to the CIMP typical of SSA/Ps' putative descendant colon cancers, we refer to the SSA/P methylation phenotype as proto-CIMP. Verification studies of six hypermethylated regions in an independent series of precancers demonstrated DNA methylation markers' high potential for predicting the diagnosis of SSA/Ps and cADNs. Surprisingly, proto-CIMP in SSA/Ps was associated with upregulated gene expression; downregulation was more common in cADNs. In conclusion, the epigenetic landscape of SSA/Ps differs markedly from that of cADNs. These differences are a potentially rich source of novel tissue-based and noninvasive biomarkers. [ABSTRACT FROM AUTHOR]

Abstract: Background and Aim: Although sessile serrated adenoma/polyps (SSA/Ps) are considered to be premalignant lesions and rapidly progress to carcinomas after they develop cytological dysplasia (CD), a treatment strategy for SSA/Ps in Asian countries is still being debated and has not yet been established. The present study aimed to propose a treatment strategy for SSA/Ps. Methods: Histopathological data of patients, who underwent colonoscopy at our center between January 2011 and December 2016, were reviewed. Data of patients with ≥ 1 SSA/P were retrieved, and clinicopathological characteristics were retrospectively analyzed. Results: A total of 281 patients with 326 SSA/Ps, including 258 patients who had 300 SSA/Ps without CD (SSA/Ps‐CD[−]) and 23 patients who had 26 SSA/Ps with CD (SSA/Ps‐CD[+]), were evaluated in this study. Although SSA/Ps‐CD(+) were often found in older female patients and in the proximal colon, there were no significant differences between SSA/Ps‐CD(−) and SSA/Ps‐CD(+). Endoscopic morphological findings, such as large or small nodules on the surface and partial protrusion of the lesions, were significantly more common in SSA/Ps‐CD(+) than in SSA/Ps‐CD(−). Although the diagnostic ability of nodule/protrusion in lesions to predict CD within SSA/Ps was very high with an accuracy of 93.9% and a negative predictive value of 95.4%, sensitivity was low at 46.2%. SSA/Ps‐CD(+) were significantly larger than SSA/Ps‐CD(−), and the rate of CD within SSA/Ps significantly increased with lesion size (≤ 5 mm, 0%; 6–9 mm, 6.0%; ≥ 10 mm, 13.6%). Conclusion: The study proposes removing all SSA/Ps ≥ 6 mm in order to remove high‐risk SSA/Ps‐CD(+), with high sensitivity. [ABSTRACT FROM AUTHOR]

Accumulating data indicates that certain microRNAs (miRNAs or miRs) are differently expressed in samples of tumors and paired non-tumorous samples taken from the same patients with colorectal tumors. We previously reported to clarify the relationship between the expression of the miRNAs and the endoscopic morphological appearance of the colorectal tumors. In this report, we focused on colorectal adenoma (tubular or tubulovillous adenoma), or tubular early carcinoma or type 2 adenocarcinoma, familial adenomatous polyposis (FAP), ulcerative colitis-associated tumor (UCAT), and sessile serrated adenoma/polyp (SSA/P). We tried to clarify the relationship between the expression of the miRNAs and the colorectal tumor development. The expression levels of miR-143, -145, and -34a were reduced in most of the polypoid and FAP tumors compared with those in the flat elevated, UCAT, SSA/P ones. In type 2 adenocarcinomas, the expression profile of these miRNAs was similar to those of the polypoid and FAP tumors. The expression levels of miR-7 and -21 were up-regulated in non-granular type of laterally spreading tumor, UCAT, and SSA/P compared with those in polypoid and FAP tumors. These findings indicated that the expression of onco-related miRNAs was closely associated with the development and endoscopic appearance of colorectal tumors. [ABSTRACT FROM AUTHOR]

The histopathological characteristics of colorectal submucosal invasive carcinoma arising in sessile serrated adenoma/polyp (SSA/P), a rare malignant tumour, have not yet been fully elucidated. To investigate the features of such, we retrospectively analysed 40 submucosal invasive carcinomas with SSA/P (CA-SSA/P) and compared them to 129 cases of submucosal invasive carcinoma with conventional tubular adenoma (CA-AD). We additionally performed hMLH1 immunostaining. CA-SSA/Ps were significantly smaller than CA-ADs (P < 0.001). Histologically, well to moderately differentiated adenocarcinoma was predominant in both CA-SSA/Ps and CA-ADs. No significant differences in depth of invasion were found between the two groups. However, lymphatic invasion was more often found in CA-SSA/Ps (30%) than in CA-ADs (13%; P = 0.028), as was lymph node metastasis (CA-SSA/Ps, 28%; CA-ADs, 7%; P = 0.011). Furthermore, mucinous component and serrated architecture were significantly more frequent in CA-SSA/Ps (30 and 63%) than in CA-ADs (5 and 18%; P < 0.001, respectively). Tumour-infiltrating lymphocytes and Crohn-like inflammatory reaction were also more frequently found in CA-SSA/Ps (70 and 30%) than in CA-ADs (31 and 9%; P ≤ 0.001, respectively), whereas the opposite was true of desmoplastic reaction (CA-SSA/Ps, 35%; CA-ADs, 67%; P < 0.001). Loss of hMLH1 expression was more frequent in CA-SSA/P cases (93%) than in CA-AD cases (5%; P < 0.001). In conclusion, CA-SSA/P lesions exhibit a higher potential for lymphatic invasion and lymph node metastasis and have distinct histopathological features, including mucinous component, serrated architecture, tumour-infiltrating lymphocytes, Crohn-like inflammatory reaction, and absence of desmoplastic reaction, compared to their conventional counterparts. [ABSTRACT FROM AUTHOR]

Abstract: Background and Aim: Endoscopic diagnosis of sessile serrated adenoma/polyp (SSA/P) is challenging because of their subtle appearance. Narrow‐band imaging (NBI) is useful for diagnosis, but its utility with concurrent chromoendoscopy (CE), especially to detect small SSA/P, is unproven. Methods: This prospective study enrolled 367 consecutive patients who underwent screening colonoscopy with the finding of serrated polyps. Patients were divided into derivation and validation cohorts: Diagnostic criteria using different endoscopic modalities were generated by regression analysis in the derivation cohort and were validated in the validation cohort for sensitivity, specificity, and accuracy. Results: There were 180 patients with 119 SSA/P and 147 hyperplastic polyps (HP) in the derivation cohort and 187 patients with 177 SSA/P and 125 HP in the validation cohort. With white‐light endoscopy plus NBI, mucus cap, surface grooves, and expanded crypt were most associated with SSA/P. With white‐light endoscopy plus CE, II‐O pit pattern, mucus cap, and superficial telangiectasia were most associated with SSA/P. With the combined use of these three modalities, II‐O pit pattern, mucus cap, and surface grooves were most associated with SSA/P. For large serrated polyp, NBI in combination with CE had a better accuracy than NBI alone (91% vs 86%, P = 0.025) to distinguish SSA/P from HP. CE alone had a better accuracy than NBI alone for distinguishing small SSA/P from small HP (85% vs 72%, P < 0.0001). Conclusion: Compared with NBI alone, adjunctive use of CE can improve the diagnostic accuracy for distinguishing SSA/P from HP, especially for small SSA/P. [ABSTRACT FROM AUTHOR]

The adenoma-carcinoma sequence (ACS) and the serrated pathway are two distinct developmental routes leading to the formation of colorectal carcinoma (CRC). However, the mechanism triggered by the serrated pathway remains unclear. Therefore, to clarify the molecular and clinicopathological characteristics of the serrated tumorigenic pathway, immunohistochemistry was used to examine the expression of Fragile Histidine Triad (FHIT), cyclooxygenase-2 (COX-2), MutL homolog 1 (MLH1), MutS protein homolog 2 (MSH2) and P53 in endoscopically resected samples of 62 serrated polyps. These samples included 20 hyperplastic polyps (HPs), 16 traditional serrated adenomas (TSAs), 26 sessile serrated adenoma/polyps (SSA/Ps), 20 non-serrated adenomas, 20 carcinoma in adenomas (CIAs) and 18 early pure CRCs without any adenoma component (EPCs). FHIT expression was markedly reduced or absent in 50% of TSA samples, 92.3% of SSA/Ps and 44% of EPCs, but only rarely in HPs, non-serrated adenomas and CIAs. COX-2 expression was more common in non-serrated adenomas compared with in serrated polyps, and was present in 25 and 3.2% of the cases respectively (P<0.01). Furthermore, COX-2 expression was more frequent in CIAs (60%) compared with in EPCs (22.2%; P<0.05). The incidence of negative COX-2 expression was higher in FHIT-negative SSA/Ps compared with in FHIT-positive SSA/Ps (P=0.08). A total of 16.7% of EPC samples and 11.5% of SSA/Ps demonstrated a loss of MLH1/MSH2 expression, but none of the other tumor types did. P53 overexpression was significantly increased in EPC (77.8%) and CIA (60%) samples compared with in HP (0%), TSA (6.6%), SSA/P (0%) and non-serrated adenoma (10%) samples (P<0.01). These findings demonstrated that there are different expression patterns between the serrated pathway and ACS, indicating that aberrant FHIT and inhibited COX-2 expression may be associated with serrated tumorigenesis. In addition, this data indicated that EPC may contain tumors derived from the serrated pathway as well as ACS. [ABSTRACT FROM AUTHOR]

Background/aims: The serrated pathway accounts for 15-25% of sporadic colorectal cancer (CRC). In our study, we sought to accurately characterize sessile serrated polyps (SSP) in a population by electronically interrogating colonoscopy patients' endoscopy and pathology reports using a rules-based text search of pre-defined SSP-related terms. To this aim, we compared a sample of putative SSP and hyperplastic polyps (HP) using our algorithm to a determination of SSP or HP by pathologist and molecular examination to determine the feasibility of large-scale identification of SSP in electronic medical records.Methods: In 23,990 endoscopy reports from colonoscopies with pathology performed at a University of Utah Healthcare facility in 2000-2012, we identified serrated lesions and categorized each as putative SSP or HP using a text search algorithm. We obtained 93 tissue samples for histologic and molecular analysis.Results: Serrated polyps were categorized as putative SSP (N = 920) and putative HP (N = 7159) by text search algorithm. Histologic examination of 93 samples identified 37 SSP, 11 probable SSP, and 45 HP. Of 26 putative SSP, 25 were SSP/probable SSP (96%) by histology. Of 67 putative HP, 44 were HP (66%) by histology. Reducing size criterion from ≥1 to ≥5 mm in the search algorithm caused improved sensitivity (77.1%) without decline in specificity (97.8%).Conclusions: A simple rules-based search to identify SSP provides "proof of principle" that SSP can be identified in a large electronic record set. Pilot data indicate defining large, right-sided polyps as ≥5 mm provides adequate sensitivity to detect SSP from electronic records while maintaining high specificity. [ABSTRACT FROM AUTHOR]

Aim Sessile serrated adenomas/polyps ( SSA/Ps) have been proposed as precursors of colorectal cancer. The aims of this investigation were to compare the endoscopic findings of SSA/Ps with those of other serrated lesions and to compare the histological findings of SSA/Ps with those of conventional adenomas. Method We retrospectively reviewed colonoscopy records at our institution from 1984 to 2013 and identified cases of endoscopically or surgically resected conventional adenomas and serrated lesions, including SSA/Ps, hyperplastic polyps ( HPs) and traditional serrated adenomas ( TSAs). The colonoscopic findings of SSA/Ps were compared with those of the other two serrated lesions and histological findings were compared among all groups of lesions. Results There were 79 HPs in 68 patients, 77 SSA/Ps in 63 patients, 167 TSAs in 145 patients and 6324 conventional adenomas in 4129 patients. The inverted type and flat-elevated type were more frequent among SSA/Ps than among the other two types of serrated lesions. Magnifying colonoscopy revealed that a round and open pit pattern, expanded crypt openings and varicose microvascular vessels were more frequently observed among SSA/Ps than among the other types. The incidence of high-grade dysplasia or carcinoma among SSA/Ps (13.0%) was significantly higher than that among HPs (0%, P < 0.001) and equivalent to that among conventional adenomas (12.3%). Conclusion SSA/Ps have colonoscopic features distinct from those of HPs and TSAs. The malignant potential of SSA/Ps seems to be equal to that of conventional adenomas. [ABSTRACT FROM AUTHOR]

Background/Aims: Serrated lesions (SLs) of the large bowel occasionally manifest as inverted growths with endophytic expansion within the muscularis mucosa. The aims of this investigation were to investigate the incidence of inverted SLs (ISLs) among SLs and to describe the clinicopathologic features. Methods: We reviewed the colonoscopy records from 2006 to 2014 at our institution and identified cases of endoscopically or surgically resected SLs, including hyperplastic polyps (HPs), sessile serrated adenomas/polyps (SSA/ Ps) and traditional serrated adenomas (TSAs). The incidence of ISLs among the SLs and their colonoscopic findings were investigated retrospectively. Results: There were 35 HPs in 30 patients, 80 SSA/Ps in 65 patients and 70 TSAs in 65 patients. The incidence of ISLs was significantly higher among SSA/Ps (8.8%) and HPs (5.7%) than among TSAs (0%; p = 0.04). A predominant right-sided location, a flat-elevated configuration with a central depression and round-open pit pattern or expanded crypt openings were characteristic of ISLs of the SSA/P type. Conclusions: Right-sided flat lesions with a central depression and round or expanded crypts are indicative of ISLs of the SSA/P type. [ABSTRACT FROM AUTHOR]

Based on the World Health Organization (WHO) criteria, serrated lesions were classified as sessile serrated adenoma/polyp (SSA/P), traditional serrated adenoma (TSA), and hyperplastic polyp (HP). Large serrated lesions are found to be associated with advanced colonic adenoma in the colon. Serrated lesions of the colorectum are believed to account for 15-20 % of all colorectal cancers via the 'serrated neoplastic pathway' with SSA/P being the main precursor lesion. Serrated lesions are also thought to account for around 30 % of cancers that develop after a negative colonoscopy or the interval cancers. While serrated lesions are often flat or sessile and inconspicuous on conventional white light colonoscopy, missed lesions are not uncommon. Increased detection of serrated lesions may potentially reduce the incidence and mortality of colorectal cancers, especially the risk of interval cancers. Further research shall be directed to improve detection of serrated lesions by colonoscopy. [ABSTRACT FROM AUTHOR]

Background and aim: Sessile serrated adenoma/polyps (SSAPs) are suspected to have a high malignant potential, although few reports have evaluated the incidence of carcinomas derived from SSAPs using the new classification for serrated polyps (SPs). The aim of study was to compare the frequency of cancer coexisting with the various SP subtypes including mixed polyps (MIXs) and conventional adenomas (CADs). Methods: A total of 18,667 CADs were identified between April 2005 and December 2011, and 1858 SPs (re-classified as SSAP, hyperplastic polyp (HP), traditional serrated adenoma (TSA), or MIX) were removed via snare polypectomy, endoscopic mucosal resection, or endoscopic sub-mucosal dissection. Results: Among 1160 HP lesions, 1 (0.1 %) coexisting sub-mucosal invasive carcinoma (T1) was detected. Among 430 SSAP lesions, 3 (0.7 %) high-grade dysplasia (HGD/Tis) and 1 (0.2 %) T1 were detected. All of the lesions were detected in the proximal colon, with a mean tumor diameter of 18 mm (SD 9 mm). Among 212 TSA lesions, 3 (1 %) HGD/Tis were detected but no T1 cancer. Among 56 MIX lesions, 9 (16 %) HGD/Tis and 1 (2 %) T1 cancers were detected, and among 18,677 CAD lesions, 964 (5 %) HGD/Tis and 166 (1 %) T1 cancers were identified. Conclusions: Among the resected lesions that were detected during endoscopic examination, a smaller proportion (1 %) of SSAPs harbored HGD or coexisting cancer, compared to CAD or MIX lesions. Therefore, more attention should be paid to accurately identifying lesions endoscopically for intentional resection and the surveillance of each SP subtype. [ABSTRACT FROM AUTHOR]

Background: Differentiating sessile serrated adenoma/polyp (SSA/P) from hyperplastic polyp (HP) is clinically important in determining the necessity of endoscopic resection or recommending appropriate surveillance. There are few reports of characterization of SSA/P using narrowband imaging and chromoendoscopy with and without magnification. We aimed to establish imaging criteria to aid real-time diagnosis of SSA/P. Methods: Patients with pale sessile or flat lesions of 6 mm or greater were prospectively enrolled in this multicenter trial. Nine endoscopic criteria, determined in real time, were investigated for possible association with SSA/P. Endoscopic mucosal resection was performed; specimens were retrieved and analyzed by histopathological examination. Results: In 63 patients, 89 lesions were detected, including 41 HP, 38 SSA/P, five mixed polyps, and five other lesions. Right-side colon location, lesion size of 10 mm or greater, excessive mucus, the presence of a varicose microvascular vessel (VMV) noted with high-magnification narrowband imaging, and type III pit pattern were each commonly associated with SSA/P compared with HP. Multivariate analysis substantiated three independent endoscopic criteria for SSA/P: the presence of VMV ( p = 0.001), lesion size of 10 mm or greater ( p = 0.0017), and right-side location ( p = 0.0041), with odds ratios of 8.2, 7.2, and 6.1, respectively. The presence of VMV had a significantly higher specificity (87.8 %) than the other two independent endoscopic criteria ( p = 0.0007 and p = 0.0008, respectively), but a lower sensitivity (57.9 %), whereas a combination of the three criteria (two or more positive) increased the sensitivity significantly (89.5 % and p = 0.0033) and had a higher degree of accuracy (82.3 %). Conclusions: Three endoscopic criteria individually and in combination were effective in predicting a diagnosis of SSA/P without the need for chromoendoscopy. [ABSTRACT FROM AUTHOR]