Effect of fecal immunochemical test cut-off levels on adenoma detection rate: a systematic review and meta-analysis.

BACKGROUND: Adenoma detection rate (ADR) is higher after a positive fecal immunochemical test (FIT) compared to direct screening colonoscopy. OBJECTIVE: This meta-analysis evaluated how ADR, the rates of advanced adenoma detection (AADR), colorectal cancer detection (CDR), and sessile serrated lesion detection (SSLDR) are affected by different FIT positivity thresholds. METHODS: We searched MEDLINE, EMBASE, CINAHL, and EBM Reviews databases for studies reporting ADR, AADR, CDR, and SSLDR according to different FIT cut-off values in asymptomatic average-risk individuals aged 50-74 years old. Data were stratified according to sex, age, time to colonoscopy, publication year, continent, and FIT kit type. Study quality, heterogeneity, and publication bias were assessed. RESULTS: Overall, 4280 articles were retrieved and fifty-eight studies were included (277,661 FIT-positive colonoscopies; mean cecal intubation 96.3%; mean age 60.8 years; male 52.1%). Mean ADR was 56.1% (95% CI 53.4 - 58.7%), while mean AADR, CDR, and SSLDR were 27.2% (95% CI 24.4 - 30.1%), 5.3% (95% CI 4.7 - 6.0%), and 3.0% (95% CI 1.7 - 4.6%), respectively. For each 20 µg Hb/g increase in FIT cut-off level, ADR increased by 1.54% (95% CI 0.52 - 2.56%, p < 0.01), AADR by 3.90% (95% CI 2.76 - 5.05%, p < 0.01) and CDR by 1.46% (95% CI 0.66 - 2.24%, p < 0.01). Many detection rates were greater amongst males and Europeans. CONCLUSIONS: ADRs in FIT-positive colonoscopies are influenced by the adopted FIT positivity threshold, and identified targets, importantly, proved to be higher than most current societal recommendations.

Linked color imaging improves colorectal lesion detection especially for low performance endoscopists: An international trial in Asia.

BACKGROUND AND AIM: Linked color imaging (LCI) is an image-enhanced endoscopy technique that accentuates the color difference between red and white, potentially improving the adenoma detection rate (ADR). However, it remains unclear whether LCI performance in detecting colorectal lesions differs based on endoscopists' experience levels. We aimed to evaluate the differences in LCI efficacy based on the experience levels of endoscopists by conducting an exploratory analysis. METHODS: In this post hoc analysis of an international randomized controlled trial comparing the detection of adenoma and other lesions using colonoscopy with LCI and high-definition white light imaging (WLI), we included patients from 11 institutions across four countries/regions: Japan, Thailand, Taiwan, and Singapore. We retrospectively reviewed differences in the lesion detection of LCI according to endoscopists' colonoscopy history or ADR. RESULTS: We included 1692 and 1138 patients who underwent colonoscopies performed by 54 experts (experience of ≥ 5000 colonoscopies) and by 43 non-experts (experience of < 5000 colonoscopies), respectively. Both expert and non-expert groups showed a significant improvement in ADR with LCI compared to WLI (expert, 61.7% vs 46.4%; P < 0.001; non-expert, 56.6% vs 46.4%; P < 0.001). LCI had no effect on sessile serrated lesion detection rate in non-experts (3.1% vs 2.5%; P = 0.518). LCI significantly improved detection rates in endoscopists with relatively low detection performance, defined as an ADR < 50%. CONCLUSIONS: This exploratory study analyzed data from a previous trial and revealed that LCI is useful for both experts and non-experts and is even more beneficial for endoscopists with relatively low detection performance using WLI.

Colorectal Sessile Serrated Lesion Detection Using Linked Color Imaging: A Multicenter, Parallel Randomized Controlled Trial.

BACKGROUND & AIMS: Linked color imaging (LCI) is a novel technology that improves the color differences between colorectal lesions and the surrounding mucosa. The present study aims to compare the detection of colorectal sessile serrated lesions (SSL) using LCI with white light imaging (WLI). METHOD: A large-scale, multicenter, parallel prospective randomized controlled trial was conducted in 4 hospitals in China. The participants were randomly assigned to the LCI group and WLI group. The primary endpoint was the SSL detection rate (SDR). RESULTS: A total of 884 patients were involved in the intention-to-treat analysis, with 441 patients in the LCI group and 443 patients in the WLI group. The total polyp detection rate, adenoma detection rate, and SDR were 51.8%, 35.7%, and 8.6%, respectively. The SDR was significantly higher in the LCI group than in the WLI group (11.3% vs 5.9%, P = .004). Furthermore, LCI significantly increased the number of polyps and adenomas detected per patient, when compared with WLI (P < .05). In addition, there was higher detection rate of diminutive and flat lesions in the LCI group (P < .05). Multivariate analysis revealed that LCI is an independent factor associated with SDR (hazard ratio, 1.990; 95% confidence interval, 1.203-3.293; P = .007), along with withdrawal time (hazard ratio, 1.157; 95% confidence interval, 1.060-1.263; P = .001) and operator experience (hazard ratio, 1.850; 95% confidence interval, 1.045-3.273; P = .035). CONCLUSIONS: LCI is significantly superior to WLI for SSL detection, and may improve polyp and adenoma detection. LCI can be recommended as an appropriate method for routine inspection during colonoscopy (http://www.chictr.org.cn number, ChiCTR2000035705).

Linked-Color Imaging Detects More Colorectal Adenoma and Serrated Lesions: An International Randomized Controlled Trial.

BACKGROUND & AIMS: Effects of linked-color imaging (LCI) on colorectal lesion detection and colonoscopy quality remain controversial. This study compared the detection rates of adenoma and other precursor lesions using LCI vs white-light imaging (WLI) during screening, diagnostic, and surveillance colonoscopies. METHODS: This randomized controlled trial was performed at 11 institutions in 4 Asian countries/regions. Patients with abdominal symptoms, a primary screening colonoscopy, positive fecal immunochemical test results, or undergoing postpolypectomy surveillance were recruited and randomly assigned in a 1:1 ratio to either the LCI or high-definition WLI group. The primary outcome was adenoma detection rate (ADR). Secondary outcomes were polyp detection rate, advanced ADR, sessile serrated lesion (SSL) detection rate, and the mean number of adenomas per colonoscopy. The recommended surveillance schedule distribution after trial colonoscopy was analyzed. RESULTS: Between November 2020 and January 2022, there were 3050 participants (LCI, n = 1527; WLI, n = 1523) recruited. The LCI group ADR was significantly higher than the WLI group ADR using intention-to-treat (58.7% vs 46.7%; P < .01) and per-protocol analyses (59.6% vs 46.4%; P < .01). The LCI group polyp detection rates (68.6% vs 59.5%; P < .01), SSL detection rates (4.8% vs 2.8%; P < .01), and adenomas per colonoscopy (1.48 vs 1.02; P < .01) also were significantly higher. However, the advanced ADR was not significantly different (13.2% vs 11.0%; P = .06). Significantly more patients in the LCI group had shorter recommended surveillance schedules than the WLI group (P < .01). CONCLUSIONS: Compared with WLI, LCI improved adenoma and other polyp detection rates, including SSLs, resulting in alteration of the recommended surveillance schedule after screening, diagnostic, and postpolypectomy surveillance colonoscopies. TRIAL REGISTRATION NUMBER: UMIN000042432 (https://www.umin.ac.jp/ctr/index.htm).

Validation of hypermethylated DNA regions found in colorectal cancers as potential aging-independent biomarkers of precancerous colorectal lesions.

BACKGROUND: We previously identified 16,772 colorectal cancer-associated hypermethylated DNA regions that were also detectable in precancerous colorectal lesions (preCRCs) and unrelated to normal mucosal aging. We have now conducted a study to validate 990 of these differentially methylated DNA regions (DMRs) in a new series of preCRCs. METHODS: We used targeted bisulfite sequencing to validate these 990 potential biomarkers in 59 preCRC tissue samples (41 conventional adenomas, 18 sessile serrated lesions), each with a patient-matched normal mucosal sample. Based on differential DNA methylation tests, a panel of candidate DMRs was chosen on a subset of our cohort and then validated on the remaining part of our cohort and two publicly available datasets with respect to their stratifying potential between preCRCs and normal mucosa. RESULTS: Strong statistical significance for the difference in methylation levels was observed across the full set of 990 investigated DMRs. From these, a selected candidate panel of 30 DMRs correctly identified 58/59 tumors (area under the receiver operating curve: 0.998). CONCLUSIONS: These validated DNA hypermethylation markers can be exploited to develop more accurate noninvasive colorectal tumor screening assays.

A Comparison of Incomplete Resection Rate of Large and Small Colorectal Polyps by Cold Snare Polypectomy.

BACKGROUND & AIMS: There are limited data regarding the safety and efficacy of cold snare polypectomy (CSP) for large colorectal polyps. We evaluated factors affecting the clinical outcomes of CSP for polyps between 5 and 15 mm in size. METHODS: This was a prospective single-center observational study involving 1000 patients undergoing colonoscopy. Polyps (5-15 mm) were removed using CSP, and biopsies were taken from the resection margin. The primary outcome was the incomplete resection rate (IRR), and was determined by the presence of residual neoplasia on biopsy. Correlations between IRR and polyp size, morphology, histology, and resection time were assessed by generalized estimating equation model. RESULTS: A total of 440 neoplastic polyps were removed from 261 patients. The overall IRR was 2.27%, 1.98% for small (5-9 mm) vs 3.45% for large (10-15 mm) polyps (P = .411). In univariate analysis, the IRR was more likely to be related to sessile serrated lesions (odds ratio [OR], 6.93; 95% confidence interval [CI], 1.88-25.45; P = .004), piecemeal resection (OR, 11.83; 95% CI, 1.20-116.49; P = .034), and prolonged resection time >60 seconds (OR, 7.56; 95% CI, 1.75-32.69; P = .007). In multivariable regression analysis, sessile serrated lesions (OR, 6.45; 95% CI, 1.48-28.03; P = .013) and resection time (OR, 7.39; 95% CI, 1.48-36.96; P = .015, respectively) were independent risk factors for IRR. Immediate bleeding was more frequent with resection of large polyps (6.90% vs 1.42%; P = .003). No recurrence was seen on follow-up colonoscopy in 37 cases with large polyps. CONCLUSIONS: CSP is safe and effective for removal of colorectal polyps up to 15 mm in size, with a low IRR. (ClinicalTrials.gov; Number: NCT03647176).

Risk of Colorectal Cancer in Serrated Polyposis Syndrome: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Serrated polyposis syndrome (SPS) is characterized by development of numerous serrated lesions throughout the colorectum and increased risk of colorectal cancer (CRC). However, SPS has been an underrecognized CRC predisposition syndrome, and the true risk of CRC in SPS, both overall and in surveillance, is not known. The aim of this systematic review and meta-analysis is to describe the risk of CRC in patients with SPS. METHODS: Electronic databases were searched on March 25, 2021, for studies describing CRC risk in SPS. Random-effects meta-analysis was performed to assess pooled risk of CRC among SPS patients. Primary outcomes were risk of CRC at time of SPS diagnosis and during surveillance following diagnosis of SPS. Secondary outcomes included risk of CRC prior to diagnosis of SPS and effect of World Health Organization subtype on CRC risk. RESULTS: Thirty-six studies including 2788 patients with SPS were included in the analysis. Overall risk of CRC in SPS was 19.9% (95% confidence interval [CI], 15.3%-24.5%). CRC risk at the time of diagnosis was 14.7% (95% CI, 11.4%-18.8%), while risk during surveillance was 2.8% (95% CI, 1.8%-4.4%), or 7 cases per 1000 person-years. SPS patients also had a high incidence of history of CRC prior to SPS diagnosis (7.0%; 95% CI, 4.6%-11.7). Subgroup analysis did not reveal any significant differences based on World Health Organization subtype. CONCLUSIONS: Our meta-analysis demonstrated that patients with SPS have an elevated risk of CRC, which is highest at the time of diagnosis and suggests the importance of early SPS recognition and screening to modify CRC risk. The persistently elevated CRC risk during surveillance supports current guidelines recommending heightened surveillance protocols.

Head to head: should we adopt the term 'sessile serrated lesion'?

The precursor lesion for the ~30% of colon carcinomas developing along the serrated pathway was first described in detail in 1996, and was named sessile serrated adenoma in 2003. Although the entity itself was controversial initially, over time the concept of a serrated pathway initiated by this lesion has become well accepted in the medical community. The name sessile serrated adenoma, however, has been controversial since the beginning and continues to be controversial. Alternative names, including serrated polyp with abnormal proliferation, sessile serrated polyp and, most recently, sessile serrated lesion, have been proposed. Despite the fact that the term sessile serrated lesion was adopted by the World Health Organization in 2019, none of these terms has received universal acceptance. In this article, arguments for and against adopting the term sessile serrated lesion are discussed in detail.

Disparate age and sex distribution of sessile serrated lesions and conventional adenomas in an outpatient colonoscopy population-implications for colorectal cancer screening?

PURPOSE: Colorectal cancer (CRC) is increasingly diagnosed in individuals aged < 50 years, resulting in advocacy of screening from age 45 years. Despite existing knowledge associating CRC with conventional adenomas, the significance of sessile serrated lesions (SSLs) on the burden of CRC is less detailed. We aimed to provide contemporary estimates for SSL prevalence and examine patient and procedure factors associated with SSL detection. METHODS: Retrospective observational study examining associations between SSL and conventional adenoma detection, polyp histopathology, patient, and procedure characteristics in an outpatient colonoscopy unit over 12 months. RESULTS: From 2097 colonoscopies, SSL detection was 13.8% overall and 12.5% in patients < 50 years. SSLs were mostly proximal in location (64%), and SSL detection was significantly higher in females compared with males (16.2% vs. 11.7%, p = 0.003), particularly in those < 50 years (16.8% vs. 8.6%, p < 0.001). In multivariable analysis, SSL detection was associated with female sex (adjusted odds ratio [aOR] 1.48, 95% confidence interval [CI] 1.15-1.91), synchronous conventional adenoma detection (aOR 1.36, 95% CI 1.04-1.78) and BMI ≥ 25 kg/m2 (aOR 1.34, 95% CI 1.02-1.77). Conventional adenoma detection was 33.6% and associated with age ≥ 50 years (aOR 3.57, 95% CI 2.84-4.47) and synchronous SSL detection (aOR 1.36, 95% CI 1.03-1.79). CONCLUSIONS: We observed age and sex disparities in polyp types and prevalence in this outpatient colonoscopy population. SSLs were most prevalent in females aged < 50 years, suggesting a potential increased susceptibility of young females to SSLs and CRC. Our findings may have implications for the design of CRC screening programs.

Irrigating Acetic Acid Solution During Colonoscopy for the Detection of Sessile Serrated Neoplasia: A Randomized Controlled Trial.

BACKGROUND: Misdiagnosed sessile serrated lesions (SSLs) are important precursors for interval colorectal cancers. AIMS: We investigated the usage of acetic acid (AA) solution for improving the detection of SSLs in the right colon in a randomized controlled trial. METHODS: A tandem observation of the right colon was performed in 412 consecutive patients. A first inspection was performed under white light high-definition endoscopy. In the AA group, a low concentration vinegar solution (AA: 0.005%) irrigated by a water pump in the right colon was compared with a plain solution of normal saline (NS) in the diagnostic yield of SSLs during the second inspection. Secondary outcomes in overall polyp detection were measured. RESULTS: Qualitative comparisons showed significant differences in the detection rates of all polyps except adenomas, with remarkable improvement in the demonstration of advanced (> 20 mm), SSLs, and hyperplastic polyps during the second inspection of the right colon using the AA solution. Significant improvement was also noted in the AA group, as far as the mean number of polyps/patient detected, not only in SSLs (AA group: 0.14 vs. NS group: 0.01, P < 0.001), but also in all histological types and all size-categories in the right colon. Small (≤ 9 mm) polyps were detected at a higher rate in the sigmoid colon expanding the effect of the method in the rest of the colon. CONCLUSION: AA-assisted colonoscopy led to a significant increase in SSLs detection rate in the right colon in a safe, quick, and effective manner.

Chemoprevention for Colorectal Cancers: Are Chemopreventive Effects Different Between Left and Right Sided Colorectal Cancers?

BACKGROUND AND AIMS: Recent studies have suggested that right- and left-sided colorectal cancers (CRCs) are molecularly distinct. In this study, we examined the association between the risk of right- and left-sided CRC and drug use to estimate their chemopreventive effects METHODS: This multicenter retrospective cohort study was conducted using the data of hospitalized patients between 2014 and 2019 from nine hospital databases. The primary outcomes were right- and left-sided CRC. We evaluated the association of CRCs with drug use and clinical factors. Odds ratios adjusted for age, sex, Charlson Comorbidity Index scores, and smoking status were calculated. We also compared the transcriptional profiling in precancerous lesions, including sessile serrated lesions (SSLs) RESULTS: A total of 307,938 patients, including 2745 with right-sided CRC and 4819 with left-sided CRC, were analyzed. The use of nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, cyclooxygenase-2 inhibitors, and steroids was associated with a lower risk of both right- and left-sided CRCs. In contrast, statins, other lipid-lowering agents, and metformin were associated with a lower risk of left-sided CRC. Transcriptomic analysis showed that SSL, which predominantly develops in the right colon, was associated with a lower expression of lipid metabolism-related genes. CONCLUSIONS: Targeting lipid metabolism may be useful for chemoprevention of left-sided CRCs, while development of right-sided CRCs may be independent of this pathway.

Sessile serrated lesions: Clinicopathological characteristics, endoscopic diagnosis, and management.

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.

Linked color imaging improves visibility of colorectal serrated lesion by high color contrast to surrounding mucosa.

OBJECTIVES: This study aimed to objectively evaluate the efficacy of linked color imaging (LCI) in diagnosing colorectal serrated lesions by utilizing visibility scores and color differences. METHODS: We examined 89 serrated lesions, including 36 hyperplastic polyps (HPs), 47 sessile serrated lesions (SSLs), and six traditional serrated adenomas (TSAs). Visibility changes were scored by six endoscopists as follows: 4, excellent; 3, good; 2, fair; and 1, poor. Furthermore, images obtained by white-light imaging (WLI) or LCI were assessed using the CIELAB color space in the lesion and adjacent mucosa. We calculated the mean color values (L*, a*, and b*) measured at five regions of interest of the sample lesion and surrounding mucosa and derived the color difference (ΔE*). RESULTS: The visibility scores of both HPs and SSLs in LCI were significantly higher than that in WLI (HPs, 3.67/2.89, P < 0.001; SSLs, 3.07/2.36, P < 0.001). Furthermore, SSLs showed a significantly higher L* value and significantly lower a* and b* values in LCI than the adjacent mucosae (L*, 61.76/58.23, P = 0.016; a*, 14.91/17.58, P = 0.019; b*, 20.42/24.21, P = 0.007), while WLI produced no significant difference in any color value. A similar trend was apparent in HPs. In all serrated groups, LCI revealed significantly greater ΔE* values between the lesion and adjacent mucosa than WLI (HPs, 11.54/6.12; SSLs, 13.43/7.67; TSAs, 35.00/22.48). CONCLUSION: Linked color imaging showed higher color contrast between serrated lesions and the surrounding mucosae compared with WLI, indicating improved visibility of colorectal serrated lesion using LCI.

Receptor tyrosine kinase fusions act as a significant alternative driver of the serrated pathway in colorectal cancer development.

Serrated polyps are a clinically and molecularly heterogeneous group of lesions that can contribute to the development of colorectal cancers (CRCs). However, the molecular mechanism underlying the development of serrated lesions is still not well understood. Here, we combined multiple approaches to analyze the genetic alterations in 86 colorectal adenomas (including 35 sessile serrated lesions, 15 traditional adenomas, and 36 conventional adenomatous polyps). We also investigated the in vitro and in vivo oncogenic properties of a novel variant of the NCOA4-RET fusion gene. Molecular profiling revealed that sessile serrated lesions and traditional serrated adenomas have distinct clinicopathological and molecular features. Moreover, we identified receptor tyrosine kinase translocations exclusively in sessile serrated lesions (17%), and the observation was validated in a separate cohort of 34 sessile serrated lesions (15%). The kinase fusions as well as the BRAF and KRAS mutations were mutually exclusive to each other. Ectopic expression of a novel variant of the NCOA4-RET fusion gene promoted cell proliferation in vitro and in vivo, and the proliferation was significantly suppressed by RET kinase inhibitors. All of these underscored the importance of mitogen-activated protein kinase (MAPK) pathway activation in the serrated pathway of colorectal tumorigenesis. In addition, we demonstrated that the kinase fusion may occur early in the precursor lesion and subsequent loss of TP53 may drives the transformation to carcinoma during serrated tumorigenesis. In conclusion, we identified kinase fusions as a significant alternative driver of the serrated pathway in colorectal cancer development, and detecting their presence may serve as a biomarker for the diagnosis of sessile serrated lesions. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Features associated with high-risk sessile serrated polyps at index and follow-up colonoscopy.

BACKGROUND AND AIM: Clinically significant serrated polyps are precursors of colorectal cancers, with features considered high risk including size ≥10 mm, dysplasia, and presence of synchronous conventional adenoma. While these features have been described in cohorts undergoing screening colonoscopy, there is little information regarding the prevalence and patient characteristics associated with high-risk sessile serrated polyps (SSPs) in those undergoing surveillance colonoscopy. METHODS: Polyp pathology at the index and first follow-up colonoscopy performed between 2004 and 2019 were examined in patients enrolled in a surveillance program because of an index finding of adenoma and/or SSP. Demographics and pathology features for SSP were compared between the colonoscopies. RESULTS: Of 6297 patients undergoing index colonoscopy, 2035 underwent follow-up colonoscopy after 3.3 years (interquartile range 2.1-4.8 years). The proportion with SSP decreased from 7.6% at index to 5.0% at follow-up (P < 0.001); however, the proportion of SSPs that were considered high risk was not different between the colonoscopies (62.8% vs 62.4%). Female gender was associated with the presence of high-risk SSP at index colonoscopy (odds ratio [OR] 1.62, 95% confidence interval [CI] 1.28-2.06), while age ≥75 years (OR 3.38, 95% CI 1.67-6.81) and previous high-risk SSP (OR 9.40, 95% CI 4.23-20.88) were independently associated with high-risk SSP at follow-up. CONCLUSIONS: The prevalence of SSP falls by one-third at first follow-up colonoscopy although the proportion of SSP with high-risk features remains the same. While females were more likely to have a high-risk SSP at the index colonoscopy, those at greatest risk for high-risk SSP at follow-up colonoscopy were age >75 years and an index high-risk SSP.

Curcumin Chemoprevention Reduces the Incidence of Braf Mutant Colorectal Cancer in a Preclinical Study.

BACKGROUND: Colorectal cancer is a leading cause of cancer-related death worldwide and approximately 20% of cases can be attributed to a mutation in the BRAF oncogene. Curcumin is a promising chemopreventive agent with various anti-cancer benefits. Although curcumin has been reported to have poor bioavailability, this limitation has been overcome by the formulation of nano-carriers. In this preclinical study, we investigated the ability of an improved formulation of curcumin to reduce the incidence of Braf mutant carcinoma. AIM: To investigate curcumin as a chemopreventive for Braf mutant colorectal cancer in a preclinical study utilizing a murine model of serrated neoplasia. METHODS: An intestine-specific Braf mutant murine model (BrafV637E/+/Villin-CreERT2/+) was administered curcumin micelles (240 mg/kg, n = 69) in normal drinking water. Mice in the control group consumed normal drinking water (n = 83). Mice were euthanized at 14 months and the incidence of murine serrated lesions and carcinoma in each cohort were determined by histologic examination. RESULTS: At completion of the study (14 months), it was found that curcumin did not reduce the incidence or multiplicity of murine serrated lesions but did significantly reduce the number of invasive carcinomas (RR 0.83, 95% CI 0.69-0.9985, P = 0.0360) compared to control. CONCLUSIONS: We have performed the first long-term study assessing curcumin's effect on the development of serrated neoplasia. We found that curcumin significantly reduces the risk of developing Braf mutant colorectal cancer. Our data supports further investigation of curcumin as a chemopreventive to reduce the risk of colorectal cancer arising via the serrated pathway.

Sessile Serrated Lesion of the Appendix in a Teenage Girl.

According to the literature, serrated lesions and polyps of the appendix are extremely rare in children or teenagers. Herein, we present the pathologic and molecular features of a sessile serrated lesion (SSL) that was incidentally found in the appendix of a teenage girl. Our findings not only illustrate that appendiceal SSL may occur in young patients such as teenagers but also confirm further that BRAF V600E mutation may be found in a subset of these neoplastic lesions.

Usefulness of the Japan narrow-band imaging expert team classification system for the diagnosis of sessile serrated lesion with dysplasia/carcinoma.

BACKGROUND: Sessile serrated lesion (SSL) is a colorectal polyp that has malignant potential. However, the dysplastic components within an SSL can be difficult to diagnose with conventional endoscopy, because most SSLs with dysplasia/carcinoma have subtle mucosal features. Many studies have indicated that narrow-band imaging (NBI) observations of colorectal polyps are very useful, accurate predictors of histology. We aimed to verify the usefulness of the Japan NBI Expert Team (JNET) classification system for the diagnosis of SSLs with dysplasia/carcinoma. METHODS: We examined 709 endoscopically or surgically resected lesions that were pathologically diagnosed as SSL, including 647 with no dysplasia, 37 with low-grade dysplasia, 15 with high-grade dysplasia, and 10 with submucosal invasive carcinoma. We retrospectively evaluated their clinicopathologic characteristics and conventional endoscopic and magnifying NBI endoscopic findings using the JNET system. RESULTS: Cases in all groups were more frequently located in the proximal colon. Submucosal invasive carcinomas were significantly larger than no dysplasia and low-grade dysplasia lesions. Almost all studied lesions (96.3%) were covered with a mucus cap. Five hundred and eighty (81.8%) lesions exhibited dark spots inside the crypts, which are NBI findings' characteristic of SSL. As for the JNET classification of magnifying NBI endoscopic findings, all 709 lesions showed Type 1. Six hundred and eighteen (95.5%) SSLs with no dysplasia lesions exhibited Type 1 only, whereas 52 (83.9%) SSLs with dysplasia/carcinoma had a combination of Type 1 and Type 2A, 2B, or 3, corresponding to SSL and dysplasia/carcinoma, respectively. The JNET classification had high sensitivity (83.9%), specificity (95.5%), and overall diagnostic accuracy (94.5%) for diagnosing SSLs with dysplasia/carcinoma. CONCLUSIONS: Use of magnifying NBI endoscopy with the JNET classification might be useful for diagnosing SSLs with dysplasia/carcinoma. This increased awareness may also improve the recognition of SSLs with dysplasia/carcinoma.

[Pathohistology of polyps of the gastrointestinal tract]. / Pathohistologie von Polypen des Gastrointestinaltrakts.

Polyps of the gastrointestinal tract encompass a variety of epithelial and non-epithelial tumour-like conditions. The most common polyps are epithelial lesions. In the upper gastrointestinal tract, reactive inflammatory changes and hyperplastic polyps dominate, whereas true neoplastic polyps, like adenomas, are much more common in the colorectum. In addition to neoplasias such as adenomas, non-neoplastic polyps such as hyperplastic polyps of the stomach may also be associated with an increased risk of malignancy. The risk of malignancy is determined by the histological subtype of polyp, as well as the size, presence and degree of dysplasia. The term "dysplasia" has been reintroduced for adenomas in the current 2019 World Health Organization (WHO) classification and replaces "intraepithelial neoplasia". A further change is the term "sessile serrated lesion" with and without dysplasia, which was formerly known as sessile serrated adenoma.

Patient and Physician Factors Associated with Adenoma and Sessile Serrated Lesion Detection Rates.

BACKGROUND AND AIMS: Sessile serrated lesions (SSLs) have been increasingly recognized as precursors to colorectal cancer. Unlike adenoma detection rate (ADR), there is currently no agreed-upon benchmark for SSL detection rate (SSLDR), and data on factors that impact SSL detection are limited. We aimed to identify patient, endoscopist, and procedural factors associated with SSL and adenoma detection. METHODS: We used a single-center electronic endoscopy database to identify all patients ages ≥ 50 years who underwent outpatient screening colonoscopy from January 1, 2012, to June 30, 2018. Univariable Chi-square analysis was used to determine patient, endoscopist, and procedure-related factors associated with SSL or adenoma detection. We used logistic regression with generalized estimating equations, accounting for clustering by individual endoscopist, to determine factors independently associated with ADR and SSLDR. RESULTS: We identified 10,538 unique patients who underwent colonoscopy performed by 28 endoscopists. Overall SSLDR was 2.2%, and overall ADR was 29.1%. On multivariable analysis, patient age, sex, BMI, smoking, endoscopist withdrawal time, and year of colonoscopy were independent predictors of ADR. Smoking and year of colonoscopy were independent predictors of SSLDR. Sub-optimal bowel preparation was inversely associated with SSL detection but not ADR. CONCLUSIONS: In this large study of patients undergoing average-risk screening colonoscopy, overall SSLDR was low, indicating that methods for increasing SSLDR are needed. Our findings suggest that endoscopists may take into account risk factors for SSLs, such as smoking history, and recognize that the detection of such lesions, even more so than for adenomas, is dependent on optimal bowel preparation.