Recent advances in screening programs and the development of innovative therapeutic strategies have significantly improved the clinical outcomes of cancer patients. However, many patients still experience treatment failure, primarily due to inherent or acquired drug resistance mechanisms. This challenge underscores the urgent need for novel therapeutic targets for the effective treatment of malignancies, as well as cancer-specific biomarkers to enhance early diagnosis and guide interventions. Epigenetic mechanisms, including DNA methylation, have recently garnered growing interest as key regulators of gene expression under both physiological and pathological conditions. Although epigenetic dysregulations are reliable tumor hallmarks, DNA methylation is still not routinely integrated into clinical practice, highlighting the need for further research to translate preclinical findings from the bench to the bedside. On these bases, the present review aims to illustrate the state of the art regarding the role of DNA methylation in cancer, describing the technologies currently available for DNA methylation profiling. Furthermore, the latest evidence on the application of DNA methylation hotspots in cancer diagnosis and prognosis, as well as the impact of epidrugs in cancer care, is discussed to provide a comprehensive overview of the potential clinical relevance of DNA methylation in advancing personalized medicine.

Proximal sessile serrated lesions (PSSL) are increasingly recognized as significant precursors of interval colon cancer. We aimed to assess the PSSL detection rates during non-screening colonoscopies and whether there are associations between PSSL detection rate and the established colonoscopy key performance indicators (KPI).

We retrospectively collected data of all non-screening colonoscopies performed by independent endoscopists at a large teaching hospital between June and December 2019. Data regarding endoscopists' KPIs, including polyp detection rate (PDR), cecal intubation rate (CIR), and colonoscopy withdrawal time (CWT), were retrieved from the national endoscopy database. SSL resected proximal to the splenic flexure were identified by an expert pathologist. Associations between PSSL detection rate and the different KPIs were assessed using Spearman's test.

A total of 2956 colonoscopies performed by 33 endoscopists were included. The mean PSSL detection rate was 0.7% (SD 1.5), the mean PDR was 37.1% (SD 17), the mean CIR was 91.3% (SD 6), and the mean CWT was nine minutes (SD 2). There was marked variability in PSSL detection rates between endoscopists (range 0 - 6.5%). PSSL detection rate positively correlated with CWT (r=0.34, p=0.04) but not with the other KPIs.

The wide variability in PSSL detection between endoscopists is concerning of high miss rates and despite achieving the national benchmarks for the established KPIs, many endoscopists still had low PSSL detection rates. Therefore, PSSL detection rate should be considered as an independent KPI.

Postcolonoscopy colorectal cancers primarily occur in the right-sided colon because of missed adenomas and serrated polyps (SPs). Water exchange (WE) improves cleanliness and visibility of the right-sided colon. We hypothesized that WE could reduce the right-sided colon adenoma (rAMR) and SP miss rate (rSPMR) compared with standard colonoscopy.

We randomly assigned 386 colonoscopy patients to insertion with either WE or CO 2 insufflation. During the first withdrawal, polypectomies were performed up to the hepatic flexure. A second endoscopist, blinded to the insertion technique, re-examined the right-sided colon. The miss rate was determined by dividing the number of additional adenomas or SPs by the total number detected in both examinations. The primary outcome was the combined rAMR and rSPMR.

WE significantly decreased the combined rAMR and rSPMR (22.2% vs 32.2%, P < 0.001) and rSPMR alone (22.5% vs 37.1%, P = 0.002) compared with CO 2 insufflation, but not rAMR (21.8% vs 29.8%, P = 0.079). In addition, WE significantly increased the detection of SP per colonoscopy (SP per colonoscopy) in the right-sided colon (0.95 ± 1.56 vs 0.50 ± 0.79, P < 0.001). Multivariate logistic regression analysis showed that ≥2 SPs in the right-sided colon were an independent predictor of rSPMR (odds ratio, 3.47; 95% confidence interval, 1.89─6.38), along with a higher right-sided colon Boston Bowel Preparation Scale score (odds ratio, 0.55; 95% confidence interval, 0.32─0.94).

The significant reduction in rSPMR and increase in right-sided colon SP per colonoscopy suggest that colonoscopy insertion using WE is a valid alternative to CO 2 insufflation (clinical trial registration number: NCT04124393).

Sessile serrated lesions (SSLs) are obscured lesions predominantly in the right-sided colon and associated with interval colorectal cancer; however, their prevalence and risk factors among younger individuals remain unclear.

This retrospective study enrolled individuals who underwent index colonoscopy. The primary outcome was the SSL prevalence in the younger (<50 years) and older (≥50 years) age groups, while the secondary outcomes included clinically significant serrated polyps (CSSPs). Multivariable logistic regression was employed to identify predictors.

Of the 9854 eligible individuals, 4712 (47.8%) were categorized into the younger age group. Individuals in the younger age group exhibited lower prevalences of adenomas (22.6% vs. 46.2%; P<0.001) and right-sided adenomas (11.2% vs. 27.2%; P<0.001) compared with their older counterparts. However, both groups exhibited a similar prevalence of SSLs (7.2% vs. 6.5%; P=0.16) and CSSPs (10.3% vs. 10.3%;P=0.96). Multivariable analysis revealed that age 40-49 years (odds ratio [OR] 1.81, 95%CI 1.01-3.23), longer withdrawal time (OR 1.17, 95%CI 1.14-1.20, per minute increment), and endoscopist performance (OR 3.35, 95%CI 2.44-4.58) were independent predictors of SSL detection in the younger age group. No significant correlation was observed between adenoma and SSL detection rates among endoscopists.

SSLs are not uncommon among younger individuals. Moreover, diligent effort and expertise are of paramount importance in SSL detection. Future studies should explore the clinical significance of SSLs in individuals of younger age.

High-risk adenomas predict metachronous advanced adenomatous neoplasia. Limited data exist on predictors of metachronous advanced serrated lesions (mASLs). We analyzed clinical and endoscopic predictors of mASLs.

In this retrospective cohort study, adults with >1 outpatient colonoscopy between 2008 and 2019 at a tertiary center were included. Serrated lesions (SLs) included sessile SLs (SSLs), traditional serrated adenomas (TSAs), and hyperplastic polyps (HPs). Patient and endoscopic characteristics were obtained using electronic medical records. Five-year cumulative incidence of mASL (HP ≥10 mm, SSL ≥10 mm or with dysplasia, any TSA) and factors associated with mASL were evaluated using Kaplan-Meier estimates and Cox proportional hazards models.

A total of 4990 patients were included and 45.4% were women. Mean age was 60.9 ± 9.2 years and median follow-up time was 3.7 years. Female sex and active smoking were associated with mASL. Endoscopically, any SSL and TSA were associated with mASL. The 5-year cumulative incidence for mASL was 26% (95% confidence interval [CI], 18%-32%) for SSL ≥10 mm, 17% (95% CI, 3.5%-29%) for HP ≥10 mm, 21% (95% CI, 0%-42%) for 3-4 SSLs <10 mm, 18% (95% CI, 0%-38%) for TSA, and 27% (95% CI, 3.6%-45%) for SSL with low-grade dysplasia. Baseline synchronous nonadvanced SL and nonadvanced adenoma were not associated with mASL.

Our data support current recommendations for a 3-year surveillance interval in patients with baseline SSL ≥10 mm, SSL with dysplasia, and TSA. A 3-year interval may be more appropriate than 3-5 years for patients with baseline HP ≥10 mm or 3-4 SSLs <10 mm. Patients with synchronous nonadvanced SLs and adenomas do not appear to be at increased risk of mASL.

One goal of colorectal cancer (CRC) screening is to prevent CRC incidence by removing precancerous colonic polyps, which are detected in up to 50% of screening examinations. Yet, the lifetime risk of CRC is 3.9%-4.3%, so it is clear that most of these individuals with polyps would not develop CRC in their lifetime. It is, therefore, a challenge to determine which individuals with polyps will benefit from follow-up, and at what intervals. There is some evidence that individuals with advanced polyps, based on size and histology, benefit from intensive surveillance. However, a large proportion of individuals will have small polyps without advanced histologic features (ie, "nonadvanced"), where the benefits of surveillance are uncertain and controversial. Demand for surveillance will further increase as more polyps are detected due to increased screening uptake, recent United States recommendations to expand screening to younger individuals, and emergence of polyp detection technology. We review the current understanding and clinical implications of the natural history, biology, and outcomes associated with various categories of colon polyps based on size, histology, and number. Our aims are to highlight key knowledge gaps, specifically focusing on certain categories of polyps that may not be associated with future CRC risk, and to provide insights to inform research priorities and potential management strategies. Optimization of CRC prevention programs based on updated knowledge about the future risks associated with various colon polyps is essential to ensure cost-effective screening and surveillance, wise use of resources, and inform efforts to personalize recommendations.

Sessile serrated lesions (SSLs) are considered precancerous colorectal lesions that should be detected and removed to prevent colorectal cancer. Previous studies in Vietnam mainly investigated the adenoma pathway, with limited data on the serrated pathway.

To evaluate the prevalence, risk factors, and BRAF mutations of SSLs in the Vietnamese population.

This is a cross-sectional study conducted on patients with lower gastrointestinal symptoms who underwent colonoscopy at a tertiary hospital in Vietnam. SSLs were diagnosed on histopathology according to the 2019 World Health Organization classification. BRAF mutation analysis was performed using the Sanger DNA sequencing method. The multivariate logistic regression model was used to determine SSL-associated factors.

There were 2489 patients, with a mean age of 52.1 ± 13.1 and a female-to-male ratio of 1:1.1. The prevalence of SSLs was 4.2% [95% confidence interval (CI): 3.5-5.1]. In the multivariate analysis, factors significantly associated with SSLs were age ≥ 40 [odds ratio (OR): 3.303; 95%CI: 1.607-6.790], male sex (OR: 2.032; 95%CI: 1.204-3.429), diabetes mellitus (OR: 2.721; 95%CI: 1.551-4.772), and hypertension (OR: 1.650, 95%CI: 1.045-2.605). The rate of BRAF mutations in SSLs was 35.5%.

The prevalence of SSLs was 4.2%. BRAF mutations were present in one-third of SSLs. Significant risk factors for SSLs included age ≥ 40, male sex, diabetes mellitus, and hypertension.

We used New Hampshire Colonoscopy Registry data to examine the association between postcolonoscopy colorectal cancer (PCCRC) and sessile serrated detection rates (SSLDRs).

We included patients with either a colonoscopy or a CRC diagnosis in the NH State Cancer Registry. PCCRC was any CRC diagnosed ≥ 6 months after index examination.

Of 26,901 patients, 162 were diagnosed with PCCRC. The hazard ratio for PCCRC was lowest for patients whose endoscopists had the highest SSLDR quintile (≥6%) (hazard ratio 0.29; 95% confidence interval 0.16-0.50).

Endoscopists with higher SSLDRs had lower risks of PCCRC. These data validate SSLDR as a clinically relevant quality measure.

Based on published evidence and our expert experience, we provide recommendations to maximize the efficacy, safety, efficiency, and cost-effectiveness of routine colonoscopy. High-quality colonoscopy begins with colon preparation using a split or same-day dose and preferably a low-volume regimen for optimal patient tolerance and compliance. Successful cecal intubation can be achieved by choosing the correct colonoscope and using techniques to facilitate navigation through challenges such as severe angulations and redundant colons. Safety is a primary goal, and complications such as perforation and splenic rupture can be prevented by avoiding pushing through fixed resistance and avoiding loops in proximal colon. Furthermore, barotrauma can be avoided by converting to water filling only (no gas insufflation) in every patient with a narrowed, angulated sigmoid. Optimal polyp detection relies primarily on compulsive attention to inspection as manifested by adequate inspection time, vigorous probing of the spaces between haustral folds, washing and removing residual debris, and achieving full distention. Achieving minimum recommended adenoma detection rate thresholds (30% in men and 20% in women) is mandatory, and colonoscopists should aspire to adenoma detection rate approaching 50% in screening patients. Distal attachments can improve mucosal exposure and increase detection while shortening withdrawal times. Complete resection of polyps complements polyp detection in preventing colorectal cancer. Cold resection is the preferred method for all polyps < 10 mm. For effective cold resection, an adequate rim of normal tissue should be captured in the snare. Finally, cost-effective high-quality colonoscopy requires the procedure not be overused, as demonstrated by following updated United States Multi Society Task Force on Colorectal Cancer postpolypectomy surveillance recommendations.

Colonic SSLs are thought to predispose to ∼30% of colonic adenocarcinomas. This increased risk, compared to benign HPs, makes their distinction vitally important. However, no gold standard exists to differentiate them, and wide observer variability is reported. To better distinguish these polyps, we investigated 94 serrated polyps (53 SSLs and 41 HPs) using an easy-to-apply pathologic scoring system that combines, for the first time, three established distinguishing features: polyp morphology, location, and size. As an additional novel approach, polyp size was assessed by serrated biopsy number compared to endoscopic size. RNA expression profiling served as an additional biomarker. The considerable morphologic overlap across serrated polyps was quantitated for the first time. Interobserver variability was assessed by 8 expert gastrointestinal pathologists. By ROC analysis, polyp size by biopsy number performed best, followed by polyp location and morphology (areas under the curves [AUCs] = 85.9%, 81.2%, and 65.9%, respectively). Optimal discrimination combined all 3 features (AUC = 92.9%). For polyp size, the biopsy number proved superior to endoscopic size (AUC = 85.9% versus 55.2%, P = .001). Interobserver variability analysis yielded the highest reported Fleiss and Kappa statistics (0.879) and percent agreement (96.8%), showing great promise toward improved diagnosis. The proposed 3-criteria pathologic system, combining size by biopsy number, location, and morphology, yields an improved, easy-to-use, and highly reproducible diagnostic approach for differentiating SSLs and HPs.

Worldwide, gastrointestinal (GI) cancers account for a significant amount of cancer-related mortality. Tests that allow an early diagnosis could lead to an improvement in patient survival. Liquid biopsies (LBs) due to their non-invasive nature as well as low risk are the current focus of cancer research and could be a promising tool for early cancer detection. LB involves the sampling of any biological fluid (e.g., blood, urine, saliva) to enrich and analyze the tumor's biological material. LBs can detect tumor-associated components such as circulating tumor DNA (ctDNA), extracellular vesicles (EVs), and circulating tumor cells (CTCs). These components can reflect the status of the disease and can facilitate clinical decisions. LBs offer a unique and new way to assess cancers at all stages of treatment, from cancer screenings to prognosis to management of multidisciplinary therapies. In this review, we will provide insights into the current status of the various types of LBs enabling early detection and monitoring of GI cancers and their use in in vitro diagnostics.

Serrated polyps (SPs) are precursors to one-third of colorectal cancers (CRCs), with histological subtypes: hyperplastic polyps (HPs), sessile serrated lesions (SSLs) and traditional serrated adenomas (TSAs). The incidence of early-onset CRC before the age of 50 is increasing, with limited understanding of SPs in younger cohorts. Using a large colonoscopy-based cohort, we characterized epidemiologic profiles of SP subtypes, compared to conventional adenomas, with secondary analysis on early-onset polyps. Ninety-four thousand four hundred and twenty-seven patients underwent screening colonoscopies between 2010 and 2018. Demographic, endoscopic and histopathologic characteristics of each polyp subtype were described. High-risk polyps included SSLs ≥10 mm/with dysplasia and conventional adenomas ≥10 mm/with tubulovillous/villous histology/high-grade dysplasia. We examined polyp prevalence with age and compared early- (age < 50) and late-onset polyps (age ≥ 50). Eighteen thousand one hundred and twenty-five patients had SPs (4357 SSLs, 15 415 HPs, 120 TSAs) and 26 699 had conventional adenomas. High-risk SSLs were enriched in the ascending colon (44.1% vs 2.6-35.8% for other locations; P < .003). Early- and late-onset SPs had similar subsite distribution. Early-onset conventional adenomas were more enriched in the distal colon/rectum (51.8% vs 43.4%, P < .001). Multiple conventional adenomas were more represented in late-onset groups (40.8% vs 33.8%, P < .001), with no difference in SSLs. The prevalence of conventional adenomas/high-risk conventional adenomas increased continuously with age, whereas the prevalence of SSLs/high-risk SSLs was stable from age 40 years onwards. A higher proportion of women were diagnosed with early-onset than late-onset SSLs (62.9% vs 57.6%, P = .03). Conventional adenomas, SSLs, early- and late-onset polyps have distinct epidemiology. The findings have implications for improved colonoscopy screening and surveillance and understanding the etiologic heterogeneity of CRC.

Melanosis coli is characterized by brown mucosa with pigmentation. Studies have showed an increased adenoma detection rate in melanosis patients, whether it is caused by a contrast effect or an oncogenic effect is still controversial. The detection of serrated polys in melanosis patients remains unknown.

The study aimed to clarify the correlation of adenoma detection rate with melanosis coli and discuss outcomes in less-experienced endoscopists. Serrated polyp detection rate was also been investigated.

A total of 2150 patients and 39,630 controls were enrolled. A propensity score matching method was used to balance covariates between the two groups. The detection of polyps, adenomas, serrated polyps, and their features was analyzed.

The polyp detection rate (44.65% vs 41.01%, P = 0.005) and adenoma detection rate (30.34% vs 23.92%, P < 0.001) were significantly higher, and the serrated polyp detection rate (0.93% vs 1.58%, P = 0.033) was significantly lower in melanosis coli. The percentage of low-risk adenomas (44.60% vs 39.16%, P < 0.001) and polyps with 6 to 10 mm in size (20.16% vs 16.21%, P < 0.001) were higher in melanosis coli. The detection of large serrated polyps was lower (0.11% vs 0.41%, P = 0.026) in melanosis coli.

Melanosis coli correlates with an increased adenoma detection rate. The detection of large serrated polyps was lower in melanosis patients. Melanosis coli may not be considered a precancerous lesion.

Colonoscopic polypectomy is effective in decreasing the incidence and mortality of colorectal cancer (CRC). Premalignant polyps discovered during colonoscopy are associated with the risk of metachronous advanced neoplasia. Postpolypectomy surveillance is the most important method for managing advanced metachronous neoplasia. A more efficient and evidence-based guideline for postpolypectomy surveillance is required because of the limited medical resources and concerns regarding colonoscopy complications. In these consensus guidelines, an analytic approach was used to address all reliable evidence to interpret the predictors of CRC or advanced neoplasia during surveillance colonoscopy. The key recommendations state that the high-risk findings for metachronous CRC following polypectomy are as follows: adenoma ≥10 mm in size; 3 to 5 (or more) adenomas; tubulovillous or villous adenoma; adenoma containing high-grade dysplasia; traditional serrated adenoma; sessile serrated lesion containing any grade of dysplasia; serrated polyp of at least 10 mm in size; and 3 to 5 (or more) sessile serrated lesions. More studies are needed to fully comprehend the patients who are most likely to benefit from surveillance colonoscopy and the ideal surveillance interval to prevent metachronous CRC.

Background and study aims  We anecdotally encounter cases where referring endoscopists made errors in endoscopic interpretation of a colorectal lesion, sometimes combined with pathology errors at the referring centers, resulting in referral to our center for endoscopic resection. In this paper, we describe the frequency and nature of endoscopic and pathology errors leading to consultation for endoscopic resection. Patients and methods  Review of 760 consecutive referrals to our center over a 26-month interval. Results  In total, 28 (3.7 %) of all referred patients had ≥ 1 lesion that did not require any resection after investigation. There were 12 cases (1.6 % of all referrals) involving errors by both the referring endoscopist and the pathologist at the referring center. Errors commonly involved the ileocecal valve, lipomas, and mucosal prolapse changes. There were 15 additional referrals (2.0 % of all referrals) where no neoplastic lesion was identified at our center and either no biopsy was taken at the referring center (n = 9 patients, 10 lesions), the patient was referred although biopsy showed no neoplasia (n = 6), or the referring doctor correctly interpreted the lesion (lipoma), but the outside pathologist incorrectly reported adenoma (n = 1). Conclusions  Endoscopists at tertiary centers should expect referrals to clarify the nature of colorectal lesions as neoplastic or non-neoplastic. Community endoscopists with equivocal endoscopic findings and unexpected or equivocal pathology results can consider pathology review at their center or at an expert center before referral for endoscopic or surgical resection.

Patients with serrated polyps are at increased risk for post-colonoscopy colorectal cancer (PCCRC); however, evidence for a dedicated serrated polyp detection rate is lacking. The aim of this study was to investigate the association of the proximal serrated polyp detection rate (PSDR) and adenoma detection rate (ADR) with PCCRC death.

This was a retrospective analysis within the Austrian quality assurance program for screening colonoscopy. Spearman's rank coefficient was calculated for the assessment of association between ADR and PSDR. Whether ADR or PSDR were associated with colorectal cancer mortality was assessed by Cox proportional hazards model.

229 /729 screening colonoscopies performed by 308 endoscopists were analyzed. The ADR (hazard ratio [HR] per 1 percentage point increase 0.98, 95 %CI 0.96-0.99) as well as the PSDR (HR per 1 percentage point increase 0.97, 95 %CI 0.94-0.99) were significantly associated with PCCRC death. The correlation coefficient of the ADR and PSDR calculated at every colonoscopy was 0.70 (95 %CI 0.70-0.71), and the corresponding PSDR value for an ADR performance standard of 25 % was 11.1 %. At the end of the study period, 86 endoscopists (27.9 %) reached an ADR of > 25 % and a PSDR of > 11.1 %.

The ADR as well as the PSDR were associated with PCCRC death. Striving for a high PSDR in addition to a high ADR might reduce the risk for PCCRC mortality in patients undergoing screening colonoscopy.

Sessile serrated lesions (SSLs) act as precursors to colorectal cancer, sometimes harbor carcinomas, and are sometimes incompletely resected. We aimed to evaluate local recurrence after endoscopic resection of SSL ≥10 mm.

This prospective, single-arm, observational study was performed at eight Japanese tertiary institutions. Colorectal lesions ≥10 mm were resected endoscopically, and the pathological diagnosis was either an SSL or hyperplastic polyp (HP). Follow-up colonoscopy was performed 1 year later, and the local recurrence was evaluated by biopsy.

From October 2018 to September 2021, 104 cases with 123 lesions were registered. Among the pathologically diagnosed 105 SSLs and 18 HPs, 95 and 7 lesions were diagnosed as SSLs and HPs, respectively, by central pathological review. Among the 104 endoscopically diagnosed SSLs, 86 were diagnosed as SSLs, whereas among the 11 endoscopically diagnosed HPs, two were diagnosed as HPs by central pathological review (the rest were SSLs). Among the 95 patients with 113 lesions who underwent follow-up colonoscopy, resection scars were identified in 95 (84%) lesions. Three (3.1%; 95% confidence interval 0.6-8.7%) local recurrences were diagnosed pathologically among 98 pathologically diagnosed SSLs. Two (6%) local recurrences were diagnosed in patients with SSLs ≥20 mm.

The local recurrence rate after endoscopic resection of SSLs ≥10 mm was 3.1%. Careful follow-up is recommended after endoscopic resection of large SSLs. Endoscopically diagnosed HPs ≥10 mm were sometimes pathologically diagnosed as SSL and should be considered for resection.

Colonoscopic polypectomy is effective in decreasing the incidence and mortality of colorectal cancer (CRC). Premalignant polyps discovered during colonoscopy are associated with the risk of metachronous advanced neoplasia. Postpolypectomy surveillance is the most important method for managing advanced metachronous neoplasia. A more efficient and evidence-based guideline for postpolypectomy surveillance is required because of the limited medical resources and concerns regarding colonoscopy complications. In these consensus guidelines, an analytic approach was used to address all reliable evidence to interpret the predictors of CRC or advanced neoplasia during surveillance colonoscopy. The key recommendations state that the high-risk findings for metachronous CRC following polypectomy are as follows: 1) adenoma ≥10 mm in size; 2) 3-5 (or more) adenomas; 3) tubulovillous or villous adenoma; 4) adenoma containing high-grade dysplasia; 5) traditional serrated adenoma; 6) sessile serrated lesion (SSL) containing any grade of dysplasia; 7) serrated polyp of at least 10 mm in size; and 8) 3-5 (or more) SSLs. More studies are needed to fully comprehend the patients who are most likely to benefit from surveillance colonoscopy and the ideal surveillance interval to prevent metachronous CRC.

Colonoscopic polypectomy is effective in decreasing the incidence and mortality of colorectal cancer (CRC). Premalignant polyps discovered during colonoscopy are associated with the risk of metachronous advanced neoplasia. Postpolypectomy surveillance is the most important method for managing advanced metachronous neoplasia. A more efficient and evidence-based guideline for postpolypectomy surveillance is required because of the limited medical resources and concerns regarding colonoscopy complications. In these consensus guidelines, an analytic approach was used to address all reliable evidence to interpret the predictors of CRC or advanced neoplasia during surveillance colonoscopy. The key recommendations state that the high-risk findings for metachronous CRC following polypectomy are as follows: 1) adenoma ≥10 mm in size; 2) 3-5 (or more) adenomas; 3) tubulovillous or villous adenoma; 4) adenoma containing high-grade dysplasia; 5) traditional serrated adenoma; 6) sessile serrated lesion (SSL) containing any grade of dysplasia; 7) serrated polyp of at least 10 mm in size; and 8) 3-5 (or more) SSLs. More studies are needed to fully comprehend the patients who are most likely to benefit from surveillance colonoscopy and the ideal surveillance interval to prevent metachronous CRC.

Higher adenoma detection rates reduce the risk of postcolonoscopy colorectal cancer (PCCRC). Clinically significant serrated polyps (CSSPs; defined as any sessile serrated polyp, traditional serrated adenoma, large [≥1 cm] or proximal hyperplastic polyp >5 mm) also lead to PCCRC, but there are no data on associated CSSP detection rates (CSSDRs). We used data from the New Hampshire Colonoscopy Registry (NHCR) to investigate the association between PCCRC risk and endoscopist CSSDR.

We included NHCR patients with 1 or more follow-up events: either a colonoscopy or a colorectal cancer (CRC) diagnosis identified through linkage with the New Hampshire State Cancer Registry. We defined our outcome, PCCRC, in 3 time periods: CRC diagnosed 6 to 36 months, 6 to 60 months, or all examinations (6 months or longer) after an index examination. We excluded patients with CRC diagnosed at or within 6 months of the index examination, with incomplete examinations, or with inflammatory bowel disease. The exposure variable was endoscopist CSSDR at the index colonoscopy. Cox regression was used to model the hazard of PCCRC on CSSDR controlling for age, sex, index findings, year of examination, personal history of colorectal neoplasia, and having more than 1 surveillance examination.

One hundred twenty-eight patients with CRC diagnosed at least 6 months after their index examination were included. Our cohort included 142 endoscopists (92 gastroenterologists). We observed that the risk for PCCRC 6 months or longer after the index examination was significantly lower for examinations performed by endoscopists with CSSDRs of 3% to <9% (hazard ratio [HR], .57; 95% confidence interval [CI], .39-.83) or 9% or higher (HR, .39; 95% CI, .20-.78) relative to those with CSSDRs under 3%.

Our study is the first to demonstrate a lower PCCRC risk after examinations performed by endoscopists with higher CSSDRs. Both CSSDRs of 9% and 3% to <9% had statistically lower risk of PCCRC than CSSDRs of <3%. These data validate CSSDR as a clinically relevant quality measure for endoscopists.

Colorectal cancer is the second leading cause of cancer-associated mortality, with a lifetime risk of approximately 4% to 5%. Colorectal cancer develops from the sequential acquisition of defined genetic mutations in the colonic epithelium. Tumorigenesis from normal tissue to cancer occurs largely through 3 pathways: the chromosomal instability pathway, the microsatellite instability pathway, and the sessile serrated pathway. Colorectal cancer incidence and mortality have decreased by approximately 35% since the beginning of screening programs in the 1990s, although other factors such as use of aspirin for coronary disease prevention and decreased smoking rates may also be important. In this review, we discuss the etiology, epidemiology, and histology of colorectal polyps and cancer.

Sessile serrated lesions (SSLs) develop colorectal cancer (CRC), through a critical intermediary stage of SSL with dysplasia (SSLd). In this prospective observational study, we aimed to assess clinicopathological correlates of SSLd in the setting of a high lesion-detection rate.

Patients diagnosed with SSL and SSLd from February 2018 until January 2020 were prospectively recruited, and SSLd specimens were re-evaluated by 2 expert pathologists in a blinded manner. Associations were analyzed using multivariate logistic regression models.

A total of 6425 patients underwent 7423 colonoscopies, and 2671 SSLs were resected from 1047 patients. The overall SSL detection rate per colonoscopy was 15.9%. The median age of patients with SSL was 54 years (interquartile range, 39-66), and 43.3% were male. After pathologist review, 24 SSLds were confirmed in 20 patients. The median size of SSLd was 8 mm (interquartile range, 5.75-15.25), and 13 of 24 SSLds were <10 mm in size. After multivariate analysis, older age (odds ratio = 1.07, 95% confidence interval = 1.03-1.1) and higher number of synchronous SSLs (odds ratio = 1.12, 95% confidence interval = 1.02-1.23) were associated with the presence of dysplasia. Patient sex and number and size of synchronous adenomas were not associated with the presence of SSLd. Seven of 20 patients with SSLd had synchronous or metachronous SSLd. Six of 20 patients with SSLd met the diagnostic criteria for serrated polyposis syndrome.

The overall SSL detection rate was 15.9%, and 0.9% of SSLs were dysplastic. Older age and higher number of synchronous SSL were risk factors for the presence of dysplasia in SSLs. Thirty percent of patients with SSLd had serrated polyposis syndrome, and 35% had multiple SSLd.

Conventional adenomas (CAs) and serrated polyps (SPs) are precursors to colorectal cancer (CRC). Understanding metachronous cancer risk is poor due to lack of accurate large-volume datasets. We outline the use of natural language processing (NLP) in forming the Partners Colonoscopy Cohort, an integrated longitudinal cohort of patients undergoing colonoscopies.

We identified endoscopy quality data from endoscopy reports for colonoscopies performed from 2007 to 2018 in a large integrated healthcare system, Mass General Brigham). Through modification of an established NLP pipeline, we extracted histopathological data (polyp location, histology and dysplasia) from corresponding pathology reports. Pathology and endoscopy data were merged by polyp location using a four-stage algorithm. NLP and merging procedures were validated by manual review of 500 pathology reports.

305,656 colonoscopies in 213,924 patients were identified. After merging, 76,137 patients had matched polyp data for 334,750 polyps. CAs and SPs were present in 86,707 (28.5%) and 55,373 (18.2%) colonoscopies. Among patients with polyps at index screening colonoscopy, 14,931 (33.4%) had follow-up colonoscopy (median 46.4, interquartile range 33.8-62.4 months); 91 (0.2%) and 1127 (2.5%) patients developed metachronous CRC and high-risk polyps (polyps ≥ 10 mm or CAs having high-grade dysplasia/villous/tublovillous histology or SPs with dysplasia). Genetic data were available for 23,787 (31.7%) patients with polyps from the Partners Biobank. The validation study showed a positive predictive value of 100% for polyp histology and locations.

We created the Partners Colonoscopy Cohort providing essential infrastructure for future studies to better understand the natural history of CRC and improve screening and post-polypectomy strategies.

Background and study aims  Fujifilm has developed a novel ELUXEO 7000 endoscope system that employs light-emitting diodes (LEDs) at four different wavelengths as light sources that enable blue light imaging (BLI), linked color imaging (LCI), and high-definition white-light endoscopy (HD-WLE). The aim of this study was to address the diagnostic accuracy of real-time polyp characterization using BLI, LCI and HD-WLE (ELUXEO 7000 endoscopy system). Patients methods  This is a prespecified post-hoc analysis of a prospective study in which 22 experienced endoscopists (> 2,000 colonoscopies) from eight international centers participated. Using a combination of BLI, LCI, and HD-WLE, lesions were endoscopically characterized including a high- or low-confidence statement. Per protocol, digital images were created from all three imaging modalities. Histopathology was the reference standard. Endoscopists were familiar with polyp characterization, but did not take dedicated training for purposes of this study. Results  Overall, 341 lesions were detected in 332 patients. Of the lesions, 269 histologically confirmed polyps with an optical diagnosis were included for analysis (165 adenomas, 27 sessile serrated lesions, and 77 hyperplastic polyps). Overall, polyp characterization was performed with high confidence in 82.9 %. The overall accuracy for polyp characterization was 75.1 % (95 % confidence interval [CI] 69.5-80.1 %), compared with an accuracy of 78.0 % (95 % CI 72.0-83.2 %) for high confidence assignments. The accuracy for endoscopic characterization for diminutive polyps was 74.7 % (95 %CI 68.4-80.3 %), compared with an accuracy of 78.2 % (95 % CI 71.4-84.0 %) for high-confidence assignments. Conclusions  The diagnostic accuracy of BLI, LCI, and HD-WLE by experienced endoscopist for real-time polyp characterization seems limited (NCT03344289).

Aim: Sessile serrated adenomas (SSAs) are premalignant lesions driven by the BRAF^V600E mutation to give rise to colorectal cancers (CRCs). They are often missed during white light colonoscopy because of their subtle appearance. Previously, a fluorescently labeled 7mer peptide KCCFPAQ was shown to detect SSAs in vivo. We aim to identify the target of this peptide. Results: Peroxiredoxin-1 (Prdx1) was identified as the binding partner of the peptide ligand. In vitro binding assays and immunofluorescence staining of human colon specimens ex vivo supported this result. Prdx1 was overexpressed on the membrane of cells with the BRAF^V600E mutation, and this effect was dependent on oxidative stress. RKO cells harboring the BRAF^V600E mutation and human SSA specimens showed higher oxidative stress as well as elevated levels of Prdx1 on the cell membrane. Innovation and Conclusion: These results suggest that Prdx1 is overexpressed on the cell surface in the presence of oxidative stress and can serve as an imaging biomarker for in vivo detection of SSAs. Antioxid. Redox Signal. 36, 39-56.

BACKGROUND : The European Society of Gastrointestinal Endoscopy (ESGE) has developed a core curriculum for high quality optical diagnosis training for practice across Europe. The development of easy-to-measure competence standards for optical diagnosis can optimize clinical decision-making in endoscopy. This manuscript represents an official Position Statement of the ESGE aiming to define simple, safe, and easy-to-measure competence standards for endoscopists and artificial intelligence systems performing optical diagnosis of diminutive colorectal polyps (1 - 5 mm). METHODS : A panel of European experts in optical diagnosis participated in a modified Delphi process to reach consensus on Simple Optical Diagnosis Accuracy (SODA) competence standards for implementation of the optical diagnosis strategy for diminutive colorectal polyps. In order to assess the clinical benefits and harms of implementing optical diagnosis with different competence standards, a systematic literature search was performed. This was complemented with the results from a recently performed simulation study that provides guidance for setting alternative competence standards for optical diagnosis. Proposed competence standards were based on literature search and simulation study results. Competence standards were accepted if at least 80 % agreement was reached after a maximum of three voting rounds. RECOMMENDATION 1:  In order to implement the leave-in-situ strategy for diminutive colorectal lesions (1-5 mm), it is clinically acceptable if, during real-time colonoscopy, at least 90 % sensitivity and 80 % specificity is achieved for high confidence endoscopic characterization of colorectal neoplasia of 1-5 mm in the rectosigmoid. Histopathology is used as the gold standard.Level of agreement 95 %. RECOMMENDATION 2:  In order to implement the resect-and-discard strategy for diminutive colorectal lesions (1-5 mm), it is clinically acceptable if, during real-time colonoscopy, at least 80 % sensitivity and 80 % specificity is achieved for high confidence endoscopic characterization of colorectal neoplasia of 1-5 mm. Histopathology is used as the gold standard.Level of agreement 100 %. CONCLUSION : The developed SODA competence standards define diagnostic performance thresholds in relation to clinical consequences, for training and for use when auditing the optical diagnosis of diminutive colorectal polyps.

The aim of this systemic review and meta-analysis was to evaluate the prevalence of sessile serrated lesion (SSL) and its relationship to synchronous colorectal advanced neoplasia.

Comprehensive, computerized research was performed on PubMed and published from 1 January 2010 to 6 July 2018 which searched relevant articles without any language limitations. Clinical trials were included in the narrative systemic review if they matched the following inclusion criteria: (1) published as a case-controlled study, cohort study or cross-sectional study; (2) defined objectively for diagnosis of SSL within the studies; (3) addressed the prevalence and characteristics of SSL. Within these trials, if they met additional criteria involving the reported outcome of risk regarding advanced neoplasia in relation to SSL, they were enrolled into meta-analysis.

Forty-one trials were enrolled for the systematic review, with a total of eight analyzed for the meta-analysis. The prevalence of all SSL ranged from 0.038 to 20.23% and the prevalence by pooled analysis was 2.7%. In a subgroup analysis, the overall prevalence of SSL during the periods of 2010-2014 and 2015-2018 was shown to be 2.7 and 2.8%, respectively. We calculated the pooled data on the cancer risk of SSL and the risk of synchronous advanced neoplasia in patients with SSL made available from the eight trials, which resulted in a pooled odds ratio of 3.53 (95% confidence interval 2.39-5.20, I2 = 4%, P = 0.40).

In this systemic review, SSL was found to be associated with an increased risk of synchronous advanced neoplasia in the colorectum.

Background: The serrated pathway for colorectal cancer (CRC) development is increasingly recognized. Patients with sessile serrated lesions (SSLs) that are large (≥10 mm) and/or have dysplasia (i.e., high-risk SSLs) are at higher risk of progression to CRC. Detection of SSLs is challenging given their predominantly flat and right-sided location. The yield of non-invasive screening tests for detection of high-risk SSLs is unclear. Objective: The aim of this study was to compare non-invasive screen detection of high-risk SSLs between the multi-target stool DNA test (mt-sDNA; Cologuard) and CT colonography (CTC). Methods: This retrospective study included 7974 asymptomatic adults (4705 women, 3269 men; mean age 60.0 years) who underwent CRC screening at a single center by mt-sDNA (Cologuard) from 2014-2019 (n=3987) or by CTC from 2009-2019 (n=3987). Clinical interpretations of CTC examinations were recorded. Subsequent colonoscopy findings and histology of resected polyps were also recorded. Chi-square or two-sample t tests were used to compare results between mt-sDNA and CTC using 6-mm and 10-mm thresholds for test positivity. Results: The overall colonoscopy referral rate for a positive screening test was 13.1% (522/3987) for mt-sDNA versus 12.2% (487/3987; p=.23) and 6.5% (260/3987; p<.001) for CTC at 6-mm and 10-mm thresholds, respectively. The PPV for high-risk SSLs was 5.5% (26/476) for mt-sDNA, versus 14.4% (66/457; p<.001) and 25.9% (63/243; p<.001) for CTC at 6-mm and 10-mm thresholds, respectively. The overall screening yield of high-risk SSLs was 0.7% (26/3987) for mt-sDNA versus 1.7% (66/3987; p<.001) and 1.6% (63/3987; p<.001) for CTC at 6-mm and 10-mm thresholds, respectively. Conclusions: CTC at 6-mm and 10-mm thresholds had significantly higher yield and PPV for high-risk SSLs compared with mt-sDNA. Clinical Impact: The significantly higher detection of high-risk SSLs by CTC than by mt-sDNA should be included in discussions with patients who decline colonoscopy and opt for noninvasive screening.

Leaving no significant polyp behind while avoiding risks due to unnecessary resections is a commonsense strategy to safely and effectively prevent colorectal cancer (CRC) with colonoscopy. It also alludes to polyps worth removing and, therefore, worth finding. The majority of "worthy" precancerous polyps are adenomas, which for over 2 decades, have received the most attention in performance research and metrics. Consequently, the detection rate of adenomas is currently the only validated, outcome-based measure of colonoscopy demonstrated to correlate with reduced risk of postcolonoscopy CRC. However, a third or more of postcolonoscopy CRCs originate from sessile serrated polyps (SSPs), which are notoriously difficult to find, diagnose and completely resect. Among serrated polyps, the agreement among pathologists differentiating SSPs from non-neoplastic hyperplastic polyps is moderate at best. This lack of ground truth precludes SSPs from consideration in primary metrics of colonoscopy quality or performance of novel polyp detection technologies. By instead leveraging the distinct endoscopic and clinical features of serrated polyps, including those considered important due to proximal location and larger size, clinically significant serrated polyps represent serrated polyps worth removing, enriched with subtle precancerous SSPs. With the explosion of technologies to assist polyp detection, now is the time to broaden benchmarks to include clinically significant serrated polypss alongside adenomas, a measure that is relevant both for assessing the performance of endoscopists, and for assessing new polyp detection technologies.

Mortality from colorectal cancer is reduced through screening and early detection; moreover, removal of neoplastic lesions can reduce cancer incidence. While understanding of the risk factors, pathogenesis, and precursor lesions of colorectal cancer has advanced, the cause of the recent increase in cancer among young adults is largely unknown. Multiple invasive, semi- and non-invasive screening modalities have emerged over the past decade. The current emphasis on quality of colonoscopy has improved the effectiveness of screening and prevention, and the role of new technologies in detection of neoplasia, such as artificial intelligence, is rapidly emerging. The overall screening rates in the US, however, are suboptimal, and few interventions have been shown to increase screening uptake. This review provides an overview of colorectal cancer, the current status of screening efforts, and the tools available to reduce mortality from colorectal cancer.

To clarify how often postoperative surveillance colonoscopy should be undertaken based on the risk factors for the development of metachronous cancer (MC) and advanced adenoma (AA) after surgery for colorectal cancer.

We collected data of consecutive patients who underwent curative resection for primary colorectal cancer between 2005 and 2012, with preoperative colonoscopy and surveillance colonoscopy at 1 year after surgery (406 patients, mean age: 69 years, 59% male). The detection rates of AA (with villous features, > 10 mm or high-grade dysplasia) and MC by surveillance colonoscopy were the primary outcomes.

At 5 years, colonoscopy was performed as postoperative surveillance an average of 3.2 times. AA and MC were detected in 57 (14.0%) and 18 patients (4.4%), respectively. Both lesions were more common in the right colon (n = 43) than in the left colon (n = 28). The detection rate did not differ to a statistically significant extent according to the number of colonoscopies performed for surveillance (p = 0.21). However, after left-sided colectomy, both types of lesions were more commonly detected in those who received ≥ 3 colonoscopies than in those with one or two colonoscopies (p = 0.04).

A remaining right colon after left-sided colectomy was associated with a higher risk of developing AA and MC. Physicians should consider performing surveillance colonoscopy more frequently if the right colon remains after surgery.

The adenoma detection rate at screening (ADR) predicts interval colorectal cancer. Monitoring other lesion detection rates and colonoscopy indications has been proposed. We developed a comprehensive, automated colonoscopy audit program based on standardized clinical documentation, explored detection rates across indications, and developed the Adenoma Detection Rate - Extended to all Screening / Surveillance (ADR-ESS) score.

In a prospective cohort study, we calculated overall and advanced adenoma and sessile serrated lesion (SSL) detection rates among 15,253 colonoscopies by 35 endoscopists from 4 endoscopy units across all colonoscopy indications. We explored correlations between detection rates, and the precision and stability of ADR-ESS versus ADR.

The overall "screening, first" ADR was 36.3% (95% confidence interval [CI], 34.5%-38.1%). The adenoma detection rate was lower for "screening, not first" (relative rate [RR], 0.80; 95% CI, 0.74-0.87) and "family history" (RR, 0.84; 95% CI, 0.74-0.96), and higher for "surveillance" (RR, 1.22; 95% CI, 1.15-1.31) and "follow-up, FIT" (RR, 1.21; 95% CI, 1.07-1.37). For "screening, first," the detection rates for advanced adenoma, SSL, and advanced SSL were 6.7% (95% CI, 5.7%-7.7%), 7.2% (95% CI, 6.2%-8.2%), and 2.6% (95% CI, 2.0%-3.2%), respectively. Adenoma and SSL detection were correlated (r = 0.44; P = .008). ADR-ESS had substantially narrower confidence intervals and less period-to-period variability than ADR, and was not improved by weighting for indication volume and correction for detection by indication.

Comprehensive, automated colonoscopy audit based on standardized clinical documentation is feasible. Adenoma detection is a fair but imperfect proxy for SSL detection. ADR-ESS increases the precision of adenoma detection assessments and emphasizes quality across colonoscopy indications.