Low-risk Adenomas Research Articles

Novel blood-based biomarker candidates in screening for colorectal cancer.

244 Background: Colorectal cancer (CRC) is the third most common cancer worldwide motivating national screening strategies utilizing fecal immunochemical tests (FIT). Blood-based biomarkers could be an alternative method to increase compliance in population-based screening programs for early detection of CRC. We aimed to identify new blood-based biomarkers that could be potential candidates for use in colorectal cancer screening. Methods: In a nested cohort study of 1967 FIT positive participants of the Danish CRC screening program serum levels of GDF-15, hepsin, IL-8, keratin1-10, L1CAM, MIA, monocyte MCP-1, NSE and OPG were measured using the Luminex xMAP immunoassay platform. Main outcomes were CRC vs non-CRC and CRC, high-risk adenomas (HRA) or medium-risk adenomas (MRA) vs low-risk adenomas (LRA) or clean colorectum. Odds ratios for associations between biomarker expressions and outcomes were calculated using logistic regression models and visualized by area under the receiver operating characteristic (ROC) curve (AUC). Analyses were made on the Luminex biomarkers alone and with addition of clinical and demographic information. Results: FIT-induced colonoscopies detected 240 CRCs and 625 HRA or MRA. Multivariate analyses using all biomarkers and age found hepsin, IL-8 and OPG significantly (p<0.001) associated in relation to the main outcome (CRC vs non-CRC) with odds ratios of 0.74 [0.59-0.92], 2.59 [2.12-3.15] and 0.90 [0.82-0.99], respectively. The full model using all biomarkers and age presented an AUC of 0.73 [0.70-0.77]. Conclusions: Changed serum levels of nine novel biomarkers seem to be potential predictors for early detection of CRC, especially hepsin, IL-8 and OPG. [Table: see text]

Potential Impact of Extending Surveillance Intervals for Patients With 1-2 Low-Risk Adenomas.

Potential Impact of Extending Surveillance Intervals for Patients With 1-2 Low-Risk Adenomas.

Adherence to Recommendations for Repeat Surveillance After Publication of New Postpolypectomy Guidelines.

The 2012 and 2020 US Multi-Society Task Force postpolypectomy guidelines have recommended progressively longer surveillance intervals for patients with low-risk adenomas (LRAs). These guidelines require data from past colonoscopies. We examined the impact of the 2012 guidelines for second surveillance on clinical practice, including the availability of prior colonoscopy data, with the aim of informing the implementation of the 2020 guidelines. We identified surveillance colonoscopies at Stanford Health Care and the Palo Alto Veterans Affairs Health Care System in 3 periods: preguideline (March-August 2012), postguideline (January-June 2013), and delayed postguideline (July-September 2017). We collected data on the most recent previous colonoscopy, findings at the study entry surveillance colonoscopy, and recommendations for subsequent surveillance. Among 977 patients, the most recent prior colonoscopy data were available in 78% of preguideline, 78% of postguideline, and 61% of delayed postguideline cases (P < .001). The fraction of surveillance colonoscopy reports that deferred recommendations awaiting pathology increased from 6% to 11% in preguideline and postguideline to 59% in delayed postguideline cases (P < .001). Overall adherence to guidelines for subsequent surveillance was similar in all 3 periods (54%-67%; P= .089). In the postguideline and delayed postguideline periods combined, a 10-year subsequent surveillance interval was recommended in 0 of 29 cases with LRA followed by normal surveillance colonoscopy. In patients undergoing surveillance, prior colonoscopy data were not always available and recommendations were often deferred awaiting pathology. Adherence to subsequent surveillance guidelines was suboptimal, especially for LRA followed by normal colonoscopy. Strategies addressing these gaps are needed to optimize implementation of the updated 2020 postpolypectomy guidelines.

Post-Colonoscopy Colorectal Cancer Etiologies in a Large Integrated US Health Care Setting

Post-Colonoscopy Colorectal Cancer Etiologies in a Large Integrated US Health Care Setting

Comparative Performance of Artificial Intelligence Optical Diagnosis Systems for Leaving in Situ Colorectal Polyps

Comparative Performance of Artificial Intelligence Optical Diagnosis Systems for Leaving in Situ Colorectal Polyps

Rates of repeated colonoscopies to clean the colon from low-risk and high-risk adenomas: results from the EPoS trials

ObjectiveHigh-quality colonoscopy (adequate bowel preparation, whole-colon visualisation and removal of all neoplastic polyps) is a prerequisite to start polyp surveillance, and is ideally achieved in one colonoscopy. In a large...

Real-world compliance with the 2020 U.S. Multi-Society Task Force on Colorectal Cancer polypectomy surveillance guidelines: an observational study

Overuse of screening colonoscopy increases cost and procedural adverse events, but inadequate surveillance can miss the development of colorectal cancer. We measured compliance with the 2020 U.S. Multi-Society Task Force on Colorectal Cancer (USMSTF) polypectomy surveillance guidelines in clinical records and a survey. We performed a retrospective study comparing surveillance intervals for first-time average-risk colonoscopies with the 2020 USMSTF guidelines. Cases were analyzed from 3 intervals (March 2021 to May 2021, November 2021 to January 2022, and April 2022 to May 2022), collectively termed the postguideline period, and a baseline period from November 2019 to January 2020. Real-world compliance rates were compared with results of a survey conducted between November 2020 and February2021. Overall compliance was 48.9% among 532 colonoscopies, ranging from 8.3% for low-risk adenomas (LRAs), 88.3% for high-risk adenomas, 63.1% for sessile serrated polyps (SSPs), and 88.6% for hyperplastic polyps. Compliance for LRA increased from the baseline period (.8% vs 8.3%, P= .003), and 95.3% of nonadherent LRA cases followed the 2012 USMSTF guidelines. Compliance for LRAs was 18.6% among respondents who provided a compliant surveillance interval for LRAs in the survey. Noncompliance was associated with finishing training >10 years ago (odds ratio, 1.9; 95% confidence interval, 1.4-2.7) and performing over 800 colonoscopies annually (odds ratio, 2.0; 95% confidence interval, 1.5-2.6). Adoption of the 2020 USMSTF surveillance guidelines remains low at 2 years. Further research into outcomes for patients with LRAs and SSPs may increase guideline adoption.

Updates in Screening Recommendations for Colorectal Cancer

In the past 2 years, several significant changes have been made to the NCCN Guidelines for Colorectal Cancer (CRC) Screening. The age for initiation of screening average-risk adults has been lowered from age 50 to 45 years—without differentiation by age and race—and from age50 to 45 years for those with second- and third-degree relatives with CRC. For several groups, surveillance intervals have been changed. Patients with 1 or 2 low-risk adenomas at index colonoscopy, on the other hand, can now wait 10 years rather than 5 to 7 years between surveillance examinations. The first surveillance examination following resection of large adenomas or sessile serrated polyps (SSPs) with unfavorable-risk characteristics or that were removed piecemeal should now occur at 6 months. For patients with ≥10 adenomas and SSPs on a single colonoscopy, time to first surveillance was lowered to 1 year.

Arterial stiffness is associated with high-risk colorectal adenomas and serrated lesions: A cross-sectional study in a Taiwanese population

BackgroundLittle is currently known about the association between arterial stiffness and colorectal serrated lesions. This study was aimed toward an investigation of the association between arterial stiffness and colorectal precancerous lesions, including colorectal adenomas and serrated lesions. Methods7262 eligible adult subjects who underwent health check-ups with colonoscopies and brachial-ankle pulse wave velocity (baPWV) were recruited. Patients were categorized as polyp-free, low-risk and high-risk adenomas, and low-risk and high-risk serrated lesions based on the presence of polyps. The severity of arterial stiffness was categorized into four subgroups based on the baPWV quartile. ResultsAfter adjusting for multiple covariates, the baPWV values were found to be positively correlated with the occurrence of low-risk adenomas. With respect to high-risk polyps, the third and highest baPWV quartiles were significantly associated with the occurrence of both high-risk adenomas and high-risk serrated lesions. A more significant association was found in the highest baPWV quartiles combined with smoking in cases classified with high-risk serrated lesions. ConclusionsIncreased arterial stiffness was independently associated with precancerous colorectal lesions, not only adenomas but also high-risk serrated lesions. Individuals with increased arterial stiffness, especially those who are smokers, should be more aware of the risk of colorectal cancer.

Incidence and Mortality of Post-Polypectomy Colorectal Cancer in Patients with Low-Risk Adenomas: A Systematic Review and Meta-Analysis of Observational Studies

Introduction: The long-term risks of post-polypectomy colorectal cancer (CRC) incidence and mortality among patients with low-risk adenomas (LRAs) are unclear. This study aimed to perform a systematic review and meta-analysis of the risk of CRC incidence and mortality following LRAs removal. Methods: We searched the PubMed, Embase, and Cochrane library for studies that reported the risk of metachronous CRC incidence and mortality after colonoscopy. The primary outcome was the risk of CRC incidence and mortality in patients with LRAs. Random-effects models were used to calculate the pooled risk ratio (RR) with a 95% confidence interval (CI). Results: Thirteen observational studies with 1,750,305 patients (45.4% male; follow-up: 4.5–16.5 years) were included. A meta-analysis of seven studies showed a higher CRC incidence in patients with LRAs than those without adenomas (per 10,000 person-years: 5.2 vs. 3.9; RR 1.25 [95% CI 1.05–1.49], I² = 0%). However, the CRC-related death rate was not significantly different between the two groups (RR 1.13 [95% CI 0.75–1.69], I² = 0%). When compared with the general population, the meta-analysis showed a significantly lower risk of CRC incidence in patients with LRAs (RR 0.59 [95% CI 0.45–0.77], I² = 0%), and another three studies, which could not be pooled, showed a reduction in the risk of CRC-related death in the LRAs group. Conclusions: Patients with LRAs have a small but higher risk of post-polypectomy CRC incidence than patients without adenomas. The marginally higher absolute incidence seemed insufficient for more intensive surveillance colonoscopy, but the significant difference suggested different follow-up strategies between patients with LRAs and those without adenomas.

Polygenic Risk Score for Defining Personalized Surveillance Intervals After Adenoma Detection and Removal at Colonoscopy

Polygenic risk scores (PRSs) could help to define personalized colorectal cancer (CRC) screening strategies. The aim of this study was to evaluate whether a PRS, along with adenoma characteristics, could help to define more personalized and risk-adapted surveillance intervals. In a population-based, case-control study from Germany, detailed information on previous colonoscopies and a PRS based on 140 CRC-related, single-nucleotide polymorphisms was obtained from 4696 CRC cases and 3709 controls. Participants were classified as having low, medium, or high genetic risk according to tertiles of PRSs among controls. We calculated the absolute risk of CRC based on the PRS and colonoscopy history and findings. We observed major variations of CRC risk according to the PRS, including among individuals with detection and removal of adenomas at colonoscopy. For instance, the estimated 10-year absolute risk of CRC for 50-year-old men and women with no polyps, for whom repeat screening colonoscopy is recommended after 10 years only, was 0.2%. Equivalent absolute risks were estimated for people with low-risk adenomas and low PRS. However, the same levels of absolute risk were reached within 3 to 5 years by those with low-risk adenomas and high PRS and with high-risk adenomas irrespective of the PRS. Consideration of genetic predisposition to CRC risk, as determined by a PRS, could help to define personalized, risk-adapted surveillance intervals after detection and removal of adenomas at screening colonoscopy. However, whether the risk variation is strong enough to direct clinical risk stratification needs to be explored further.

The COlorectal NEoplasia Endoscopic Classification to Choose the Treatment classification for identification of large laterally spreading lesions lacking submucosal carcinomas: A prospective study of 663 lesions.

IntroductionOptical diagnosis is necessary when selecting the resection modality for large superficial colorectal lesions. The COlorectal NEoplasia Endoscopic Classification to Choose the Treatment (CONECCT) encompasses overt (irregular pit or vascular pattern) and covert (macroscopic features) signs of carcinoma in an all‐in‐one classification using validated criteria. The CONECCT IIC subtype corresponds to adenomas with a high risk of superficial carcinoma that should be resected en bloc with free margins.MethodsThis prospective multicentre study investigated the diagnostic accuracy of the CONECCT classification for predicting submucosal invasion in colorectal lesions >20 mm. Optical diagnosis before en bloc resection by endoscopic submucosal dissection (ESD) was compared with the final histological diagnosis. Diagnostic accuracy for the CONECCT IIC subtype was compared with literature‐validated features of concern considered to be risk factors for submucosal invasion (non‐granular large spreading tumour [NG LST], macronodule >1 cm, SANO IIIA area, and Paris 0‐IIC area).ResultsSix hundred 63 lesions removed by ESD were assessed. The en bloc, R0, and curative resection rates were respectively 96%, 85%, and 81%. The CONECCT classification had a sensitivity (Se) of 100%, specificity (Sp) of 26.2%, positive predictive value of 11.6%, and negative predictive value (NPV) of 100% for predicting at least submucosal adenocarcinoma. The sensitivity of CONECCT IIC (100%) to predict submucosal cancer was superior to all other criteria evaluated. COlorectal NEoplasia Endoscopic Classification to Choose the Treatment IIC lesions constituted 11.5% of all submucosal carcinomas.ConclusionThe CONECCT classification, which combines covert and overt signs of carcinoma, identifies with very perfect sensitivity (Se 100%, NPV 100%) the 30% of low‐risk adenomas in large laterally spreading lesions treatable by piecemeal endoscopic mucosal resection or ESD according to expertise without undertreatment. However, the low specificity of CONECCT leads to a large number of potentially not indicated ESDs for suspected high‐risk lesions.

Circulating tumor DNA-based early detection of precancerous colorectal lesions using QClamp XNA-mediated real-time PCR.

The mutation status of the gene involved in early colorectal carcinogenesis and micro-invasive liquid biopsy allows detection of mutated circulating tumor DNA (ctDNA). Early detection of precancerous lesions and CRC is vital in proper treatment and hence associated to patient survival. The frequency of APC, CTNNB1, KRAS, and BRAF mutations in circulating free DNA (cfDNA) were analyzed to evaluate the performance of the mutated ctDNA in detecting polyp and adenoma using highly sensitive QClamp XNA based PCR. A total of 71 patients with low-risk adenoma or polyps were screened and there was no significant difference in the distribution of mutations gender, age, long-term medication, smoking history, alcohol drinking, and fecal occult blood. The positive predictive value (PPV) of the four genes' panel to detect low-risk adenoma and polyps was 39.44% (n = 28/71). Specifically, of all the 71 cases studied, there were 20 cases (28.2%) with APC mutations, 7 cases (9.9%) with CTNNB1 mutations, 4 cases (5.6%) with KRAS mutations, and 2 cases (2.8%) with BRAF mutations. Most mutations occurred at APC876. The four genes' panel detected by XNA-based PCR technique might be suited to efficiently and micro-invasively detect genetic alterations in cfDNA of patients with precancerous colorectal lesions.

Low potency of fecal immunological surveillance testing soon after negative colonoscopy or resection of low-risk adenoma in average-risk patients.

Postcolonoscopy surveillance colonoscopy based on positive fecal occult blood testing (FOBT) is often performed, although its long-term efficacy has not been established. The aim of this study was to clarify the low potency of FOBT surveillance at short intervals after colonoscopy. Colonoscopy was performed in 1308 average-risk patients, based on positive results of immunological FOBT [fecal immunological test (FIT)]. Patients were stratified according to the length of time since their last colonoscopy and their colonoscopy results [no adenoma or 1-2 small (<10 mm) adenomas]. Tumor detection rates were determined. The baseline patients characteristics did not differ between the groups. The advanced lesion detection rate (ALDR) among the patients who had never undergone a colonoscopy was 21.9% [95% confidence interval (CI), 19.1-25.0%]. Among the patients who had no adenoma detected in the previous colonoscopy within the past 5 years, the past 5-10 years and over 10 years, the ALDRs were 2.5% (95% CI, 1.0-5.5%), 4.1% (95% CI, 1.5-9.4%) and 9.3% (95% CI, 3.1-22.2%), respectively. Among the patients who had 1-2 small adenomas, the ALDRs were 7.4% (95% CI, 3.4-14.8%), 12.1% (95% CI, 4.2-27.9%) and 27.8% (95% CI, 12.2-51.2%), respectively. Invasive cancer was not observed in any patients within 5 years since the prior colonoscopy. In average-risk patients whose prior colonoscopy detected no adenomas or low-risk adenomas, postcolonoscopy surveillance by FIT has a low positive predictive value within a 5-year interval.

Long-term colorectal cancer incidence and mortality after adenoma removal in women and men.

Women and men with colorectal adenomas are at increased risk of colorectal cancer and colonoscopic surveillance is recommended. However, the long-term cancer risk remains unknown. To investigate colorectal cancer incidence and mortality after adenoma removal in women and men METHODS: We identified all individuals who had adenomas removed in Norway from 1993 to 2007, with follow-up through 2018. We calculated standardized incidence ratios (SIR) and incidence-based mortality ratios (SMR) with 95% confidence intervals (CI) for colorectal cancer in women and men using the female and male population for comparison. We defined high-risk adenomas as ≥2 adenomas, villous component, or high-grade dysplasia. The cohort comprised 40293 individuals. During median follow-up of 13.0years, 1079 women (5.5%) and 866 men (4.2%) developed colorectal cancer; 328 women (1.7%) and 275 men (1.3%) died of colorectal cancer. Colorectal cancer incidence was more increased in women (SIR 1.64, 95% CI 1.54-1.74) than in men (SIR 1.12, 95% CI 1.05-1.19). Colorectal cancer mortality was increased in women (SMR 1.13, 95% CI 1.02-1.26) and reduced in men (SMR 0.79, 95% CI 0.71-0.89). Women with high-risk adenomas had an increased risk of colorectal cancer death (SMR 1.37, 95% CI 1.19-1.57); women with low-risk adenomas (SMR 0.90, 95% CI 0.76-1.07) and men with high-risk adenomas had a similar risk (SMR 0.89, 95% CI 0.76-1.04), while men with low-risk adenomas had reduced risk (SMR 0.70, 95% CI 0.59-0.84). After adenoma removal, women had an increased risk of colorectal cancer death, while men had reduced risk, compared to the general female and male populations. Sex-specific surveillance recommendations after adenoma removal should be considered.

S234 Small Low-Risk Tubular Adenomas 5-9 mm Have an Increased Risk for Post Colonoscopy Colorectal Cancer: Data From the New Hampshire Colonoscopy Registry

S234 Small Low-Risk Tubular Adenomas 5-9 mm Have an Increased Risk for Post Colonoscopy Colorectal Cancer: Data From the New Hampshire Colonoscopy Registry

Small sessile serrated polyps might not be at a higher risk for future advanced neoplasia than low-risk adenomas or polyp-free groups

Background Polypectomy surveillance colonoscopy is recommended according to the risk stratification of initially removed polyps. This study aimed to evaluate the risk of advanced neoplasia following low-risk SSPs compared with that following LRAs and polyp-free groups. Materials and methods From September 2013 to August 2017, asymptomatic Koreans aged 50–75 years who underwent surveillance colonoscopy post-baseline colonoscopy were enrolled. The 1314 participants who met the study design criteria were stratified into three groups according to the presence of LRAs or low-risk SSPs. The rate of advanced neoplasia was then compared between groups by surveillance colonoscopy. Results A total of 1314 participants were classified according to baseline colonoscopy findings: no polyp (n = 551), LRA (n = 707), and low-risk SSP (n = 56). All participants underwent surveillance colonoscopy after an average of 28.1 ± 8.7 months. The rate of advanced neoplasia at surveillance was not different between groups: no polyp group (13/551, 2.4%), LRA group (27/707, 3.8%), and low-risk SSP group (0/56, 0%). The LRA group exhibited a significantly higher rate of low- and high-risk polyps (47.5, 13.4%) than did the no polyp (35.6, 7.4%, p < .001, p = .001), but no significant differences to the low-risk SSP group (35.7, 7.1%, p = .117, p = .253), respectively. Conclusions Patients with low-risk SSPs were not at a higher risk of advanced neoplasia than LRA patients, even in the polyp-free group. We suggest that surveillance colonoscopy after the removal of low-risk SSPs is not required more often than for LRAs.

Risk of post colonoscopy colorectal cancer following screening colonoscopy with low-risk or no adenomas: A population-based study.

In the Danish faecal occult blood test based bowel cancer screening programme, the first round was rolled out over 4years. After roll-out, the planned faecal test recall procedure for individuals with either no or low risk adenomas at colonoscopy is 8 and 2years, respectively. Here, we aimed to investigate the post colonoscopy colorectal cancer incidence in these two groups. All Danish screening individuals from 2014 to 2015 with a positive faecal test and either no or low risk adenomas at colonoscopy were included and followed for 3years post screening for the event of colorectal cancer through national registries. Out of 533,023 submitted faecal tests and 36,673 positive tests, 17,627 had no or low risk adenomas. We identified 60 (0.34%) individuals diagnosed with colorectal cancer within 3years, 18 (0.29%) in the low risk adenoma group, and 42 (0.37%) in the no adenomas group (p=0.44). Advancing age (HR=1.079, p<0.001) and higher faecal test value (HR=1.001, p=0.002) increased hazard of colorectal cancer occurrence, whereas male sex (HR=1.3, p=0.308) and having low risk adenomas (HR=0.729, p=0.264) did not. We found no difference in post colonoscopy colorectal cancer occurrence between individuals with either no or low risk adenomas. Instead, advancing age and increased faecal test value was associated with a higher risk of post colonoscopy colorectal cancer.

Cost-effectiveness analysis of different screening strategies for colorectal cancer in Guangzhou, southern China: a Markov simulation analysis based on natural community screening results

ObjectivesTo evaluate the cost-effectiveness of four different primary screening strategies: high-risk factor questionnaire (HRFQ) alone, single immunochemical faecal occult blood test (iFOBT), double iFOBT and HRFQ+double iFOBT for colorectal cancer...

Evaluation of a 92 multiplex protein panel in detection of colorectal cancer and high-risk adenoma in 784 symptomatic individuals.

Blood-based protein biomarkers for detection of colorectal cancer (CRC) have been submitted to intense research to improve the full potential in screening for CRC. The aim was to explore the diagnostic performance of 92 proteins related to inflammation and carcinogenesis in detection of CRC or precancerous lesions. Blood-samples were collected from 4,698 individuals undergoing colonoscopy. An explorative unmatched case-control study was designed with 294 cases (individuals with CRC or high-risk colorectal adenoma) and 490 controls (individuals with low-risk colorectal adenoma, non-malignant findings or clean colorectum at colonoscopy). Protein profiling was performed by multiplex proximity extension assay. Statistical analyses were performed as univariate and multivariate logistic regression analyses. Univariably, CSF-1, MMP12 and IL8 demonstrated superior performance in discrimination of individuals with CRC. Recurrently, IL8 was included as contributor in majority of multivariate models discriminating individuals with CRC. The multivariate evaluation in discrimination of individuals with CRC demonstrated AUC=ROC 0.82, sensitivity = 0.39 at specificity = 0.80. Discrimination of individuals with late stage CRC from individuals with clean colorectum demonstrated AUC=ROC 0.90, sensitivity = 0.58 at specificity = 0.80. A subset of biomarker candidates, specifically IL8, investigated in the present study suggest a potential as blood-based biomarkers in screening of CRC.