Advanced Colorectal Lesions Research Articles

Comparison between 16S rRNA and shotgun sequencing in colorectal cancer, advanced colorectal lesions, and healthy human gut microbiota

BackgroundGut dysbiosis has been associated with colorectal cancer (CRC), the third most prevalent cancer in the world. This study compares microbiota taxonomic and abundance results obtained by 16S rRNA gene sequencing (16S) and whole shotgun metagenomic sequencing to investigate their reliability for bacteria profiling. The experimental design included 156 human stool samples from healthy controls, advanced (high-risk) colorectal lesion patients (HRL), and CRC cases, with each sample sequenced using both 16S and shotgun methods. We thoroughly compared both sequencing technologies at the species, genus, and family annotation levels, the abundance differences in these taxa, sparsity, alpha and beta diversities, ability to train prediction models, and the similarity of the microbial signature derived from these models.ResultsAs expected, the results showed that 16S detects only part of the gut microbiota community revealed by shotgun, although some genera were only profiled by 16S. The 16S abundance data was sparser and exhibited lower alpha diversity. In lower taxonomic ranks, shotgun and 16S highly differed, partially due to a disagreement in reference databases. When considering only shared taxa, the abundance was positively correlated between the two strategies. We also found a moderate correlation between the shotgun and 16S alpha-diversity measures, as well as their PCoAs. Regarding the machine learning models, only some of the shotgun models showed some degree of predictive power in an independent test set, but we could not demonstrate a clear superiority of one technology over the other. Microbial signatures from both sequencing techniques revealed taxa previously associated with CRC development, e.g., Parvimonas micra.ConclusionsShotgun and 16S sequencing provide two different lenses to examine microbial communities. While we have demonstrated that they can unravel common patterns (including microbial signatures), shotgun often gives a more detailed snapshot than 16S, both in depth and breadth. Instead, 16S will tend to show only part of the picture, giving greater weight to dominant bacteria in a sample. Therefore, we recommend choosing one or another sequencing technique before launching a study. Specifically, shotgun sequencing is preferred for stool microbiome samples and in-depth analyses, while 16S is more suitable for tissue samples and studies with targeted aims.

Identifying the best cutoff value of the fecal occult blood immunochemical test in the detection of advanced and neoplastic colorectal lesions.

Screening is an effective tool for detecting colorectal lesions in asymptomatic subjects. There is a positive correlation between fecal immunochemical test (FIT) values and the size of tumors. Despite the efficacy of screening, the detection of colorectal cancer (CRC) remains low. The primary objective was to evaluate the best FIT cutoff value for detecting advanced adenomas and CRC among individuals at average risk in a country with a high incidence and morbidity from CRC. This observational and prospective study analyzed consecutive cases in 1461 asymptomatic subjects with a positive FIT (≥ 100 ng hemoglobin [Hb]/mL) referred for colonoscopy (2012-2015) at a tertiary center in Uruguay. Colorectal lesions were detected in 35.3% (516/1461) of cases, with a mean age of 62.8 ± 8.3 years. About 53.2% were men and 65.1% of the tumors were located in the left side of the colon. The size of the lesion and FIT values (p = 0.001) were positively correlated. Laterally spreading tumors predominated in the right colon (586 ng Hb/mL; 95% Confidence interval [CI] 443.4-760). One hundred and thirty-five (26%) lesions were advanced adenomas (15 ± 6.7 mm); 694.6 ng/mL; 95% CI 632.4-756.9). The highest diagnostic yield (0.5112) for advanced adenomas was at a FIT level of 400 ng Hb/mL (accuracy 88.6%). There were significant differences in FIT values early and advanced CRC (927 ng/mL; [95% CI: 637-1082] vs. 1453 [95% CI: 1352-1594; p = 0.001]). A FIT value of 400 ng Hb/mL was the best diagnostic yield to detect advanced adenomas and CRC. This value is useful during the COVID-19 pandemic as it allows prioritization of colonoscopy to those most at risk of significant disease, thus reducing risks to both patients and healthcare workers.

The Diagnostic Accuracy of a Fecal Immunochemical Test in Detecting Colorectal Cancer and Advanced Precancerous Colorectal Neoplasia in Patients with Iron Deficiency: A Protocol for Systematic Review and Meta-Analysis.

Background. Iron deficiency (ID) is a common micronutrient deficiency and the leading cause of anemia worldwide. ID can be caused by chronic occult blood loss from colorectal neoplasia including colorectal cancer (CRC) and advanced precancerous colorectal lesions. Current guidelines recommend colonoscopy in both men and postmenopausal women presenting with ID anemia (IDA). However, there is controversy on the investigation of patients presenting with a lower risk of CRC including younger women with ID and those with nonanemic ID (NAID). There is a need for a triaging tool to identify which ID patients may benefit from colonoscopy. The fecal immunochemical test (FIT) is sensitive for CRC screening in an asymptomatic population, but its role in ID patients is unclear. The aim of this study is to conduct a systematic review to determine the diagnostic accuracy of FIT for detecting CRC and advanced precancerous neoplasia in individuals presenting with ID with or without anemia. Methods and Analysis. This protocol conforms with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols and Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy. A comprehensive search of the MEDLINE, Embase, and Web of Science databases will be undertaken for studies published after 2010 which involve patients with ID, who completed a FIT in the 6 months prior to colonoscopy, with FIT sensitivity and specificity calculated against the reference standard colonoscopy. The search will be limited to studies conducted after 2010 to reduce variability in colonoscopy quality. Risk of bias assessment will be conducted using the Quality Assessment of Diagnostic Accuracy Studies version 2. FIT sensitivity and specificity will be the primary measure of diagnostic accuracy, and data will be analysed using a random effects meta-analysis. Discussion. This review and meta-analysis will be the first to systematically explore the value of the FIT as a triaging tool for patients with ID. This trial is registered with CRD42022367162.

Colorectal polyp classification and management of complex polyps for surgeon endoscopists.

SummaryIncreasing familiarity with advanced endoscopic excision techniques allows for more colorectal lesions to be removed without major surgery. Endoscopic excision with negative margins is adequate for most polyps and low-risk T1 cancers. The use of modern polyp classification techniques based on size, morphology and pit pattern by an experienced endoscopist allow for an optical diagnosis of these lesions and can predict, with high accuracy, which lesions contain malignant disease and the level of invasion. A surgeon endoscopist must be able to recognize which complex polyps can be resected with advanced polypectomy techniques and which require upfront surgery. We aimed to provide an overview of polyp classification techniques to help surgeons select the correct treatment algorithm for advanced colorectal lesions based on their visual characteristics at index endoscopy.

Associations of red and processed meat intake with screen-detected colorectal lesions.

Limited data exist regarding the role of meat consumption in early-stage colorectal carcinogenesis. We examined associations of red and processed meat intake with screen-detected colorectal lesions in immunochemical fecal occult blood test (FIT)-positive participants, enrolled in the Norwegian CRCbiome study during 2017-2021, aged 55-77 years. Absolute and energy-adjusted intakes of red and processed meat (combined and individually) were assessed using a validated, semiquantitative food frequency questionnaire. Associations between meat intake and screen-detected colorectal lesions were examined using multinomial logistic regression analyses with adjustment for key covariates. Of 1,162 participants with available dietary data, 319 (27%) presented with advanced colorectal lesions at colonoscopy. High vs low energy-adjusted intakes of red and processed meat combined, as well as red meat alone, were borderline to significantly positively associated with advanced colorectal lesions (ORs (95% CIs) of 1.24 (0.98, 1.57) and 1.34 (1.07, 1.69), respectively). A significant dose-response-relationship was also observed for absolute intake levels (OR (95% CI) of 1.32 (1.09, 1.60) per 100 g/day increase in red and processed meat). For processed meat, no association was observed between energy-adjusted intakes and advanced colorectal lesions. A significant positive association was, however, observed for the small proportion of participants (10%) with absolute intake levels ≥100 vs <50 g/day (OR (95% CI) of 1.19 (1.09, 1.31)). In summary, high intakes of red and processed meat were associated with presence of advanced colorectal lesions at colonoscopy in FIT-positive participants. The study demonstrates a potential role of using dietary data to improve the performance of FIT-based screening.

Colon Sparing Endoscopic Full-Thickness Resection for Advanced Colorectal Lesions: Is It Time for Global Adoption?

The majority of colon lesions are <10 mm in size and are easily resected by endoscopists with appropriate basic training. Lesions ≥10 mm in size are difficult to remove technically and are associated with higher rates of incomplete resection. Currently, the main endoscopic approaches include endoscopic mucosal resection (EMR) for lesions without submucosal invasion, and endoscopic submucosal dissection (ESD) for relatively larger lesions involving the superficial submucosal layer. Both of these approaches have limitations, EMR cannot reliably ensure complete resection for larger tumors and recurrence is a key limitation. ESD reliably provides complete resection and an accurate pathological diagnosis but is associated with risk such as perforation or bleeding. In addition, both EMR and ESD may be ineffective in treating subepithelial lesions that extend beyond the submucosa. Endoscopic full-thickness resection (EFTR) is an emerging innovative endoscopic therapy which was developed to overcome the limitations of EMR and ESD. Advantages include enabling a transmural resection, complete resection of complex colorectal lesions involving the mucosa to the muscularis propria. Recent studies comparing EFTR with current resection techniques and radical surgery for relatively complicated and larger lesion have provided promising results. If the current trajectory of research and development is maintained, EFTR will likely to become a strong contender as an alternative standard of care for advanced colonic lesions. In the current study we aimed to address this need, and highlighted the areas of future research, while stressing the need for multinational collaboration provide the steppingstone(s) needed to bring EFTR to the mainstream.

Adherence to endoscopic surveillance for advanced lesions and colorectal cancer in inflammatory bowel disease: an AEG and GETECCU collaborative cohort study.

Patients with colonic inflammatory bowel disease (IBD) have a high risk of colorectal cancer (CRC). Current guidelines recommend endoscopic surveillance, yet epidemiological studies show poor compliance. The aims of our study were to analyse adherence to endoscopic surveillance, its impact on advanced colorectal lesions, and risk factors of non-adherence. A retrospective multicentre study of IBD patients with criteria for CRC surveillance, diagnosed between 2005 and 2008 and followed up to 2020, was performed. Following European guidelines, patients were stratified into risk groups and adherence was considered when surveillance was performed according to the recommendations (±1year). Cox-proportional regression analyses were used to compare the risk of lesions. p-values below 0.05 were considered significant. A total of 1031 patients (732 ulcerative colitis, 259 Crohn's disease and 40 indeterminate colitis; mean age of 36±15years) were recruited from 25 Spanish centres. Endoscopic screening was performed in 86% of cases. Adherence to guidelines was 27% (95% confidence interval, CI =24-29). Advanced lesions and CRC were detected in 38 (4%) and 7 (0.7%) patients respectively. Adherence was associated with increased detection of advanced lesions (HR=3.59; 95% CI=1.3-10.1; p=0.016). Risk of delay or non-performance of endoscopic follow-up was higher as risk groups increased (OR=3.524; 95% CI=2.462-5.044; p<0.001 and OR=4.291; 95%CI=2.409-7.644; p<0.001 for intermediate- and high- vs low-risk groups). Adherence to endoscopic surveillance allows earlier detection of advanced lesions but is low. Groups at higher risk of CRC are associated with lower adherence.

The CRCbiome study: a large prospective cohort study examining the role of lifestyle and the gut microbiome in colorectal cancer screening participants

BackgroundColorectal cancer (CRC) screening reduces CRC incidence and mortality. However, current screening methods are either hampered by invasiveness or suboptimal performance, limiting their effectiveness as primary screening methods. To aid in the development of a non-invasive screening test with improved sensitivity and specificity, we have initiated a prospective biomarker study (CRCbiome), nested within a large randomized CRC screening trial in Norway. We aim to develop a microbiome-based classification algorithm to identify advanced colorectal lesions in screening participants testing positive for an immunochemical fecal occult blood test (FIT). We will also examine interactions with host factors, diet, lifestyle and prescription drugs. The prospective nature of the study also enables the analysis of changes in the gut microbiome following the removal of precancerous lesions.MethodsThe CRCbiome study recruits participants enrolled in the Bowel Cancer Screening in Norway (BCSN) study, a randomized trial initiated in 2012 comparing once-only sigmoidoscopy to repeated biennial FIT, where women and men aged 50–74 years at study entry are invited to participate. Since 2017, participants randomized to FIT screening with a positive test result have been invited to join the CRCbiome study. Self-reported diet, lifestyle and demographic data are collected prior to colonoscopy after the positive FIT-test (baseline). Screening data, including colonoscopy findings are obtained from the BCSN database. Fecal samples for gut microbiome analyses are collected both before and 2 and 12 months after colonoscopy. Samples are analyzed using metagenome sequencing, with taxonomy profiles, and gene and pathway content as primary measures. CRCbiome data will also be linked to national registries to obtain information on prescription histories and cancer relevant outcomes occurring during the 10 year follow-up period.DiscussionThe CRCbiome study will increase our understanding of how the gut microbiome, in combination with lifestyle and environmental factors, influences the early stages of colorectal carcinogenesis. This knowledge will be crucial to develop microbiome-based screening tools for CRC. By evaluating biomarker performance in a screening setting, using samples from the target population, the generalizability of the findings to future screening cohorts is likely to be high.Trial registrationClinicalTrials.gov Identifier: NCT01538550.

Diagnostic yield of colonoscopy surveillance in testicular cancer survivors treated with platinum-based chemotherapy: study protocol of a prospective cross-sectional cohort study

BackgroundTesticular cancer (TC) survivors have an increased risk of various second primary malignancies. A recent cohort study detected an increased risk of colorectal cancer (CRC) in TC survivors treated with platinum-based chemotherapy with a hazard ratio of 3.9. CRC risk increased with higher cisplatin-dose. We know that colonoscopy surveillance in high-risk populations results in reduced incidence and mortality of CRC. TC survivors treated with platinum-based chemotherapy can potentially benefit from colonoscopy surveillance; however, to which extent is unknown. Furthermore, the pathogenesis of these secondary CRCs is unknown, and better insights into the carcinogenesis may affect surveillance decisions.MethodsThis prospective multicenter study will be performed in four Dutch hospitals. TC survivors are eligible if treated with ≥ 3 cycles of cisplatin before age 50. Colonoscopy will be performed ≥ 8 years after initial treatment (minimum and maximum ages at colonoscopy, 35 and 75 years, respectively). The primary aim of the study is the diagnostic yield of advanced neoplasia detected during colonoscopy. As secondary aim, we will evaluate the molecular profile of advanced colorectal neoplasia and will assess current platinum levels in blood and urine and correlate blood-platinum levels with prevalence of colorectal lesions. Furthermore, we will investigate effectiveness of fecal immunochemical testing (FIT) and burden of colonoscopy by two questionnaires. Demographic data, previous history, results of colonoscopy, hemoglobin level of FIT and results of molecular and platinum levels will be obtained. Yield of colonoscopy will be determined by detection rate of adenoma and serrated lesions, advanced adenoma detection rate and CRC detection rate. The MISCAN model will be used for cost-effectiveness analyses of CRC surveillance. With 234 participants undergoing colonoscopy, we can detect an absolute difference of 6% of advanced neoplasia with 80% power.DiscussionTC survivors treated with cisplatin-based chemotherapy can benefit from CRC surveillance. Evaluation of the diagnostic performance and patient acceptance of CRC surveillance is of importance to develop surveillance recommendations. Insight into the carcinogenesis of cisplatin-related advanced colorectal lesions will contribute to CRC prevention in the increasing number of TC survivors. The results may also be important for the many other cancer survivors treated with platinum-based chemotherapy.Trial registrationClinical Trials: NCT04180033, November 27, 2019, https://clinicaltrials.gov/ct2/show/NCT04180033.

Effects of Somatic Methylation in Colonic Polyps on Risk of Developing Metachronous Advanced Colorectal Lesions.

Simple SummaryPost-polypectomy endoscopic surveillance is predominantly based on the size and number of polyps found at baseline. The utility of molecular markers for predicting the risk of metachronous advanced lesions remains poorly investigated. Patients with CpG island methylator phenotype (CIMP)+ polyps show a higher risk of developing advanced lesions at follow-up. This fact is independent of polyp size and other factors classically related to advanced lesion development. Addition of CIMP status improved the metachronous advanced colorectal lesion (MACL) risk estimation, especially the sensitivity. CIMP may be a useful marker for endoscopic surveillance after polypectomy.The utility of molecular markers for predicting the risk of metachronous advanced colorectal lesions (MACLs) remains poorly investigated. We examined the relationship between somatic hypermethylation in polyps at baseline and the risk of developing MACL. This retrospective cohort study included 281 consecutive patients with colonic polyps who were enrolled between 2007 and 2009 and followed-up until 2014. MACLs were defined as adenomas of ≥10 mm, high-grade dysplasia, or with a villous component; and serrated lesions of ≥10 mm or with dysplasia. In total, 595 polyps were removed at baseline colonoscopy and analyzed for pathological characteristics and CpG island methylator phenotype (CIMP) using the MS-MLPA (Methylation-Specific -- Multiplex Ligation-dependent Probe Amplification) technique. Forty-five patients (16.0%) showed at least one CIMP+ polyp. MACL risk was higher in patients with CIMP+ polyps (odds ratio (OR), 4.50; 95% CI, 1.78–11.4; p = 0.002). Patients with CIMP+ polyps also exhibited shorter time to MACL development (33.8 months vs. 50.1 months; p < 0.001), even with adjustment for polyp size and number (OR, 2.40; 95% CI, 1.33–4.34). Adding CIMP analysis improved the sensitivity (57.0% to 70.9%), negative predictive value (71.1% to 77.3%), and overall accuracy (49.8% to 52.0%) for MACL risk estimation. These results highlight that CIMP may be a useful marker for endoscopic surveillance.

Colorectal cancer screening programme: is the French faecal immunological test (FIT) threshold optimal?

Background:In France, the colorectal cancer organised screening programme uses the faecal immunological test. A positive test ⩾30 μg Hb/g of stool leads to a colonoscopy for identification of potential colorectal lesions. Cut-off values vary from 20 to 47 μg Hb/g of stool in Western countries. We herein question this threshold’s relevance in a French population and perform a retrospective observational study using the Parisian database between 1 April 2015 and 31 December 2018.Methods:Rates of participation, numbers of positive faecal immunological test (FIT), detection rates and positive predictive values for advanced adenomas and/or colorectal cancer were determined. Mean positivity values for colorectal lesions were calculated.Results:In our population, there were 4.1% positive tests and 67.6% colonoscopy results available with final reports. Positive predictive value for advanced adenomas and colorectal cancer were 30% [95% confidence interval (CI) 29.8–30.3] and 7.4% (95% CI 7.35–7.52), respectively. The mean positivity value for all positive tests in our population was 101.7 µg Hb/g of stool (95% CI 85–118.3). There were 1136 normal colonoscopies (21.4%) with a mean positivity value of 88.6 μg Hb/g of stool. Following a negative test in a first screening campaign, 40.8% of patients in our population performed a second test with a positivity rate of 1.3% and with the encounter of 81 colorectal cancers. The risk of having a positive test during the second screening campaign and finding advanced colorectal lesions significantly increased (all p < 0.001) when comparing negative FIT results ranging between 15 and 29 μg Hb/g of stool to 0 and 14 μg Hb/g of stool from the previous campaign.Conclusion:Using the current positivity threshold, some patients were considered negative with a delay in colorectal cancer diagnosis, suggesting the threshold could be lowered. Also, the mean positivity value for normal colonoscopies was high, raising the question of upper gastrointestinal bleeding.

Association between lifestyle and site-specific advanced colorectal lesions in screening with faecal immunochemical test and sigmoidoscopy

BackgroundLifestyle factors may help to identify individuals at high-risk for colorectal cancer (CRC). AimsTo examine the association between lifestyle, referral for follow-up colonoscopy and proximal neoplasia detection in CRC screening. MethodsIn this observational study, 14,832 individuals aged 50–74 years were invited to faecal immunochemical test (FIT) or sigmoidoscopy screening. Advanced lesions (AL), including advanced adenomas, advanced serrated lesions and CRC were divided according to location: distal-only, or proximal with or without distal AL. We collected information on smoking habit, body mass index and alcohol intake through a questionnaire. ResultsOut of 3,318 FIT and 2,988 sigmoidoscopy participants, 516 (16%) and 338 (11%), respectively, were referred for follow-up colonoscopy after a positive screening test. Two-hundred-and-fifty-six (4%) had distal-only and 119 (2%) proximal AL. In FIT participants, obesity and high alcohol intake were associated with proximal AL; odds ratio (95% confidence interval) 2.68 (1.36–5.26) and 2.16 (1.08–4.30), respectively. In sigmoidoscopy participants, current smoking was associated with proximal AL; 4.58 (2.24–9.38), and current smoking and obesity were associated with referral for colonoscopy; 2.80 (2.02–3.89) and 1.42 (1.01–2.00), respectively. ConclusionCurrent smoking, obesity and high alcohol intake were associated with screen-detected proximal colorectal AL. Current smoking and obesity were associated with referral for follow-up colonoscopy in sigmoidoscopy screening.

Traditional serrated adenoma-like lesions in patients with inflammatory bowel disease

Patients with inflammatory bowel disease (IBD) have an increased risk of colorectal carcinoma. The significance of serrated lesions resembling traditional serrated adenoma (TSA) in IBD patients is unclear. In this retrospective study, we analyzed 52 TSA-like lesions arising in 30 IBD patients and diagnosed in colectomy or endoscopic specimens. The 27 colectomy lesions presented predominantly as ill-defined areas with granular appearance, with a median size of 15 mm, located throughout the large bowel and associated with synchronous advanced colorectal lesions in 58%. Low-grade serrated dysplasia was present in 56%, high-grade serrated dysplasia in 37%, and TSA-type cytology in 7%. Increased Ki-67 immunostaining and abnormal p53 expression were identified in 96% and 48%, respectively; 74% had a KRAS mutation, and 4% had a BRAF mutation. Endoscopically resectable TSA-like lesions were all discrete polypoid lesions, smaller in size (median 9 mm), predominantly in the distal large bowel, with an adjacent precursor polyp in 24%, and associated with synchronous and metachronous advanced colorectal lesions in 6%. Most (92%) show TSA-type cytology. p53 overexpression was present in 4%, KRAS mutation in 41%, and BRAF mutation in 32%. None of the 52 TSA-like lesions demonstrated loss of MLH1 or SATB2 expression by immunohistochemistry. On follow-up, 4 patients were diagnosed with colorectal carcinoma or high-grade adenomatous IBD-associated dysplasia. None of the patients with lesions showing TSA-type cytology only developed an advanced lesion. Our findings suggest that some TSA-like lesions, essentially from colectomy, may represent a form of IBD-associated dysplasia associated with an increased risk of advanced neoplasia.

Clinicopathological features of advanced colorectal serrated lesions: A single‐center study in China

A growing body of evidence indicates that patients with colorectal serrated lesions, especially advanced serrated lesions (ASLs), are at risk of subsequent malignancy. This study aimed to analyze the clinicopathological features of ASLs and the association between ASLs and synchronous advanced colorectal neoplasia (sACN) in a single center of China. A retrospective cross-sectional study of consecutive symptomatic patients and healthy individuals who underwent colonoscopy between January 2010 and March 2016 was performed. Clinicopathological characteritics of the patients with ASLs were documented from the colonoscopy database. Colorectal serrated lesions were pathologically confirmed in 277 (N = 38 981, 0.7%) cases. Among them, 156 (56.3%) were found to have ASLs, with a total of 161 lesions including 71 sessile serrated adenoma/polyps (SSA/P) and 90 traditional serrated adenomas (TSAs). There were no differences in age and gender between the ASL and non-ASL patients. Among the 161 ASLs, 29 (18.0%) were ≥10 mm in diameter. Compared with non-ASLs, ASLs appeared more in the proximal colon (P = 0.007). Flat and subpedunculated lesions were more commonly found in the ASL group compared with the non-ASL group. Nearly all ASLs (160/161) had dysplasia. Moreover, 16 sACN lesions were found in 156 ASL patients, and large diameter (≥10 mm) might be a significant risk factor for sACN (odds ratio 4.35, 95% confidence interval 1.467-12.894, P < 0.05). ASLs are more likely to occur in the proximal colon, and mainly present as flat and sub-pedunculated types. Large ASLs are significantly associated with sACN.

Long-term outcomes of endoscopic submucosal dissection for high-grade dysplasia and early-stage carcinoma in the colorectum

BackgroundColorectal carcinomas (CRCs) arise from premalignant precursors in an adenoma-carcinoma sequence, in which adenoma with high-grade dysplasia (HGD) and early-stage carcinoma are defined as advanced neoplasia. A limited number of studies have evaluated the long-term outcomes of endoscopic submucosal dissection (ESD) for advanced colorectal neoplasia. This study aimed to assess the efficacy and safety of ESD for advanced colorectal neoplasia as well as the long-term outcomes, including local recurrence and metastasis.MethodsWe analyzed data collected from 610 consecutive patients with 616 advanced colorectal neoplasia lesions treated with ESD between January 2007 and December 2013. Clinical, endoscopic, and histological data were collected over a median follow-up period of 58 months to determine tumor stage and type, resection status, complications, tumor recurrence, and distant metastasis.ResultsThe overall rates of en bloc resection, histological complete resection, and major complications were 94.3%, 89.4%, and 2.3%, respectively. Hybrid ESD was an independent factor of piecemeal resection. Tumor location in the colon was associated with increased risk of ESD-related complications. During the follow-up period, all patients remained free of metastasis. However, local recurrence occurred in 4 patients (0.8%); piecemeal resection was a risk factor.ConclusionsESD is effective and safe for resection of advanced colorectal neoplasia, with a high en bloc resection rate and favorable long-term outcomes. ESD is indicated for the treatment of HGD and early-stage CRC to obtain curative resection and reduce local recurrence rate.

Multitarget stool DNA tests increases colorectal cancer screening among previously noncompliant Medicare patients.

AIMTo determine the uptake of noninvasive multitarget stool DNA (mt-sDNA) in a cohort of colorectal cancer (CRC) screening non-compliant average-risk Medicare patients.METHODSThis cross sectional primary care office-based study examined mt-sDNA uptake in routine clinical practice among 393 colorectal cancer screening non-compliant Medicare patients ages 50-85 ordered by 77 physicians in a multispecialty group practice (USMD Physician Services, Dallas, TX) from October, 2014-September, 2015. Investigators performed a Health Insurance Portability and Accountability Act compliant retrospective review of electronic health records to identify mt-sDNA use in patients who were either > 10 years since last colonoscopy and/or > 1 year since last fecal occult blood test. Test positive patients were advised to get diagnostic colonoscopy and thereafter patients were characterized by the most clinically significant lesion documented on histopathology of biopsies or excisional tissue. Descriptive statistics were employed. Key outcome measures included mt-sDNA compliance and diagnostic colonoscopy compliance on positive cases.RESULTSOver 12 mo, 77 providers ordered 393 mt-sDNA studies with 347 completed (88.3% compliance). Patient mean age was 69.8 (50-85) and patients were 64% female. Mt-sDNA was negative in 85.3% (296/347) and positive in 14.7% (51/347). Follow-up colonoscopy was performed in 49 positive patients (96.1% colonoscopy compliance) with two patients lost to follow up. Index findings included: colon cancer (4/49, 8.2%), advanced adenomas (21/49, 42.9%), non-advanced adenomas (15/49, 30.6%), and negative results (9/49, 18.4%). The positive predictive value for advanced colorectal lesions was 51.0% and for any colorectal neoplasia was 81.6%. The mean age of patients with colorectal cancer was 70.3 and all CRC's were localized Stage I (2) and Stage II (2), three were located in the proximal colon and one was located in the distal colon.CONCLUSIONMt-sDNA provided medical benefit to screening noncompliant Medicare population. High compliance with mt-sDNA and subsequent follow-up diagnostic colonoscopy identified patients with clinically critical advanced colorectal neoplasia.

Abstract LB-296: Multi-target sDNA increases colorectal cancer screening among previously non-compliant patients: The USMD physician services experience

Abstract Background: The multi-target stool DNA test (mt-sDNA) is an FDA approved, high sensitivity, colorectal cancer screening test. We evaluated mt-sDNA in non-screening-compliant Medicare patients and assessed compliance and diagnostic colonoscopy usage and correlated positive mt-sDNA results with colonoscopy findings. Methods: We performed a retrospective medical records review (October 2014 - September 2015) to identify mt-sDNA use in average-risk Medicare eligible patients treated by USMD Physician Services (Dallas, Tx) who were not previously compliant with colon cancer screening. We offered mt-sDNA to patients who were either &amp;gt;10 years since last colonoscopy and/or &amp;gt;1 yr. since last fecal occult blood test. Follow-up colonoscopy was advised for all patients with a positive result. Colonoscopy and pathology results were reviewed with patient classification based on the most significant pathology finding (index lesion). Size, location and total number of polyps and adenomas were tabulated. Results: Over 12 months, 77 providers ordered 393 mt-sDNA studies with 347 completed (88.3% compliance). Patient mean age was 69.8 (50-85) and patients were 64% female. Mt-sDNA was negative in 85.3% (296/347) and positive in 14.7% (51/347). Follow-up colonoscopy was performed in 46 positive patients (90.2% colonoscopy compliance) with 3 patients refusing colonoscopy and two patients lost to follow up. Index findings included: colon cancer (4/46, 8.7%), advanced adenomas (21/46, 45.6%), non-advanced adenoma (9/46, 19.6%), and negative results (12/46,23.0%). The positive predictive value for advanced colorectal lesions was 54.3% and for any colorectal neoplasia was 73.9%. Conclusions: The availability of mt-sDNA provided significant medical benefit to our previously screening non-compliant Medicare population. Patients with clinically critical advanced colorectal neoplasia were identified in this cohort due to high compliance with both mt-sDNA screening and follow-up diagnostic colonoscopy. Citation Format: Mark Prince, Lynn Lester, Rupal Chinawala, Barry M. Berger. Multi-target sDNA increases colorectal cancer screening among previously non-compliant patients: The USMD physician services experience. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-296.

Mo1692 Detection of Advanced Colorectal Lesions in Asymptomatic Individuals; Comparison of FIT, Clinical Risk Factors and Stool DNA

Mo1692 Detection of Advanced Colorectal Lesions in Asymptomatic Individuals; Comparison of FIT, Clinical Risk Factors and Stool DNA

Qualitative Fecal Immunochemical Testing Does Not Reliably Detect Advanced Colorectal Lesions and High-Risk Adenoma Multiplicity in a VA Screening Population

Introduction: Colonoscopy is the preferred test for colorectal cancer (CRC) screening and prevention, but it is resource intensive. Fecal immunochemical testing (FIT) is an alternative strategy for average risk screening, but it has less impact on cancer prevention, primarily identifying individuals with prevalent cancer. The aim of our study was to test the hypothesis that one time qualitative FIT reliably identifies patients with advanced colorectal neoplasia and those at highest risk for CRC in a VA screening population. Methods: FIT and colonoscopy are often ordered simultaneously by referring providers for screening purposes at our institution. We retrospectively analyzed data from the year 2014 of 48 consecutive patients with a (+)FIT who underwent diagnostic colonoscopy by two experienced endoscopists and compared findings to 100 consecutive age and endoscopist matched controls who underwent screening colonoscopy during the same time period with a (-)FIT obtained within a year of their examination. Findings were recorded for FIT (+) and (-) groups, including adenoma detection rates (ADR), proximal colon adenoma detection rates (pADR), mean adenomas per colonoscopy (APC), adenoma multiplicity, presence of advanced adenomas (≥1cm, villous histology or high grade dysplasia), cancer and detection of clinically significant serrated lesions (sessile serrated polyps, proximal colon serrated lesions, serrated lesions in any location ≥1cm). Results:Table 1 compares results. Patient age, ADR, pADR, adenoma multiplicity (≥3 adenomas) and clinically significant serrated lesion detection rates were similar in both groups. No invasive cancer was diagnosed in either group. Advanced adenomas (33% v. 9%, p=0.0007) and high-risk adenoma multiplicity (≥3 adenomas with at least one ≥1cm or ≥5 adenomas) (39.6% v. 16%, p=0.003) were significantly more common in the FIT(+) group. FIT failed to detect 35% of individuals with advanced lesions (advanced adenoma or ≥3 adenomas), including 16% with high-risk adenoma multiplicity.Table 1Conclusion: Patients with a (+)FIT have a significantly higher likelihood of advanced colorectal neoplasia, but a (-)FIT does not reliably exclude patients with clinically significant colorectal neoplasia and those at increased risk for advanced lesions. FIT(+) patients should be prioritized for access to colonoscopy, but colonoscopy should be advocated as the test of choice for CRC screening and prevention, even after (-)FIT, in a VA population.

P-196 New perspective for detecting advanced colorectal neoplastic lesions by cytogenetic biomarkers in average risk patients

P-196 New perspective for detecting advanced colorectal neoplastic lesions by cytogenetic biomarkers in average risk patients