Detection Of Colorectal Neoplasia Research Articles

Proton pump inhibitors reduce the accuracy of faecal immunochemical test for detecting advanced colorectal neoplasia in symptomatic patients.

BackgroundThe faecal immunochemical test (FIT) is used in colorectal cancer (CRC) screening and for the detection of advanced colorectal neoplasia (AN) in symptomatic patients, but its accuracy could be improved. Our objective was to assess the impact of proton pump inhibitors (PPI) on the accuracy of the FIT in the detection of AN, namely advanced colorectal adenoma and CRC.Methods and findingsWe performed a prospective study of 1002 individuals referred for a diagnostic colonoscopy at Bellvitge University Hospital from September 2011 through to October 2012. An exhaustive interview was performed by a gastroenterologist, prescription drug dispensing database was reviewed and the patient was given a FIT prior to colonoscopy. The positivity threshold of FIT used was ≥ 20 μg Hb/g feces and the main outcome was AN. AN was detected in 13.2% (133) of patients. The accuracy of FIT for detecting AN in the PPI users and non-PPI users were: sensitivity 43.0% vs 65.6%, P = 0.009; specificity 86.9% vs 92.3%, P = 0.010; and, predictive positive value 34.4% vs 55.5%, P = 0.007, respectively. In multivariate analysis, adjusting for potential confounders, PPIs were associated with false positives in AN detection by FIT (OR 1.63 CI 95% 1.02–2.59, P < 0.037). The ROC curve for the FIT in the detection of AN in the PPI users and non-PPI users was 0.68 (CI 95% 0.61–0.76) and 0.85 (CI 95% 0.79–0.90).ConclusionsPPI therapy reduces the accuracy of FIT for detecting AN in symptomatic patients.

Risk stratification for colorectal neoplasia detection in the Flemish colorectal cancer screening programme

BackgroundThe quantitative faecal immunochemical test (FIT) detects pre-cancerous lesions and colorectal cancer (CRC). Current CRC screening programmes are based upon a binary FIT result. This study evaluates the possibility of personalised risk prediction, based on FIT, age and gender to gain more insight into improving discrimination between normal outcomes, pre-cancerous lesions, carcinoma in situ and CRC working towards a more tailored screening approach. MethodsIn this retrospective study, from October 2013 until July 2016, data from 57,421 participants who underwent a colonoscopy after a positive FIT in the Flemish CRC screening programme were analysed using a multinomial multivariable logistic regression model. ResultsA significant difference in risk of detecting neoplasia was found between the established risk profiles based on the combination of the quantitative FIT, age and gender. The odds for detecting CRC in men aged 74, with a FIT result of ≥1000 ng/ml, was higher by a factor of 58.43 than that for women aged 56, with a FIT result of 75 ng/ml. ConclusionA large difference in risk with regard to the detection of colorectal neoplasia was found, based on demographics of the population. For some participants, the chance of finding no anomalies was more than 60%. Including additional variables in a prediction model could further increase discrimination between outcomes and practicality.

Tu1963 - Feasibility, Safety, and Initial Efficacy of Cathepsinactivatable Fluorescent Probes for Molecular Detection of Colorectal and Esophageal Neoplasia

Tu1963 - Feasibility, Safety, and Initial Efficacy of Cathepsinactivatable Fluorescent Probes for Molecular Detection of Colorectal and Esophageal Neoplasia

A new approach to epigenome-wide discovery of non-invasive methylation biomarkers for colorectal cancer screening in circulating cell-free DNA using pooled samples

BackgroundColorectal cancer is the fourth cause of cancer-related deaths worldwide, though detection at early stages associates with good prognosis. Thus, there is a clear demand for novel non-invasive tests for the early detection of colorectal cancer and premalignant advanced adenomas, to be used in population-wide screening programs. Aberrant DNA methylation detected in liquid biopsies, such as serum circulating cell-free DNA (cfDNA), is a promising source of non-invasive biomarkers. This study aimed to assess the feasibility of using cfDNA pooled samples to identify potential serum methylation biomarkers for the detection of advanced colorectal neoplasia (colorectal cancer or advanced adenomas) using microarray-based technology.ResultscfDNA was extracted from serum samples from 20 individuals with no colorectal findings, 20 patients with advanced adenomas, and 20 patients with colorectal cancer (stages I and II). Two pooled samples were prepared for each pathological group using equal amounts of cfDNA from 10 individuals, sex-, age-, and recruitment hospital-matched. We measured the methylation levels of 866,836 CpG positions across the genome using the MethylationEPIC array. Pooled serum cfDNA methylation data meets the quality requirements. The proportion of detected CpG in all pools (> 99% with detection p value < 0.01) exceeded Illumina Infinium methylation data quality metrics of the number of sites detected. The differential methylation analysis revealed 1384 CpG sites (5% false discovery rate) with at least 10% difference in the methylation level between no colorectal findings controls and advanced neoplasia, the majority of which were hypomethylated. Unsupervised clustering showed that cfDNA methylation patterns can distinguish advanced neoplasia from healthy controls, as well as separate tumor tissue from healthy mucosa in an independent dataset. We also observed that advanced adenomas and stage I/II colorectal cancer methylation profiles, grouped as advanced neoplasia, are largely homogenous and clustered close together.ConclusionsThis preliminary study shows the viability of microarray-based methylation biomarker discovery using pooled serum cfDNA samples as an alternative approach to tissue specimens. Our strategy sets an open door for deciphering new non-invasive biomarkers not only for colorectal cancer detection, but also for other types of cancers.

Blood free-circulating DNA testing by highly sensitive methylation assay to diagnose colorectal neoplasias.

Although methylated TWIST1 is a biomarker of colorectal neoplasia, its detection from serum samples is very difficult by conventional bisulfite-based methylation assays. Therefore, we have developed a new methylation assay that enables counting of even one copy of a methylated gene in a small DNA sample amount without DNA bisulfite treatment. We performed this study to evaluate the sensitivity and specificity of serum DNA testing by the new methylation assay in combination with and without the fecal immunochemical test for hemoglobin for the detection of colorectal neoplasia. This study comprised 113 patients with colorectal neoplasia and 25 control individuals. For the new methylation assay, DNA was treated in two stages with methylation-sensitive restriction enzymes, followed by measurement of copy numbers of hTERT and methylated TWIST1 by multiplex droplet digital PCR. The fecal immunochemical test had a sensitivity of 8.0% for non-advanced adenoma, 24.3% for advanced adenoma, and 44.4% for colorectal cancer, and a specificity of 88.0%. The new assay had a sensitivity of 36.0% for non-advanced adenoma, 30.0% for advanced adenoma, and 44.4% for colorectal cancer, and a specificity of 92.0%. Combination of the both tests increased the sensitivity to 40.0%, 45.7%, and 72.2% for the detection of non-advanced adenoma, advanced adenoma, and colorectal cancer, respectively, and resulted in a specificity of 84.0%. Combination of both tests may provide an alternative screening strategy for colorectal neoplasia including potentially precancerous lesions and colorectal cancer.

An Update on Surveillance in Ulcerative Colitis.

Patients with long-standing ulcerative colitis have an increased risk for the development of colorectal cancer (CRC). Colitis-related dysplasia appears to confer the greatest risk. Colonoscopic surveillance to detect dysplasia has been advocated by gastrointestinal societies. The aim of surveillance is the reduction of mortality and morbidity of CRC through detection and resection of dysplasia or detecting CRC at an earlier and potentially curable stage. Traditional surveillance has relied on mucosal assessment with targeted biopsy of visible lesions and random biopsy sampling on the premise that dysplasia was not visible at endoscopy. Advances in optical technology permitting increased detection of dysplasia and evidence that most dysplasia is visible has had practice-changing implications. Emerging evidence favours chromoendoscopy (CE) for dysplasia detection and is gaining wider acceptance through recent international (International Consensus Statement on Surveillance and Management of Dysplasia in Inflammatory Bowel Disease (SCENIC)) recommendations and endorsed by many gastrointestinal societies. Adoption of CE as the gold standard of surveillance has been met with by scepticism, from conflicting data, operational barriers and the need to understand the true impact of increasingly higher dysplasia detection on overall CRC mortality. Valid debate notwithstanding, implementation of a risk stratification protocol that includes CE is an effective approach allowing earlier detection of dysplasia and colorectal neoplasia, determination of surveillance intervals with appropriate allocation of resources and limiting morbidity from CRC and colonoscopy itself. Further prospective data should define the true and long-term impact of dysplasia detection with modern techniques.

Computed tomography colonography versus colonoscopy for the diagnosis of colorectal cancer: a systematic review and meta-analysis.

Colorectal cancer (CRC) is a significant cause of morbidity and mortality. Optical colonoscopy (OC) is the first choice of investigation for assessing the state of the colon and it is excellent for CRC screening. Newer technologies such as computed tomography colonography (CTC) may also be useful in CRC screening. This systematic review compares the benefits of CTC and OC for CRC screening. This review includes all the available randomized clinical trials comparing CTC and OC for CRC screening in asymptomatic patients. Three studies were included in the systematic review and were submitted for meta-analysis. In the analysis of participation rates, only 2,333 of 8,104 (29%) patients who were invited for screening underwent the CTC, and only 1,486 of the 7,310 (20%) patients who were invited for screening underwent OC. The absolute risk difference in participation rate in the two procedures was 0.1 (95% CI, 0.05–0.14) in favor of CTC. In the analysis of advanced colorectal neoplasia (ACN) detection rates, 2,357 patients undergoing CTC and 1,524 patients undergoing OC were included. Of these, 135 patients (5.7%) who underwent a CTC and 130 patients (8.5%) who underwent an OC were diagnosed with ACN. The absolute risk difference in ACN detection rate in the two procedure types was −0.02 (with a 95% CI between −0.04 and −0.00) in favor of OC. CTC is an option for CRC screening in asymptomatic patients. However, as CTC was inferior in detecting ACN, it should not replace OC, which remains the gold standard.

Utility of the multitarget stool DNA test for detection of colorectal neoplasia

Colorectal cancer (CRC) is an ideal target for screening because it and its precursor lesions are prevalent and can be detected at curable stages among asymptomatic persons. Different screening strategies have been shown to reduce CRC incidence and mortality; therefore, CRC screening is widely recommended. However, despite these demonstrated benefits, a large percentage of the population remains unscreened and efforts are underway in multiple countries to improve screening participation. The multitarget stool DNA test (MT-sDNA) is a new noninvasive option for CRC screening that is a now recommended as a primary CRC screening strategy in the updated guidelines by the US Preventive Services Task Force, American Cancer Society and National Comprehensive Cancer Network. MT-sDNA has high accuracy for detection of both CRC and polyps at the greatest risk of progression, and has potential to improve screening uptake and effectiveness. This review provides a summary of MT-sDNA performance for detection of colorectal neoplasia and a perspective on the value it adds to our screening tool kit.

Targeting Mucosal Endothelin-A-Receptor Expression by Fluorescence Endoscopy is Feasible to Detect and Characterize Colitis-Associated Cancer in Mice.

To facilitate onsite decision-making during endoscopy, both accurate detection and in vivo characterization of preneoplasia are prerequisites. However, no endoscopy technique is available that meets both demands satisfactorily. We evaluated endothelin-receptor A (ETAR)-guided fluorescence endoscopy (FE) in vivo and fluorescence reflectance imaging (FRI) ex vivo for detection and characterization of early dysplastic colitis-associated colonic lesions. Colorectal cancerogenesis was investigated in the inflammatory driven AOM-DSS model and spontaneous adenoma development in ApcMin mice. A Cy5.5-labeled nonpeptidic ETAR-specific imaging probe was injected intravenously to assess tumor development in vivo by white light endoscopy (WLE) and FE. Ex vivo tumors were evaluated by FRI, histological examination, and western blot analysis. In addition, tissue samples from patients with colitis-associated malignant and nonmalignant mucosal alterations were analyzed. Specificity experiments were performed using an unspecific Cy3.5-glycine tracer. Overall, 62 adenomas were observed. FE was able to detect and quantify ETAR expression targeting the ETAR-specific photoprobe. A significantly higher fluorescent contrast was detected in colonic adenomas compared to adjacent nonmalignant mucosa by FE (64.3 ± 7.9 vs. 56.6. ± 7.0; P < 0.001). These results were confirmed by FRI examination, immunochemistry, and western blot analysis. Additionally, ETAR expression in samples from human patients with colitis-associated cancer was highly elevated compared to nonmalignant alterations. Specificity experiments indicated a high binding-specificity of the applied ETAR photoprobe (1.4 ± 0.3 vs. 2.5 ± 0.7; P < 0.001). We introduced ETAR guided FE in mice for successful in vivo detection and characterization of colorectal neoplasia on a molecular level.

Identification and validation of colorectal neoplasia-specific methylation biomarkers based on CTCF-binding sites.

To date, the sensitivity of currently available biomarkers based on the methylation of gene promoters is suboptimal for detecting adenomas and early-stage colorectal cancer (CRC). We aimed to develop biomarkers with methylated DNA binding sites of the multifunctional transcriptional factor CTCF for early detection of CRC. Using combined analyses of genome-wide occupation and the methylation profile of CTCF-binding sites, we identified candidate CTCF-binding sites. Then, we applied methylation-sensitive high-resolution melting (MS-HRM) and mass spectrometry analysis to screen and validate these candidate sites in diverse sample sets. We identified a set of colorectal neoplasia-specific biomarkers with robust performance. The top five biomarkers were selected and recommended for early detection of colorectal neoplasia. All of the five novel biomarkers exhibited a more robust discriminatory performance than that by BMP3 and NDRG4, two currently acknowledged robust methylation biomarkers. When the five new biomarkers were considered as a marker panel and tumor-positive was defined as having two or more (of the five) positive biomarkers, the marker panel could achieve a sensitivity of 91.67% for adenomas, 97.44% for Stage I CRC, 94.06% for Stage II CRC, 93.62% for Stage III CRC, and 93.54% for total colorectal tumors with a specificity of 94.05%. To our knowledge, this is the first study for colorectal neoplasia-specific methylation biomarkers based on CTCF-binding sites. Using a similar strategy, CTCF-binding sites could be potentially developed into biomarkers for other tumors. In summary, this study opens a new area in developing biomarkers for tumor prevention and treatment.

Performance of quantitative immunochemical test for fecal hemoglobin for surveillance of colorectal neoplasia after polypectomy in clinical practice

SummaryAimsWe examined the yield of immunochemical test for fecal hemoglobin (FIT) for the post‐polypectomy individuals in a colorectal cancer screening program.MethodsWe enrolled 50‐75 years average‐risk individuals who attended a biennial FIT‐based colorectal cancer screening program from March 2010 to December 2011 (index round) and from January 2012 to December 2013 (repeated round). Colonoscopy was recommended to the participants with an FIT ≧ 30 μg Hb/g feces.Participants identified with adenomas and removed by polypectomy in the index round were defined as surveillance group (Sur‐G). Participants with an FIT &lt; 30 μg Hb/g feces in the index round or identified as non‐neoplastic findings of the indexed colonoscopy were defined as repeated screening group (Rsc‐G). We compared key quality indicators for FIT and colonoscopy between Sur‐G and Rsc‐G according to the findings of the repeated round. A p &lt; 0.05 determined by chi‐square test was defined as significant.ResultsThere were 222 post‐polypectomy surveillance (Sur‐G) and 7311 repeated screening individuals (Rsc‐G) enrolled for analysis. The FIT positivity rate, colonoscopy compliance rate and colorectal neoplasia (CRN) detection rate were 504 of 7311 (6.9%) vs. 46 of 222 (20.7%) (p &lt; 0.001); 381 of 504 (75.6%) vs. 44 of 46 (95.7%) (p &lt; 0.001) and 207 of 504 (41.1%) vs. 32 of 46 (69.6%) (p &lt; 0.001) for Rsc‐G and Sur‐G respectively. The FIT positivity rate, colonoscopy compliance rate and CRN detection rate were significantly higher in the Sur‐G.ConclusionsOur results suggest individuals after polypectomy still had high risk of CRN. Biennial FIT may play a role for post‐polypectomy surveillance. Subsequent prospective study is necessary to evaluate the effectiveness of FIT for post‐polypectomy surveillance.Copyright © 2017, The Gastroenterological Society of Taiwan, The Digestive Endoscopy Society of Taiwan and Taiwan Association for the Study of the Liver.

Fecal immunochemical tests for surveillance of the colorectal neoplasia after polypectomy

Fecal immunochemical tests for surveillance of the colorectal neoplasia after polypectomy

Serum DCLK1 as a Biomarker for Adenoma and Colorectal Neoplasia Detection in Patients Referred for Colonoscopy

Introduction: Doublecortin-like kinase 1 (DCLK1), a putative tumor stem cell marker has been shown to be highly expressed in the stromal and epithelial compartments in colon and pancreatic cancer as well as Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). The aim of this study was to investigate whether DCLK1 can be used as an early diagnostic marker for adenoma detection and colorectal neoplasia in serum. Methods: Consecutive patients referred to the Oklahoma City VA Medical Center for colonoscopy were prospectively enrolled into the study from January to May 2017. Five milliliters (mls) of blood was drawn from each patient prior to colonoscopy. During colonoscopy biopsies were obtained and/or polypectomy was performed if indicated and sent to pathology. Tissue samples were stratified into groups after microscopic analysis; normal (n=13), hyperplastic polyp (HP; n=25), tubular adenoma (TA; n=80), tubular adenoma with high-grade dysplasia and colorectal adenocarcinoma (HGD and CRC; n=4). DCLK1 expression in serum was determined by ELISA and correlated with histopathology findings. Results: The study population consisted of 122 patients with mean age of 63.4 years; 94.3% were male. Majority (79.4%) were Caucasian. Increased expression of DCLK1 was found in the serum of patients in the HGD/CRC group compared to the other groups (normal, HP and TA; P=0.006). Increased expression of DCLK1 was also found in the serum of patients with diabetes (P=0.01). After controlling for diabetes, the difference in serum DCLK1 levels among the 4 histologic groups remained (p =0.0002). There was no association between serum DCLK1 expression and age, gender, ethnicity, BMI, tobacco use, alcohol use, personal or family history of colon polyps and/or CRC, polyp size, total polyp burden, or history of other GI cancers (all P>0.05), suggesting that DCLK1 expression in serum is independent of established risk factors for colon polyps and CRC. Conclusion: DCLK 1 may represent a novel molecular marker for detection of adenoma and CRC in serum. However, our results need to be interpreted with caution given the small number of patients in the HGD/CRC group. Enrollment of more patients in the normal and HGD/CRC groups will provide more robust results.Table: Table. Serum DCLK1 Concentration (ELISA) ng/mlFigure: Serum DCLK1 expression level by histology group.

Diagnostic Accuracy of Optical Detection of Residual Colorectal Neoplasia After Endoscopic Mucosal Resection: Impact of Endoclip Closure at EMR Site

Introduction: Application of clips after EMR may reduce post EMR bleeding but also interfere with the recurrent adenoma detection at follow up due to nodular distortions of scar tissue. This could lead to an overtreatment of benign lesions. In a prospective trial, we aimed to evaluate the diagnostic accuracy of white light and narrow band imaging (NBI) with near-focus capability in recurrent adenoma detection with or without clip artifact. Methods: This prospective trial was started in January 2016 and is ongoing. Consecutive patients undergoing follow-up colonoscopy after a previous EMR of ≥20mm colorectal polyps were included. Endoscopists predicted the presence of neoplasia recurrence of EMR scars with or without clip artifact and their level of confidence (high or low) based on visual assessment of the previous EMR site subsequently with the four modalities 1) white light without and 2) with near-focus, and 3) NBI without and 4) with near-focus. Each EMR site was biopsied as a reference standard and histology assessed by a pathologist blinded to the endoscopist's visual assessment. Diagnostic accuracy was calculated for all diagnostic modalities for the real-time endoscopic assessment of the EMR scar tissue with or without clip artifacts. Results: A total of 172 patients (54% male, mean age: 65 years with 180 scar sites were included perprotocol, with a median follow up of 8 months (range: 3-71 months). At the original EMR, clips were used in 82/180 (45%) lesions. The rate of post-EMR scar clip artifact was 61% (50 of 82). Diagnostic accuracy for all EMR-scar sites with or without clip- artifact and confidence level in real time are shown at Table 1 and 2. The prevalence of residual neoplasia was 25% for all EMR scars. 27% of cases were over treated for benign disease when clips were used versus 8% of cases when clips were not used. Overall, clips reduced the proportion of high confidence diagnoses and appeared to lower the accuracy of EMR scar assessment in low confidence diagnoses but not for high confidence diagnoses.Table: Table. Diagnostic value of optical detection of residual neoplasia with or without clip artifactConclusion: These results suggest that clips used to close colonic EMR defects may impair the ability to accurately assess the EMR scar at follow up. Clips reduced the proportion of high confidence diagnoses as well as the accuracy of scar assessment in low confidence diagnoses, and furthermore, increased the proportion of over treated benign clip artifact. Alternative methods to potentially reduce post-EMR bleeding are needed.

A Lower Hemoglobin Concentration Cutoff for Abnormal Fecal Immunochemical Testing Substantially Increases Colorectal Cancer and Advanced Neoplasia Detection in a System Level Mailed Outreach Program

A Lower Hemoglobin Concentration Cutoff for Abnormal Fecal Immunochemical Testing Substantially Increases Colorectal Cancer and Advanced Neoplasia Detection in a System Level Mailed Outreach Program

Stool DNA Test of Methylated Syndecan-2 for the Early Detection of Colorectal Neoplasia.

Background: Although the incidence of colorectal cancer is steadily increasing, screening for colorectal cancer with conventional approaches is not routinely performed in China. Noninvasive screening methods are attractive options to resolve this issue. Syndecan-2 (SDC2) is frequently methylated in colorectal cancer. However, the value of a stool test of methylated SDC2 for the detection of colorectal cancer is unknown.Methods: Methylation status of SDC2 was tested in cell lines and 398 colorectal tissue samples and further evaluated with 497 stool samples, including 196 from colorectal cancer patients, 122 from adenoma patients, and 179 from normal individuals, using real-time methylation-specific PCR. The impacts of one quantitative partial stool sampling device and 17 potentially interfering substances on the performance of fecal methylated SDC2 were also analyzed. SDC2 expression was also measured.Results:SDC2 methylation level was higher in 96.8% (120/124) of colorectal cancer tissues compared with paired adjacent normal epithelia. Stool test of methylated SDC2 detected 81.1% (159/196) of colorectal cancer and 58.2% (71/122) of adenomas at a specificity of 93.3% (167/179). No significant difference was found between partial and whole stool collection on colorectal cancer detection (P > 0.05, R2 = 0.80). Among 17 interfering substances, only berberine at high concentrations inhibited fecal detection of methylated SDC2SDC2 was overexpressed in colorectal cancer tissues compared with normal epithelia.Conclusions: Fecal methylated SDC2 is a valuable biomarker for the noninvasive detection of colorectal neoplasms.Impact: Stool DNA test of methylated SDC2 would serve as an alternative method for screening colorectal neoplasms. Cancer Epidemiol Biomarkers Prev; 26(9); 1411-9. ©2017 AACR.

Highlights of This Issue

Estimating the shared heritability between cancers will inform common biological mechanisms and future studies. Lindström and colleagues estimated the pair-wise genetic correlation between breast, colorectal, lung, ovarian, pancreatic, and prostate cancer using data on 66,958 cases and 70,665 controls of European ancestry. The authors observed genetic correlations between pancreatic and colorectal cancer, lung and colorectal cancer, lung and breast cancer, and colorectal and breast cancer. In contrast, prostate cancer did not share an appreciable proportion of heritability with other cancers. Overall, the results indicate modest genetic correlations between cancers; in particular, breast, colorectal, and lung cancer share some degree of genetic basis.Breast cancer is the most common cancer in young women worldwide. Risk factors for breast cancer may differ before and after menopause, but few cohort studies have sufficient numbers of cases among premenopausal women to study potential risk factors adequately in this group. To address this gap, the Premenopausal Breast Cancer Collaborative Group pooled data from 20 cohorts internationally, including a total of 21,766 incident breast cancers diagnosed among 1,030,761 women before age 55. Initial aims focused on the role of adiposity, physical activity, and recent pregnancy, with opportunities for collaborative research on other hypotheses.This study by Niu and colleagues reported the development of one stool DNA test with methylated Syndecan-2 gene for the early detection of colorectal neoplasia. The authors evaluated the test in 497 stool samples, and found that it could detect 81.1% of colorectal cancers and 58.2% of advanced adenomas at a specificity of 93.3%. Furthermore, they also proved that the performance of this stool test was not affected by common interfering substances except berberine. This novel test would serve as an alternative method for screening colorectal neoplasia.Approximately 72 percent of oropharyngeal cancers are attributable to infection with human papillomavirus (HPV). Only 41% of Texas girls and 24% of boys ages 13 to 17 had completed the HPV vaccination series in 2015. The treatment costs saved by preventing future cases of oropharyngeal cancer is important for decisions about investments to increase the HPV immunization rate. We estimated the average two-year healthcare cost per incident case in Texas from the 2011–2014 Truven MarketScan Commercial Claims and Encounter Database. The cost was $160,639 among 467 patients, compared with $20,890 for 467 propensity score matched controls. The difference represents potential savings per case avoided by HPV immunization.

Optimizing the quality of endoscopy in inflammatory bowel disease: focus on surveillance and management of colorectal dysplasia using interactive image- and video-based teaching

Varying recommendations regarding the detection and management of dysplasia can lead to uncertainty and may impede the uptake of strategies that could improve surveillance in patients with inflammatory bowel disease (IBD). An educational event was held to assist in disseminating the recently published Surveillance for Colorectal Endoscopic Neoplasia Detection and Management in Inflammatory Bowel Disease Patients: International Consensus Recommendations (SCENIC). Specialists in IBD and endoscopy led the Optimizing Quality of Endoscopy in IBD course. The American Society for Gastrointestinal Endoscopy (ASGE) organized the course, and the Crohn's and Colitis Foundation of America (CCFA) provided endorsement. One was held in March 2015 at the ASGE Institute for Training and Technology in Chicago, Illinois, and the second in September 2016 preceding the ASGE Endofest in Chandler, Arizona. The program included interactive case-based discussions and didactic presentations on topics including the rationale and current approach of surveillance in IBD; endoscopic characterization and nomenclature of active and quiescent disease; detection of dysplasia during IBD surveillance; role of image-enhanced endoscopy in IBD surveillance, with a focus on chromoendoscopy technique; and management of dysplasia in IBD. Participants were surveyed before and after the course to assess their perspectives and practice. Eighteen presenters or panel members and approximately 92 IBD and endoscopist physician leaders attended the meeting. Most attendees were aged 30 to 49 years (88.1%), had been in practice less than 10 years (89.7%), were from academic medical centers (90.7%), and spent >50% of their time caring for patients with IBD (59.7%). Recommended quality improvements for endoscopy in IBD included the use of endoscopic scoring systems to describe disease activity, the use of a modified Paris classification to characterize visible dysplastic lesions (polypoid, nonpolypoid with description of presence of ulcer and distinct or indistinct borders), the use of chromoendoscopy for dysplasia detection, and the endoscopic removal of visible dysplastic lesions. In the follow-up survey, participants were asked to indicate whether they had changed their practice as a result of attending the course. Ninety-three percent (93%) indicated they had changed their practice. For dysplasia detection, the use of chromoendoscopy increased: 51.7% of respondents reported using chromoendoscopy in most surveillance colonoscopies compared with 34.3% before the course. For dysplasia management, the use of EMR increased for polypoid and nonpolypoid lesions 10 to 20mm in size; and the referral of dysplastic lesions 20mm or larger that appeared endoscopically resectable shifted toward removal by an experienced endoscopist. Evidence-based advances in endoscopy have occurred in the characterization and nomenclature of active and quiescent disease, polypoid and nonpolypoid dysplasia in IBD, and in the detection and management of dysplasia in colonic IBD. Implementation of updated guidelines and recommendations into clinical practice may be facilitated by interactive image- and video-based courses on the topic.

Assessment of Bone Morphogenetic Protein 3 Methylation in Iranian Patients with Colorectal Cancer.

BACKGROUND Colorectal cancer (CRC) is a common cancer that results in outstanding morbidity and mortality worldwide. DNA methylation is one of the most important epigenetic events that is thought to occur during the early stages of oncogenic transformation especially in CRC. The aim of this study was to investigate whether hypermethylation of bone morphogenetic protein 3 (BMP3) in tissue samples is implicated in Iranian patients with CRC. METHODS From fresh frozen tissue samples of 30 patients with CRC, the DNA was isolated, treated with sodium bisulfite and analyzed by methylation-specific polymerase chain reaction with primers specific for methylated or unmethylated promoter sequences of the BMP3 gene. Demographic characteristics of the patients including age, sex, tumor grade, location, stage, and TNM classification were evaluated and the relationship between hypermethylation of the gene and clinicopathological features was analyzed. RESULTS Methylation of the BMP3 promoter was often present in the DNA extracted from the tumoral tissues. A sensitivity of 56.66% and specificity of 93.3% were attained in the detection of colorectal neoplasia. CONCLUSION We assumed that solely BMP3 methylation analysis in our population is not sufficient to select the gene as a screening biomarker and it should be considered in combination with other markers to screen for detection of colorectal cancer.

Clinical and pathological features of upper gastrointestinal serrated lesions

Objective To analyze the clinical and pathological features of upper gastrointestinal serrated lesions. Methods A total of 21 patients with upper gastrointestinal serrated lesions in Tianjin Medical University General Hospital between January 2011 and December 2015 were retrospective analyzed. Data of the patients including demographics, clinical and pathological features were collected. Among the 21 patients, 18 patients, who underwent colonoscopy simultaneously or within six months, were selected as the study group, each patient was compared to 4 randomly selected controls without serrated lesions, who also underwent colonoscopy within the same time period. Differences of colorectal neoplasia detection were analyzed between the cases and controls. Results The mean age of 21 patients was 55.3±17.2 years, and 11 cases were male. Involving the locations of serrated lesions, 17 cases were found in the stomach (including 3 in the cardia, 9 in the corpus, and 5 in the antrum), and followed by 3 in the duodenum and 1 in lower esophagus. The mucosa pathological morphology showed that 6 cases were serrated hyperplasia, 8 cases were hyperplastic polyps, 6 cases were serrated adenomas with low grade dysplasia and 1 case was in the duodenum intramucosal carcinoma. Seven (38.9%) colorectal adenomas were found in the study group, including 3 (16.7%) non-advanced colorectal adenomas and 4 (22.2%) advanced colorectal adenomas. Eight (11.1%) colorectal adenomas were found in the control group, including 5 (6.9%) non-advanced colorectal adenomas and 3 (4.2%) advanced colorectal adenomas. The rate of colorectal adenoma detection in the study group was significantly higher than that in the control group (38.9% VS 11.1%, P=0.010, OR=5.091, 95%CI: 1.534-16.890). Conclusion Upper gastrointestinal serrated lesions can be found in various mucosal lesions with different pathological morphologies. Moreover colonoscopy is likely to be recommended to detect concurrent colorectal adenoma for these patients. Key words: Endoscopy; Upper gastrointestinal tract; Serrated lesions; Colorectal adenoma