Negative Colonoscopy Results Research Articles

A Stool DNA-Based SDC2 Methylation Test for the Early Detection of Colorectal Cancer in an Asymptomatic, High-Risk Population: A Multicenter Prospective Randomized Trial.

Noninvasive stool DNA-based methylation testing has emerged as an effective strategy for the early colorectal cancer (CRC) detection. Syndecan-2 (SDC2) methylation frequently occurs in all stages of CRC; therefore, the aim of this study was to evaluate the clinical performance of a stool DNA-based SDC2 methylation test for detecting CRC in asymptomatic or high-risk CRC populations. This multicenter prospective study was conducted to determine the clinical performance of the SDC2 methylation test on stool DNA using real-time polymerase chain reaction. Stool samples were collected from asymptomatic individuals before colonoscopy, and the test results were independently analyzed through comparison with colonoscopic findings and pathological outcomes as reference standards. Of the 1,124 evaluable participants, 20 had CRC, 73 had advanced adenomatous polyps (≥1.0 cm), 469 had nonadvanced adenomatous polyps (<1.0 cm), 178 had non-neoplastic polyps, and 384 had negative colonoscopy results. The stool SDC2 methylation test had a sensitivity and specificity of 95.0% and 81.5%, respectively, for detecting CRC, while the sensitivity for detecting advanced adenomatous polyps and CRC was 58.1%. The rate of adenoma detection increased with polyp size (P < 0.01), and sensitivity was not associated with CRC stage (P = 0.864). The stool DNA-based SDC2 methylation test attained a high sensitivity for CRC detection in an asymptomatic high-risk population. Further large-scale clinical studies are required to validate the clinical utility of this test as a population-based CRC screening tool.

Factors associated with precancerous stomach lesions and progresion: A 7-year multi-center prospective cohort study on the low incidence of gastric cancer in central Saudi Arabia.

In Saudi Arabia (SA) no data are available on precancerous stomach lesions (PSLs) or the associated risk factors. We aimed to identify PSLs and investigate factors associated with PSLs and their progression. This 7-year prospective study screened for PSLs in asymptomatic Saudi patients aged 45-75 years in central SA (n = 35,640). Those who had high-sensitivity guaiac fecal occult blood tests (HSgFOBT+) and negative colonoscopy results (n = 1242) were subjected to upper GI endoscopy to identify PSLs and were followed up every 3 years or earlier, depending on the type of PSL. Factors associated with PSLs were investigated. The 7-year participation rate was 86.9% (1080/1242). The 7-year prevalence of PSLs was 30.9% (334/1080). The incidence rate of PSLs was 134 new cases/100,000 population/year, total population at risk - 35,640 and 44.3 new cases/1,000 persons/year among the 1080 participants with HSgFOBT+ and negative colonoscopy results. Among the 334 participants with PSLs, 8 (2.4%) had neoplastic progression to GC during the surveillance period. Age, Helicobacter pylori infection, smoking status, a diet with preserved salty foods, low income, and a family history of GC were associated with PSLs. The incidence of GC is low in central SA, but screening for PSLs among participants with HSgFOBT+ and negative colonoscopy findings may contribute to the early detection and subsequent treatment of GC. HP eradication, not smoking, normal body weight, and adhering to a healthy diet seem to be potential factors associated with the development of PSLs. Further studies are needed to search if such interventions would decrease the incidence of PSLs and progression to early GC.

P1228 The EISER Study: Identifying Microbial Factors Associated with Subclinical Gut Inflammation in Psoriatic Arthritis Patients Who Develop Inflammatory Bowel Disease

Abstract Background Nearly 8% of patients with spondyloarthritis (SpA) manifest symptoms that are compatible with active inflammatory bowel disease (IBD). It is well established that microbial dysbiosis is associated with different immune-mediated diseases. We therefore hypothesized that the gut microbiome could be a modulator of intestinal inflammation and factor in the pathogenesis of IBD in SpA patients. Methods As part of the EISER study, we selected a subset of 193 subjects diagnosed with psoriatic arthritis (PsA), a form of SpA, who had no prior diagnosis of IBD. The presence of subclinical symptoms compatible with IBD was evaluated at time of enrollment. For patients with fCAL levels of 80 µg/g or higher, colonoscopy was performed and histological analysis of biopsies collected during the procedure were used to diagnose IBD. Capsule endoscopy was performed on those patients with a negative colonoscopy result. Stool samples were collected from all participants, and microbial DNA was extracted for shotgun metagenomic sequencing using the Illumina HiSeq platform. Sequenced data was processed using MetaPhlAn 4 to estimate taxonomic composition, MMEDS for overall microbiome analysis, and R for additional statistical analyses. Results Twenty-five out of 193 subjects in our cohort (12.95%) had symptoms that were compatible with subclinical IBD (sIBD) and five patients (2.6% of total) were confirmed to have clinical IBD (cIBD). The use of nonsteroidal anti-inflammatory drugs (NSAIDs) resulted in significant differences in overall alpha (Shannon entropy, p=0.03) and beta microbial diversity (PERMANOVA, p=0.043), while the use of proton-pump inhibitors (PPI) resulted in significant differences in beta diversity (PERMANOVA, p= 0.036). Patients with cIBD had significantly higher abundance of taxa including Prevotella copri and Prevotella stercorea. P. copri, P. stercorea and fCAL were all significantly elevated in cIBD patients (Wilcoxon’s p=0.0278, 0.0007, 0.0161), although with a larger effect size in P. copri and P. stercorea (Cohen’s D: P. copri = 1.074; P. stercorea = 1.269; fCAL= 0.629). fCAL was also significantly elevated in patients who used PPIs (p= 4.456e-11), while P. copri and P. stercorea abundances were not impacted (Wilcoxon’s p: P. copri = 0.2394; P. stercorea = 0.0643). Conclusion Microbiome composition was impacted by the use of NSAIDs and PPI. We identified taxa differentially enriched in cIBD patients, including Prevotella copri and P. stercorea. Importantly, while fCAL was significantly higher in cIBD patients, its discriminatory power was not as strong as that of P. copri and P. stercorea, suggesting that these taxa could be potentially used as biomarkers of co-morbid IBD in patients with PsA.

Epidemiology, Risk Factors for Gastric Cancer and Surveillance of Premalignant Gastric Lesions: A Prospective Cohort Study of Central Saudi Arabia.

(1) Background: Saudi Arabia (SA) is a country with a low incidence of gastric cancer (GC). In this study, we sought to assess the epidemiology of GC, its clinicopathological profiles, and its association with risk factors as well as to identify premalignant gastric lesions (PGL) and examine neoplastic progression. (2) Methods: This five-year prospective study screened for GC and PGL in asymptomatic Saudi patients, aged 45-75 years (n = 35,640) and living in Al Kharj, Riyadh province in central SA. Those who were positive in a high-sensitivity guaiac fecal occult blood test (HSgFOBT+) and had negative results in colonoscopy offered to undergo upper GI endoscopy (n = 1242). Factors associated with GC were examined. (3) Results: The five-year participation rate was 87% (1080/1242). The incidence rate of GC was 26.9 new cases per 100,000 population per year (9.6 new cases per year/total population at risk-35,640), and it was 8.9 cases per 1000 persons per year among the 1080 subjects with HSgFOBT+ and negative colonoscopy results. The five-year mortality rate was 67% among patients with GC (n = 48), 3.0% among participants in the gastric screening program (n = 1080) and 0.09% among the original population participating in the colorectal screening program (n = 35,640). Intestinal-type adenocarcinoma was the most frequent type (77%), with the tumor most commonly located in the antrum (41%). Overall, 334 participants had PGL, and seven of them (2.1%) showed neoplastic progression to GC during the follow-up. Factors associated with GC were age, Helicobacter pylori (HP) infection, obesity (body mass index BMI > 30), smoking, a diet of salty preserved foods, low income and a family history of GC. (4) Conclusions: The incidence of GC is low in central SA, but screening for PGL and GC among patients with HSgFOBT+ and negative colonoscopy may prevent or result in the early treatment of GC. HP eradication, normal body weight, not smoking and adhering to a healthy diet can reduce the risk of GC. The resulting data provide important input for the improvement of national guidelines.

A female with recurrent gastrointestinal bleeding: an obscure diminutive lesion requiring a massive blood transfusion.

Obscure gastrointestinal bleeding (OGIB) is bleeding of unknown origin after a negative initial or primary colonoscopy and upper endoscopy result. Small bowel bleeding accounts for 5% of GI bleeding but it is the most prominent cause of OGIB. We present a case with an obscure diminutive polypoid vascular anomaly of small intestine. In this case, intraoperative enteroscopy seems to be the last trump card for OGIB, especially for large amount loss of blood. It not only helped to find the obscure cause for bleeding, but also preserved the small intestine.

Endoscopists’ recommendations after a false positive multitarget stool DNA test: results from a multicenter study

Endoscopists’ recommendations after a false positive multitarget stool DNA test: results from a multicenter study

Efficacy of Early Video Capsule Endoscopy for Acute Overt Lower Gastrointestinal Bleeding with Colonic Diverticulosis: A Prospective Observational Study

Background/Aims: Although most patients with presumptive colonic diverticular bleeding (CDB) do not undergo a small bowel investigation in clinical practice, no prospective study supports this management. We evaluated the utility of early small bowel capsule endoscopy (CE) after negative colonoscopy results. Methods: This prospective study evaluated the diagnostic yield of early small bowel CE (≤3 days from visit) for consecutive patients with acute-onset hematochezia, when colonoscopy found colonic diverticulosis but did not identify the definite bleeding source (n = 51; presumptive CDB). As a matched control for comparing clinical outcomes, presumptive CDB patients without CE (n = 51) were retrospectively extracted. Results: On CE for the prospective cohort, the rates of total positive findings, P2 findings (high bleeding potential according to the P classification), and blood pooling in the colon were 57%, 12% (ulceration, 8%; angioectasia, 4%), and 24%, respectively. The rates of rebleeding within 30 and 365 days were 16% and 29% in the prospective cohort with CE, respectively, and were not significantly different from those in the retrospective cohort without CE (10% and 25%, respectively). In addition, thromboembolism and mortality within 30 and 365 days were not significantly different between those with and without CE. Conclusion: Early CE detected a suspected small bowel bleeding source in 12% of acute-onset presumptive CDB patients but did not significantly improve major clinical outcomes. Therefore, routine CE is unnecessary for presumptive CDB patients after colonoscopy (UMIN000026676).

Study of diagnostic value of congenital hypertrophy of retinal pigment epithelium in Chinese familial adenomatous polyposis patients.

Congenital hypertrophy of retinal pigment epithelium (CHRPE) is an important characteristic of familial adenomatous polyposis (FAP) patients. However, more evidence about its sensitivity, specificity, and diagnostic value for FAP is needed to determine whether CHRPE is a reliable marker. Clinical features of FAP patients were investigated using in-person evaluations. Family members of FAP patients were evaluated with an indirect ophthalmoscope to determine whether they had CHRPE. We defined three diagnostic criteria for CHRPE (criteria A, B and C) based on their shape, quantity and size. Those with negative colonoscopy results and gene mutation results were classified as healthy controls. Of a total of 23 FAP families, 21 families were CHRPE-positive (91.3%). Among those 21 families, 47 individuals had CHRPE, including 33 FAP patients, 9 APC gene mutation carriers, and 5 individuals younger than 18 years who were later confirmed to have FAP. Fifty individuals had no CHRPE (5 FAP patients and 45 individuals without APC gene mutations and colorectal adenoma). The average number of CHRPE lesions per person was 5.81, and CHRPE was located mostly in the posterior pole in the eye fundus; 76.7% of individuals had CHRPE in both eyes. The sensitivity of the three CHRPE criteria ranged from 78.8 to 90.4%, with the highest sensitivity found for criterion A (90.4%), which had a specificity of 100% for healthy controls and sporadic colorectal cancer patients. CHRPE has vital diagnostic and screening value because of its high sensitivity for discovering FAP and APC gene mutation carriers.

One negative colonoscopy associated with a significant reduction in colorectal cancer risk.

An observational study published in the Annals of Internal Medicine1 found significant reductions in both colorectal cancer (CRC) incidence and mortality associated with a single negative high-quality screening colonoscopy. The findings indicate an 84% reduction in incidence and a 90% reduction in mortality for up to 17.4 years. As a result, the study authors suggest that the currently recommended 10-year screening interval is safe and could safely be extended. Under current guidelines, average-risk individuals aged 50 years or older who have previously had negative colonoscopy results are recommended to undergo screening every 10 years. That recommendation is based on estimates for how long it takes for adenomas and carcinomas to develop. However, longterm data are lacking on optimum follow-up intervals. The study was conducted by researchers from the Maria Sklodowska-Curie National Research Institute for Oncology in Warsaw, Poland. They analyzed a screening registry of 165,887 people and assessed both long-term CRC risk and CRC death after a single negative low- or high-quality screening colonoscopy. Their findings show that although a single negative screening colonoscopy was associated with significantly reduced CRC incidence and mortality during the 17-year screening period, only a high-quality colonoscopy led to a profound and stable reduction. Among women, high quality was key for long-term efficacy in screening colonoscopy in the proximal colon. These findings are particularly important because previous studies have questioned the efficacy of colonoscopy in the proximal colon as well as screening sigmoidoscopy in women.

Abstract 269: Small non-coding RNA profiling in stool and plasma samples to explore potential biomarkers for colorectal cancer diagnosis

Abstract Colorectal cancer (CRC) is one of the most frequent cancers worldwide. The available screening tests have reduced the incidence and mortality for this cancer; however, the research of new potential molecular biomarkers to use concomitantly could improve advanced adenomas/CRC early detection. Small non-coding RNAs (sncRNAs) are stable, easy detectable molecules that have been found dysregulated in several diseases including CRC. Besides the most studied microRNAs (miRNAs), sncRNAs include also P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), small nuclear RNAs (snRNAs), transfer RNAs (tRNAs) and other miscellaneous RNAs, all with key roles in post-transcriptional regulation. The aim of the present study was to identify by next-generation sequencing (NGS) signatures of sncRNAs other than miRNAs, in fecal and plasma extracellular vesicles (EVs) samples potentially able to detect patients with adenomas or CRC. We initially performed a small RNA-sequencing in samples from 221 subjects collected at colonoscopy. The group included: i) 80 healthy subjects with negative colonoscopy results; (ii) 43 adenoma patients; (iii) 41 individuals with inflammatory bowel disease and (iv) 57 newly diagnosed CRC patients. A computational pipeline for the identification of sncRNAs after miRNA mapping reads was previously implemented by our group. In stool samples, comparing the categories of interest mentioned above, we identified 395 differentially expressed sncRNAs (DEsncRNAs), mainly piRNAs (46.3%) and tRNAs (43.6%) (likelihood ratio test adjusting for sex and age, FDR adjusted p ≤ 0.05). Similarly, a group of 32 DEsncRNAs was detected in plasma EVs with piRNAs (41%) and tRNAs (44%) resulting among the most altered. Small RNA-sequencing has also been performed in a subset of 24 paired colorectal tumor and adjacent non-malignant tissues from the CRC patients for whom stool and plasma samples were analysed. Fifty-seven DEsncRNAs were found in tumor vs. non-malignant adjacent tissue with a similar distribution of dysregulated sncRNA biotypes. Some DEsncRNAs were shared between stool and tissues (n=35), plasma EVs and tissues (n=11) and, interestingly, among the profiles of the three different biospecimens (n=10). To validate our findings, we also sequenced stool samples from an independent cohort from the Czech Republic (at present 22 healthy subjects, 19 with inflammations, 21 with adenomas and 34 CRC patients). A total of 100 DEsncRNAs were detected in this validation cohort, among which 43 overlapped with those detected in the Italian cohort. In conclusions, we show that besides the most widely performed miRNA profiling, also the detection of sncRNAs in surrogate tissues by NGS may help to identify reliable and comparable results with those of primary tissues. To further investigate these molecules may provide new accurate markers for CRC diagnostic purposes. Citation Format: Antonio Francavilla, Sonia Tarallo, Giulio Ferrero, Francesca Cordero, Gaetano Gallo, Veronika Vymetalkova, Ludmila Vodickova, Pavel Vodicka, Barbara Pardini, Alessio Naccarati. Small non-coding RNA profiling in stool and plasma samples to explore potential biomarkers for colorectal cancer diagnosis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 269.

Low Risk of Advanced Neoplasms for up to 20 Years After Negative Colonoscopy Result: Potential for Personalized Follow-up Screening Intervals

Low Risk of Advanced Neoplasms for up to 20 Years After Negative Colonoscopy Result: Potential for Personalized Follow-up Screening Intervals

Positive Fecal Immunochemical Test Results Are Associated with Increased Risks of Esophageal, Stomach, and Small Intestine Cancers.

Background: The current guideline does not recommend upper gastrointestinal evaluation for patients with a positive fecal immunochemical test (FIT) and negative colonoscopy results. However, this indication was based on low-quality evidence as data on this issue are very limited. We assessed the risk of proximal cancers (oral or throat, esophageal, stomach, and small intestine cancers) after negative or positive FIT results in the Korean National Cancer Screening Program (NCSP). Methods: Using the NCSP databases, we collected data on participants who underwent FIT between 2009 and 2011. Participants were classified based on FIT results and colorectal cancer (CRC) diagnosed within 1 year after FIT as FIT− (n = 5,551,755), FIT+/CRC− (n = 368,553), and FIT+/CRC+ (n = 12,236). Results: The incidence rates of overall proximal cancers in FIT−, FIT+/CRC−, and FIT+/CRC+ patients within 1, 2, and 3 years after FIT were 0.38%, 0.68%, and 2.26%; 0.57%, 0.93%, and 2.74%; and 0.79%, 1.21%, and 3.15%, respectively. After adjusting confounding variables, the risks of esophageal, stomach, and small intestine cancers as well as overall proximal cancers within 1, 2, and 3 years after FIT were higher in FIT+/CRC− patients than those in FIT− patients. However, the risk of oral or throat cancer did not differ between FIT− and FIT+/CRC− patients. The risks for oral or throat cancer and small intestine cancer were higher in FIT+/CRC+ patients than those in FIT+/CRC− patients. Conclusions: In this population-based study, FIT+/CRC− patients were at higher risk for esophageal, stomach, and small intestine cancers than were FIT− patients, suggesting that positive FIT results were associated with these cancers.

Early detection of colorectal cancer based on presence of methylated syndecan-2 (SDC2) in stool DNA

BackgroundColorectal cancer (CRC) screening can effectively reduce disease-related mortality by detecting CRC at earlier stages. We have previously demonstrated that the presence of SDC2 methylation in stool DNA is significantly associated with the occurrence of CRC regardless of clinical stage. The aim of this study was to evaluate the clinical performance of stool DNA-based SDC2 methylation test for CRC.MethodsAberrant SDC2 methylation in stool-derived DNA was measured by linear target enrichment (LTE)-quantitative methylation-specific real-time PCR (qMSP). Duplicate reactions of meSDC2 LTE-qMSP test were performed for stool samples obtained from CRC patients representing all stages (0–IV) and asymptomatic individuals who were subsequently underwent colonoscopy examination. To determine the diagnostic value of test in CRC and control groups, sensitivity and specificity were evaluated by receiver operating characteristic curve analysis.ResultsOf 585 subjects who could be evaluated, 245 had CRC, 44 had various sizes of adenomatous polyps, and 245 had negative colonoscopy results. Stool DNA-based meSDC2 LTE-qMSP showed an overall sensitivity of 90.2% with AUC of 0.902 in detecting CRC (0–IV) not associated with tumor stage, location, sex, or age (P > 0.05), with a specificity of 90.2%. Sensitivity for detecting early stages (0-II) was 89.1% (114/128). This test also detected 66.7% (2/3) and 24.4% (10/41) of advanced and non-advanced adenomas, respectively.ConclusionsResults of this study validated the capability of stool DNA based-SDC2 methylation test by LTE-qMSP for early detection of CRC patient with high specificity.Trial registrationClinicalTrials.gov, NCT03146520, Registered 10 May 2017, Retrospectively registered; however, control arm was prospectively registered.

Next endoscopic approach for acute lower gastrointestinal bleeding without an identified source on colonoscopy: upper or capsule endoscopy?

Background and study aims We evaluated the utility of esophagogastroduodenoscopy (EGD) or capsule endoscopy (CE) as the next diagnostic approach after negative colonoscopy (CS) results in acute-onset hematochezia. Patients and methods We retrospectively analyzed 401 patients emergently hospitalized for acute hematochezia who underwent CS within 48 hours of arriving at two large emergency hospitals and in whom a definitive bleeding source was not identified. The positive endoscopic findings, requirement for additional therapeutic procedures, and 30-day rebleeding rates were compared among three strategies: EGD following CS (CS-EGD), CE following CS (CS-CE), and CS alone. Predictors of positive endoscopic findings in the CS-EGD strategy were determined. Results The rates of positive endoscopic findings and requirement for additional therapeutic procedures were 22 % and 16 %, respectively, in CS-EGD and 50 % and 28 % in CS-CE. The 30-day rebleeding rate did not significantly decrease in CS-EGD (8 %) or CS-CE (11 %) compared with CS alone (12 %). The rate of additional endoscopic therapies was lower in patients with a colonic diverticulum than in those without (CS-EGD: 3 % vs. 33 %, P = 0.007; CS-CE: 11 % vs. 44 %, P = 0.147). A history of syncope, low blood pressure, blood urea nitrogen/creatinine ratio of ≥ 30, and low albumin level significantly predicted EGD findings after negative CS results ( P < 0.05). Conclusions When the definitive bleeding source is not identified by colonoscopy in patients with acute hematochezia, adjunctive endoscopy helps to identify the etiology and enables subsequent therapy, especially for patients without a colonic diverticulum. Upper gastrointestinal endoscopy is indicated for severe bleeding; other patients may be candidates for capsule endoscopy.

Long-term Risk of Colorectal Cancer and Related Deaths After a Colonoscopy With Normal Findings

Guidelines recommend a 10-year rescreening interval after a colonoscopy with normal findings (negative colonoscopy results), but evidence supporting this recommendation is limited. To examine the long-term risks of colorectal cancer and colorectal cancer deaths after a negative colonoscopy result, in comparison with individuals unscreened, in a large, community-based setting. A retrospective cohort study was conducted in an integrated health care delivery organization serving more than 4 million members across Northern California. A total of 1 251 318 average-risk screening-eligible patients (age 50-75 years) between January 1, 1998, and December 31, 2015, were included. The study was concluded on December 31, 2016. Screening was examined as a time-varying exposure; all participants contributed person-time unscreened until they were either screened or censored. If the screening received was a negative colonoscopy result, the participants contributed person-time in the negative colonoscopy results group until they were censored. Using Cox proportional hazards regression models, the hazard ratios (HRs) for colorectal cancer and related deaths were calculated according to time since negative colonoscopy result (or since cohort entry for those unscreened). Hazard ratios were adjusted for age, sex, race/ethnicity, Charlson comorbidity score, and body mass index. Of the 1 251 318 patients, 613 692 were men (49.0%); mean age was 55.6 (7.0) years. Compared with the unscreened participants, those with a negative colonoscopy result had a reduced risk of colorectal cancer and related deaths throughout the more than 12-year follow-up period, and although reductions in risk were attenuated with increasing years of follow-up, there was a 46% lower risk of colorectal cancer (hazard ratio, 0.54; 95% CI, 0.31-0.94) and 88% lower risk of related deaths (hazard ratio, 0.12; 95% CI, 0.02-0.82) at the current guideline-recommended 10-year rescreening interval. A negative colonoscopy result in average-risk patients was associated with a lower risk of colorectal cancer and related deaths for more than 12 years after examination, compared with unscreened patients. Our study findings may be able to inform guidelines for rescreening after a negative colonoscopy result and future studies to evaluate the costs and benefits of earlier vs later rescreening intervals.

Divergent Long-Term Detection Rates of Proximal and Distal Advanced Neoplasia in Fecal Immunochemical Test Screening Programs: A Retrospective Cohort Study.

Short-term studies have reported that the fecal immunochemical test (FIT) is less accurate in detecting proximal than distal colorectal neoplasia. To assess the long-term detection rates for advanced adenoma and colorectal cancer (CRC), according to anatomical location. Retrospective study. Population-based, organized screening program in the Veneto region of Italy. Persons aged 50 to 69 years who completed 6 rounds of FIT screening. At each screening round, the detection rates for advanced adenoma and cancer, as well as the proportional interval cancer rate (PICR), were calculated by anatomical location (proximal colon, distal colon, or rectum). Between 2002 and 2014, a total of 123347 participants had 441647 FITs. The numbers of advanced adenomas and cancer cases detected, respectively, were 1704 and 200 in the proximal colon, 3703 and 324 in the distal colon, and 1220 and 209 in the rectum. Although the detection rate for proximal colon cancer declined only from the first to the second screening round (0.63 to 0.36 per 1000 screenees), the rate for both distal colon and rectal cancer steadily decreased across 6 rounds (distal colon, 1.65 in the first round to 0.17 in the sixth; rectum, 0.82 in the first round to 0.17 in the sixth). Similar trends were found for advanced adenoma (proximal colon, 5.32 in the first round to 4.22 in the sixth; distal colon, 15.2 in the first round to 5.02 in the sixth). Overall, 150 cases of interval cancer were diagnosed. The PICR was higher in the proximal colon (25.2% [95% CI, 19.9% to 31.5%]) than the distal colon (6.0% [CI, 3.9% to 8.9%]) or rectum (9.9% [CI, 6.9% to 13.7%]). Participants with irregular attendance were censored. Those who had a false-positive result on a previous FIT but negative colonoscopy results were included in subsequent rounds. This FIT-based, multiple-round, long-term screening program had a negligible reduction in detection rates for neoplastic lesions in the proximal versus the distal colon after the first round. This was related to a higher PICR in the proximal colon and suboptimal efficacy in preventing the age-related proximal shifting of CRC. None.

Environmental Risk Factors Associated with Sporadic Colorectal Cancer in Isfahan, Iran

Background: Records from the cancer registry system of Iran indicate that colorectal cancer is the third most common cancer in Iranian men and fourth most common among Iranian women. In this study we have investigated the environmental factors associated with colorectal cancer in Isfahan, Iran.Methods: In this case-control study, we randomly selected 187 patients with colorectal cancer who had positive results by colonoscopy and pathology (case group) and 250 persons who had negative colonoscopy results (control group) from the Colonoscopy Unit of Al Zahra Hospital and Colorectal Cancer Center of Seyed Al Shohada Hospital from 2014 to mid-2015. This study aimed to find the risk factors for sporadic colorectal cancer; therefore, we excluded patients with positive family history. Participants completed a self-administered questionnaire that asked about sex, age, body mass index, smoking status, job-related physical activity, and nonsteroidal antiinflammatory drug consumption.Results: This study enrolled 187 colorectal cancer patients (98 males and 89 females) and 250 individuals without colorectal cancer (107 males and 143 females). Multiple analysis demonstrated a significant association of age (odds ratio: 1.04; 95% confidence interval: 1.02, 1.06) and body mass index (odds ratio: 1.09; 95% confidence interval: 1.03, 1.15) with colorectal cancer risk. Men had an almost two-fold risk compared with women (odds ratio: 1.85; 95% confidence interval: 1.14, 2.99). Subjects who did not use nonsteroidal anti-inflammatory drugs had an almost three-fold risk compared with nonsteroidal anti-inflammatory drug consumers (odds ratio: 0.34; 95% confidence interval: 0.19, 0.62). Analysis for job-related physical activity, also indicated an association between the no/low active group with colorectal cancer (odds ratio no activity: 36.09; 95% confidence interval: 10.94, 119 and odds ratio low activity: 2.96; 95% confidence interval: 1.43, 6.13).Conclusion: Knowledge of the risk factors involved in colorectal cancer incidence makes it possible to identify people at risk and begin risk reduction strategies as well as screening programs.

The factors associated with negative colonoscopy in screening subjects with positive immunochemical stool occult blood test outcomes

BackgroundThe immunochemical fecal occult blood test (iFOBT) is an alternative method to colonoscopy that can be used for colorectal cancer (CRC) screening. If the iFOBT result is positive, a colonoscopy is recommended. In this retrospective study, we identify factors associated with negative colonoscopy and positive iFOBT results obtained during CRC screening. MethodsWe collected data for subjects who received a colonoscopy at Taipei Veterans General Hospital after receiving a positive iFOBT result during CRC screening from January 2015 to December 2015. Subjects' baseline data, medications, and co-morbidities as well as colonoscopy and histological findings were recorded. A negative colonoscopy result was defined as no detection of any colorectal neoplasia including non-advanced adenoma, advanced adenoma, and adenocarciona. Multivariate logistic regression analysis was conducted to identify the associated factors in screening subjects with positive iFOBT but negative colonoscopy results. Results559 (46.3%) out of 1207 eligible study subjects received a colonoscopy with a negative result. Multivariate logistic regression analysis revealed that the use of antiplatelets [odds ratio (OR) = 0.654; 95% confidence interval (CI), 0.434–0.986], occurrence of hemorrhoid (OR = 0.595; 95% CI, 0.460–0.768), and the existence of colitis/ulcer (OR = 0.358; 95% CI, 0.162–0.789) were independent factors associated with negative colonoscopy but positive iFOBT results during CRC screening. The colon clean level, underlying diseases of gastrointestinal bleeding tendency (e.g., chronic kidney disease, cirrhosis), and the use of anticoagulant or nonsteroidal anti-inflammatory agents were not associated with negative colonoscopy and positive iFOBT results. ConclusionThe use of antiplatelet agents and the presence of hemorrhoids and colitis/ulcers were factors associated with negative colonoscopy and positive iFOBT results.

Cost-effectiveness of colorectal cancer screening protocols in urban Chinese populations.

Colorectal cancer (CRC) takes a second and fourth position in the incidence and mortality lists respectively among all malignant tumors in urban populations in China. This study was designed to evaluate the cost-effectiveness of two different CRC screening protocols: faecal occult blood test (FOBT) alone, and FOBT plus a high-risk factor questionnaire (HRFQ) as the respective initial screens, followed by colonoscopy. We developed a Markov model to simulate the progression of a cohort of 100,000 average risk asymptomatic individuals moving through a defined series of states between the ages of 40 to 74 years. The parameters used for the modeling came from the CESP (Comparison and Evaluation of Screening Programs for Colorectal Cancer in Urban Communities in China) study and published literature. Eight CRC screening scenarios were tested in the Markov model. The cost-effectiveness of CRC screening under each scenario was measured by an incremental cost-effectiveness ratio (ICER) compared with a scenario without CRC screening. The study revealed that a combined use of FOBT and HRFQ is preferable in CRC screening programs as an initial screening instrument. Annual FOBT+HRFQ screening is recommended for those who have a negative initial result and those who have a positive result but have failed to continue to colonoscopic examination. Repeated colonoscopy (for those with a positive result in initial screening but a negative colonoscopy result) should be performed at a ten-year interval instead of one-year. Such a protocol would cost 7732 Yuan per life year saved, which is the most cost-effective option. In conclusion, the current Chinese Trial Version for CRC Screening Strategy should be revised in line with the most cost-effective protocol identified in this study.

Rescreening of persons with a negative colonoscopy result: results from a microsimulation model.

Persons with a negative result on screening colonoscopy are recommended to repeat the procedure in 10 years. To assess the effectiveness and costs of colonoscopy versus other rescreening strategies after an initial negative colonoscopy result. Microsimulation model. Literature and data from the Surveillance, Epidemiology, and End Results program. Persons aged 50 years who had no adenomas or cancer detected on screening colonoscopy. Lifetime. Societal. No further screening or rescreening starting at age 60 years with colonoscopy every 10 years, annual highly sensitive guaiac fecal occult blood testing (HSFOBT), annual fecal immunochemical testing (FIT), or computed tomographic colonography (CTC) every 5 years. Lifetime cases of colorectal cancer, life expectancy, and lifetime costs per 1000 persons, assuming either perfect or imperfect adherence. Rescreening with any method substantially reduced the risk for colorectal cancer compared with no further screening (range, 7.7 to 12.6 lifetime cases per 1000 persons [perfect adherence] and 17.7 to 20.9 lifetime cases per 1000 persons [imperfect adherence] vs. 31.3 lifetime cases per 1000 persons with no further screening). In both adherence scenarios, the differences in life-years across rescreening strategies were small (range, 30 893 to 30 902 life-years per 1000 persons [perfect adherence] vs. 30 865 to 30 869 life-years per 1000 persons [imperfect adherence]). Rescreening with HSFOBT, FIT, or CTC had fewer complications and was less costly than continuing colonoscopy. Results were sensitive to test-specific adherence rates. Data on adherence to rescreening were limited. Compared with the currently recommended strategy of continuing colonoscopy every 10 years after an initial negative examination, rescreening at age 60 years with annual HSFOBT, annual FIT, or CTC every 5 years provides approximately the same benefit in life-years with fewer complications at a lower cost. Therefore, it is reasonable to use other methods to rescreen persons with negative colonoscopy results. National Cancer Institute.