Colorectal Cancer Screening among Government Servants in Brunei Darussalam

Background: This study concerns uptake and results of colorectal cancer (CRC) screening of governmentservant as part of the Health Screening Program that was conducted in Brunei Darussalam in 2009. Materialsand Methods: Government servants above the age of 40 or with family history of CRC were screened with a singlefecal occult blood test (FIT, immunohistochemistry). Among 11,576 eligible subjects, 7,360 (66.9%) returned theirspecimen. Subjects with positive family history of CRC (n=329) or polyps (n=135) were advised to attend clinicsto arrange screening. All the subjects with positive FIT (n=142, 1.9%) were referred to the endoscopy unit forcounselling for screening colonoscopy. Results: Overall only 17.7% of eligible subjects attended for screening;54.9% (n=79/142) of positive FIT, 8.8% (n=29/329) of positive family history of CRC and none with history ofpolyps (n=0/135). Of these, only 54 patients (50.5%) agreed for colonoscopy, 52 (48.6%) declined as they wereasymptomatic, and one was not offered (0.9%) due to his very young age. On screening colonoscopy, 12.9% (n=7)had advanced lesions including a sigmoid carcinoma in situ and six advanced polyps. The other findings includednon advanced polyps (n=21), diverticular (n=11) and hemorrhoids (n=26). One patient who missed his screeningcolonoscopy appointment re-presented two years later and was diagnosed with advanced right sided CRC. Allthe advanced lesions were detected in patients with positive FIT, giving a yield of 20.5% for advanced lesionsincluding cancers in the 5.1% FIT positive subjects. Conclusions: Our study showed screening for CRC evenwith a single FIT was effective. However, the uptake rate was poor with just over half of the patients agreeing toscreening colonoscopy. Measures to increase public awareness are important. Since one limitation of our studywas the relatively small sample size, larger studies should be conduced in future.     

Fecal immunochemical test accuracy in familial risk colorectal cancer screening

There is little information on fecal immunochemical test (FIT) in familial risk colorectal cancer (CRC) screening. Our study assesses FIT accuracy, number needed to scope (NNS) and cost to detect a CRC and an advanced neoplasia (AN) in this setting. We performed a multicentric, prospective, double‐blind study of diagnostic tests on individuals with first‐degree relatives (FDRs) with CRC submitted to screening colonoscopy. Two stool samples were collected and fecal hemoglobin in the first sample (FIT1) and the highest in both samples (FITmax) were determined. Areas under the curve (AUC) for CRC and AN as well as the best FIT1 and FITmax cutoff value for CRC were determined. At this threshold, NNS and the cost per lesion detected were calculated. A total of 595 individuals were included (one FDR > 60 years, 413; two FDR or one ≤ 60 years, 182). AN and CRC were found in 64 (10.8%) and six (1%) patients, respectively. For CRC diagnosis, FIT1 AUC was 0.96 [95% confidence interval (CI): 0.95–0.98] and FITmax AUC was 0.95 (95% CI: 0.93–0.97). For AN diagnosis, FIT1 and FITmax AUC were 0.74 (95% CI: 0.66–0.82). The best cutoff point for CRC was 115. At this threshold, the NNS to detect a CRC was 5.67 and 7.67, and the cost per CRC was 1,064€ and 1591.33€ on FIT1 and FITmax strategies, respectively. FIT shows high accuracy to detect CRC in familial CRC screening. Performing two tests does not improve diagnostic accuracy, but increases cost and NNS to detect a lesion.     

Factors associated with interval colorectal cancer after negative FIT: Results of two screening rounds in the Dutch FIT-based CRC screening program

The interval colorectal cancer (CRC) rate after negative fecal immunochemical testing (FIT) is an important quality indicator of CRC screening programs. We analyzed the outcomes of two rounds of the FIT-based CRC screening program in the Netherlands, using data from individuals who participated in FIT-screening from 2014 to 2017. Data of individuals with one prior negative FIT (first round) or two prior negative FITs (first and second round) were included. Outcomes included the incidence of interval CRC in FIT-negative participants (<47 μg Hb/g feces [μg/g]), FIT-sensitivity, and the probability of detecting an interval CRC by fecal hemoglobin concentration (f-Hb). FIT-sensitivity was estimated using the detection method and the proportional incidence method (based on expected CRC incidence). Logistic regression analysis was performed to estimate whether f-Hb affects probability of detecting interval CRC, adjusted for sex- and age-differences. Incidence of interval CRC was 10.4 per 10 000 participants after the first and 9.6 after the second screening round. FIT-sensitivity based on the detection method was 84.4% (95%CI 83.8-85.0) in the first and 73.5% (95% CI 71.8-75.2) in the second screening round. The proportional incidence method resulted in a FIT-sensitivity of 76.4% (95%CI 73.3-79.6) in the first and 79.1% (95%CI 73.7-85.3) in the second screening round. After one negative FIT, participants with f-Hb just below the cut-off (>40-46.9 μg/g) had a higher probability of detecting an interval CRC (OR 16.9; 95%CI: 14.0-20.4) than had participants with unmeasurable f-Hb (0-2.6 μg/g). After two screening rounds, the odds ratio for interval CRC was 12.0 (95%CI: 7.8-17.6) for participants with f-Hb just below the cut-off compared with participants with unmeasurable f-Hb. After both screening rounds, the Dutch CRC screening program had a low incidence of interval CRC and an associated high FIT-sensitivity. Our findings suggest there is a potential for further optimizing CRC screening programs with the use of risk-stratified CRC screening based on prior f-Hb.     

Impact of time between faecal immunochemical tests in colorectal cancer screening on screening results: A natural experiment

Repeated rounds of faecal immunochemical testing (FIT) for occult blood is a common method for screening for colorectal cancer (CRC). However, the time interval between FIT rounds is not thoroughly investigated. In a CRC screening trial in South-Eastern Norway, individuals were invited for biennial FIT between 2012 and 2019. The positivity threshold was >15 mcg haemoglobin/g faeces (mcg/g). Due to organizational challenges, the interval between screening rounds randomly varied between 1.5 and 3.5 years, forming a natural experiment. We investigated the detection rate of CRC and advanced neoplasia (AN: CRC or advanced adenoma) at the subsequent round (FIT₂), according to the faecal haemoglobin concentration (f-Hb) at the initial screening round (FIT₁), and time between the two screening rounds. 18 522 individuals with negative FIT₁ who attended FIT₂ were included in this study. 245 AN were detected at FIT₂, of which 34 were CRC. The CRC detection rate at FIT₂ for participants with FIT₁ = 0 mcg/g was 0.09% while it was 0.28% for participant with 0 > FIT₁ ≤ 15 mcg/g; odds ratio (OR) 3.22, 95% CI 1.49-6.95. For each 3 months' increment between FITs, the OR for detecting CRC was 1.33 (95% CI 0.98-1.79), while the OR was 1.13 (1.02-1.26) for AN. Individuals with FIT₁-value of 0 mcg/g, had a lower AN detection rate compared with participants with 0 > FIT₁ ≤ 15 mcg/g, irrespective of time between tests. Although CRC and AN detection rates increase with increasing time interval between FITs, individuals with undetectable f-Hb at first screen have substantially lower risk of CRC at the next screening round compared with individuals with detectable f-Hb.     

Improving Participation in Colorectal Cancer Screening: a Randomised Controlled Trial of Sequential Offers of Faecal then Blood Based Non-Invasive Tests

Background: Poor participation rates are often observed in colorectal cancer (CRC) screening programs utilising faecal occult blood tests. This may be from dislike of faecal sampling, or having benign bleeding conditions that can interfere with test results. These barriers may be circumvented by offering a blood-based DNA test for screening. The aim was to determine if program participation could be increased by offering a blood test following faecal immunochemical test (FIT) non-participation. Materials and Methods: People were invited into a CRC screening study through their General Practice and randomised into control or intervention (n=600/group). Both groups were mailed a FIT (matching conventional screening programs). Participation was defined as FIT completion within 12wk. Intervention group non-participants were offered a screening blood test (methylated BCAT1/IKZF1). Overall participation was compared between the groups. Results: After 12wk, FIT participation was 82% and 81% in the control and intervention groups. In the intervention 96 FIT nonparticipants were offered the blood test - 22 completed this test and 19 completed the FIT instead. Total screening in the intervention group was greater than the control (88% vs 82%, p<0.01). Of 12 invitees who indicated that FIT was inappropriate for them (mainly due to bleeding conditions), 10 completed the blood test (83%). Conclusions: Offering a blood test to FIT non-participants increased overall screening participation compared to a conventional FIT program. Blood test participation was particularly high in invitees who considered FIT to be inappropriate for them. A blood test may be a useful adjunct test within a FIT program.     

Regional, Racial, and Gender Differences in Colorectal Cancer Screening in Middle-aged African-Americans and Whites

African-Americans have higher incidence and mortality from colorectal cancer than non-African-Americans. Early detection with colorectal cancer (CRC) screening reduces untimely death because the test can detect abnormalities and precancerous polyps in the colon and rectum. However, African-Americans aged 50 and older continue to have low CRC screening adherence. A retrospective analysis was conducted on data from the 2010 National Health Interview Survey to examine trends in self-reported CRC screening by geographic region, race, and gender. African-Americans, particularly men, were less likely to have been screened for colon cancer compared to all races and genders in this study. Individuals in the south were more likely to receive CRC screening than other regions. Colon cancer education and interventions are needed among low-adherent groups to promote the benefits of early detection with CRC screening.     

Strong subsite‐specific variation in detecting advanced adenomas by fecal immunochemical testing for hemoglobin

Fecal immunochemical tests (FITs) for hemoglobin are increasingly recommended and used in colorectal cancer (CRC) screening. We aimed to provide a detailed assessment of the sensitivity of FIT according to type and subsite of neoplasms in a true screening setting. A quantitative FIT (FOB Gold, Sentinel Diagnostics, Milano, Italy) was applied prior to colonoscopy by 3,466 participants of the German screening colonoscopy program. Subsite specific sensitivity for various types of colorectal neoplasms was derived by comparing FIT results with findings at screening colonoscopy. The most advanced finding at colonoscopy was CRC, advanced adenoma, and nonadvanced adenoma in 29, 354 and 686 cases, respectively. Per‐adenoma sensitivity for large advanced adenomas (>1 cm) strongly varied by location (p < 0.001): cecum: 0/14 (0%), ascending colon and right flexure: 11/43 (26%), transverse colon and left flexure: 2/14 (14%), descending colon: 7/12 (58%), sigmoid colon: 47/92 (51%), rectum: 14/39 (36%). By contrast, the FIT detected all of 5 proximal CRC and 23 out of 24 (96%) distal CRCs, whereas per‐adenoma sensitivity of both proximal (17/259, 7%) and distal nonadvanced adenomas (20/237, 8%) essentially equaled the false positivity rate among those without neoplasms (152/2,397, 6%). In conclusion, we found a very large gradient of subsite specific FIT sensitivity for detecting large advanced adenomas ranging from 0% for advanced adenomas located in the cecum to >50% for those located in the descending or sigmoid colon. By contrast, FIT sensitivity was uniformly excellent for CRC and uniformly poor for nonadvanced adenomas, regardless of their location.     

Lack of Association between Red Meat Consumption and a Positive Fecal Immunochemical Colorectal Cancer Screening Test in Khon Kaen,Thailand: a Population- Based Randomized Controlled Trial

Background: There is convincing evidence from epidemiological studies that meat consumption increases colorectal cancer (CRC) risk. However, assessment of any association with a positive fecal immunochemical test (FIT) in CRC screening has been limited. If a link could be shown this might be helpful for establishing a risk group for colonoscopy. Objective: This study aimed to assess any association between meat consumption and other lifestyle factors and a positive FIT result in a Thai population. Methods: A cross-sectional analytical study was conducted with 1,167 participants in a population-based randomized controlled trial. CRC was screened from May 2016 - February 2017. Subjects aged 45-74 years who met the eligibility criteria were randomly allocated to the study arm. A positive FIT was determined with cut-off 100 ng/mL. Multiple logistic regression was used to analyze any relationship between lifestyle factors and a positive FIT. Result: The total number of subjects was 1,060 (90.8% return rate of FIT). With FIT100, FIT150, and FIT200, positive tests were found in 92 (8.68%), 74 (6.98%), and 60 (5.66%), respectively. No significant associations were noted with any of the variables, except for being aged 60-74 years (ORadj = 1.62, 95% CI: 1.03-2.54) Borderline significance was observed for high consumption of vegetables (ORadj = 0.62, 95% CI: 0.36-1.07) and being male (ORadj = 1.39, 95% CI: 0.87-2.22). Conclusion: Despite the evidence from the literature, no association was here found between a positive FIT result and meat consumption or other well-established lifestyle parameters. Being aged 60-74 years was a risk factor which should be taken into account in CRC screening strategy in countries like Thailand with limited access to endoscopy.     

Prevalence of Colorectal Polyps in a Group of Subjects at Average-risk of Colorectal Cancer Undergoing Colonoscopic Screening in Tehran,Iran between 2008 and 2013

Background: Colorectal cancer (CRC) is one of the prime causes of mortality around the globe, with asignificantly rising incidence in the Middle East region in recent decades. Since detection of CRC in the earlystages is an important issue, and also since to date there are no comprehensive epidemiologic studies depictingthe Middle East region with special attention to the average risk group, further investigation is of significantnecessity in this regard. Aim: Our aim was to investigate the prevalence of preneoplastic and neoplastic lesionsof the colon in an average risk population. Materials and Methods: A total of 1,208 eligible asymptomatic,average- risk adults older than 40 years of age, referred to Firuzgar Hospotal in the years 2008-2012, wereenrolled. They underwent colonoscopy screening and all polypoid lesions were removed and examined by anexpert gastrointestinal pathologist. The lesions were classified by size, location, numbers and pathologic findings.Size of lesions was measured objectively by endoscopists. Results: The mean age of participants was 56.5 ± 9.59and 51.6% were male. The overall polyp detection rate was 199/1208 (16.5 %), 26 subjects having non-neoplasticpolyps, including hyperplastic lesions, and 173/1208 (14.3%) having neoplastic polyps, of which 26 (2.15%) wereadvanced neoplasms .The prevalence of colorectal neoplasia was more common among the 50-59 age group.Advanced adenoma was more frequent among the 60-69 age group. The majority of adenomas were detectedin the distal colon, but a quarter of advanced adenomas were found in the proximal colon; advance age andmale gender was associated with the presence of adenoma. Conclusions: It seems that CRC screening amongaverage-risk population might be recommended in countries such as Iran. However, sigmioidoscopy alone wouldmiss many colorectal adenomas. Furthermore, the 50-59 age group could be considered as an appropriate targetpopulation for this purpose in Iran.     

The second round of the Dutch colorectal cancer screening program: Impact of an increased fecal immunochemical test cut-off level on yield of screening

The Dutch colorectal cancer (CRC) screening program started in 2014, inviting the target population biennially to perform a fecal immunochemical test (FIT). We obtained prospectively collected data from the national screening information-system to present the results of the second round (2016) and evaluate the impact of increasing the FIT cut-off halfway through the first round from 15 to 47 μg Hb/g feces on outcomes in the second round. Second round screening was done with a 47 μg Hb/g feces FIT cut-off. Participants were classified based on first round participation status as either FIT (15,47) or FIT (47,47) participants, and previous nonparticipants. In total, 348,891 (75.9%) out of 459,740 invitees participated in the second round. Participation rates were 93.4% among previous participants and 21.0% among previous non-participants. FIT(47,47) participants had a significantly higher detection rate of AN (15.3 vs. 10.4 per 1,000 participants) compared to FIT(15,47) participants in the second round, while their cumulative detection rate of AN over two rounds was significantly lower (45.6 vs. 52.6 per 1,000 participants). Our results showed that participation in the Dutch CRC screening program was consistently high and that second round detection rates depended on the first round FIT cut-off. The cumulative detection over two rounds was higher among FIT(15,47) participants. These findings suggest that a substantial part of, but not all the missed findings in the first round due to the increased FIT cut-off were detected in the subsequent round.     

Optimizing Screening for Colorectal Cancer: An Algorithm Combining Fecal Immunochemical Test,Blood-Based Cancer-Associated Proteins and Demographics to Reduce Colonoscopy Burden

BackgroundFecal Immunochemical Test (FIT) is widely used in population-based screening for colorectal cancer (CRC). This had led to major challenges regarding colonoscopy capacity. Methods to maintain high sensitivity without compromising the colonoscopy capacity are needed. This study investigates an algorithm that combines FIT result, blood-based biomarkers associated with CRC, and individual demographics, to triage subjects sent for colonoscopy among a FIT positive (FIT⁺) screening population and thereby reduce the colonoscopy burden.Materials and methodsFrom the Danish National Colorectal Cancer Screening Program, 4048 FIT⁺ (≥100 ng/mL Hemoglobin) subjects were included and analyzed for a panel of 9 cancer-associated biomarkers using the ARCHITECT i2000. Two algorithms were developed: 1) a predefined algorithm based on clinically available biomarkers: FIT, age, CEA, hsCRP and Ferritin; and 2) an exploratory algorithm adding additional biomarkers: TIMP-1, Pepsinogen-2, HE4, CyFra21-1, Galectin-3, B2M and sex to the predefined algorithm. The diagnostic performances for discriminating subjects with or without CRC in the 2 models were benchmarked against the FIT alone using logistic regression modeling.ResultsThe discrimination of CRC showed an area under the curve (AUC) of 73.7 (70.5-76.9) for the predefined model, 75.3 (72.1-78.4) for the exploratory model, and 68.9 (65.5-72.2) for FIT alone. Both models performed significantly better (P < .001) than the FIT model. The models were benchmarked vs. FIT at cutoffs of 100, 200, 300, 400, and 500 ng/mL Hemoglobin using corresponding numbers of true positives and false positives. All performance metrics were improved at all cutoffs.ConclusionA screening algorithm including a combination of FIT result, blood-based biomarkers and demographics outperforms FIT in discriminating subjects with or without CRC in a screening population with FIT results above 100 ng/mL Hemoglobin.     

Preferences and Acceptance of Colorectal Cancer Screening in Thailand

Colorectal cancer (CRC) is now common in Thailand with an increase in incidence over time. Health authoritiesare planning to implement a nationwide CRC screening program using fecal immunochemical test (FIT) as aprimary screening tool. This study aimed to estimate preferences and acceptance of FIT and colonoscopy, explorefactors influencing the acceptance, and investigate reasons behind choosing and rejecting to screen before theprogram was implemented. Patients aged 50-69, visiting the primary care unit during the study period, wereinvited to join this study. Patients with a history of cancer or past CRC screening were excluded. Face-to-faceinterviews were conducted. Subjects were informed about CRC and the screening tests: FIT and colonoscopy.Then, they were asked for their opinions regarding the screening. The total number of subjects was 437 (86.7%response rate). Fifty-eight percent were females. The median age was 58 years. FIT was accepted by 74.1% ofsubjects compared to 55.6% for colonoscopy. The acceptance of colonoscopy was associated with perceivedsusceptibility to CRC and family history of cancer. No symptoms, unwilling to screen, healthy, too busy and anxiousabout diagnosis were reasons for refusing to screen. FIT was preferred for its simplicity and non-invasivenesscompared with colonoscopy. Those rejecting FIT expressed a strong preference for colonoscopy. Subjects chosecolonoscopy because of its accuracy; it was refused for the process and complications. If the screening programis implemented for the entire target population in Thailand, we estimate that 106,546 will have a positive FIT,between 8,618 and 12,749 identified with advanced adenoma and between 2,645 and 3,912 identified with CRCin the first round of the program.     

The Role of CT Colonography as a Screening Tool for Colorectal Cancer

Most colorectal cancers (CRC) are preventable through screening and polyp removal; however, CRC remains fixed as the second leading cause of cancer mortality in the USA. This is largely due to suboptimal screening participation. This review of current literature explores the use of CT colonography (CTC), also known as virtual colonoscopy, as another option for CRC screening. Relevant recent research topics include exploring the elimination of pre-procedure colon cleansing, the extension of recommended CTC screening intervals, the implications of extracolonic findings, and the significance of CTC radiation dose in a benefit/risk analysis. Peer-reviewed literature supports CTC as a viable option to safely screen average and moderate risk patients for CRC with polyps and cancer detection rates comparable to optical colonoscopy. CTC has the potential to raise CRC screening rates in population health management efforts.     

Mobile Health Interventions for Improving Colorectal Cancer Screening Rates: A Systematic Review and Meta-Analysis

Objective: The aim of this systematic review and meta-analysis was to determine the efficacy of different mHealth interventions in increasing colorectal cancer (CRC) screening rates. Methods: A literature search for eligible studies was done in ClinicalTrials.gov, PubMed, and Scopus in October 2020. Included studies were randomized controlled trials done on adults due for CRC screening, who received either an mHealth intervention to promote screening or usual care. The primary outcome from these studies was completion of CRC screening. Two reviewers independently worked on selecting studies, collecting data, and determining risk of bias. Adjusted odds ratios (AOR) for CRC screening rates were summarized into a Forest plot. Results: A total of ten trials from three continents were included in the qualitative analysis. Risk of bias is low in terms of randomization, but high in terms of participant blinding, due to the nature of the interventions. Meta-analysis of four trials showed low clinical and statistical heterogeneity (I2=0%). Overall, the use of mHealth interventions is associated with higher CRC screening uptake when compared to usual care (AOR 1.33; 95% CI, 1.20-1.46). This effect was seen across different types of mHealth interventions, which included automated and non-automated telephone education and text-message reminders. Conclusion: This study showed that mHealth is associated with increased CRC screening participation regardless of the type of intervention used.     

Alteration of Leptin and Adiponectin in Multistep Colorectal Tumorigenesis

Background: There is an established link between obesity related metabolic derangement and colorectal cancer development. Recently, we developed a metabolic-colorectal cancer risk score. In this follow-up study, we studied its association with colorectal neoplasm by measuring two major metabolic syndrome biomarkers, leptin and adiponectin. Objectives: To evaluate the serum levels of leptin and adiponectin in patients with colorectal polyps and colorectal cancer and to determine any correlation with metabolic risk score. Results: In total, 130 individuals were studied: 30 controls without colonic pathology, 18 with colonic adenoma (CAP), and 82 with colorectal adenocarcinoma (CRC, 17 cases of T1-2 and 65 cases of T3-4). The metabolic risk scores in CAP and T1-2 CRC were higher than those in the controls and T3-4 CRC cases. There were no statistically significant differences in leptin levels among CAPs, CRCs, and controls. Both leptin and adiponectin levels reflected differences in body mass index and metabolic risk scores. Cases in the CAP group and early T-stage CRC groups had lower adiponectin levels (14.03 and 13.01 mg/ml, respectively) than the no polyps group (19.5mg/ml, p = 0.03). The average serum adiponectin level in the invasive cancer group (18.5 ng/ml) was comparable with that of the control group. Conclusions: The level of serum adiponectin was positively correlated with the metabolic risk score. Decreased serum adiponectin was significantly associated with the development of colorectal adenoma and early stage colorectal carcinoma.     

Uptake of faecal immunochemical test screening among nonparticipants in a flexible sigmoidoscopy screening programme

Screening programmes based on single modality testing may prevent individuals with a preference for a different test from participating. We conducted a population-based trial to determine whether nonparticipants in flexible sigmoidoscopy (FS) screening were willing to attend faecal immunochemical test (FIT) screening. In total, 8,407 subjects were invited in a primary FS screening programme. Invitees did not know at the time of FS invitation that nonparticipants would be offered FIT screening. A total of 4,407 nonparticipants of FS screening were invited for FIT screening (cut-off 50 ng haemoglobin/ml). The participation rate to FS screening was 31% [95% confidence interval (CI): 30-32%]. Among the FS nonparticipants 25% (CI: 24-26%) did attended FIT screening. The participation rate of the two-stage recruitment for FS and FIT screening was 45% (CI: 44-46%). FIT screenees were older (p = 0.02), more often women (p < 0.001) and had a lower social economic status (p = 0.01) than FS screenees. The detection rate (DR) for advanced adenoma was 3.5% (CI: 2.5-4.8%), and for colorectal cancer (CRC) it was 0.3% (CI: 0.1-0.8%) among participants to FIT screening. The DR of the two-stage recruitment was 6.1% (n = 202) for an advanced adenoma and 0.5% (n = 16) for a CRC. In conclusion, offering FIT screening to nonparticipants in a FS screening programme increases the overall participation rate considerably, as a quarter of nonparticipants of FS screening was willing to attend FIT screening. The participation rate remains lower for primary FIT screening in the same population (62%). Women in the target population were more likely to refuse FS than FIT screening. Countries introducing FS screening should be aware of these preferences.     

The Optimal Cut-Off Level of The Fecal Immunochemical Test For Colorectal Cancer Screening in a Country with Limited Colonoscopy Resources: A Multi-Center Study from Thailand

Background: Selecting the cut-off point for the fecal immunochemical test (FIT) for colorectal cancer (CRC) screening programs is of prime importance. The balance between the test performance for detecting advanced neoplasia and the available colonoscopy resources should be considered. We aimed to identify the optimal cut-off of FIT for advanced neoplasia in order to minimize colonoscopy burden. Methods: We conducted a multi-center study in 6 hospitals from diverse regions of Thailand. Asymptomatic participants, aged 50-75 years, were tested with one-time quantitative FIT (OC-SENSOR, Eiken Chemical Co.,Ltd., Tokyo, Japan) and all participants underwent colonoscopy. We assessed test performance in detecting advanced neoplasia (advanced adenoma and CRC) and measured the burden of colonoscopy with different cut-offs [25 (FIT25), 50 (FIT50), 100 (FIT100), 150 (FIT150), and 200 (FIT200)ng/ml]. Results: Among 1,479 participants, advanced neoplasia and CRC were found in 137 (9.3%) and 14 (0.9%), respectively. From FIT25 to FIT200, the positivity rate decreased from 18% to 4.9%. For advanced neoplasia, an increased cut-off decreased sensitivity from 42.3% to 16.8% but increased specificity from 84.2% to 96.3%. The increased cut-off increased the positive predictive value (PPV) from 21.5% to 31.5%. However, all cut-off points provided a high negative predictive value (NPV) (>90%). For CRC, the miss rate for FIT25 to FIT 150 was the same (n=3, 21%), whereas that with FIT200 increased to 35% (n=5). Conclusions: In a country with limited-colonoscopy resources, using FIT150 may be preferred because it offers both high PPV and NPV for advanced neoplasia detection. It could also decrease colonoscopy workload, while maintaining a CRC miss rate similar to those with lower cut-offs.     

Colorectal cancer screening by double contrast barium enema in Thai people

Purpose: The incidence of colorectal cancer (CRC) has been increasing in Asian countries including Thailand.Double contrast barium enema (DCBE) is one of the investigation tools used in CRC screening. This study aimedto determine the incidence of colorectal neoplasm detected at screening by DCBE in Thai people. Methods:The computerized radiology database of screening DCBE in Thai adults between June 2009 and October 2011at the Faculty of Medicine, Siriraj Hospital, was reviewed. DCBE examination performed in a surveillanceprogram after curative CRC resection or the removal of colorectal polyps was also considered as a screeningDCBE. Results: A total of 819 screening DCBEs performed during this 28-month period were analyzed. Themean age of patients was 59.8 ± 13.6 years. Of the total, 467 (57%) were male. A family history of CRC and aprevious history of curative CRC resection or polyp removal were noted in 34 patients (4%) and 124 patients(15%), respectively. A total of 31 patients (3.8%; 95%CI = 2.7%-5.3%) were reported to have colorectal polypor mass demonstrated on DCBE. Of these, follow-up endoscopy was performed in 20 cases (65%). Accordingto pathological results, the incidence of advanced adenoma and CRC detected at screening DCBE was 0.7%(95%CI = 0.3%-1.6%; n=6) and 0.4% (95%CI = 0.1%-1.1%; n=3), respectively. Conclusions: The screeningDCBE performed in Thai adults had a diagnostic yield of 0.7% for advanced adenoma and 0.4% for CRC.     

Colorectal polypectomy and risk of colorectal cancer by subsite: the Fukuoka Colorectal Cancer study

BACKGROUND: Colorectal adenomas are well-established precursor lesions for colorectal cancer and removal of polyps is deemed to reduce the risk of colorectal cancer. However, benefit of colorectal polypectomy in routine practice is still uncertain. We therefore investigated subsite-specific risks of colorectal cancer in relation to history of colorectal polypectomy in a case-control study. METHODS: Both case patients and control subjects were residents aged 20-74 years in Fukuoka City and three adjacent areas. The case group comprised 840 patients undergoing surgery for a first diagnosis of colorectal cancer, while the control subjects were 833 residents who were selected in the community by two-stage random sampling. Past history of selected diseases, surgery and lifestyle factors were ascertained by in-person interview. Statistical adjustment was made for sex, 5-year age class, residence, smoking, alcohol drinking, physical activity, body mass index and parental history of colorectal cancer. RESULTS: Overall, 74 case patients (9%) and 85 control subjects (10%) reported a prior history of colorectal polyps, and 50 cases (6%) and 64 controls (8%) had a history of colorectal polypectomy. The adjusted odds ratio associated with colorectal polypectomy was 0.71 (95% confidence interval [CI] 0.48-1.06) for the overall risk of colorectal cancer. The corresponding values for cancer of the proximal colon, distal colon, and rectum were 1.68 (95% CI 0.98-2.88), 0.71 (95% CI 0.41-1.26) and 0.24 (95% CI 0.11-0.52), respectively. CONCLUSIONS: The findings indicate that colorectal polypectomy in current practice confers a decreased risk of rectal cancer and possibly of distal colon cancer.     

DNA methylation of phosphatase and actin regulator 3 detects colorectal cancer in stool and complements FIT

Using a bioinformatics-based strategy, we set out to identify hypermethylated genes that could serve as biomarkers for early detection of colorectal cancer (CRC) in stool. In addition, the complementary value to a Fecal Immunochemical Test (FIT) was evaluated. Candidate genes were selected by applying cluster alignment and computational analysis of promoter regions to microarray-expression data of colorectal adenomas and carcinomas. DNA methylation was measured by quantitative methylation-specific PCR on 34 normal colon mucosa, 71 advanced adenoma, and 64 CRC tissues. The performance as biomarker was tested in whole stool samples from in total 193 subjects, including 19 with advanced adenoma and 66 with CRC. For a large proportion of these series, methylation data for GATA4 and OSMR were available for comparison. The complementary value to FIT was measured in stool subsamples from 92 subjects including 44 with advanced adenoma or CRC. Phosphatase and Actin Regulator 3 (PHACTR3) was identified as a novel hypermethylated gene showing more than 70-fold increased DNA methylation levels in advanced neoplasia compared with normal colon mucosa. In a stool training set, PHACTR3 methylation showed a sensitivity of 55% (95% CI: 33-75) for CRC and a specificity of 95% (95% CI: 87-98). In a stool validation set, sensitivity reached 66% (95% CI: 50-79) for CRC and 32% (95% CI: 14-57) for advanced adenomas at a specificity of 100% (95% CI: 86-100). Adding PHACTR3 methylation to FIT increased sensitivity for CRC up to 15%. PHACTR3 is a new hypermethylated gene in CRC with a good performance in stool DNA testing and has complementary value to FIT.