Test performance of immunologic fecal occult blood testing and sigmoidoscopy compared with primary colonoscopy screening for colorectal advanced adenomas

Given the current increase in colorectal cancer screening, information on performance of screening tests is needed, especially in groups with a presumed lower test performance. We compared test performance of immunologic fecal occult blood testing (FIT) and pseudosigmoidoscopy with colonoscopy for detection of advanced adenomas in an average risk screening population. In addition, we explored the influence of gender, age, and location on test performance. FIT was collected prior to colonoscopy with a 50 ng/mL cutoff point. FIT results and complete colonoscopy findings were available from 329 subjects (mean age: 54.6 ± 3.7 years, 58.4% women). Advanced adenomas were detected in 38 (11.6%) of 329 subjects. Sensitivity for advanced adenomas of FIT and sigmoidoscopy were 15.8% (95% CI: 6.0-31.3) and 73.7% (95% CI: 56.9-86.6), respectively. No sensitivity improvement was obtained using the combination of sigmoidoscopy and FIT. Mean fecal hemoglobin in FIT positives was significantly lower for participants with only proximal adenomas versus those with distal ones (P = 0.008), for women versus men (P = 0.023), and for younger (<55 years) versus older (≥55 years) subjects (P = 0.029). Sensitivities of FIT were 0.0% (95% CI: 0.0-30.9) in subjects with only proximal versus 21.4% (95% CI: 8.3-41.0) in those with distal nonadvanced adenomas; 5.3% (95% CI: 0.0-26.0) in women versus 26.3% (95% CI: 9.2-51.2) in men; 9.5% (95% CI: 1.2-30.4) in younger versus 23.5% (95% CI: 6.8-49.9) in older subjects. Sigmoidoscopy had a significantly higher sensitivity for advanced adenomas than FIT. A single FIT showed very low sensitivity, especially in subjects with only proximal nonadvanced adenomas, in women, and in younger subjects. This points to the existence of "low" FIT performance in subgroups and the need for more tailored screening strategies.     

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.     

Optimizing the colorectal cancer screening programme using faecal immunochemical test (FIT) in Flanders,Belgium from the “interval cancer” perspective

Background Interval cancer (IC) is a critical issue in colorectal cancer (CRC) screening. We identified factors associated with ICs after faecal immunochemical test (FIT) screening and explored the impact of lowering FIT cut-off or shortening screening interval on FIT-ICs in Flanders.Methods FIT participants diagnosed with a CRC during 2013–2018 were included. Factors associated with FIT-ICs were identified using logistic regression. Distributions of FIT results among FIT-ICs were examined.Results In total, 10,122 screen-detected CRCs and 1534 FIT-ICs were included (FIT-IC proportion of 13%). FIT-ICs occurred more frequently in women (OR 1.58 [95% CI 1.41–1.76]) and ages 70–74 (OR 1.35 [1.14–1.59]). FIT-ICs were more often right-sided (OR 3.53 [2.98–4.20]), advanced stage (stage IV: OR 7.15 [5.76–8.88]), and high grade (poorly/undifferentiated: OR 2.57 [2.08–3.18]). The majority (83–92%) of FIT-ICs would still be missed if FIT cut-off was lowered from 15 to 10 µg Hb/g or screening interval was shortened from 2 to 1 year.Conclusions FIT-ICs were more common in women, older age, right-sided location, advanced stage and high grade. In Flanders, lowering FIT cut-off (to 10 µg Hb/g) or shortening screening interval (to 1 year) would have a minimal impact on FIT-ICs.Subject terms: Cancer screening, Risk factors, Colorectal cancer     

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.     

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.     

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.     

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.     

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.     

Screening for colorectal cancer: random comparison of guaiac and immunochemical faecal occult blood testing at different cut-off levels

Immunochemical faecal occult blood testing (FIT) provides quantitative test results, which allows optimisation of the cut-off value for follow-up colonoscopy. We conducted a randomised population-based trial to determine test characteristics of FIT (OC-Sensor micro, Eiken, Japan) screening at different cut-off levels and compare these with guaiac-based faecal occult blood test (gFOBT) screening in an average risk population. A representative sample of the Dutch population (n=10 011), aged 50–74 years, was 1 : 1 randomised before invitation to gFOBT and FIT screening. Colonoscopy was offered to screenees with a positive gFOBT or FIT (cut-off 50 ng haemoglobin/ml). When varying the cut-off level between 50 and 200 ng ml⁻¹, the positivity rate of FIT ranged between 8.1% (95% CI: 7.2–9.1%) and 3.5% (95% CI: 2.9–4.2%), the detection rate of advanced neoplasia ranged between 3.2% (95% CI: 2.6–3.9%) and 2.1% (95% CI: 1.6–2.6%), and the specificity ranged between 95.5% (95% CI: 94.5–96.3%) and 98.8% (95% CI: 98.4–99.0%). At a cut-off value of 75 ng ml⁻¹, the detection rate was two times higher than with gFOBT screening (gFOBT: 1.2%; FIT: 2.5%; P<0.001), whereas the number needed to scope (NNscope) to find one screenee with advanced neoplasia was similar (2.2 vs 1.9; P=0.69). Immunochemical faecal occult blood testing is considerably more effective than gFOBT screening within the range of tested cut-off values. From our experience, a cut-off value of 75 ng ml⁻¹ provided an adequate positivity rate and an acceptable trade-off between detection rate and NNscope.     

Adenoma characteristics associated with post-polypectomy proximal colon cancer incidence: a retrospective cohort study

Background Colorectal cancer (CRC) screening is less effective at reducing cancer incidence in the proximal colon compared to the distal colorectum. We aimed to identify adenoma characteristics associated with proximal colon cancer (PCC).Methods Endoscopy and pathology data for patients with ≥1 adenoma detected at baseline colonoscopy were obtained from 17 UK hospitals between 2001 and 2010. Multivariable Cox regression models were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for PCC, and, for comparison, distal CRC incidence, by adenoma characteristics.Results Among 18,431 patients, 152 and 105 developed PCC and distal CRC, respectively, over a median follow-up of 9.8 years. Baseline adenoma characteristics positively associated with PCC incidence included number (≥3 vs. < 3: aHR 2.10, 95% CI: 1.42–3.09), histology (tubulovillous/villous vs. tubular: aHR 1.61, 95% CI: 1.10–2.35) and location (any proximal vs. distal only: aHR 1.70, 95% CI: 1.20–2.42), for which there was borderline evidence of heterogeneity by subsite (p = 0.055). Adenoma dysplasia (high vs. low grade) was associated with distal CRC (aHR 2.42, 95% CI: 1.44–4.04), but not PCC (p-heterogeneity = 0.023).Conclusions Baseline adenoma number, histology and proximal location were independently associated with PCC and may be important to identify patients at higher risk for post-polypectomy PCC.Subject terms: Epidemiology, Cancer epidemiology, Cancer screening, Colorectal cancer, Cancer prevention     

Coupling radiomics analysis of CT image with diversification of tumor ecosystem: A new insight to overall survival in stage I−III colorectal cancer

ObjectiveThis study aimed to establish a method to predict the overall survival (OS) of patients with stage I−III colorectal cancer (CRC) through coupling radiomics analysis of CT images with the measurement of tumor ecosystem diversification.MethodsWe retrospectively identified 161 consecutive patients with stage I−III CRC who had underwent radical resection as a training cohort. A total of 248 patients were recruited for temporary independent validation as external validation cohort 1, with 103 patients from an external institute as the external validation cohort 2. CT image features to describe tumor spatial heterogeneity leveraging the measurement of diversification of tumor ecosystem, were extracted to build a marker, termed the EcoRad signature. Multivariate Cox regression was used to assess the EcoRad signature, with a prediction model constructed to demonstrate its incremental value to the traditional staging system for OS prediction.ResultsThe EcoRad signature was significantly associated with OS in the training cohort [hazard ratio (HR)=6.670; 95% confidence interval (95% CI): 3.433−12.956; P<0.001), external validation cohort 1 (HR=2.866; 95% CI: 1.646−4.990; P<0.001) and external validation cohort 2 (HR=3.342; 95% CI: 1.289−8.663; P=0.002). Incorporating the EcoRad signature into the prediction model presented a higher prediction ability (P<0.001) with respect to the C-index (0.813, 95% CI: 0.804−0.822 in the training cohort; 0.758, 95% CI: 0.751−0.765 in the external validation cohort 1; and 0.746, 95% CI: 0.722−0.770 in external validation cohort 2), compared with the reference model that only incorporated tumor, node, metastasis (TNM) system, as well as a better calibration, improved reclassification and superior clinical usefulness.ConclusionsThis study establishes a method to measure the spatial heterogeneity of CRC through coupling radiomics analysis with measurement of diversification of the tumor ecosystem, and suggests that this approach could effectively predict OS and could be used as a supplement for risk stratification among stage I−III CRC patients.     

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.     

A systematic review and meta-analysis on the efficacy of Compound Kushen Injection in 3 kinds of digestive tract tumor

BackgroundChemotherapy has become the main means to prolong the life of patients with advanced digestive tract cancer; however, it is associated with serious toxicity and side effects. Compound Kushen Injection (CKI) is a pure Chinese herbal preparation, which can assist chemotherapy, inhibit tumor cell proliferation, and reduce adverse reactions of chemotherapy. In this study, we systematically evaluated reports of CKI as an adjuvant to chemotherapeutic treatment of digestive tract cancer in recent years and provided evidence for clinical diagnosis and treatment.MethodsThe databases of PubMed, Chinese Biomedical Literature (CBM), China National Knowledge Infrastructure (CNKI) and Web Of Science were searched for clinical randomized controlled trials (RCTs) related to adjuvant chemotherapy with CKI in the treatment of advanced gastrointestinal tumors published from January 2000 to September 2021. After screening the qualified literatures, RevMan 5.4 software was used to evaluate the bias of the included literatures and perform meta-analysis.ResultsA total of 12 articles were included in the selection, incorporating 1080 study participants in all; meta-analysis results showed that application of the CKI in the process of chemotherapy for digestive tract tumors could improve the efficacy [odds ratio (OR) =3.11; 95% confidence interval (CI): 2.26 to 4.47, Z=7.00, P<0.00001], increase the patients’ median survival time (months) (OR =3.00; 95% CI: 1.47 to 4.52, Z=3.84, P=0.0001), increase the level of CD3⁺ [mean difference (MD) =4.11; 95% CI: 3.24 to 4.98], CD4⁺ level (MD =8.24; 95% CI: 3.72 to 12.76), reduce the CD8⁺ level (MD =−5.42; 95% CI: −8.09 to −2.76), reduce the tumor markers carcinoembryonic antigen (CEA; MD =−14.26; 95% CI: −14.81 to −13.71), CA199 (MD =−138.87; 95% CI: −143.21 to −132.52), and reduce the adverse reactions of chemotherapy: leukopenia (OR =0.28; 95% CI: 0.19 to 0.43), thrombocytopenia (OR =0.38; 95% CI: 0.24 to 061), decreased hemoglobin (OR =0.55; 95% CI: 0.31 to 0.98), and nausea and vomiting symptoms (OR =0.35; 95% CI: 0.24 to 0.53).DiscussionAdjuvant chemotherapy with CKI in the treatment of digestive tract tumors can effectively improve the symptoms of patients, improve immunity, reduce the level of serum tumor markers, improve efficacy, and reduce toxic and side effects.     

Faecal immunochemical test for patients with ‘high-risk’ bowel symptoms: a large prospective cohort study and updated literature review

Background We evaluated whether faecal immunochemical testing (FIT) can rule out colorectal cancer (CRC) among patients presenting with ‘high-risk’ symptoms requiring definitive investigation.Methods Three thousand five hundred and ninety-six symptomatic patients referred to the standard urgent CRC pathway were recruited in a multi-centre observational study. They completed FIT in addition to standard investigations. CRC miss rate (percentage of CRC cases with low quantitative faecal haemoglobin [f-Hb] measurement) and specificity (percentage of patients without cancer with low f-Hb) were calculated. We also provided an updated literature review.Results Ninety patients had CRC. At f-Hb < 10 µg/g, the miss rate was 16.7% (specificity 80.1%). At f-Hb < 4 µg/g, the miss rate was 12.2% (specificity 73%), which became 3.3% if low FIT plus the absence of anaemia and abdominal pain were considered (specificity 51%). Within meta-analyses of 9 UK studies, the pooled miss rate was 7.2% (specificity 74%) for f-Hb < 4 µg/g.Discussion FIT alone as a triage tool would miss an estimated 1 in 8 cases in our study (1 in 14 from meta-analysis), while many people without CRC could avoid investigations. FIT can focus secondary care diagnostic capacity on patients most at risk of CRC, but more work on safety netting is required before incorporating FIT triage into the urgent diagnostic pathway.Subject terms: Colorectal cancer, Diagnostic markers     

Factors associated with false-positive fecal immunochemical tests in a large German colorectal cancer screening study

In recent years fecal immunochemical tests (FITs) have been offered as a primary screening test for colorectal cancer (CRC) in a growing number of countries. Our study aims to identify factors associated with apparently false-positive results of FITs. In this cross-sectional study within the German population-based screening colonoscopy program, participants were invited to provide a stool sample for FIT prior to colonoscopy. Four thousand six hundred and fifty six participants aged 50–79 years with no known history of CRC or inflammatory bowel disease (IBD) and no findings of neoplasms at screening colonoscopy were included in the current analyses. Main outcome measures were rates and factors associated with apparently false-positive FIT results. Apparently false-positive FIT results were found for 378 participants (8.1%). Male sex (OR = 1.30, 95%CI 1.03, 1.62), age ≥65 years (OR = 1.27, 95%CI 1.01, 1.59), a BMI ≥30 kg/m² (OR = 1.81, 95%CI 1.36, 2.40), current smoking (OR = 1.63, 95%CI 1.18, 2.25), use of aspirin (OR = 1.36, 95%CI 1.02, 1.82) and a new diagnosis of IBD (OR = 9.13, 95%CI 2.18, 38.19) or other non-neoplastic findings (OR = 1.86, 95%CI 1.37, 2.51) at screening colonoscopy were independently associated with significantly increased odds of a positive FIT. Although considered false positive in the context of CRC screening, the identified factors associated with apparently false-positive FIT results are known risk factors for and may point to conditions other than colorectal neoplasms that may be potential sources of gastrointestinal bleeding, potentially requiring further medical follow up.     

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.     

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.     

Making colonoscopy-based screening more efficient: A “gateopener” approach

Screening colonoscopy for early detection and prevention of colorectal cancer (CRC) is mostly used inefficiently. Here, we assessed the potential of an innovative approach to colonoscopy-based screening, by use of a single, low threshold fecal immunochemical test (FIT) as a “gateopener” for screening colonoscopy. Using COSIMO, a validated simulation model, we modeled scenarios including either direct invitation to screening colonoscopy or an alternative approach involving mailing a single (“gateopener”) FIT along with an invitation to colonoscopy contingent on a FIT value above a low threshold yielding a 50% positivity rate (ie, every other pretest will be positive). Under plausible assumptions on screening offer adherence, we found that such “gateopener screening” (use of screening colonoscopy contingent on a positive, low threshold gateopener FIT) approximately doubled cancer detection rates vs conventional screening. In those spared from screening colonoscopy due to a negative gateopener FIT pretest, numbers needed to screen were 10-times higher vs those for individuals with a positive FIT, peaking in >2000 and >3800 (hypothetically) needed colonoscopies to detect one case of cancer in men and women, respectively. Gateopener screening resulted in 42%-51% and 59%-65% more prevented CRC cases and deaths, respectively. In summary, by directing colonoscopy capacities to those most likely to benefit, offering screening colonoscopy contingent on a “gateopener” low-threshold FIT would substantially enhance efficiency of colonoscopy screening.     

Participation and detection rates by age and sex for colonoscopy versus fecal immunochemical testing in colorectal cancer screening

Purpose

To compare two strategies for colorectal cancer screening: one-time colonoscopy versus fecal immunochemical testing (FIT) (and colonoscopy for positive) every 2 years, in order to determine which strategy provides the highest participation and detection rates in groups of sex and age.

Methods

This analysis was performed with data from the first screening round within the COLONPREV study, a population-based, multicenter, nationwide trial carried out in Spain. Several logistic regression models were applied to identify the influence of the screening test on participation rates and detection of proximal and distal neoplasms, as well to identify the influence of age and sex: women aged 50–59 years, women aged 60–69 years, men aged 50–59 years, and men aged 60–69 years.

Results

Participation was higher in women than in men, especially among women aged 50–59 years (25.91 % for colonoscopy and 35.81 % for FIT). Crossover from colonoscopy to FIT was higher among women than men, especially among those aged 60–69 years (30.37 %). In general, detection of any neoplasm and advanced adenoma was higher with colonoscopy than with FIT, but no significant differences were found between the two strategies for colorectal cancer detection. Detection of advanced adenoma in both arms was lower in women [specifically in women aged 50–59 years (OR 0.31; 95 % CI 0.25–0.38) than in men aged 60–69 years]. Women aged 50–59 years in the colonoscopy arm had a higher probability of detection of advanced adenoma (OR 4.49; 95 % CI 3.18–6.35), as well as of detection of neoplasms in proximal and distal locations (proximal OR 19.34; 95 % CI 12.07–31.00; distal OR 11.04; 95 % CI 8.13–15.01) than women of the same age in the FIT arm. These differences were also observed in the remaining groups but to a lesser extent.

Conclusion

Women were more likely to participate in a FIT-based strategy, especially those aged 50–59 years. The likelihood of detection of any neoplasm was higher in the colonoscopy arm for all the population groups studied, especially in women aged 50–59 years. Distinct population groups should be informed of the benefits of each screening strategy so that they may take informed decisions.     

Pain threshold,anxiety and other factors affect intensity of postoperative pain in gastric cancer patients: A prospective cohort study

ObjectiveThis prospective cohort study explored factors related to postoperative pain in gastric cancer patients.MethodsA total of 236 patients who underwent gastrectomy were enrolled. All patients enrolled in the study completed the Hospital Anxiety and Depression Scale (HADS) questionnaire and Life Orientation Test-Revised (LOT-R) questionnaire on the day before surgery. Heat pain threshold (HPT), cold pain threshold (CPT) and pressure pain threshold (PPT) were measured for all patients one day prior to surgery and demographic details were collected. All patients were connected to a patient-controlled intravenous analgesia (PCIA) pump at the end of the surgery. The occurrence of postoperative pain was used as a dependent variable, and multivariate logistic regression analyses were conducted to screen for factors affecting postoperative pain.ResultsIn total, 83 patients (35.2%) had postoperative pain. Body mass index (BMI) ≥28 kg/m² [odds ratio (OR): 2.67; 95% confidence interval (95% CI): 1.07−6.67], total gastrectomy (OR: 2.64; 95% CI: 1.42−4.91), preoperative anxiety score ≥8 (OR: 2.37; 95% CI: 1.12−5.02), heat pain threshold ≤4.9 s (OR: 2.14; 95% CI: 1.06−4.32), pressure pain threshold ≤4 g (OR: 2.05; 95% CI: 1.05−4.03), and female gender (OR: 1.99; 95% CI: 1.04−3.83) were risk factors for postoperative pain. ConclusionsObesity, wide range of gastrectomy, high preoperative anxiety, low HPT and PPT, and female gender are associated with increased risk for postoperative pain.