Arthur K.C. Luk

Association between serrated polyps and the risk of synchronous advanced colorectal neoplasia in average-risk individuals

Serrated polyps of the colorectum have distinct histological features and malignant potential.

Quantitation of faecal Fusobacterium improves faecal immunochemical test in detecting advanced colorectal neoplasia

Objective There is a need for an improved biomarker for colorectal cancer (CRC) and advanced adenoma. We evaluated faecal microbial markers for clinical use in detecting CRC and advanced adenoma. Design We measured relative abundance of Fusobacterium nucleatum (Fn), Peptostreptococcus anaerobius (Pa) and Parvimonas micra (Pm) by quantitative PCR in 309 subjects, including 104 patients with CRC, 103 patients with advanced adenoma and 102 controls. We evaluated the diagnostic performance of these biomarkers with respect to faecal immunochemical test (FIT), and validated the results in an independent cohort of 181 subjects. Results The abundance was higher for all three individual markers in patients with CRC than controls (p<0.001), and for marker Fn in patients with advanced adenoma than controls (p=0.022). The marker Fn, when combined with FIT, showed superior sensitivity (92.3% vs 73.1%, p<0.001) and area under the receiver-operating characteristic curve (AUC) (0.95 vs 0.86, p<0.001) than stand-alone FIT in detecting CRC in the same patient cohort. This combined test also increased the sensitivity (38.6% vs 15.5%, p<0.001) and AUC (0.65 vs 0.57, p=0.007) for detecting advanced adenoma. The performance gain for both CRC and advanced adenoma was confirmed in the validation cohort (p=0.0014 and p=0.031, respectively). Conclusions This study identified marker Fn as a valuable marker to improve diagnostic performance of FIT, providing a complementary role to detect lesions missed by FIT alone. This simple approach may improve the clinical utility of the current FIT, and takes one step further towards a non-invasive, potentially more accurate and affordable diagnosis of advanced colorectal neoplasia.

The knowledge of colorectal cancer symptoms and risk factors among 10,078 screening participants: are high risk individuals more knowledgeable?

Objectives We tested the a priori hypothesis that self-perceived and real presences of risks for colorectal cancer (CRC) are associated with better knowledge of the symptoms and risk factors for CRC, respectively. Methods One territory-wide invitation for free CRC screening between 2008 to 2012 recruited asymptomatic screening participants aged 50–70 years in Hong Kong. They completed survey items on self-perceived and real presences of risks for CRC (advanced age, male gender, positive family history and smoking) as predictors, and knowledge of CRC symptoms and risk factors as outcome measures, respectively. Their associations were evaluated by binary logistic regression analyses. Results From 10,078 eligible participants (average age 59 years), the mean knowledge scores for symptoms and risk factors were 3.23 and 4.06, respectively (both score range 0–9). Male gender (adjusted odds ratio [AOR] = 1.34, 95% C.I. 1.20–1.50, p<0.01), self-perception as not having any risks for CRC (AOR = 1.12, 95% C.I. 1.01–1.24, p = 0.033) or uncertainty about having risks (AOR = 1.94, 95% C.I. 1.55–2.43, p<0.001), smoking (AOR 1.38, 95% C.I. 1.11–1.72, p = 0.004), and the absence of family history (AOR 0.61 to 0.78 for those with positive family history, p<0.001) were associated with poorer knowledge scores (≤4) of CRC symptoms. These factors remained significant for knowledge of risk factors. Conclusions Male and smokers were more likely to have poorer knowledge but family history of CRC was associated with better knowledge. Since screening of these higher risk individuals could lead to greater yield of colorectal neoplasm, educational interventions targeted to male smokers were recommended.

Diagnostic Accuracy of a Qualitative Fecal Immunochemical Test Varies With Location of Neoplasia But Not Number of Specimens

BACKGROUND & AIMS We compared the accuracy of a qualitative fecal immunochemical test (FIT) in identifying patients with proximal vs distal advanced neoplasia and evaluated whether analysis of 2 specimens performed better than analysis of 1 specimen. Distal advanced neoplasia was defined as colorectal cancer (CRC), any colorectal adenoma ≥10 mm in diameter, high-grade dysplasia, or a lesion with villous or tubulovillous histologic characteristics in a location distal to the splenic flexure, including the descending colon, the rectosigmoid, and the rectum. METHODS We collected data from 5343 subjects (50-70 years old) who received 2 FITs (Hemosure; cutoff value, 10 μg hemoglobin/g feces) before colonoscopy in an invitational CRC screening program in Hong Kong from 2008 through 2012. We calculated the FITs sensitivity, specificity, positive predictive value (PPV), and negative predictive value in detecting colorectal neoplasia. RESULTS Of the participants, 13.6%, 12.2%, and 6.0% had distal, proximal, and synchronous distal or proximal neoplasia, respectively. Advanced neoplasia was detected in 291 subjects (5.4%); 22 (0.4%) had CRC. FIT detected distal advanced adenoma with 39.7% sensitivity (95% confidence interval [CI], 32.0%-48.0%) vs proximal advanced adenoma with 25.0% sensitivity (95% CI, 17.3%-34.6%; P = .014), distal advanced neoplasia with 40.0% sensitivity (95% CI, 32.5%-47.9%) vs proximal advanced neoplasia with 27.9% sensitivity (95% CI, 20.0%-37.4%; P = .039), and any distal adenoma ≥10 mm, irrespective of other lesion characteristics, with 39.5% sensitivity (95% CI, 31.0%-48.7%) vs. proximal adenoma with 25.3% sensitivity (95% CI, 16.5%-36.6%; P = .038). The specificity of FIT in detecting CRC was similar between the proximal and distal colon. FIT detected distal lesions with higher PPV than proximal lesions. One FIT detected advanced neoplasia with 31.8% sensitivity (95% CI, 25.9%-38.4%) and 92.4% specificity (95% CI, 91.6%-93.2%), whereas 2 FITs detected advanced neoplasia with 34.1% sensitivity (95% CI, 28.0%-40.8%; P = .617) and 91.9% specificity (95% CI, 91.0%-92.7%; P = .327). FIT detected distal advanced neoplasia with greater sensitivity and higher PPV than proximal advanced neoplasia. CONCLUSIONS In an analysis of data from subjects who underwent CRC screening in Hong Kong, FIT detected distal advanced neoplasia with higher sensitivity than proximal advanced neoplasia. Analysis of 1 vs 2 specimens by FIT identified advanced neoplasia with similar test characteristics.

Prospective cohort study of compliance with faecal immunochemical tests for colorectal cancer screening in Hong Kong.

OBJECTIVE This study aims to examine the rate and determinants of faecal immunochemical test (FIT) compliance over a four-year period among asymptomatic participants in a colorectal cancer (CRC) screening programme in Hong Kong. METHOD Self-referred screening participants aged between 50 and 70 years who chose FIT for annual screening were followed up for four years (2008-2012). All participants were reminded up to three times yearly for FIT retrieval within two months of the expected screening date. The proportions of screening participants who failed to adhere to annual FIT tests in 1, 2, 3 and 4-years, respectively, after the initial screening uptake were evaluated. The factors associated with non-compliance with FITs in any year were assessed by a binary logistic regression analysis. RESULTS From 5700 consecutive screening participants, the compliance rates to FIT were 95.1%, 79.9%, 66.2% and 68.4% at years one to four, respectively. The proportions of people missing one, two and three tests were 6.2%, 19.6% and 2.1%, respectively. From multivariate regression analysis, male subjects, younger participants, smokers and those with positive family history of CRC were more likely to be non-compliant. CONCLUSION Participants identified as at higher risk for screening non-compliance should be especially considered for individual reminders to enhance screening effectiveness.

Informed Choice vs. No Choice in Colorectal Cancer Screening Tests: A Prospective Cohort Study in Real-Life Screening Practice

OBJECTIVES:The objective of this study was to compare the level of adherence to colorectal cancer (CRC) screening programs among screening participants offered vs. not offered informed choices on screening modality.METHODS:We recruited 10,606 screening participants aged 50–70 years, including 6,397 subjects who were offered a choice of yearly fecal immunochemical test (FIT) for up to 3 years vs. one colonoscopy, and 4,209 subjects who were offered either FIT or colonoscopy without choice. They were prospectively followed up for 3 years. The proportion of screening participants who returned their specimens in all subsequent years (FIT group) and the attendance rate of scheduled endoscopy appointment (colonoscopy group) were compared between those with vs. without choice.RESULTS:The adherence rate with FIT was 97.6%, 84.1%, and 72.6% in the first 3 years of follow-up, respectively, among those who were offered a choice. The adherence rate with FIT was 97.5%, 78.4%, and 62.8%, respectively, among those without choices. The proportion of subjects attending colonoscopy was 95.7% (choice offered) and 90.6% (no choice). From binary logistic regression analysis, participants who were offered informed choice were significantly more likely to adhere to the program when compared with those without test choices (odds ratio (OR)=2.54, 95% confidence interval (CI): 2.30–2.82, P<0.001). The respective adjusted OR for the FIT and colonoscopy groups was 1.60 (95% CI: 1.42–1.80, P<0.001) and 2.53 (95% CI: 1.94–3.31, P<0.001).CONCLUSIONS:This study found that patients who were offered an informed choice for screening had higher adherence rates than patients who were not offered a choice in real-life practices, suggesting that providing screening test options for CRC screening is preferred.

Prediction of proximal advanced neoplasia: a comparison of four existing sigmoidoscopy-based strategies in a Chinese population

Objective To compare the performance of existing sigmoidoscopy-based strategies in predicting advanced proximal neoplasia (APN) in an asymptomatic Chinese cohort. Design We included all screening participants aged 50–70 years who received colonoscopy between 2008 and 2014 in Hong Kong. Sigmoidoscopy yield was estimated from the colonoscopic findings based on the: (1) UK flexible sigmoidoscopy; (2) Screening for COlon REctum (SCORE); (3) NORwegian Colorectal Cancer Prevention (NORCCAP) trials and (4) US clinical index based on age, gender and distal findings. The sensitivity, specificity, the number of subjects needed to screen (NNS) and the number of subjects needed to refer (NNR) for colonoscopy to detect one APN were evaluated. Binary logistic regression modelling identified the distal findings associated with APN. Results From 5879 eligible subjects, 132 (2.2%) had APN. The US strategy achieved the highest sensitivity for APN detection (42.0%) and the UK criteria attained the highest specificity (96%). The US criteria led to the lowest NNS (92 vs 103–267) and the UK criteria required the least NNR (12 vs 16–21). Using the US strategy, the rates of APN detected were 1.4% (low-risk group), 2.2% (intermediate risk) and 5.9% (high risk). The c-statistics of the UK, SCORE, NORCCAP and the US criteria were 0.55±0.03; 0.59±0.03; 0.59±0.03 and 0.62±0.05 respectively. Conclusions The US criteria had the highest sensitivity for detection of APN and lowest NNS and the UK score had the highest specificity and the lowest NNR. The performance of all these four criteria to predict APN is limited, highlighting an urgent need to devise a novel APN prediction system for Asian subjects.

Colorectal Cancer Screening Based on Age and Gender: A Cost-Effectiveness Analysis

AbstractWe evaluated whether age- and gender-based colorectal cancer screening is cost-effective.Recent studies in the United States identified age and gender as 2 important variables predicting advanced proximal neoplasia, and that women aged <60 to 70 years were more suited for sigmoidoscopy screening due to their low risk of proximal neoplasia. Yet, quantitative assessment of the incremental benefits, risks, and cost remains to be performed.Primary care screening practice (2008–2015).A Markov modeling was constructed using data from a screening cohort. The following strategies were compared according to the Incremental Cost Effectiveness Ratio (ICER) for 1 life-year saved: flexible sigmoidoscopy (FS) 5 yearly; colonoscopy 10 yearly; FS for each woman at 50- and 55-year old followed by colonoscopy at 60- and 70-year old; FS for each woman at 50-, 55-, 60-, and 65-year old followed by colonoscopy at 70-year old; FS for each woman at 50-, 55-, 60-, 65-, and 70-year old. All male subjects received colonoscopy at 50-, 60-, and 70-year old under strategies 3 to 5.From a hypothetical population of 100,000 asymptomatic subjects, strategy 2 could save the largest number of life-years (4226 vs 2268 to 3841 by other strategies). When compared with no screening, strategy 5 had the lowest ICER (US

Determinants of Bowel Preparation Quality and Its Association With Adenoma Detection: A Prospective Colonoscopy Study

42,515), followed by strategy 3 (US

Screening strategies for colorectal cancer among patients with nonalcoholic fatty liver disease and family history

43,517), strategy 2 (US