Accuracy, Acceptability, and Application: Fecal Immunochemical Tests for Early Detection of Advanced Neoplasia in Colonoscopy-Based Surveillance.

BACKGROUND: The fecal immunochemical test (FIT) is widely used in colorectal cancer (CRC) screening, but limited data exist for its application in individuals at above-average risk for CRC who complete surveillance colonoscopies. AIM: To assess the accuracy, acceptability, and effectiveness of FIT in the interval between surveillance colonoscopies, for predicting advanced neoplasia (advanced adenoma or CRC) at the next colonoscopy. METHODS: Individuals enrolled in an Australian surveillance program were included. Diagnostic accuracy was determined for 614 individuals completing a two-sample FIT (OC-Sensor) ≤ 3 months preceding surveillance colonoscopy. 386 Individuals were surveyed to assess acceptability of interval FIT. Additionally, a retrospective analysis was performed on 7331 individuals offered interval FIT between colonoscopies, where a positive FIT (≥ 20 µg hemoglobin/g feces) triggered an early colonoscopy. Associations between interval FIT results and advanced neoplasia were determined using regression analysis. RESULTS: FIT detected CRC and advanced adenoma with sensitivities of 60.0% (3/5) and 27.1% (35/129), respectively. Most (89.1%, 344/386) survey respondents preferred completing interval FIT every 1-2 years. The detection rate of interval FIT for advanced neoplasia decreased with increasing FIT completion. Individuals returning a positive FIT had a higher risk of advanced neoplasia than those who did not complete FIT. Positive interval FIT reduced time-to-diagnosis for CRC and advanced adenoma by a median of 30 and 20 months, respectively. CONCLUSION: Interval FIT was well accepted and enabled earlier detection of advanced neoplasia in individuals at above-average risk of CRC. Given that interval FIT predicts advanced neoplasia, it may be used to personalize surveillance colonoscopy intervals.

Surveillance colonoscopy findings in asymptomatic participants over 75 years of age.

Background and Aim: Surveillance colonoscopy for colorectal cancer (CRC) is generally not recommended beyond 75 years of age. The study determined incidence and predictors of advanced adenoma and CRC in older individuals undergoing surveillance colonoscopy. Methods: This was a retrospective cohort study of asymptomatic older participants (≥75 years), enrolled in a South Australian CRC surveillance program who underwent colonoscopy (2015-2020). Clinical records were extracted for demographics, personal or family history of CRC, comorbidities, polypharmacy, and colonoscopy findings. The associations between clinical variables and advanced adenoma or CRC at surveillance were assessed with multivariable Poisson regression analysis. Results: Totally 698 surveillance colonoscopies were analyzed from 574 participants aged 75-91 years (55.6% male). The incidence of CRC was 1.6% (11/698), while 37.9% (260/698) of procedures had advanced adenoma detected. Previous CRC (incidence rate ratio [IRR] 5.9, 95% CI 1.5-22.5), age ≥85 years (IRR 5.8, 95% CI 1.6-20.1) and active smoking (IRR 4.9, 95% CI 1.0-24.4) were independently associated with CRC diagnosis, while advanced adenoma at immediately preceding colonoscopy (IRR 1.6, 95% CI 1.3-2.0) and polypharmacy (IRR 1.2, 95% CI 1.0-1.5) were associated with advanced adenoma at surveillance colonoscopy in asymptomatic older participants (≥75 years). Conclusion: Advanced neoplasia was found in more than one third of the surveillance procedures completed in this cohort. Continuation of surveillance beyond age 75 yeasrs may be considered in participants who have previous CRC or are active smokers (provided they are fit to undergo colonoscopy). In other cases, such as past advanced adenoma only, the need for ongoing surveillance should be considered alongside participant preference and health status.

Improving Concordance Between Clinicians With Australian Guidelines for Bowel Cancer Prevention Using a Digital Application: Randomized Controlled Crossover Study.

BACKGROUND: Australia's bowel cancer prevention guidelines, following a recent revision, are among the most complex in the world. Detailed decision tables outline screening or surveillance recommendations for 230 case scenarios alongside cessation recommendations for older patients. While these guidelines can help better allocate limited colonoscopy resources, their increasing complexity may limit their adoption and potential benefits. Therefore, tools to support clinicians in navigating these guidelines could be essential for national bowel cancer prevention efforts. Digital applications (DAs) represent a potentially inexpensive and scalable solution but are yet to be tested for this purpose. OBJECTIVE: This study aims to assess whether a DA could increase clinician adherence to Australia's new colorectal cancer screening and surveillance guidelines and determine whether improved usability correlates with greater conformance to guidelines. METHODS: As part of a randomized controlled crossover study, we created a clinical vignette quiz to evaluate the efficacy of a DA in comparison with the standard resource (SR) for making screening and surveillance decisions. Briefings were provided to study participants, which were tailored to their level of familiarity with the guidelines. We measured the adherence of clinicians according to their number of guideline-concordant responses to the scenarios in the quiz using either the DA or the SR. The maximum score was 18, with higher scores indicating improved adherence. We also tested the DA's usability using the System Usability Scale. RESULTS: Of 117 participants, 80 were included in the final analysis. Using the SR, the adherence of participants was rated a median (IQR) score of 10 (7.75-13) out of 18. The participants' adherence improved by 40% (relative risk 1.4, P<.001) when using the DA, reaching a median (IQR) score of 14 (12-17) out of 18. The DA was rated highly for usability with a median (IQR) score of 90 (72.5-95) and ranked in the 96th percentile of systems. There was a moderate correlation between the usability of the DA and better adherence (rs=0.4; P<.001). No differences between the adherence of specialists and nonspecialists were found, either with the SR (10 vs 9; P=.47) or with the DA (13 vs 15; P=.24). There was no significant association between participants who were less adherent with the DA (n=17) and their age (P=.06), experience with decision support tools (P=.51), or academic involvement with a university (P=.39). CONCLUSIONS: DAs can significantly improve the adoption of complex Australian bowel cancer prevention guidelines. As screening and surveillance guidelines become increasingly complex and personalized, these tools will be crucial to help clinicians accurately determine the most appropriate recommendations for their patients. Additional research to understand why some practitioners perform worse with DAs is required. Further improvements in application usability may optimize guideline concordance further.

Comparing the resource implications of old and new colorectal adenoma surveillance guidelines in Australia.

BACKGROUND: The latest update to the Australian adenoma surveillance guideline in 2018 introduced a novel risk stratification system with updated surveillance recommendations. The resource implications of adopting this new system are unclear. AIMS: To quanitfy the resource demands of adopting new over old adenoma surveillance guidelines. METHODS: We studied data from 2443 patients undergoing colonoscopies, in which a clinically significant lesion was identified in their latest, or previous procedure(s) across five Australian hospitals. We excluded procedures with inflammatory bowel disease, new or prior history of colorectal cancer or resection, inadequate bowel preparation and incomplete procedures. Old and new Australian surveillance intervals were calculated according to the number, size and histological characteristics of lesions identified. We used these data to compare the rate of procedures according to each guideline. RESULTS: Based on the procedures for 766 patients, the new surveillance guidelines significantly increased the number of procedures allocated an interval of 1 year (relative risk (RR): 1.57, P = 0.009) and 10 years (RR: 3.83, P < 0.00001) and reduced those allocated to half a year (RR: 0.08, P = 0.00219), 3 years (RR: 0.51, P < 0.00001) and 5 years (RR: 0.59, P < 0.00001). Overall, this reduced the relative number of surveillance procedures by 21% over 10 years (25.92 vs 32.78 procedures/100 patient-years), which increased to 22% after excluding patients 75 or older at the time of surveillance (19.9 vs 25.65 procedures/100 patient-years). CONCLUSION: The adoption of the latest Australian adenoma surveillance guidelines can reduce demand for surveillance colonoscopy by more than a fifth (21-22%) over 10 years.

The Diagnostic Performance of Fecal Immunochemical Tests for Detecting Advanced Neoplasia at Surveillance Colonoscopy.

BACKGROUND & AIMS: An increasing burden on health care resources has resulted in a backlog of individuals requiring colonoscopy, with delays in surveillance possibly detrimental for individuals at increased risk of colorectal cancer (CRC). This study investigated the use of a 2-sample fecal immunochemical test (FIT) to establish those most likely to have advanced neoplasia (AN) and in need of prioritized surveillance colonoscopy. METHODS: This was a prospective study conducted in the tertiary care setting. Participants completed a 2-sample FIT (OC-Sensor, Eiken Chemical Company) within 90 days of surveillance colonoscopy. The sensitivity of FIT for detection of AN (CRC or advanced adenoma) in moderate- and high-risk individuals was determined at fecal hemoglobin thresholds between 2 and 80 µg/g feces. RESULTS: A total of 766 patients were included (median age, 66.1 years [interquartile range, 58.1-72.9]; 49.9% male), with AN detected in 8.6% (66/766, including 5 CRC). For moderate-risk individuals (with prior history of adenoma or a significant family history of CRC), sensitivity of FIT for AN ranged from 73.5% at 2 µg/g feces, to 10.2% at 80 µg/g feces. For high-risk conditions (confirmed/suspected genetic syndromes or prior CRC), sensitivity of FIT was similar, ranging from 70.6% at the lowest positivity threshold of 2 µg/g feces, to 11.8% at 80 µg/g feces. Independent variables in the whole cohort for association with detection of AN at surveillance colonoscopy were age (odds ratio, 1.03; 95% confidence interval, 1.00-1.06) and FIT hemoglobin result ≥10 µg/g feces (odds ratio, 1.81; 95% confidence interval, 1.04-3.16). CONCLUSIONS: The use of FIT before surveillance colonoscopy provides clinicians with insights into the risk of AN. This raises the possibility of a method to triage individuals, facilitating the more efficient management of endoscopic resources.

Low Incidence of Colorectal Advanced Neoplasia During Surveillance in Individuals with a Family History of Colorectal Cancer.

BACKGROUND: Family history of colorectal cancer (CRC) is used to stratify individuals into risk categories which determine timing of initial screening and ongoing CRC surveillance. Evidence for long-term CRC risk following a normal index colonoscopy in family history populations is limited. AIMS: To assess the incidence of advanced neoplasia and associated risk factors in a population undergoing surveillance colonoscopies due to family history of CRC. METHODS: Surveillance colonoscopy findings were examined in 425 individuals with a family history of CRC, a normal index colonoscopy and a minimum of 10 years of follow-up colonoscopies. Advanced neoplasia risk was determined for three CRC family history categories (near-average, medium and high-risk), accounting for demographics and time after the first colonoscopy. RESULTS: The median follow-up was 13.5 years (IQR 11.5-16.0), with an incidence of advanced neoplasia of 14.35% (61/425). The number of affected relatives and age of CRC diagnosis in the youngest relative did not predict the risk of advanced neoplasia (p > 0.05), with no significant differences in advanced neoplasia incidence between the family history categories (p = 0.16). Patients ≥ 60 years showed a fourfold (HR 4.14, 95% CI 1.33-12.89) higher advanced neoplasia risk during surveillance than those < 40 years at index colonoscopy. With each subsequent negative colonoscopy, the risk of advanced neoplasia at ongoing surveillance was reduced. CONCLUSIONS: The incidence of advanced neoplasia was low (14.35%), regardless of the family history risk category, with older age being the main risk for advanced neoplasia. Delaying onset of colonoscopy or lengthening surveillance intervals could be a more efficient use of resources in this population.

FIT for purpose: study protocol for a randomized controlled trial to personalize surveillance colonoscopy for individuals at elevated risk of colorectal cancer.

PURPOSE: There is increasing demand for colorectal cancer (CRC) surveillance, but healthcare capacity is limited. The burden on colonoscopy resources could be reduced by personalizing surveillance frequency using the fecal immunochemical test (FIT). This study will determine the safety, cost-effectiveness, and patient acceptance of using FIT to extend surveillance colonoscopy intervals for individuals at elevated risk of CRC. METHODS: This multicenter, prospective, randomized controlled trial will invite participants who are scheduled for surveillance colonoscopy (due to a personal history of adenomas or a family history of CRC) and who have returned a low fecal hemoglobin (< 2 µg Hb/g feces; F-Hb) using a two-sample FIT (OC Sensor, Eiken Chemical Company) in the prior 3 years. A total of 1344 individuals will be randomized to either surveillance colonoscopy as scheduled or delayed by 1 or 2 years for individuals originally recommended a 3- or 5-year surveillance interval, respectively. The primary endpoint is incidence of advanced neoplasia (advanced adenoma and/or CRC). Secondary endpoints include cost-effectiveness and consumer acceptability of extending surveillance intervals, determined using surveys and discrete choice experiments. CONCLUSION: This study will establish the safety, cost-effectiveness, and acceptability of utilizing a low FIT Hb result to extend colonoscopy surveillance intervals in a cohort at elevated risk for CRC. This personalized approach to CRC surveillance will lead to a reduction in unnecessary colonoscopies, increases in healthcare savings, and a better patient experience.  TRIAL REGISTRATION: Registration was approved on December 9, 2019 with the Australian New Zealand Clinical Trials Registry ANZCTR 12619001743156.

Simple Novel Screening Tool for Obstructive Sleep Apnea in Inflammatory Bowel Disease.

Background: Inflammatory bowel disease (IBD) has been associated with an increased risk of obstructive sleep apnea (OSA). We aimed to examine the associations of obstructive sleep apnea, sleepiness, and IBD-related data and comorbidities, with the aim of developing a screening tool for sleep apnea in this population. Methods: An online survey of adults with IBD was administered which included measures of assessment of the risk of OSA, and measures of IBD activity, IBD-related disability, anxiety, and depression. Logistic regression was performed to investigate the associations between the risk of OSA and IBD data, medications, demographics, and mental health conditions. Further models were built for an outcome of severe daytime sleepiness and a combined outcome of risk of OSA and at least mild daytime sleepiness. A simple score was constructed for the purpose of screening for OSA. Results: There were 670 responses to the online questionnaire. The median age was 41 years, the majority had Crohn's disease (57%), the median disease duration was 11.9 years, and approximately half were on biologics (50.5%). Moderate-high risk of OSA was demonstrated in 22.6% of the cohort. A multivariate regression model for moderate-high risk of OSA included increasing age, obesity, smoking, and abdominal pain subscore. For a combined outcome of moderate-high risk of OSA and at least mild daytime sleepiness, a multivariate model included abdominal pain, age, smoking, obesity, and clinically significant depression. A simple score was constructed for screening for OSA utilizing age, obesity, IBD activity, and smoking status with an area under the receiver-operating curve of 0.77. A score >2 had a sensitivity of 89% and a specificity of 56% for moderate-high risk of OSA and could be utilized for screening for OSA in the IBD clinic. Conclusions: Over one-fifth of an IBD cohort met significantly high-risk criteria for OSA to warrant referral for a diagnostic sleep study. The risk of OSA was associated with abdominal pain, along with more traditional risk factors such as smoking, increasing age, and obesity. Consideration should be given for screening for OSA in IBD patients utilizing a novel screening tool that utilizes parameters typically available in IBD clinic.

Multiple Negative Fecal Immunochemical Tests Reduce Risk of Advanced Neoplasia in a Colonoscopy Surveillance Program.

BACKGROUND & AIMS: In above-average-risk individuals undergoing colonoscopy-based surveillance for colorectal cancer (CRC), screening with fecal immunochemical tests (FIT) between colonoscopies might facilitate personalization of surveillance intervals. Because a negative FIT is associated with a reduced risk for CRC, we examined the relationship between number of rounds of negative FIT and risk for advanced neoplasia in individuals undergoing surveillance colonoscopy. METHODS: We conducted a retrospective cohort study on 4021 surveillance intervals in 3369 individuals (50-74 years), who had completed a 2-sample FIT between colonoscopies, from 1 to 4 rounds at 1-2 yearly intervals, each with a negative result (<20 µg hemoglobin/g feces). Incidence of advanced neoplasia (CRC or advanced adenoma) was determined at the follow-up colonoscopy. Competing-risk regression was used to assess the association between multiple negative FIT results and the risk of advanced neoplasia within 2 years. RESULTS: The incidence of advanced neoplasia in the cohort was 9.9% and decreased with increasing numbers of rounds of negative FIT results: 11.1% after 1 negative FIT to 5.7% after 4 negative FIT. The risk of advanced neoplasia was significantly lower in participants with 3 (subdistribution hazard ratio, 0.50; 95% confidence interval, 0.24-0.97) and 4 (subdistribution hazard ratio, 0.33; 95% confidence interval, 0.15-0.73) rounds of negative FIT compared with only 1 negative FIT. CONCLUSIONS: There was a low risk of advanced neoplasia after multiple rounds of negative FIT in above-average-risk people undergoing surveillance with no neoplasia or nonadvanced adenoma at prior colonoscopy. This supports the use of interval FIT to personalize surveillance by lengthening colonoscopy intervals following multiple negative FIT results.

Quality of colonoscopy performed by medical or surgical specialists and trainees in five Australian hospitals.

BACKGROUND: Ensuring colonoscopy procedure quality is vital to the success of screening and surveillance programmes for bowel cancer in Australia. However, the data on the performance of quality metrics, through adequate adenoma detection, bowel preparation, and procedure completion rates, in the Australian public sector is limited. Understanding these can inform quality improvement to further strengthen our capacity for prevention and early detection of colorectal cancer. AIM: To determine the quality of colonoscopy in Australian teaching hospitals and their association with proceduralist specialty, trainee involvement, and location. METHODS: We retrospectively evaluated 2443 consecutive colonoscopy procedure reports from 1 January to 1 April, 2018 from five public teaching tertiary hospitals in Australia (median 60 years old, 49% male). Data for bowel preparation quality, procedure completion rates, and detection rates of clinically significant adenomas, conventional adenomas, and serrated lesions was collected and compared to national criteria for quality in colonoscopy. Participating hospital, proceduralist specialty, and trainee involvement indicators were used for stratification. Data was analysed using Chi-squared tests of independence, Mann-Whitney U, One-way ANOVA, and multivariate binary logistic regression. RESULTS: Fifty-two point two percent (n = 1276) and 43.3% (n = 1057) were performed by medical and surgical proceduralists respectively, whilst 29.8% (n = 728) involved a trainee. Inadequate bowel preparation affected 7.3% of all procedures. The procedure completion rate was 95.1%, which increased to 97.5% after adjustment for bowel preparation quality. The pooled cancer, adenoma, and serrated lesion detection rates for all five hospitals were 3.5%, 40%, and 5.9% respectively. Assessed hospitals varied significantly by patient age (P < 0.001), work-force composition (P < 0.001), adequacy of bowel preparation (P < 0.001), and adenoma detection rate (P < 0.001). Two hospitals (40%) did not meet all national criteria for quality, due to a procedure completion rate of 94.5% or serrated lesion detection rate of 2.6%. Although lower than the other hospitals, the difference was not significant. Compared with surgical specialists, procedures performed by medical specialists involved older patients [65 years (inter-quartile range, IQR 58-73) vs 64 years (IQR 56-71); P = 0.04] and were associated with a higher adenoma detection rate [odds ratio (OR) 1.53; confidence interval: 1.21-1.94; P < 0.001]. Procedures involving trainee proceduralists were not associated with differences in the detection of cancer, adenoma, or serrated lesions, compared with specialists, or according to their medical or surgical background. On multivariate analysis, cancer detection was positively associated with patient age (OR 1.04; P < 0.001) and negatively associated with medical compared to surgical proceduralists (OR 0.54; P = 0.04). Conventional adenoma detection rates were independently associated with increasing patient age (OR 1.04; P < 0.001), positively associated with medical compared to surgical proceduralists (OR 1.41; P = 0.002) and negatively associated with male gender (OR 0.53; P < 0.001). CONCLUSION: Significant differences in the quality of colonoscopy in Australia exist, even when national benchmarks are achieved. The role of possible contributing factors, like procedural specialty and patient gender need further evaluation.

Faecal immunochemical test mitigates risk of delayed colonoscopy in people with elevated risk of colorectal neoplasia.

BACKGROUND AND AIM: Surveillance colonoscopies may be delayed because of pressure on resources, such as the COVID-19 pandemic. This study aimed to determine whether delayed surveillance colonoscopy increases the risk for advanced neoplasia and whether interval screening with faecal immunochemical tests (FITs) and other known risk factors can mitigate this risk. METHODS: A retrospective cohort study of individuals undergoing surveillance colonoscopy for personal or family history of colorectal neoplasia was being provided with FIT between colonoscopies. Colonoscopy ≥ 6 months after the guideline-recommended interval was considered "delayed." Individuals were stratified based on prime colonoscopy findings to nonneoplastic findings, non-advanced adenoma, and advanced adenoma. The relative risk (RR) for developing advanced neoplasia was determined using a robust multivariable modified Poisson regression. RESULTS: Of 2548 surveillance colonoscopies, 1457 (57.18%) were delayed. Prior advanced adenoma, older age (> 60 years) and nonparticipation in interval FIT were associated with increased risk for advanced neoplasia (P < 0.05). There was a trend to increased risk in those with prior advanced adenoma with an increasing colonoscopy delay (P trend = 0.01). In participants who did not complete interval FIT and having advanced adenoma in the prime colonoscopy, risk of advanced neoplasia was 2.48 times higher (RR = 2.48, 95% confidence interval: 1.20-5.13) in participants who had beyond 2 years of delayed colonoscopy compared with those with on-time colonoscopy. Colonoscopy delay did not increase the risk of advanced neoplasia in participants with negative interval FIT results. CONCLUSION: Surveillance colonoscopy can be safely extended beyond 6 months in elevated colorectal cancer risk patients who do not have prior advanced adenoma diagnosis, particularly if interval FIT is negative.

Circulating Dipeptidyl Peptidase Activity Is a Potential Biomarker for Inflammatory Bowel Disease.

INTRODUCTION: Dipeptidyl peptidase (DPP)-4 is part of a larger family of proteases referred to as DPPs. DPP4 has been suggested as a possible biomarker for inflammatory bowel disease (IBD). Circulating DPP4 (cDPP4) enzyme activity was investigated as a potential biomarker for IBD. In addition, DPP enzyme activity and gene expression were quantified in colonic tissue of patients with IBD and non-IBD. METHODS: In study 1, DPP enzyme activity was quantified in plasma samples from 220 patients with IBD (Crohn's disease [CD] n = 130 and ulcerative colitis [UC] n = 90) and non-IBD controls (n = 26) using a colorimetric assay. In study 2, tissue and plasma samples were collected from 26 patients with IBD and 20 non-IBD controls. Plasma C-reactive protein (CRP) was quantified in all patients. Colonic DPP4, DPP8, DPP9, and fibroblast activation protein (FAP) gene expression was determined by quantitative polymerase chain reaction. cDPP and cFAP enzyme activity was also measured. Sensitivity and specificity were determined by receiver operating characteristic curve analysis. RESULTS: In study 1, total cDPP activity was found to differentiate patients with CD with active disease (n = 18) from those in remission (n = 19; sensitivity 78% and specificity 63%). In study 2, total cDPP and cFAP activity was 28% and 48% lower in patients with elevated CRP (>10 mg/L), respectively, compared with patients with normal CRP. Gene expression of DPP4, FAP, and DPP8 was also significantly higher in colonic biopsies from patients with IBD compared with non-IBD patients (P < 0.05). DISCUSSION: Our findings implicate the DPP enzyme family in intestinal inflammation and suggest future biomarker applications to differentiate the pathophysiological aspects of IBD.

The influence of the surveillance time interval on the risk of advanced neoplasia after non-advanced adenoma removal.

OBJECTIVES: To investigate the incidence of advanced neoplasia (colorectal cancer or advanced adenoma) at surveillance colonoscopy following removal of non-advanced adenoma; to determine whether the time interval before surveillance colonoscopy influences the likelihood of advanced neoplasia. DESIGN: Retrospective cohort study. SETTING, PARTICIPANTS: Patients enrolled in a South Australian surveillance colonoscopy program with findings of non-advanced adenoma during 1999-2016 who subsequently underwent surveillance colonoscopy. MAIN OUTCOME MEASURES: Incidence of advanced neoplasia at follow-up surveillance colonoscopy. RESULTS: Advanced neoplasia was detected in 169 of 965 eligible surveillance colonoscopies (18%) for 904 unique patients (median age, 62.0 years; interquartile range [IQR], 54.0-69.0 years), of whom 570 were men (59.1%). The median interval between the initial and surveillance procedures was 5.2 years (IQR, 4.4-6.0 years; range, 2.0-14 years). Factors associated with increased risk of advanced neoplasia at follow-up included age (per year: odds ratio [OR], 1.03; 95% CI, 1.01-1.05), prior history of adenoma (OR, 1.48; 95% CI, 1.01-2.15), two non-advanced adenomas identified at baseline procedure (v one: OR, 1.74; 95% CI, 1.18-2.57), and time to surveillance colonoscopy (OR, 1.21; 95% CI, 1.08-1.37). The estimated incidence of advanced neoplasia was 19% five years after non-advanced adenoma removal, and 30% at ten years. CONCLUSIONS: Increasing the surveillance colonoscopy interval beyond five years after removal of non-advanced adenoma increases the risk of detection of advanced neoplasia at follow-up colonoscopy.

The impact of coronavirus disease 2019 on surveillance colonoscopies in South Australia.

BACKGROUND AND AIM: The coronavirus disease 2019 (COVID-19) global pandemic has affected elective procedures, including colonoscopy, worldwide. Delayed colorectal cancer surveillance may increase cancer risk. This study aimed to determine the impact of COVID-19 on the proportion of surveillance colonoscopies booked and completed and the extent to which that surveillance was delayed. METHODS: This was a retrospective analysis of colonoscopy data during the 3 months (April-June 2020) when clinical services were most affected by COVID-19 in South Australia compared to the same period in 2019. Data on colonoscopies and responses to surveillance recall letters were reviewed to determine the numbers and proportions of colonoscopies that were delayed. RESULTS: During 2020, the total number of colonoscopies decreased by 51.1% (n = 569) compared to 2019 (n = 1164). In 2019, 45.5% (n = 530) of colonoscopies were completed for surveillance, but this proportion decreased to 32.0% (n = 182) during 2020, an overall decrease in the number of surveillance colonoscopies of 65.6%. Of surveillance colonoscopies that were due in 2020, 46.1% (134/291) were delayed >6 months, a significant increase compared to 2019 (19.3%; 59/306, P < 0.001). A decrease in response to surveillance recall letters was only observed in patients ≥75 years, with more nonresponders (51.6%) in 2020 compared to that observed in 2019 (25.6%, P = 0.03). CONCLUSIONS: Significant delays in surveillance colonoscopies occurred during the COVID-19 pandemic in South Australia. These effects are likely to be in areas more severely affected by the pandemic. Planning for post-COVID-19 colonoscopy capacity is required to avoid cancer progression due to delays in surveillance colonoscopies.

Features associated with high-risk sessile serrated polyps at index and follow-up colonoscopy.

BACKGROUND AND AIM: Clinically significant serrated polyps are precursors of colorectal cancers, with features considered high risk including size ≥10 mm, dysplasia, and presence of synchronous conventional adenoma. While these features have been described in cohorts undergoing screening colonoscopy, there is little information regarding the prevalence and patient characteristics associated with high-risk sessile serrated polyps (SSPs) in those undergoing surveillance colonoscopy. METHODS: Polyp pathology at the index and first follow-up colonoscopy performed between 2004 and 2019 were examined in patients enrolled in a surveillance program because of an index finding of adenoma and/or SSP. Demographics and pathology features for SSP were compared between the colonoscopies. RESULTS: Of 6297 patients undergoing index colonoscopy, 2035 underwent follow-up colonoscopy after 3.3 years (interquartile range 2.1-4.8 years). The proportion with SSP decreased from 7.6% at index to 5.0% at follow-up (P < 0.001); however, the proportion of SSPs that were considered high risk was not different between the colonoscopies (62.8% vs 62.4%). Female gender was associated with the presence of high-risk SSP at index colonoscopy (odds ratio [OR] 1.62, 95% confidence interval [CI] 1.28-2.06), while age ≥75 years (OR 3.38, 95% CI 1.67-6.81) and previous high-risk SSP (OR 9.40, 95% CI 4.23-20.88) were independently associated with high-risk SSP at follow-up. CONCLUSIONS: The prevalence of SSP falls by one-third at first follow-up colonoscopy although the proportion of SSP with high-risk features remains the same. While females were more likely to have a high-risk SSP at the index colonoscopy, those at greatest risk for high-risk SSP at follow-up colonoscopy were age >75 years and an index high-risk SSP.

Vedolizumab for ulcerative colitis: Real world outcomes from a multicenter observational cohort of Australia and Oxford.

BACKGROUND: Vedolizumab (VDZ), a humanised monoclonal antibody that selectively inhibits alpha4-beta7 integrins is approved for use in adult moderate to severe ulcerative colitis (UC) patients. AIM: To assess the efficacy and safety of VDZ in the real-world management of UC in a large multicenter cohort involving two countries and to identify predictors of achieving remission. METHODS: A retrospective review of Australian and Oxford, United Kingdom data for UC patients. Clinical response at 3 mo, endoscopic remission at 6 mo and clinical remission at 3, 6 and 12 mo were assessed. Cox regression models and Kaplan Meier curves were performed to assess the time to remission, time to failure and the covariates influencing them. Safety outcomes were recorded. RESULTS: Three hundred and three UC patients from 14 centres in Australia and United Kingdom, [60% n = 182, anti-TNF naïve] were included. The clinical response was 79% at 3 mo with more Australian patients achieving clinical response compared to Oxford (83% vs 70% P = 0.01). Clinical remission for all patients was 56%, 62% and 60% at 3, 6 and 12 mo respectively. Anti-TNF naive patients were more likely to achieve remission than exposed patients at all the time points (3 mo 66% vs 40% P < 0.001, 6 mo 73% vs 46% P < 0.001, 12 mo 66% vs 51% P = 0.03). More Australian patients achieved endoscopic remission at 6 mo compared to Oxford (69% vs 43% P = 0.01). On multi-variate analysis, anti-TNF naïve patients were 1.8 (95%CI: 1.3-2.3) times more likely to achieve remission than anti-TNF exposed (P < 0.001). 32 patients (11%) had colectomy by 12 mo. CONCLUSION: VDZ was safe and effective with 60% of UC patients achieving clinical remission at 12 mo and prior anti-TNF exposure influenced this outcome.

Level of UV Exposure, Skin Type, and Age Are More Important than Thiopurine Use for Keratinocyte Carcinoma Development in IBD Patients.

BACKGROUND: Retrospective studies observe an increased risk of keratinocyte carcinomas (KCs) in patients with inflammatory bowel disease (IBD) on thiopurine (TP) medication. The role of traditional risk factors such as skin type and sun protection behavior has not been studied in this population. This study aimed to examine traditional KC risk factors and thiopurine use on skin cancer development in an IBD cohort. METHODS: Consecutive IBD patients were recruited from four specialist centers in Australia and New Zealand, each with varying UV exposure indices. Data pertaining to race, skin color, freckling and sun protection behavior, dose of TP therapy, and skin cancer development were elicited through a self-reported questionnaire. RESULTS: A total of 691 IBD patients were included with 62 reporting KC development. Thiopurine usage was similar among patients who developed skin cancer compared with those who did not (92% vs. 89%, p = 0.3). There was no statistically significant association between KC development and TP dose or 6-thioguanine nucleotide levels. In multivariate modeling, four factors were independently and significantly associated with KC: age over 61 years old versus less than 30 years old (OR 6.76; 95% CI 2.38-19.18), residing in Brisbane versus Christchurch (OR 3.3; 95% CI 1.6-6.8), never staying in the shade versus staying in the shade ≥ 50% of the time (OR 3.8; 95% CI 1.4-10.5), and having a skin type that never tanned versus other skin types (OR 6.9; 95% CI 2.9-16.0). CONCLUSION: Skin type, age, and sun protection behavior are more important risk factors for KC development than thiopurine medication use in this IBD population.

Anti-TNF Therapy in Pregnant Women With Inflammatory Bowel Disease: Effects of Therapeutic Strategies on Disease Behavior and Birth Outcomes.

BACKGROUND: Active inflammatory bowel disease (IBD) adversely affects pregnancy outcomes. Little is known about the risk of relapse after stopping anti-tumor necrosis factor (anti-TNF) treatment during pregnancy. We assessed the risk of relapse before delivery in women who discontinued anti-TNF treatment before gestational week (GW) 30, predictors of reduced infant birth weight, a marker associated with long-term adverse outcomes, and rates and satisfaction with counseling. METHODS: Pregnant women with IBD receiving anti-TNF treatment were prospectively invited to participate in an electronic questionnaire carried out in 22 hospitals in Denmark, Australia, and New Zealand from 2011 to 2015. Risk estimates were calculated, and birth weight was investigated using t tests and linear regression. RESULTS: Of 175 women invited, 153 (87%) responded. In women in remission, the relapse rate did not differ significantly between those who discontinued anti-TNF before GW 30 (1/46, 2%) compared with those who continued treatment (8/74, 11%; relative risk, 0.20; 95% confidence interval [CI], 0.02 to 1.56; P = 0.08). Relapse (P = 0.001) and continuation of anti-TNF therapy after GW 30 (P = 0.007) were independently associated with reduced mean birth weight by 367 g (95% CI, 145 to 589 g; relapse) and 274 g (95% CI, 77 to 471 g; anti-TNF exposure after GW 30). Of 134 (88%) women who received counseling, 116 (87%) were satisfied with the information provided. CONCLUSIONS: To minimize fetal exposure in women in remission, discontinuation of anti-TNF before GW 30 seems safe. Relapse and continuation of anti-TNF therapy after GW 30 were each independently associated with lower birth weight, although without an increased risk for birth weight <2500 g. Most women received and were satisfied with counseling.