Incorporating faecal haemoglobin measurement using the faecal immunochemical test (FIT) in the referral, triage and prioritisation pathway for patients with colorectal symptoms.

Incorporating faecal haemoglobin (FHb) measurement using the faecal immunochemical test (FIT) in the investigation pathway for patients with colorectal symptoms may improve access to colonoscopy for those at greatest risk of significant disease. AIM: To derive a colorectal symptom pathway incorporating standard clinical and FIT data to guide referral, triage, and prioritisation of cases in New Zealand. METHOD: Diagnostic accuracy of FIT to rule out colorectal cancer (CRC) was determined by meta-analysis. Thereafter, the risk of CRC after FIT was estimated for common clinical presentations by Bayesian methodology, using a specifically collated retrospective cohort of symptomatic cases. A symptom/FIT pathway was developed iteratively following multi-disciplinary engagement. RESULTS: Eighteen studies were included in meta-analysis. The sensitivity and specificity for CRC were 89.0% (95%CI 87.0-90.9%) and 80.1% (95%CI 77.7-82.4%) respectively, at a FHb threshold of >10mcg haemoglobin per gram stool, and 95.7% (95%CI 93.2-97.7%) and 60.5% (95%CI 53.8-67.0%) respectively, at the limit of detection. The final pathway was 97% sensitive for CRC, compared with 90% for the current direct access criteria, and requires 47% fewer colonoscopies. Estimated prevalence of CRC among those declined investigation was 0.23%. CONCLUSION: Incorporating FIT in the new patient symptomatic pathway as presented appears feasible, safe, and allows for resources to be targeted to those at greatest risk of disease. Further work is needed to ensure equity for Maori if this pathway were introduced nationally.

Improving early detection of colorectal cancer in Aotearoa New Zealand; how do the direct access criteria perform?

AIM: Colorectal cancer (CRC) is a common malignancy in New Zealand, and there is increasing pressure on investigative resources for diagnosis. The national direct access referral guidelines from the Ministry of Health (MoH) guide who should be referred for investigation, but their performance in detecting CRC and other significant diseases has not been reported previously. This paper describes the yield, by direct access criterion, of all referrals through the direct access pathway to the Canterbury District Health Board (CDHB) during 2018. METHODS: First referrals received through the direct access colonoscopy/computed tomography colonography (CTC) pathway for 2018 were audited. Patients were assigned to symptom groups corresponding to the MoH direct access criteria, and demographic data were captured. Diagnostic outcomes were collected through analysis of all endoscopy, CT colonography and histology reports in the 18 months following referral for primary analysis, with further follow-up through to May 2021 to detect missed pathology. RESULTS: Three thousand two hundred referrals were analysed, and 88.5% underwent colorectal investigation. 128 CRC were diagnosed, 176 advanced polyps, 49 cases of inflammatory bowel disease (IBD) and there were 56 other significant findings. The yield by category for the direct access criteria varied between 0-15.0%, and one urgent criterion had a CRC yield lower than two semi-urgent categories. For patients whose symptoms met at least one of the criteria, excluding those referred with suspected IBD, the combined CRC yield was 4.9%, compared with 1.8% in those who did not meet criteria. The sensitivity and specificity of the criteria for CRC (excluding IBD) was 90% and 23% respectively. There were no CRC detected during the extended follow-up period. CONCLUSION: In this referred population, the MoH direct access colonoscopy/CTC criteria varied significantly in their CRC yield, with an arbitrary distinction between urgent and semi-urgent categories. The low specificity of the criteria means the number needed to investigate to detect one CRC was one in 22. Improved diagnostic algorithms are urgently required to improve both the sensitivity and specificity, thereby more appropriately allocating finite resources to those patients who are most in need of investigation.

Long-term incidence of dysplasia and colorectal cancer in an ulcerative colitis population-based cohort.

BACKGROUND: Ulcerative colitis (UC) is a risk factor in developing colorectal cancer (CRC). Surveillance programmes aim to identify premalignant lesions to facilitate improved treatment outcomes. Recent studies have suggested that the risk of CRC in UC has decreased. This study aims to characterize the risk of CRC in UC in a population-based New Zealand cohort. METHODS: All patients in the Canterbury Inflammatory Bowel Disease Study, a comprehensive population-based cohort, were reviewed and cases of dysplasia and CRC identified. Demographic data and risk factors were assessed and standardized incidence ratios (SIRs) calculated comparing with the national population. RESULTS: A total of 518 UC cases were analysed (46.3% female). Median follow-up was 17.5 years (interquartile range 12.2-25.1 years). Neoplasia developed in 42 (8.1%) patients, 14 (2.7%) of whom had CRC. The mean age at CRC diagnosis was 63.3 years, and mean duration with UC before CRC 18.4 years (0-36.8 years). The total incidence rate was 1.35/1000 person-year duration (95% confidence interval 0.74-2.27). The age-adjusted SIR was 1.74 (95% confidence interval 1.03-2.93) compared to the New Zealand population. Risk factors for any dysplasia included disease extent and male gender. CONCLUSION: In this population-based cohort with long-term follow-up, the SIR of CRC in UC patients was significantly lower than the initial epidemiological studies although similar to more recent studies. This increased risk still justifies ongoing screening in the UC population.

Early referral for endoscopy is the most appropriate management strategy in cases of food bolus obstruction.

OBJECTIVE: To investigate the characteristics of patients presenting with oesophageal food bolus obstruction (FBO) who achieve early resolution of symptoms, and to assess the impact of medical therapies on the overall time course of FBO. METHODS: A retrospective observational study was performed in a university teaching hospital with regional acute endoscopy services. Patients presenting with symptoms of FBO were identified through clinical coding and demographic, clinical and endoscopic data extracted from the electronic medical record. The primary outcome was the time to resolution defined as the earliest of symptom resolution, endoscopic or surgical intervention or discharge. RESULTS: A total of 116 patients presented with symptoms of FBO. Twenty-seven (23.3%) had early resolution of symptoms and were discharged from the ED without acute endoscopy, the remainder were admitted for further management. Patients discharged from the ED presented to hospital sooner after the onset of symptoms (137 vs 288 min, P < 0.05), but did not differ from those admitted in any other characteristic. Seventy-one (61.2%) patients received medical therapy. There was no statistical difference in the time to resolution between those who received medical therapy and those who did not. Furthermore, the use of medical therapy was associated with a delay in referral for endoscopy (140 vs 100 min, P < 0.05). CONCLUSIONS: Time from symptom onset to presentation is the only predictor of early resolution from FBO, while medical therapy is ineffective in relieving obstruction and may delay definitive therapy. We recommend the use of an institutional management plan to facilitate early access to endoscopy in cases of FBO.

Disease activity assessment in IBD: clinical indices and biomarkers fail to predict endoscopic remission.

BACKGROUND: In the current management paradigm, mucosal healing is preferred over clinical remission as a therapeutic end point in inflammatory bowel disease (IBD) because of the benefits engendered with respect to durability of remission. Colonoscopy, however, is not suitable for regular disease monitoring, and routine clinical assessment is often inaccurate with respect to endoscopic disease activity. The current investigation set out to characterize the relationship that exists between endoscopically determined IBD activity and clinical and biochemical measures of disease severity and to determine clinically useful thresholds for use in clinical practice. METHODS: Patients attending for colonoscopy with known or suspected IBD were recruited. Clinical disease activity was recorded as per the Harvey-Bradshaw Index for Crohn's disease or the simple clinical colitis activity index for ulcerative colitis. Endoscopic activity was recorded using the simple endoscopic score for Crohn's disease or the modified Baron score for ulcerative colitis. Receiver operating characteristic analysis determined the predictive value and optimal predictive thresholds for clinical and biomarker data. RESULTS: The Harvey-Bradshaw Index was not able to distinguish active from inactive Crohn's disease. The sensitivity, specificity, and positive and negative predictive values of simple clinical colitis activity index to detect endoscopic active disease were 43%, 96%, 94%, and 51%, respectively. Any elevation of C-reactive protein or fecal calprotectin was predictive of active mucosal disease, however, no lower threshold could be identified that predicted disease in remission. CONCLUSIONS: C-reactive protein and fecal calprotectin are useful for the identification of endoscopically active IBD, but normal results do not confirm endoscopic remission.

Total soluble and endogenous secretory receptor for advanced glycation endproducts (RAGE) in IBD.

BACKGROUND AND AIMS: Recruitment and activation of neutrophils, with release of specific proteins such as S100 proteins, is a feature of inflammatory bowel disease (IBD). Soluble forms of the receptor for advanced glycation endproducts (sRAGE), and variants such as endogenous secretory (esRAGE), can act as decoy receptors by binding ligands, including S100A12. The aims of this study were to determine total sRAGE and esRAGE concentrations in patients with IBD and correlate these with C-reactive protein (CRP), endoscopic scores and clinical disease activity scores. METHODS: EDTA-plasma was collected from patients undergoing colonoscopy including those with Crohn's disease (CD: n=125), ulcerative colitis (UC: n=79) and control patients without endoscopic signs of inflammation (non-IBD: n=156). Concentrations of sRAGE and esRAGE were determined by enzyme-linked immunosorbent assay and plasma CRP concentrations measured. Standard clinical disease activity and endoscopic severity scores were defined for all subjects. RESULTS: Plasma sRAGE concentrations were lower in UC (but not CD) than non-IBD subjects (p<0.01). Whilst sRAGE concentrations correlated negatively with endoscopic activity in UC (p<0.05), this was not seen in CD. In contrast, esRAGE correlated negatively with disease activity in both UC (p=0.002) and CD (p=0.0001). Furthermore, sRAGE and esRAGE concentrations correlated inversely with CRP values (p<0.0001). CONCLUSIONS: Although total sRAGE varied with activity in UC, esRAGE concentrations correlated inversely with endoscopic disease activity and CRP levels in both UC and CD. Additional studies are required to further define the significance of sRAGE and esRAGE in IBD.

Macrophage migration inhibitory factor gene polymorphisms in inflammatory bowel disease: an association study in New Zealand Caucasians and meta-analysis.

AIM: To investigate the association of macrophage migration inhibitory factor (MIF) promoter polymorphisms with inflammatory bowel disease (IBD) risk. METHODS: One thousand and six New Zealand Caucasian cases and 540 Caucasian controls were genotyped for the MIF SNP -173G > C (rs755622) and the repeat polymorphism CATT5₋8 (rs5844572) using a pre-designed TaqMan SNP assay and capillary electrophoresis, respectively. Data were analysed for single site and haplotype association with IBD risk and phenotype. Meta-analysis was employed, to assess cumulative evidence of association of MIF -173G > C with IBD. All published genotype data for MIF -173G > C in IBD were identified using PubMed and subsequently searching the references of all PubMed-identified studies. Imputed genotypes for MIF -173G > C were generated from the Wellcome Trust Case Control Consortium (and National Institute of Diabetes and Digestive and Kidney Diseases). Separate meta-analyses were performed on Caucasian Crohn's disease (CD) (3863 patients, 6031 controls), Caucasian ulcerative colitis (UC) (1260 patients, 1987 controls), and East Asian UC (416 patients and 789 controls) datasets using the Mantel-Haenszel method. The New Zealand dataset had 93% power, and the meta-analyses had 100% power to detect an effect size of OR = 1.40 at α = 0.05, respectively. RESULTS: In our New Zealand dataset, single-site analysis found no evidence of association of MIF polymorphisms with overall risk of CD, UC, and IBD or disease phenotype (all P values > 0.05). Haplotype analysis found the CATT5/-173C haplotype occurred at a higher frequency in New Zealand controls compared to IBD patients (0.6 vs 0.01; P = 0.03, OR = 0.22; 95%CI: 0.05-0.99), but this association did not survive bonferroni correction. Meta-analysis of our New Zealand MIF -173G > C data with data from seven additional Caucasian datasets using a random effects model found no association of MIF polymorphisms with CD, UC, or overall IBD. Similarly, meta-analysis of all published MIF -173G > C data from East Asian datasets (416 UC patients, 789 controls) found no association of this promoter polymorphism with UC. CONCLUSION: We found no evidence of association of MIF promoter polymorphisms with IBD.