The incidence of early onset colorectal cancer in Aotearoa New Zealand: 2000-2020.

BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC), diagnosed before age 50, has been rising in many countries in the past few decades. This study aims to evaluate this trend in Aotearoa New Zealand and assess its impact on Maori. METHODS: Crude incidence and age-standardized incidence of colorectal cancer (CRC) was analyzed from all new cases from the Aotearoa New Zealand national cancer registry for the period 2000-2020. Trends were estimated by sex, ethnicity, age group and location of cancer and projections made to 2040. RESULTS: Between 2000 and 2020, there were a total of 56,761 cases of CRC diagnosed in Aotearoa New Zealand, 3,702 of these being EOCRC, with age-standardized incidence decreasing significantly (P = 8.2 × 10- 80) from 61.0 to 47.3 cases per 100,000. EOCRC incidence increased on average by 26% per decade (incidence rate ratio (IRR) 1.26, p = < 0.0001) at all sites (proximal colon, distal colon and rectum), while the incidence in those aged 50-79 years decreased on average by 18% per decade (IRR 0.82, p = < 0.0005), again across all sites. There was no significant average change in CRC incidence in those over 80 years. In Maori, there was no significant change in age-standardized incidence. There was however a significant increase in crude incidence rates (IRR 1.28, p = < 0.0005) driven by significant increases in EOCRC (IRR1.36, p = < 0.0005). By 2040, we predict the incidence of EOCRC will have risen from 8.00 to 14.9 per 100,000 (6.33 to 10.00 per 100,000 in Maori). However, due to the aging population an estimated 43.0% of all CRC cases will be diagnosed in those over 80 years of age (45.9% over 70 years of age in Maori). CONCLUSION: The age-standardized incidence of CRC from 2000 to 2020 decreased in Aotearoa New Zealand, but not for Maori. The incidence of EOCRC over the same period continues to rise, and at a faster rate in Maori. However, with the ageing of the population in Aotearoa New Zealand, and for Maori, CRC in the elderly will continue to dominate case numbers.

Profile of Helicobacter pylori infections among children in the South Island of New Zealand (2010-2021).

BACKGROUND: Helicobacter pylori is a gram-negative gut bacterium most often acquired during childhood. International guidelines state that children with suspected H. pylori infection should be referred to a gastroenterologist for investigation via gastroscopy and biopsy. Eradication therapy should be prescribed for children with peptic ulcer disease or following a treatment risk/benefit discussion for those with an incidental gastroscopy finding. Guidelines state that for children a "test-and-treat" approach is not warranted, contrasting recommendations for adults. The aim of this study was to profile pediatric H. pylori infections in the South Island of New Zealand (NZ) to determine diagnostic and management strategies, and adherence to international guidelines. MATERIALS AND METHODS: Retrospective data for positive H. pylori tests between 2010 and 2021 were retrieved from hospitals and regional testing laboratories throughout the South Island (NZ) for children ≤18 years. Outcome data were retrieved from tertiary care hospital records; sociodemographic, testing methods, eradication therapy, and symptoms. RESULTS: Two-hundred and forty children were identified: 105 (44%) male, mean age 13.2 years (SD 4.3). Participants of Pasifika, Asian, and Middle Eastern/Latin American/African heritage were overrepresented compared to the NZ census data. Overall, 138 (58%) children were diagnosed via stool antigen tests, 78 (32%) serum, and only 24 (10%) adhered to international guidelines in being confirmed via gastroscopy. Only 59 (25%) had a record of eradication therapy, and 39/59 (66%) were retested to determine eradication success, with 32 (82%) negative tests and seven (18%) remaining positive. Of the 181 (75%) that had eradication status unknown, 66 (28%) had a retest result available with 48 (73%) testing negative and 18 (27%) positive, suggesting a substantial proportion had received eradication therapy without adhering to international guidelines. CONCLUSIONS: International guidelines were not adhered to for most children in the study cohort. Implications of this include cost, unnecessary venipuncture, and unjustified antibiotic exposure.

Detection of Chitinase 3-Like 1 in Symptomatic Primary Care Patient Faecal Samples is Not a Reliable Biomarker of Colonic Lesions.

BACKGROUND: The current gold standard non-invasive test for detecting pre-cancerous changes is the faecal immunochemical test (FIT). However, this test can lack sensitivity and specificity and testing for another biomarker may address these limitations. Chitinase 3-like 1 (CHI3L1) is emerging as a potential biomarker of inflammation-associated carcinogenic changes in epithelial cells.  In this study CHI3L1 levels were analysed in patients and controls to determine their ability to improve detection of early CRC either alone or in combination with a FIT. METHODS: CHI3L1 levels were measured by ELISA in serum and stool samples from cohorts of CRC and healthy donors as well as stool samples from a cohort of symptomatic primary care patients. Faecal haemoglobin was also analysed in the same primary care samples using FIT. RESULTS: CHI3L1 levels were a good discriminatory marker of CRC, with no significant difference between levels detected in the stool and serum samples.  ROC curves that determined the optimal cut-point however identified that stool samples gave higher sensitivity (83% versus 69%) and specificity (89% versus 74%) than matched serum samples. Faecal CHI3L1 levels in the primary care patients were not significantly different (p=0.193) from those detected in the healthy controls. ROC curve analysis confirmed that faecal CHI3L1 levels had limited ability to discriminate between patients who did or didn't have evidence of lesions (AUC=0.52, p=0.74). Similarly, CHI3L1 levels did not reliably identify those symptomatic primary care patients who subsequently presented with early-stage disease (polyps and adenomas) or CRC. The discriminatory power of FIT was not increased by incorporating the CHI3L1 results in this setting. CONCLUSION: There was no evidence that measurement of faecal CHI3L1 has the potential to increase diagnostic accuracy, either alone or in combination with a FIT, in symptomatic primary care patients.

Could Microplastics Be a Driver for Early Onset Colorectal Cancer?

Introduction: The incidence of colorectal cancer in those under 50 years of age (early onset colorectal cancer (EOCRC)) is increasing throughout the world. This has predominantly been an increase in distal colonic and rectal cancers, which are biologically similar to late onset colorectal cancer (LOCRC) but with higher rates of mucinous or signet ring histology, or poorly differentiated cancers. The epidemiology of this change suggests that it is a cohort effect since 1960, and is most likely driven by an environmental cause. We explore the possible role of microplastics as a driver for this change. Review: The development of sporadic colorectal cancer is likely facilitated by the interaction of gut bacteria and the intestinal wall. Normally, a complex layer of luminal mucus provides colonocytes with a level of protection from the effects of these bacteria and their toxins. Plastics were first developed in the early 1900s. After 1945 they became more widely used, with a resultant dramatic increase in plastic pollution and their breakdown to microplastics. Microplastics (MPs) are consumed by humans from an early age and in increasingly large quantities. As MPs pass through the gastrointestinal tract they interact with the normal physiological mechanism of the body, particularly in the colon and rectum, where they may interact with the protective colonic mucus layer. We describe several possible mechanisms of how microplastics may disrupt this mucus layer, thus reducing its protective effect and increasing the likelihood of colorectal cancer. Conclusions: The epidemiology of increase in EOCRC suggests an environmental driver. This increase in EOCRC matches the time sequence in which we could expect to see an effect of rapid increase of MPs in the environment and, as such, we have explored possible mechanisms for this effect. We suggest that it is possible that the MPs damage the barrier integrity of the colonic mucus layer, thus reducing its protective effect. MPs in CRC pathogenesis warrants further investigation. Future directions: Further clarification needs to be sought regarding the interaction between MPs, gut microbiota and the mucus layer. This will need to be modelled in long-term animal studies to better understand how chronic consumption of environmentally-acquired MPs may contribute to an increased risk of colorectal carcinogenesis.

Sputum inflammatory, neural, and remodeling mediators in eosinophilic and noneosinophilic asthma.

BACKGROUND: Neural and remodeling mechanisms may play a role in asthma, particularly noneosinophilic asthma (NEA). OBJECTIVE: To assess sputum mediators associated with neural, remodeling, and inflammatory mechanisms in eosinophilic asthma (EA), NEA, and participants without asthma. METHODS: A total of 111 participants with and 62 without asthma (14-21 years old) underwent sputum induction, exhaled nitric oxide, atopy, and spirometry tests. There were 24 mediators measured in sputum using enzyme-linked immunosorbent assay or bead array. Eosinophilic asthma (n = 52) and NEA (n = 59) were defined using a sputum eosinophil level cut-point of greater than or equal to 2.5%. RESULTS: Elevated levels of nociceptin (median: 39.1 vs 22.4 ng/mL, P = .03), periostin (33.8 vs 9.4 ng/mL, P = .01), and ECP; (220.1 vs 83.7 ng/mL, P = .03) were found in patients with asthma compared with those without asthma. Nociceptin was elevated in EA (54.8 vs 22.4 ng/mL, P = .02) compared with participants without asthma. Eosinophilic asthma had higher levels of inflammatory mediators (ECP: 495.5 vs 100.3 ng/mL, P ≤ .01; interleukin-1ß: 285.3 vs 209.3 pg/mL, P = .03; histamine: 5805.0 vs 3172.5 pg/mL, P < .01) and remodeling mediators (VEGF-A); 3.3 vs 2.5 ng/mL, P = .03; periostin: 47.7 vs 22.1 ng/mL, P = .04) than NEA. Whereas macrophages were associated with neural mediators, for example, neurokinin A (r = 0.27, P = .01) and nociceptin (r = 0.30, P = .02), granulocytes were associated with inflammatory and remodeling mediators (eg, ECP and VEGF-A correlated with neutrophils (r = 0.53 and r = 0.33, respectively, P < .01) and eosinophils (r = 0.53 and r = 0.29 respectively, P ≤ .01). CONCLUSION: Elevated levels of nociceptin and inflammatory and remodeling markers were found in EA, but no evidence for neural and remodeling pathways was found in NEA. Neural and remodeling mechanisms seem to coexist with inflammation.

Concentrations of Plasma Amino Acids and Neurotransmitters in Participants with Functional Gut Disorders and Healthy Controls.

Amino acids are important in several biochemical pathways as precursors to neurotransmitters which impact biological processes previously linked to functional gastrointestinal disorders (FGIDs). Dietary protein consumption, metabolic host processes, and the gut microbiome can influence the plasma concentration of amino acids and neurotransmitters, and their uptake by tissues. The aim of this analysis was to quantify 19 proteogenic and 4 non-proteogenic amino acids and 19 neurotransmitters (including precursors and catabolites, herein referred to as neurotransmitters) to ascertain if their circulating concentrations differed between healthy participants and those with FGIDs. Plasma proteogenic and non-proteogenic amino acids and neurotransmitters were measured using ultra-performance liquid chromatography and liquid chromatography-mass spectrometry, respectively, from 165 participants (Rome IV: irritable bowel syndrome (IBS-constipation, IBS-diarrhea), functional constipation, functional diarrhea, and healthy controls). There were significant differences (p < 0.05) in pairwise comparisons between healthy controls and specific FGID groups for branched-chain amino acids (BCAAs), ornithine, and alpha-aminobutyric acid. No other significant differences were observed for the neurotransmitters or any other amino acids analyzed. Multivariate and bivariate correlation analyses between proteogenic and non-proteogenic amino acids and neurotransmitters for constipation (constipation (IBS-C and functional constipation) and phenotypes diarrhea (IBS-D and functional diarrhea)) and healthy controls suggested that associations between BCAAs, 5-hydroxytryptophan, and kynurenine in combination with tyrosine, 3,4-dihydroxyphenylalanine, and 3,4-dihydroxyphenylacetic acid and associations with gamma-aminobutyric acid, glutamate, asparagine, and serine are likely disrupted in FGID phenotypes. In conclusion, although correlations were evident between some proteogenic and non-proteogenic amino acids and neurotransmitters, the results showed minor concentration differences in plasma proteogenic and non-proteogenic amino acids, amino acid-derived metabolites, and neurotransmitters between FGID phenotypes and healthy controls.

Early-onset colorectal cancer: Never too young.

Nil.

Detection of Fusobacterium nucleatum DNA in primary care patient stool samples does not predict progression of colorectal neoplasia.

BACKGROUND: Carriage of certain bacterial species may represent potential biomarkers of colorectal cancer (CRC). Prominent among these is Fusobacterium nucleatum. We explored the association of F. nucleatum DNA in stool samples with the presence of colonic neoplastic lesions in a cohort of primary care patients, and compared our findings with those from an unrelated cohort of colonoscopy patients followed clinically over time. METHODS: Carriage rates of F. nucleatum in stool samples were assessed in 185 patients referred for a faecal immunochemical test (FIT) by their general practitioners (GPs). Comparisons were made with stool samples from 57 patients diagnosed with CRC and 57 age-matched healthy controls, and with tissue samples taken at colonoscopy from 150 patients with a decade of subsequent clinical follow-up. FINDINGS: F. nucleatum DNA was found at a high rate (47.0%) in stool samples from primary care patients, and more often in stool samples from CRC patients (47.4%) than in healthy controls (7.0%), (P = 7.66E-7). No association was found between carriage of F. nucleatum and FIT positivity (P = 0.588). While evidence of stool-associated F. nucleatum DNA was significantly more likely to indicate a lesion in those primary care patients progressed to colonoscopy (P = 0.023), this finding did not extend to the progression of neoplastic lesions in the 150 patients with a decade of follow up. CONCLUSION: The finding of F. nucleatum DNA at similar rates in stool samples from patients diagnosed with CRC and in primary care patients with pre-cancerous lesions supports growing awareness that the presence of these bacteria may be a biomarker for increased risk of disease. However, molecular evidence of F. nucleatum did not predict progression of colonic lesions, which may lessen the utility of this bacterium as a biomarker for increased risk of disease.

Children With Cystic Fibrosis Have Elevated Levels of Fecal Chitinase-3-like-1.

Although chitinase-3-like-1 (CHI3L1), predominately produced by epithelial cells and macrophages, is relevant to pulmonary disease in cystic fibrosis (CF), fecal levels have not yet been assessed in children with CF. Fecal CHI3L1 was measured with a commercial immunoassay using fecal samples provided by children with CF and healthy control (HC) children. Higher median (interquartile range) fecal CHI3L1 levels were seen in the 52 children with CF than in the 35 controls: 15.97 (3.34-50.53) ng/g versus 2.93 (2.13-9.27) ng/g ( P = 0.001). Fecal CHI3LI did not differ according to sex. In the children with CF, fecal CHI3L1 levels did not correlate with growth parameters nor were the levels affected by pancreatic insufficiency. Children with CF had higher fecal CHI3L1 levels, suggesting underlying gut inflammation. Further work is required to confirm the current findings and to ascertain the longer-term significance of elevated CHI3L1.

Enterotoxigenic Bacteroides fragilis activates IL-8 expression through Stat3 in colorectal cancer cells.

BACKGROUND: Enterotoxigenic Bacteroides fragilis (ETBF) has been implicated in colorectal carcinogenesis through the actions of its toxin, B. fragilis toxin (BFT). Studies on colorectal cell lines have shown that treatment with BFT causes disruption of E-cadherin leading to increased expression of the pro-inflammatory cytokine, IL-8. Stat3 activation has also been associated with ETBF-related colitis and tumour development. However, a link between E-cadherin, IL-8 and Stat3 has not been investigated in the context of ETBF infection. RESULTS: We found that co-culture of HT-29 and HCT116 colorectal cell lines with ETBF, had a similar effect on activation of IL8 gene and protein expression as treatment with purified BFT. Inhibition of Stat3 resulted in a decrease in IL-8 gene and protein expression in response to ETBF in both cell lines. A reduction in E-cadherin expression in response to ETBF treatment was not restored by blocking Stat3. CONCLUSION: We found that treatment of colorectal cancer cell lines with live cultures of ETBF had the equivalent effect on IL-8 expression as the use of purified toxin, and this may be a more representative model of ETBF-mediated colorectal carcinogenesis. IL-8 gene and protein expression was mediated through Stat3 in HT-29 and HCT116 cells, whereas disruption of E-cadherin appeared to be independent of Stat3 signalling.

Biomarkers to Detect Early-Stage Colorectal Cancer.

Colorectal cancer is a leading cause of mortality worldwide. The high incidence and the acceleration of incidence in younger people reinforces the need for better techniques of early detection. The use of noninvasive biomarkers has potential to more accurately inform how patients are prioritised for clinical investigation, which, in turn, may ultimately translate into improved survival for those subsequently found to have curable-stage CRC. This review surveys a wide range of CRC biomarkers that may (alone or in combination) identify symptomatic patients presenting in primary care who should be progressed for clinical investigation.

Australasian Pediatric Gastroenterologists' Perspectives and Practices of Celiac Disease Diagnosis and Management.

BACKGROUND: The application of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) celiac disease (CeD) guidelines by pediatric gastroenterologists in Australia and New Zealand (Australasia) is unknown. Similarly, long-term management practices for patients with CeD are also unknown in this region. AIMS: This study aimed to explore the perceptions and practices of Australasian pediatric gastroenterologists in diagnosing and managing patients with CeD. METHODS: Australasian pediatric gastroenterologists and trainees were invited to complete an anonymous online survey over a 3-week period. RESULTS: The survey was completed by 28 respondents, 24 from Australia and four from New Zealand. Tissue transglutaminase antibody IgA was the most frequently ordered initial serologic test. Fifteen (54%) respondents relied on duodenal biopsies for the confirmation of CeD, six (21%) followed the ESPGHAN guidelines and the remaining seven offered either biopsy confirmation or no-biopsy diagnosis according to the parents' wishes. Following diagnosis, five (18%) respondents discharged patients from care, three (11%) discharged patients after one follow-up visit, one (4%) reviewed patients for 12 months, six (21%) reviewed patients until celiac antibodies normalized and children were clinically asymptomatic, and 13 (46%) reviewed patients until transition to adult care. CONCLUSION: Tissue transglutaminase antibody IgA was the most common initial serologic test ordered by this group of Australasian pediatric gastroenterologists. Half of these physicians rely solely on duodenal biopsy for the confirmation of CeD diagnosis: a minority routinely use the ESPGHAN guidelines. Physicians reported a wide range of CeD follow-up practices.

Patient perceptions of current and potential inflammatory bowel disease diagnostic and monitoring tests.

BACKGROUND: Less invasive inflammatory bowel disease (IBD) tests are increasingly being incorporated into clinical practice as adjuncts to endoscopy to monitor disease activity and guide optimal care. Little is known about patient perspectives of these tests. AIMS: To assess patient perspectives of the current IBD tests and potential future tests, such as saliva, urine or breath. METHODS: New Zealand adults with IBD were invited to complete an anonymous online survey. Experiences relating to blood or faecal tests, medical imaging (abdominal ultrasound, abdominal computed tomography and magnetic resonance enterography) and colonoscopy were collected. RESULTS: Of the 117 completed surveys, 112 respondents provided background details. The majority (85%) of participants were female and 88% were aged <55 years with a mean disease duration of 8.98 years. General blood tests were reported as the most prescribed, completed, comfortable test and the least worrying test results. Imaging tests were reported as the least ordered and the most refused tests. Colonoscopy was rated as the least comfortable and generated the most worry. Test explanations by a referring clinician significantly impacted on respondents' levels of understanding across all tests, but did not affect the level of worry when receiving test results. Saliva, blood and breath tests were chosen as the most preferred disease monitoring tests. CONCLUSIONS: Patients with IBD preferred any tests less invasive than colonoscopy. An explanation by referring doctor enhanced patients' understanding, but did not necessarily influence their level of comfort or worry.

Concentrations of Fecal Bile Acids in Participants with Functional Gut Disorders and Healthy Controls.

Bile acids are metabolites involved in nutrient absorption and signaling with levels influenced by dietary intake, metabolic processes, and the gut microbiome. We aimed to quantify 23 bile acids in fecal samples to ascertain if concentrations differed between healthy participants and those with functional gut disorders. Fecal bile acids were measured using liquid chromatography-mass spectrometry (LC-MS) in the COMFORT (The Christchurch IBS cohort to investigate mechanisms for gut relief and improved transit) cohort of 250 participants with Rome IV IBS (IBS-constipation (C), IBS-diarrhea (D), IBS-mixed (M)), functional gut disorders (functional constipation (FC), functional diarrhea (FD)) and healthy controls (FC n = 35, FD n = 13, IBS-C n = 24, IBS-D n = 52, IBS-M n = 29, and control n = 97). Dietary information was recorded to ascertain three-day dietary intake before fecal samples were collected. Fecal bile acid concentrations, predominantly primary bile acids, were significantly different between all functional gut disorder participants and healthy controls (CDCA p = 0.011, CA p = 0.003) and between constipation (FC + IBS-C) and diarrhea (FD + IBS-D) groups (CDCA p = 0.001, CA p = 0.0002). Comparison of bile acids between all functional groups showed four metabolites were significantly different, although analysis of combined groups (FC + IBS-C vs. FD + IBS-D) showed that 10 metabolites were significantly different. The bile acid profiles of FD individuals were similar to those with IBS-D, and likewise, those with FC were similar to IBS-C. Individuals with a diarrhea phenotype (FD + IBS-D) had higher concentrations of bile acids compared to those with constipation (FC + IBS-C). Bile acid metabolites distinguish between individuals with functional gut disorders and healthy controls but are similar in constipation (or diarrhea) whether classified as IBS or not.

Parent Perspectives of Diagnostic and Monitoring Tests Undertaken by Their Child with Inflammatory Bowel Disease.

PURPOSE: To assess parent perspectives of the current and potential future tests for their child with inflammatory bowel disease (IBD). METHODS: New Zealand parents of a child with IBD were invited to complete an anonymous online survey. Experiences relating to their child's blood or faecal tests, medical imaging (abdominal ultrasound [US], abdominal computerised tomography [CT] and magnetic resonance enterography) and colonoscopy were collected. Perceived attitudes to potential future testing of urine, saliva, and breath, were sought. RESULTS: Twenty-eight parents, 93% female completed the survey, and 86% were aged between 35 and 54 years. Baseline information was provided by parents for 27 of 28 children, 70.3% had Crohn's disease with a mean disease duration of 2.67 years. Blood tests were the most requested and completed tests, while CT was the least ordered and most refused test. Colonoscopy was rated as the least comfortable and generated the most worry. Explanation of test significantly improved parent's levels of understanding when their child had blood, faecal, imaging (US) or colonoscopy tests. Providing an explanation, test invasiveness and the impact of the blood results may have on their child's treatment significantly improved parents' comfort levels. However, explanation of colonoscopy generated a significant parental concerns. Saliva, urine and blood tests were chosen as the most preferred disease monitoring tests. CONCLUSION: Parents preferred any tests less invasive than colonoscopy for monitoring their child's IBD. Although providing explanation of their child's tests enhanced parents' understanding, it can also affect parents' levels of concern and comfort.

APC Mutations Are Not Confined to Hotspot Regions in Early-Onset Colorectal Cancer.

While overall colorectal cancer (CRC) cases have been declining worldwide there has been an increase in the incidence of the disease among patients under 50 years of age. Mutation of the APC gene is a common early event in CRC but is reported at lower rates in early-onset colorectal cancer (EOCRC) than in older patients. Here we investigate the APC mutation status of a cohort of EOCRC patients in New Zealand using a novel sequencing approach targeting regions of the gene encompassing the vast majority of known APC mutations. Using this strategy we find a higher rate (72%) of APC mutation than previously reported in EOCRC with mutations being spread throughout the gene rather than clustered in hotspots as seen with sporadic mutations in older patients. The rate of mutations falling within hotspots was similar to those previously seen in EOCRC and as such our study has implications for sequencing strategies for EOCRC patients. Overall there were low rates of both loss of heterozygosity and microsatellite instability whereas a relatively high rate (40%) of APC promoter methylation was found, possibly reflecting increasing exposure of young people to pro-oncogenic lifestyle factors.

A Pilot Study Evaluating Novel Urinary Biomarkers for Crohn's Disease.

INTRODUCTION: Although collecting faeces and blood samples are considered non-invasive methods of monitoring Crohn's disease (CD), these methods are less preferred by some patients. This study utilized urine as an alternative to evaluate four disease biomarkers in young adults with active CD before and after exclusive enteral nutrition (EEN) therapy. METHODS: Urine samples collected at baseline (W0) and after 8 weeks (W8) of EEN therapy were assayed by ELISA for levels of intestinal fatty acid-binding protein (I-FABP), liver fatty acid-binding protein (L-FABP), claudin-3, and calprotectin. Levels of each biomarker were also compared with standard clinical parameters, including disease indexes, nutrient, and inflammatory markers. RESULTS: Of the paired urine samples from 14 patients, 10 were female and 12 were newly diagnosed with CD. Urinary I-FABP: Cr (standardized to urine Cr) levels were significantly reduced, while urinary L-FABP: Cr levels increased following EEN therapy. Urinary L-FABP: Cr correlated positively with serum insulin-like growth factor 1 (IGF-1) (r = 0.60, p = 0.02). Urinary CLND3: Cr and calprotectin: Cr levels were not significantly different after treatment. CONCLUSION: I-FABP is a potential urinary biomarker of disease activity in adults with CD, while urinary L-FABP may be an indirect marker of nutritional status in adults with CD. CLND3 and calprotectin do not appear to have roles as urinary biomarkers in CD. These findings warrant further investigations using a larger sample size.

Cohort Profile: The Christchurch IBS cOhort to investigate Mechanisms FOr gut Relief and improved Transit (COMFORT).

BACKGROUND AND AIMS: This cross-sectional observational case-control study was initiated in July 2016 with the aim of increasing an understanding of the underlying disease mechanisms in functional gastrointestinal disorders (FGIDs) including irritable bowel syndrome (IBS), functional diarrhoea (FD), and functional constipation (FC). Specific areas of interest include the effect of food, microbiome, host and microbial genetics, metabolome, and psychological variables on unexplained chronic gastrointestinal (GI) symptoms. METHODS: This study recruited consecutive patients who were attending one of two endoscopy centres in Christchurch, New Zealand, for colonoscopy and a subgroup of participants from the general public who did not undergo colonoscopy. Participants with known GI disease other than an FGID were excluded. Those with symptoms were recruited as cases, whilst those without symptoms were recruited as controls. In the days prior to preparation for colonoscopy, or an agreeable time for those not undergoing colonoscopy, demographic, symptom, psychological, dietary, and health data were collected in addition to biological samples (breath, faeces, blood, and urine). Colonic biopsies were taken at the time of colonoscopy from participants in the colonoscopy subgroup. RESULTS: Between July 2016 and December 2018, 349 participants were recruited, 315 of whom completed the study, 220 participants were from the colonoscopy subgroup, and 95 from the non-colonoscopy subgroup. This included 129 controls and 186 cases (57 IBS-diarrhoea predominant, 30 IBS-constipation predominant, 41 IBS-mixed, 42 FC, and 16 FD). The mean age of FGID cases was 53.4 years and controls 54.4 years. Cases (149/186, 80.1%) and controls (57/72, 55.8%) were predominantly female. Education levels were similar across the cohort. Smoking and alcohol rates were also similar. Biological samples were collected as planned from participants. CONCLUSIONS: The COMFORT cohort is a unique clinical cohort of FGID cases and controls with a wide range of demographic, dietary, clinical, psychological, and health data in addition to biological samples. Future research will aim to use a systems biology approach to establish the potential role of diet, host-microbiome interactions, and other factors in the pathogenesis of FGIDs.

Role of serological tests in the diagnosis of coeliac disease in children in New Zealand.

AIM: To circumvent the need for an endoscopic biopsy to establish the diagnosis of coeliac disease (CD), the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) introduced a non-biopsy pathway for selected children in 2012. This pathway was recently updated to utilise anti-tissue transglutaminase IgA (anti-TTG IgA), 10× upper limit of normal (ULN) and positive endomysial antibodies (EMA). This study focused on the retrospective application of these guidelines in children from two regions of New Zealand. METHODS: Children aged <18 years who had anti-TTG IgA measured and underwent oesophagogastroduodenoscopy over a 30-month period were identified retrospectively. Medical records were reviewed to determine whether patients subsequently had biopsy-proven CD (Marsh ≥2). RESULTS: One hundred and thirty-six children, with a mean age (±standard deviation) of 9.9 ± 4.2 years, fulfilled the study criteria and 101 (74%) of these children had positive anti-TTG IgA. Eighty-two of 136 (60%) children had biopsy-proven CD. Positive anti-TTG IgA and EMA were highly sensitive in diagnosing CD, 96.3 and 98.6%, respectively. Anti-TTG-IgA ≥10× ULN alone, and combined anti-TTG IgA ≥10× ULN with positive EMA, both provided positive predictive values of 100% in diagnosing CD. Nineteen of 103 (18%) children could have been diagnosed with CD based on the ESPGHAN non-biopsy criteria. CONCLUSION: A proportion of New Zealand children with CD can potentially be diagnosed using the latest ESPGHAN non-biopsy criteria. However, prospective studies are required to validate this conclusion.