Randomized controlled trial: Flexible sigmoidoscopy as an adjunct to faecal occult blood testing in population screening.

OBJECTIVES: Flexible sigmoidoscopy screening at around age 60 can reduce colorectal cancer incidence. Insufficient evidence exists on flexible sigmoidoscopy at age 60 in a population being offered biennial faecal occult blood test screening from age 50. This randomized controlled trial assessed if flexible sigmoidoscopy would be an effective adjunct to faecal occult blood test. METHODS: In the Scottish Bowel Screening Programme between June 2014 and December 2015, 51,769 individuals were randomized to be offered flexible sigmoidoscopy instead of faecal occult blood test at age 60 or to continue faecal occult blood test. Those not accepting flexible sigmoidoscopy and those with normal flexible sigmoidoscopy were offered faecal occult blood test. All with flexible sigmoidoscopy-detected neoplasia or a positive faecal occult blood test result were offered colonoscopy. RESULTS: Overall flexible sigmoidoscopy uptake was 17.8%, higher in men than women, and decreased with increasing deprivation (25.7% in the least to 9.2% in the most deprived quintile). In those who underwent flexible sigmoidoscopy, detection rate for colorectal cancer was 0.13%, for adenoma 7.27%, and for total neoplasia 7.40%. In those who underwent colonoscopy after a positive flexible sigmoidoscopy, detection rate for colorectal cancer was 0.28%, adenoma 8.66%, and total neoplasia 8.83%. On an intention to screen basis, there was no difference in colorectal cancer detection rate between the study and control groups. Adenoma and total neoplasia detection rate were significantly higher in the study group, with odds ratios of 5.95 (95%CI: 4.69-7.56) and 5.10 (95%CI: 4.09-6.35), respectively. CONCLUSIONS: In a single screening round at age 60, there was low uptake and neoplasia detection rate. Flexible sigmoidoscopy detected significantly more neoplasia than faecal occult blood test alone.

A prospective evaluation of the predictive value of faecal calprotectin in quiescent Crohn's disease.

BACKGROUND: Faecal calprotectin (FC) is a non-invasive marker of gastrointestinal inflammation. AIM: To determine whether higher FC levels in individuals with quiescent Crohn's disease are associated with clinical relapse over the ensuing 12 months. METHODS: A single centre prospective study was undertaken in Crohn's disease patients in clinical remission. The receiver operating characteristic (ROC) curve for the primary endpoint of clinical relapse by 12 months, based on FC at baseline, was calculated. Kaplan-Meier curves of time to relapse were based on the resulting optimal FC cutoff for predicting relapse. RESULTS: Of 97 patients recruited, 92 were either followed up for 12 months without relapsing, or reached the primary endpoint within that period. Of these, 10 (11%) relapsed by 12 months. Median FC was lower for non-relapsers, 96 µg/g (IQR 39-237), than for relapsers, 414 µg/g (IQR 259-590), (p=0.005). The area under the ROC curve to predict relapse using FC was 77.4%. An optimal cutoff FC value of 240 µg/g to predict relapse had sensitivity of 80.0% and specificity of 74.4%. Negative predictive value was 96.8% and positive predictive value was 27.6%, FC ≥240 µg/g was associated with likelihood of relapse by 12-months 12.18 (95% CI 2.55-58.2) times higher than lower values (p=0.002). CONCLUSIONS: In this prospective dataset, FC is a useful tool to help identify quiescent Crohn's disease patients at a low risk of relapse over the ensuing 12 months. FC of 240 µg/g was the optimal cutoff in this cohort.

The nonerosive reflux disease-gastroesophageal reflux disease controversy.

PURPOSE OF REVIEW: To analyse the concept of nonerosive reflux disease (NERD), examining its evolving definition and its relationship to reflux disease and functional gastrointestinal disorders. RECENT FINDINGS: The advent of the Montreal definition of gastroesophageal reflux disease (GERD) and the Rome III definition of functional upper gastrointestinal disorders has refined the concept of NERD. The high prevalence of GERD symptoms and the strong overlap between GERD and irritable bowel syndrome is due to the influence of NERD. Subtle differences exist between patterns of acid exposure in NERD and erosive disease on pH testing. Symptom generation in NERD may be influenced by altered mucosal permeability. Improvements in endoscopic technology demonstrate esophageal mucosal changes in NERD which are not seen in controls. There is a general acknowledgement that the inferior symptomatic response to acid suppression reported in NERD is attributable, at least in part, to contamination of study populations by patients with functional heartburn. SUMMARY: NERD is common and its definition continues to evolve. For the present, however, this should be considered to be heartburn with and without regurgitation due to gastroesophageal reflux in the absence of esophageal mucosal erosions. Future studies examining treatment response of GERD subgroups must exclude functional heartburn if NERD is to be properly understood.

N-nitrosamine generation from ingested nitrate via nitric oxide in subjects with and without gastroesophageal reflux.

BACKGROUND & AIMS: Nitrate ingestion leads to high luminal concentrations of nitric oxide being generated where saliva meets gastric acid. Nitric oxide generates N-nitrosative stress on reacting with oxygen at neutral pH. We aimed to ascertain if luminal nitric oxide exerts nitrosative stress in the human upper gastrointestinal tract, and to assess the influence of acid reflux on this phenomenon. METHODS: A silicone tube, segmented every 15 mm and containing phosphate buffer pH 7.4 and the secondary amine morpholine, was inserted into the upper gastrointestinal tract of 16 healthy volunteers and 16 Barrett's esophagus patients. The tube wall has the same permeability properties as an epithelial lipid membrane, allowing passage of gases such as nitric oxide, but not hydrogen ions. After 2 hours, the tube was removed and the concentrations of nitrite and N-nitrosomorpholine in each segment were measured. Healthy volunteers were studied with and without ingestion of (15)N-enriched nitrate and Barrett's esophagus patients were studied with and without stimulation of acid reflux. RESULTS: In healthy volunteers, N-nitrosomorpholine was generated in the tube sections exposed to gastric acid and increased 2-fold after nitrate. The N-nitrosomorpholine was 77% enriched with (15)N, confirming its source was the ingested nitrate. In the Barrett's patients, generation of N-nitrosomorpholine was shifted proximally with 80% of nitrosative stress occurring within the esophagus during periods of acid reflux. CONCLUSIONS: This study demonstrates the in situ formation of N-nitrosamine from dietary nitrate via nitric oxide. During acid reflux, nitrosative stress occurs almost entirely within the esophagus and may contribute toward carcinogenesis at this site.