Features of colorectal adenomas among young patients with Lynch syndrome according to path_MMR: Results from the PRED-IdF registry.

BACKGROUND: Lynch syndrome (LS) is the most frequent inherited colorectal cancer syndrome. AIM: To assess the burden of adenoma in LS patients under 50 years-old followed in the PRED-IdF network. METHODS: From January 2010 to January 2019, all patients under 50 years of age with a confirmed LS germline mutation were included. The main objective was the description of adenomas characteristics according to path_MMR. RESULTS: We analyzed data from 708 patients (mean age 34.8 ± 8.6), of which 41.8 % were male. Among these patients, 37.6% had path_MLH1, 45.4% path_MSH2, 13.9% path_MSH6, 2.9% path_PMS2, and 1.2% path_EpCAM. The analysis included 1721 (70.9%) follow-up colonoscopies. A total of 682 adenomas were detected, including 140 (20.5%) advanced adenomas. The adenoma detection rates during the first and follow-up colonoscopies were 19.2% and 20.5%, respectively. Most adenomas were <10 mm (57.9%), located in the proximal colon (334, 48.9%), and presented as non-polypoid lesions (493, 72.3%). The median growth time for adenomas was 23 months (range 9-114) irrespective of the path_MMR mutation (p = 0.62). CONCLUSION: LS patients under 50 years of age have a high burden of adenomas, particularly small non-polypoid adenomas located in the proximal colon. These results highlight the need for intensive screening, with a particular focus on the proximal colon.

Chemoprevention in hereditary digestive neoplasia: A comprehensive review.

Hereditary syndromes, such as familial adenomatous polyposis (FAP), MUTYH polyposis or Lynch syndrome, are particularly predisposing to the development of colorectal cancer. These situations have necessitated the development of adapted prevention strategies based largely on reinforced endoscopic surveillance and the search for complementary prevention strategies. This is the case for chemoprevention, which is the long-term administration of chemical agents limiting carcinogenesis, used as primary or secondary prophylaxis. The aim of this review is to present the available literature and the latest advances in chemoprevention in patients with FAP or MUTYH and other polyposis as well as in patients with Lynch syndrome. The main conclusions of the few available guidelines in these situations are also discussed.

Dietary behaviours of individuals with lynch syndrome at high risk of colorectal cancer: Results from the AAS-lynch study.

BACKGROUND & AIMS: Individuals with Lynch syndrome (LS) have a high lifetime risk of developing colorectal cancer (CRC) due to genetic alterations. Nutrition is one of the main modifiable risk factors for sporadic CRC, however this has not been established in LS patients. The present study aimed to give a detailed overview of dietary intakes in individuals with LS, and associated individual characteristics. METHODS: Dietary behaviours of individuals with LS from the AAS-Lynch clinical trial (2017-2022) were obtained using a food frequency questionnaire. Dietary intakes, food group consumption and overall diet quality (dietary patterns, adherence to the Mediterranean diet) were described according to sociodemographic, anthropometric and clinical characteristics, and compared to participants without LS from the NutriNet-Santé study (matched on sex, age, BMI and region). RESULTS: 280 individuals with LS were included in this analysis and matched with 547 controls. Compared to controls, LS patients consumed less fibre, legumes, fruit and vegetables and more red and processed meat (all p < 0.01). They also had a lower Mediterranean diet score (p = 0.002). Among LS patients, men, younger patients, or those with disadvantaged situation had a diet of poorer nutritional quality with lower adherence to a "Healthy" diet (all p ≤ 0.01). LS Patients with prevalent CRC had a higher consumption of dairy products than recommended, while those with prevalent adenoma consumed more vegetables, and less sugar and sweets (all p ≤ 0.01). CONCLUSIONS: Although patients with LS were aware of their high lifetime risk of developing cancer, their diets were not optimal and included nutritional risk factors associated to CRC.

Serious immune-related upper gastrointestinal toxicity of immune checkpoint inhibitors: a multicenter case series.

BACKGROUND: Immune checkpoint inhibitors (ICI) improve the prognosis of many cancers but cause immune-related adverse events (IrAEs). Limited data are available on upper gastrointestinal (UGI) IrAEs. We describe the clinical characteristics, prognosis, and efficacy of medical therapy in patients with UGI IrAEs. METHODS: This is a retrospective, multicenter cohort study of patients with UGI symptoms and moderate to severe endoscopic UGI lesions, occurring after ICI. Efficacy of induction medical therapy and at the most recent follow-up was assessed. RESULTS: Forty patients were included; of these, 34 (85%) received anti-PD(L)1, either alone (n = 24) or combined with anti CTLA-4 (n = 10). Eighteen patients (45%) had concomitant enterocolitis. All patients had severe endoscopic lesions (erosions, ulcerations, hemorrhage, or necrotic lesions). Three patients who received an inefficient initial medical treatment had a complicated course: One patient died of enterocolitis, one had a pneumomediastinum, and one developed an ulcerated stricture of the pylorus. Thirty-five patients (88%) were treated with corticosteroids; 28 patients (80%) responded, and 20 (57%) reached clinical remission. Eight patients were treated with infliximab, and six responded (75%). After a median follow-up of 11 months, 36 patients (90%) were in corticosteroid-free clinical remission for their UGI symptoms. Endoscopic lesions persisted in 68% of patients. CONCLUSIONS: ICI cause severe UGI IrAEs, which are associated with enterocolitis in approximately half of the patients. Most patients with UGI IrAEs respond to corticosteroids or infliximab. These data support the recommendation to treat these patients without delay and in the same way as those with enterocolitis.

MSH3: a confirmed predisposing gene for adenomatous polyposis.

BACKGROUND: The MSH3 gene is part of the DNA mismatch repair system, but has never been shown to be involved in Lynch syndrome. A first report of four patients from two families, bearing biallelic MSH3 germline variants, with a phenotype of attenuated colorectal adenomatous polyposis raised the question of its involvement in hereditary cancer predisposition. The patients' tumours exhibited elevated microsatellite alterations at selected tetranucleotide repeats (EMAST), a hallmark of MSH3 deficiency. METHODS: We report five new unrelated patients with MSH3-associated polyposis. We describe their personal and familial history and study the EMAST phenotype in various normal and tumour samples, which are relevant findings based on the rarity of this polyposis subtype so far. RESULTS: All patients had attenuated colorectal adenomatous polyposis, with duodenal polyposis in two cases. Both women had breast carcinomas. EMAST phenotype was present at various levels in different samples of the five patients, confirming the MSH3 deficiency, with a gradient of instability in polyps depending on their degree of dysplasia. The negative EMAST phenotype ruled out the diagnosis of germline MSH3 deficiency for two patients: one homozygous for a benign variant and one with a monoallelic large deletion. CONCLUSION: This report lends further credence to biallelic MSH3 germline pathogenic variants being involved in colorectal and duodenal adenomatous polyposis. Large-scale studies may help clarify the tumour spectrum and associated risks. Ascertainment of EMAST may help with the interpretation of variants of unknown significance. We recommend adding MSH3 to dedicated diagnostic gene panels.

An efficient strategy for evaluating new non-invasive screening tests for colorectal cancer: the guiding principles.

OBJECTIVE: New screening tests for colorectal cancer (CRC) are rapidly emerging. Conducting trials with mortality reduction as the end point supporting their adoption is challenging. We re-examined the principles underlying evaluation of new non-invasive tests in view of technological developments and identification of new biomarkers. DESIGN: A formal consensus approach involving a multidisciplinary expert panel revised eight previously established principles. RESULTS: Twelve newly stated principles emerged. Effectiveness of a new test can be evaluated by comparison with a proven comparator non-invasive test. The faecal immunochemical test is now considered the appropriate comparator, while colonoscopy remains the diagnostic standard. For a new test to be able to meet differing screening goals and regulatory requirements, flexibility to adjust its positivity threshold is desirable. A rigorous and efficient four-phased approach is proposed, commencing with small studies assessing the test's ability to discriminate between CRC and non-cancer states (phase I), followed by prospective estimation of accuracy across the continuum of neoplastic lesions in neoplasia-enriched populations (phase II). If these show promise, a provisional test positivity threshold is set before evaluation in typical screening populations. Phase III prospective studies determine single round intention-to-screen programme outcomes and confirm the test positivity threshold. Phase IV studies involve evaluation over repeated screening rounds with monitoring for missed lesions. Phases III and IV findings will provide the real-world data required to model test impact on CRC mortality and incidence. CONCLUSION: New non-invasive tests can be efficiently evaluated by a rigorous phased comparative approach, generating data from unbiased populations that inform predictions of their health impact.

Efficiency of Orexin-A for Inflammatory Flare and Mucosal Healing in Experimental Colitis: Comparison with the Anti-TNF Alpha Infliximab.

Inflammatory bowel diseases are chronic inflammation of the intestinal mucosa characterized by relapsing-remitting cycle periods of variable duration. Infliximab (IFX) was the first monoclonal antibody used for the treatment of Crohn's disease and ulcerative colitis (UC). High variability between treated patients and loss of IFX efficiency over time support the further development of drug therapy. An innovative approach has been suggested based on the presence of orexin receptor (OX1R) in the inflamed human epithelium of UC patients. In that context, the aim of this study was to compare, in a mouse model of chemically induced colitis, the efficacy of IFX compared to the hypothalamic peptide orexin-A (OxA). C57BL/6 mice received 3.5% dextran sodium sulfate (DSS) in drinking water for 5 days. Since the inflammatory flare was maximal at day 7, IFX or OxA was administered based on a curative perspective at that time for 4 days using intraperitoneal injection. Treatment with OxA promoted mucosal healing and decreased colonic myeloperoxidase activity, circulating concentrations of lipopolysaccharide-binding protein, IL-6 and tumor necrosis factor alpha (TNFα) and decreased expression of genes encoding cytokines in colonic tissues with better efficacy than IFX allowing for more rapid re-epithelization. This study demonstrates the comparable anti-inflammatory properties of OxA and IFX and shows that OxA is efficient in promoting mucosal healing, suggesting that OxA treatment is a promising new biotherapy.

Refinement of the Target Population for Colorectal Cancer Screening in France, Inventory as a Prelude to the Use of Medico-Administrative Database.

The study describes the level of improvement in the risk of misclassification that would be achieved by refining the campaign target population using a query in the French medico-administrative database (SNDS). The SNDS's use requires other new strategies that can minimize the number of people wrongly included in the campaigns, because its accuracy is less than 100%.

Loss of symbiotic and increase of virulent bacteria through microbial networks in Lynch syndrome colon carcinogenesis.

Purpose: Through a pilot study, we performed whole gut metagenomic analysis in 17 Lynch syndrome (LS) families, including colorectal cancer (CRC) patients and their healthy first-degree relatives. In a second asymptomatic LS cohort (n=150) undergoing colonoscopy-screening program, individuals with early precancerous lesions were compared to those with a normal colonoscopy. Since bacteria are organized into different networks within the microbiota, we compared related network structures in patients and controls. Experimental design: Fecal prokaryote DNA was extracted prior to colonoscopy for whole metagenome (n=34, pilot study) or 16s rRNA sequencing (validation study). We characterized bacteria taxonomy using Diamond/MEGAN6 and DADA2 pipelines and performed differential abundances using Shaman website. We constructed networks using SparCC inference tools and validated the construction's accuracy by performing qPCR on selected bacteria. Results: Significant differences in bacterial communities in LS-CRC patients were identified, with an enrichment of virulent bacteria and a depletion of symbionts compared to their first-degree relatives. Bacteria taxa in LS asymptomatic individuals with colonic precancerous lesions (n=79) were significantly different compared to healthy individuals (n=71). The main bacterial network structures, constructed based on bacteria-bacteria correlations in CRC (pilot study) and in asymptomatic precancerous patients (validation-study), showed a different pattern than in controls. It was characterized by virulent/symbiotic co-exclusion in both studies and illustrated (validation study) by a higher Escherichia/Bifidobacterium ratio, as assessed by qPCR. Conclusion: Enhanced fecal virulent/symbiotic bacteria ratios influence bacterial network structures. As an early event in colon carcinogenesis, these ratios can be used to identify asymptomatic LS individual with a higher risk of CRC.

Glycemic response, satiety, gastric secretions and emptying after bread consumption with water, tea or lemon juice: a randomized crossover intervention using MRI.

PURPOSE: Numerous studies, including our previous work with lemon juice, have reported that low-pH meals reduce the glycemic response to starchy foods. However, the underlying mechanism is not yet understood. Tea, for its polyphenol content, has also been investigated. The main objective of this research was to concurrently study gastric emptying, appetite perceptions and glycemic responses to bread consumed with water, tea, or lemon juice. METHODS: In this randomized, crossover intervention, ten participants consumed equal portions of bread (100 g) with 250 mL of water, water-diluted lemon juice, or black tea at breakfast. Gastric volumes, blood glucose concentrations and appetite perceptions were alternately assessed over 180 min using magnetic resonance imaging, the finger-prick method and visual analogue scales, respectively. RESULTS: Compared to water, lemon juice led to a 1.5 fold increase of the volume of gastric contents, 30 min after the meal (454.0 ± 18.6 vs. 298.4 ± 19.5 mL, [Formula: see text] ± SEM P < 0.00001). Gastric emptying was also 1.5 times faster (P < 0.01). Conversely, lemon juice elicited a lower glycemic response than water (blood glucose concentrations at t = 55 min were 35% lower, P = 0.039). Tea had no effect. Changes in appetite perceptions and gastric volumes correlated well, but with no significant differences between the meals. CONCLUSIONS: Lemon juice lowered the glycemic response and increased both gastric secretions and emptying rate. The results are compatible with the hypothesis that the reduction of the glycemic response is mainly due to the interruption of starch hydrolysis via the acid-inhibition of salivary α-amylase. TRIAL REGISTRATION NUMBER: NCT03265392, August 29, 2017.

Review Article: Gastrointestinal Bleeding Risk with Direct Oral Anticoagulants.

PURPOSE: Although direct oral anticoagulants (DOACs) are associated with an overall favourable safety profile, the risk of gastrointestinal bleeding with DOACs compared with vitamin K antagonists (VKAs) remains controversial. Accordingly, we aimed to provide a focused overview of the risk of gastrointestinal bleeding associated with dabigatran, rivaroxaban, apixaban and edoxaban and its management. METHODS: We reviewed published studies reporting on DOACs with gastrointestinal bleeding as an outcome, including randomised controlled trials (RCTs), retrospective database studies and large-scale prospective cohort studies. RESULTS: Cumulative evidence confirms no notable difference in major gastrointestinal bleeding risk between DOACs and VKAs. Moreover, gastrointestinal bleeding in DOAC-treated patients seems less severe and requires less intensive management. The main cause of upper gastrointestinal bleeding in DOAC-treated patients appears to be gastroduodenal ulcers, whereas lower gastrointestinal bleedings are mainly due to diverticula followed by angiodysplasia and haemorrhoids. The lack of head-to-head RCTs with DOACs precludes drawing conclusions on the DOAC with the lowest gastrointestinal bleeding risk. Prescribing physicians should be aware of risk factors for DOAC-related gastrointestinal bleeding (e.g. age > 65, heavy alcohol use, uncontrolled hypertension, hepatic or renal dysfunction, active cancer, anaemia) and adopt preventive measures accordingly. Management of DOAC-associated major gastrointestinal bleeding involves temporary discontinuation of the DOAC, investigation of the bleeding source and treatment of bleeding with fluid resuscitation combined with transfusion and endoscopic haemostasis. CONCLUSION: DOACs as a class do not increase the risk of major gastrointestinal bleeding compared to VKAs, which supports their continued use for different anticoagulant indications.

The Colon Endoscopic Bubble Scale (CEBuS): a two-phase evaluation study.

BACKGROUND: To date, no scale has been validated to assess bubbles associated with bowel preparation. This study aimed to develop and assess the reliability of a novel scale - the Colon Endoscopic Bubble Scale (CEBuS). METHODS: This was a multicenter, prospective, observational study with two online evaluation phases of 45 randomly distributed still colonoscopy images (15 per scale grade). Observers assessed images twice, 2 weeks apart, using CEBuS (CEBuS-0 - no or minimal bubbles, covering < 5 % of the surface; CEBuS-1 - bubbles covering 5 %-50 %; CEBuS-2 - bubbles covering > 50 %) and reporting the clinical action (do nothing; wash with water; wash with simethicone). RESULTS: CEBuS provided high levels of agreement both in evaluation Phase 1 (4 experts) and Phase 2 (6 experts and 13 non-experts), with almost perfect intraobserver reliability: kappa 0.82 (95 % confidence interval 0.75-0.88) and 0.86 (0.85-0.88); interobserver agreement - intraclass correlation coefficient (ICC) 0.83 (0.73-0.89) and 0.90 (0.86-0.94). Previous endoscopic experience had no influence on agreement among experts vs. non-experts: kappa 0.86 (0.80-0.91) vs. 0.87 (0.84-0.89) and ICC 0.91 (0.87-0.94) vs. 0.90 (0.86-0.94), respectively. Interobserver agreement on clinical action was ICC 0.63 (0.43-0.78) in Phase 1 and 0.77 (0.68-0.84) in Phase 2. Absolute agreement on clinical action per scale grade was 85 % (82-88) for CEBuS-0, 21 % (16-26) for CEBuS-1, and 74 % (70-78) for CEBuS-2. CONCLUSION: CEBuS proved to be a reliable instrument to standardize the evaluation of colonic bubbles during colonoscopy. Assessment in daily practice is warranted.

Colon capsule endoscopy in clinical practice: lessons from a national 5-year observational prospective cohort.

Background and study aims Colon capsule endoscopy (CCE) has been proposed as an alternative to colonoscopy for screening patients at average risk of colorectal cancer (CRC). A prospective national cohort was developed to assess relevance of CCE in real-life practice and its short- and long-term impacts on clinical management. Patients and methods All patients who underwent a CCE in France were prospectively enrolled from January 2011 to May 2016 and reached annually by phone until May 2017. All CCE and colonoscopy reports were systematically collected. Results During the study period, 689 CCEs were analyzed from 14 medical centers. Median follow-up time was 35 months [IQR: 12-50]. Indication for CCE was mainly for elderly patients (median age: 70 years, IQR: [61-79]) due to anesthetic or colonoscopy contraindication (n = 307; 44.6 %). Only 337 CCEs (48.9 %) were both complete and with adequate bowel preparation. Advanced neoplasia (adenoma with high-grade dysplasia or CRC) was diagnosed following 32 CCEs (4.6 %). Among patients who underwent colonoscopy or therapeutic surgery following CCE, 18.8 % of all advanced neoplasias (6/32) had not been diagnosed by CCE mainly due to technical issues. Performing a colonoscopy in the case of significant polyps or insufficient bowel cleansing or after an incomplete CCE allowed the diagnosis of 96.9 % of all identified advanced neoplasias (31/32). Conclusions Outside the scope of academic trials, improvement is needed to increase the reliability of CCE as less than half were considered optimal i. e. complete with adequate bowel cleansing. Most of missed colonic advanced neoplasia were due to incomplete CCE with distal neoplasia location.

Colorectal cancer screening programme: is the French faecal immunological test (FIT) threshold optimal?

BACKGROUND: In France, the colorectal cancer organised screening programme uses the faecal immunological test. A positive test ⩾30 µg Hb/g of stool leads to a colonoscopy for identification of potential colorectal lesions. Cut-off values vary from 20 to 47 µg Hb/g of stool in Western countries. We herein question this threshold's relevance in a French population and perform a retrospective observational study using the Parisian database between 1 April 2015 and 31 December 2018. METHODS: Rates of participation, numbers of positive faecal immunological test (FIT), detection rates and positive predictive values for advanced adenomas and/or colorectal cancer were determined. Mean positivity values for colorectal lesions were calculated. RESULTS: In our population, there were 4.1% positive tests and 67.6% colonoscopy results available with final reports. Positive predictive value for advanced adenomas and colorectal cancer were 30% [95% confidence interval (CI) 29.8-30.3] and 7.4% (95% CI 7.35-7.52), respectively. The mean positivity value for all positive tests in our population was 101.7 µg Hb/g of stool (95% CI 85-118.3). There were 1136 normal colonoscopies (21.4%) with a mean positivity value of 88.6 µg Hb/g of stool. Following a negative test in a first screening campaign, 40.8% of patients in our population performed a second test with a positivity rate of 1.3% and with the encounter of 81 colorectal cancers. The risk of having a positive test during the second screening campaign and finding advanced colorectal lesions significantly increased (all p < 0.001) when comparing negative FIT results ranging between 15 and 29 µg Hb/g of stool to 0 and 14 µg Hb/g of stool from the previous campaign. CONCLUSION: Using the current positivity threshold, some patients were considered negative with a delay in colorectal cancer diagnosis, suggesting the threshold could be lowered. Also, the mean positivity value for normal colonoscopies was high, raising the question of upper gastrointestinal bleeding.

Cost-effectiveness analysis of alternative colorectal cancer screening strategies in high-risk individuals.

BACKGROUND AND AIMS: Current guidelines recommend colonoscopy every 3-5 years for colorectal cancer (CRC) screening of individuals with a familial history of CRC. The objective of this study was to compare the cost effectiveness of screening alternatives in this population. METHODS: Eight screening strategies were compared with no screening: fecal immunochemical test (FIT), Stool DNA and blood-based screening every 2 years, colonoscopy, computed tomography colonography, colon capsules, and sigmoidoscopy every 5 years, and colonoscopy at 45 years followed, if negative, by FIT every 2 years. Screening test and procedures performance were obtained from the literature. A microsimulation model reproducing the natural history of CRC was used to estimate the cost (€2018) and effectiveness [quality-adjusted life-years (QALYs)] of each strategy. A lifetime horizon was used. Costs and effectiveness were discounted at 3.5% annually. RESULTS: Compared with no screening, colonoscopy and sigmoidoscopy at a 30% uptake were the most effective strategy (46.3 and 43.9 QALY/1000). FIT at a 30 µg/g threshold with 30% uptake was only half as effective (25.7 QALY). Colonoscopy was associated with a cost of €484,000 per 1000 individuals whereas sigmoidoscopy and FIT were associated with much lower costs (€123,610 and €66,860). Incremental cost-effectiveness rate for FIT and sigmoidoscopy were €2600/QALY (versus no screening) and €3100/QALY (versus FIT), respectively, whereas it was €150,000/QALY for colonoscopy (versus sigmoidoscopy). With a lower threshold (10 µg/g) and a higher uptake of 45%, FIT was more effective and less costly than colonoscopy at a 30% uptake and was associated with an incremental cost-effectiveness ratio (ICER) of €4240/QALY versus no screening. CONCLUSION: At 30% uptake, current screening is the most effective screening strategy for high-risk individuals but is associated with a high ICER. Sigmoidoscopy and FIT at lower thresholds (10 µg/g) and a higher uptake should be given consideration as cost-effective alternatives. PLAIN LANGUAGE SUMMARY: Cost-effectiveness analysis of colorectal cancer screening strategies in high-risk individuals Fecal occult blood testing with an immunochemical test (FIT) is generally considered as the most cost-effective alternative in colorectal cancer screening programs for average risk individuals without family history.Current screening guidelines for high-risk individuals with familial history recommend colonoscopy every 3-5 years.Colonoscopy every 3-5 years for individuals with familial history is the most effective strategy but is associated with a high incremental cost-effectiveness ratio.Compared with colonoscopy, if screening based on FIT is associated with a higher participation rate, it can achieve a similar effectiveness at a lower cost.

Dietary Patterns, Ultra-processed Food, and the Risk of Inflammatory Bowel Diseases in the NutriNet-Santé Cohort.

BACKGROUND: The incidence of inflammatory bowel diseases (IBDs) tended to increase for several decades. Diet is suspected to be a major determinant of the occurrence of these diseases. This prospective study aimed to assess the associations among occurrence of IBD, dietary patterns, and ultra-processed food in the French NutriNet-Santé cohort. METHODS: Participants of the NutriNet-Santé cohort who completed at least three 24-hour dietary records were included. Incident IBD cases were identified from 3 questionnaires and confirmed by phone or email interview. Major dietary patterns (DPs) were computed using a principal component analysis (PCA) based on 29 food groups' consumption, whereas proportions of ultra-processed foods (UPFs) were obtained using the NOVA classification. Multivariable Poisson models were performed to evaluate associations among DP quintiles, UPF proportion (UPFp) in the diet, and incident IBD. RESULTS: A total of 105,832 participants were included, contributing 238,924 person-years in a mean follow-up of 2.3 ± 2.2 years. Among them, 75 participants reported an incident IBD. Three major DPs were retained: "healthy," "traditional," and "western." No significant association was found for DPs and UPFp after adjustments for covariates. CONCLUSIONS: In this study, neither DPs nor UPF proportion in the diet were significantly associated with the risk of incident IBD after adjustments for covariates. Further studies are needed to investigate the long-term association between diet and IBD.

Lemon juice, but not tea, reduces the glycemic response to bread in healthy volunteers: a randomized crossover trial.

PURPOSE: The inhibition of enzymes that hydrolyze starch during digestion could constitute an opportunity to slow down the release, and ultimately the uptake, of starch-derived glucose. Simple dietary approaches consisting in pairing starch-rich foods with beverages that have the capacity to inhibit such enzymes could be an effective and easily implementable strategy. The objective of this work was to test the impact of black tea and lemon juice on the glycemic response to bread and subsequent energy intake in healthy adults. METHODS: A randomized crossover study was conducted with equal portions of bread (100 g) and 250 ml of water, black tea or lemon juice. Capillary blood glucose concentrations were monitored during 180 min using the finger-prick method. Ad libitum energy intake was assessed 3 h later. RESULTS: Tea had no effect on the glycemic response. Lemon juice significantly lowered the mean blood glucose concentration peak by 30% (p < 0.01) and delayed it more than 35 min (78 vs. 41 min with water, p < 0.0001). None of the tested beverages had an effect on ad libitum energy intake. CONCLUSION: These results are in agreement with previous in vitro studies showing that lowering the pH of a meal can slow down starch digestion through premature inhibition of salivary α-amylase. Furthermore, the effect of lemon juice was similar to what has been repeatedly observed with vinegar and other acidic foods. Including acidic beverages or foods in starchy meals thus appears to be a simple and effective strategy to reduce their glycemic impact.

Effect of chemoprevention by low-dose aspirin of new or recurrent colorectal adenomas in patients with Lynch syndrome (AAS-Lynch): study protocol for a multicenter, double-blind, placebo-controlled randomized controlled trial.

Lynch syndrome (LS) is the most common cause of inherited colorectal cancer (CRC) and confers a high lifetime risk of CRC estimated to be up to 60%. Colonoscopy is recommended every 2 years in LS patients above the 20-25-year-old age bracket, and every year when colonic neoplasia has been detected. Efficient chemoprevention has the potential to represent a cost-effective intervention in these high-risk patients and could allow a delay in colonoscopy surveillance. Several epidemiological studies have shown that regular use of low dose aspirin is associated with a 20 to 30% reduction in the risk of sporadic colonic adenomas and colorectal cancer regardless of family risk. However, in recent large randomized trials in specific populations, aspirin use showed no protection for colorectal cancer. A prospective randomized CAPP-2 trial evaluated the effect of aspirin use in LS patients. The primary analysis of this trial showed no significant decrease in CRC in LS patients under daily aspirin. However, a preplanned secondary analysis after an extended follow-up showed a significant reduced risk of CRC in the aspirin group in the per-protocol analysis. The real effect and clinical benefit of aspirin are still to be consolidated in this population. The AAS-Lynch trial-a prospective, multicentric, double-blind, placebo-controlled, randomized clinical trial-was designed to investigate if daily aspirin therapy, at a dose of 100 or 300 mg, would decrease the occurrence or recurrence of colorectal adenomas in patients under 75 years of age, compared with placebo. TRIAL REGISTRATION: ClinicalTrials.gov NCT02813824 . Registered on 27 June 2016. The trial was prospectively registered.