Robert Benamouzig

Daily soluble aspirin and prevention of colorectal adenoma recurrence: one-year results of the APACC trial.

BACKGROUND & AIMS Epidemiologic and experimental studies have suggested that aspirin intake reduces the risk for colorectal carcinogenesis. However, the available data are not sufficient to serve as the basis for firm recommendations. METHODS We randomly assigned 272 patients with a history of colorectal adenomas (at least one more than 5 mm in diameter, or more than 3) to daily lysine acetylsalicylate (160 or 300 mg/day) or placebo for 4 years. The primary end points were adenoma recurrence after 1 and 4 years. These results are those of the year 1 colonoscopy. RESULTS Among the 238 patients who completed the year 1 colonoscopy, at least one adenoma was observed in 38 patients of the 126 (30%) in the aspirin group and in 46 of the 112 (41%) in the placebo group; relative risk was 0.73 (95% confidence interval [CI]: 0.52-1.04; P = 0.08). At least one adenoma of more than 5 mm diameter was observed in 13 patients (10%) in the aspirin group and 26 (23%) in the placebo group (P = 0.01). The corresponding numbers for adenomas more than 10 mm in diameter were one (1%) and 7 (6%) (P = 0.05). Stepwise regression showed that independent factors associated with lower adenoma recurrence are aspirin treatment (adenoma >5 mm, P = 0.01), absence of personal history of adenoma before the entry colonoscopy (P = 0.01), and initial adenomatous polyp burden less than 10 mm (P = 0.001). CONCLUSIONS Daily soluble aspirin is associated with a reduction in the risk for recurrent adenomas found at colonoscopy 1 year after starting treatment.

Sequential release of milk protein–derived bioactive peptides in the jejunum in healthy humans

BACKGROUND The digestive hydrolysis of dietary proteins leads to the release of peptides in the intestinal tract, where they may exert a variety of functions, but their characterization and quantification are difficult. OBJECTIVES We aimed to characterize and determine kinetics of the formation of peptides present in the jejunum of humans who ingested casein or whey proteins by using mass spectrometry and to look for and quantify bioactive peptides. DESIGN Subjects were equipped with a double-lumen nasogastric tube that migrated to the proximal jejunum. A sample collection was performed for 6 h after the ingestion of 30 g (15)N-labeled casein (n = 7) or whey proteins (WPs; n = 6). Nitrogen flow rates were measured, and peptides were identified by using mass spectrometry. RESULTS After casein ingestion, medium-size peptides (750-1050 kDa) were released during 6 h, whereas larger peptides (1050-1800 kDa) were released from WPs in the first 3 h. A total of 356 and 146 peptides were detected and sequenced in the jejunum after casein and WP ingestion, respectively. β-casein was the most important precursor of peptides, including bioactive peptides with various activities. The amounts of β-casomorphins (β-casein 57-, 58-, 59-, and 60-66) and β-casein 108-113 released on the postprandial window were sufficient to elicit the biological action of these peptides (ie, opioid and antihypertensive, respectively). CONCLUSIONS Clear evidence is shown of the presence of bioactive peptides in the jejunum of healthy humans who ingested casein. Our findings raise the question about the physiologic conditions under which these peptides can express their bioactivity in humans. This trial was registered at clinicaltrials.gov as NCT00862329.

Colon capsule endoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Guideline

PillCam colon capsule endoscopy (CCE) is an innovative noninvasive, and painless ingestible capsule technique that allows exploration of the colon without the need for sedation and gas insufflation. Although it is already available in European and other countries, the clinical indications for CCE as well as the reporting and work-up of detected findings have not yet been standardized. The aim of this evidence-based and consensus-based guideline, commissioned by the European Society of Gastrointestinal Endoscopy (ESGE) is to furnish healthcare providers with a comprehensive framework for potential implementation of this technique in a clinical setting.

Luminal sulfide and large intestine mucosa: friend or foe?

Hydrogen sulfide (H2S) is present in the lumen of the human large intestine at millimolar concentrations. However, the concentration of free (unbound) sulfide is in the micromolar range due to a large capacity of fecal components to bind the sulfide. H2S can be produced by the intestinal microbiota from alimentary and endogenous sulfur-containing compounds including amino acids. At excessive concentration, H2S is known to severely inhibit cytochrome c oxidase, the terminal oxidase of the mitochondrial electron transport chain, and thus mitochondrial oxygen (O2) consumption. However, the concept that sulfide is simply a metabolic troublemaker toward colonic epithelial cells has been challenged by the discovery that micromolar concentration of H2S is able to increase the cell respiration and to energize mitochondria allowing these cells to detoxify and to recover energy from luminal sulfide. The main product of H2S metabolism by the colonic mucosa is thiosulfate. The enzymatic activities involved in sulfide oxidation by the colonic epithelial cells appear to be sulfide quinone oxidoreductase considered as the first and rate-limiting step followed presumably by the action of sulfur dioxygenase and rhodanese. From clinical studies with human volunteers and experimental works with rodents, it appears that H2S can exert mostly pro- but also anti-inflammatory effects on the colonic mucosa. From the available data, it is tempting to propose that imbalance between the luminal concentration of free sulfide and the capacity of colonic epithelial cells to metabolize this compound will result in an impairment of the colonic epithelial cell O2 consumption with consequences on the process of mucosal inflammation. In addition, endogenously produced sulfide is emerging as a prosecretory neuromodulator and as a relaxant agent toward the intestinal contractibility. Lastly, sulfide has been recently described as an agent involved in nociception in the large intestine although, depending on the experimental design, both pro- and anti-nociceptive effects have been reported.

Comparison of FDG-PET/CT and MR with diffusion-weighted imaging for assessing peritoneal carcinomatosis from gastrointestinal malignancy

ObjectivesTo assess the accuracy of FDG-PET/CT and MR with diffusion-weighted imaging (MR-DWI) for diagnosing peritoneal carcinomatosis (PC) from gastrointestinal malignancies.MethodsThirty consecutive patients referred for staging of gastrointestinal malignancy underwent FDG-PET/CT and MR-DWI in this retrospective study. Extent of PC was characterised by dividing the peritoneal cavity into three sites in each patient: right and left supramesocolic areas and inframesocolic level (total 90 sites). Presence of PC was confirmed either by surgery (18/30) or by follow-up (12/30).ResultsPC was confirmed in 19 patients (19/30). At a total of 90 sites, 27 showed proven PC. On a patient-based analysis, sensitivity, specificity, PPV, NPV and accuracy were respectively 84%, 73%, 84%, 73% and 80% for PET/CT and 84%, 82%, 89%, 75% and 83% for MR-DWI. On a site-based analysis, overall sensitivity and specificity of PET/CT (63%, 90%) and MR-DWI (74%, 97%) were not statistically different (P = 0.27). In the supramesocolic area, MR-DWI detected more sites involved than PET/CT (7/9 vs. 4/9). The sensitivities of PET and MR were lower for subcentimetre tumour implants (42%, 50%). Interobserver agreement was very good for PET/CT and good for MR-DWI.ConclusionsFDG-PET/CT and MR-DWI showed similar high accuracy in diagnosing PC. Both techniques underestimated the real extent of PC because of decreased sensitivity for subcentimetre lesions.Key Points• FDG-PET/CT and MR-DWI showed similar high accuracy for diagnosing peritoneal carcinomatosis.• In the supramesocolic area, MR-DWI could be more sensitive than PET/CT.• Both techniques showed lower sensitivity for subcentimetre lesions.• Interobserver agreement was very good for PET/CT and good for MR-DWI.

Assessment of net postprandial protein utilization of 15N-labelled milk nitrogen in human subjects.

The nutritional quality of milk proteins, evaluated both in terms of digestibility and postprandial oxidation and retention in human subjects, was investigated in this study. Five healthy adult volunteers were given 480 ml 15N-labelled milk (i.e. 190 mmol N). 15N was subsequently determined at the ileal level, using a naso-intestinal intubation technique, as well as at the faecal level. Plasma and urine were sampled for 8 h after meal ingestion. Dietary exogenous N recovered at the terminal ileum after 8 h reached 8.6 (SE 0.8) mmol while the amount collected in the faeces was 6.5 (SE 0.7) mmol after 5 d. The true ileal and faecal digestibilities were 95.5 (SE 0.4)% and 96.6 (SE 0.4)% respectively. The appearance of [15N]amino acids in the plasma was rapid and prolonged. The measurement of 15N in the body urea pool and in the N excreted in the urine allowed us to calculate the deamination occurring after [15N]milk protein absorption. The net postprandial protein utilization (i.e. NPPU = (Nabsorbed-Ndeaminated)/Ningested), calculated as an index of protein quality 8 h after milk ingestion, was 81.0 (SE 1.9)%. Our data confirm that milk protein has a high oro-ileal digestibility in man and demonstrate that milk protein has a high NPPU, an index corresponding to a period in which the dietary protein retention is maximal.

Exogenous and endogenous nitrogen flow rates and level of protein hydrolysis in the human jejunum after [15N]milk and [15N]yoghurt ingestion.

Milk and yoghurt proteins were 15N-labelled in order to measure the flow rate of exogenous N during digestion in the human intestine. After fasting overnight, sixteen healthy volunteers, each with a naso-jejunal tube, ingested either [15N]milk (n 7) or [15N]yoghurt (n 9). Jejunal samples were collected every 20 min for 4 h. A significant stimulation of endogenous N secretion was observed during the 20-60 min period after yoghurt ingestion and the 20-40 min period after milk ingestion. The endogenous N flows over a 4 h period did not differ between the groups (44.3(SEM 6.5) mmol for milk and 63.5(SEM 5.9) mmol for yoghurt). The flow rates of exogenous N indicated a delayed gastric emptying of the yoghurt N compared with N from milk. The jejunal non-protein N (NPN) flow rate increased significantly after milk and yoghurt ingestion due to an increase in the exogenous NPN flow rate. The NPN fraction of exogenous N ranged between 40 and 80%. The net gastro-jejunal absorption of exogenous N did not differ significantly between milk (56.7(SEM 8.5)%) and yoghurt (50.9(SEM 7)%). The high level of exogenous N hydrolysis is in accordance with the good digestibility of milk products. Fermentation modifies only the gastric emptying rate of N and does not affect the level of diet hydrolysis, the endogenous N stimulation or the digestibility rate.

Prevention by daily soluble aspirin of colorectal adenoma recurrence: 4-year results of the APACC randomised trial

Background Aspirin inhibits colorectal carcinogenesis. In a randomised double-blind placebo-controlled trial, daily soluble aspirin significantly reduced recurrence of colorectal adenomas at 1-year follow-up. In this study the results of daily intake of low-dose aspirin on polyp recurrence at 4-year follow-up are presented. Methods 272 patients (naive for chronic aspirin use) with colorectal adenomas were randomly assigned to treatment with lysine acetylsalicylate 160 mg/day (n=73) or 300 mg/day (n=67) or placebo (n=132) for 4 years. The primary endpoints were adenoma recurrence and adenomatous polyp burden at year 4, comparing aspirin at either dose with placebo. The same endpoints were also assessed at year 1 or 4 (last colonoscopy performed for each patient). Results At the final year 4 colonoscopy the analysis included 185 patients (55 receiving aspirin 160 mg/day, 47 aspirin 300 mg/day and 83 placebo). There was no difference in the proportion of patients with at least one recurrent adenoma between patients receiving aspirin at either dose and those treated with placebo (42/102 (41%) vs 33/83 (40%); NS) or in the adenomatous polyp burden (3.1±5.8 mm vs 3.4±6.2 mm; NS). Also, the proportion of patients with at least one advanced recurrent adenoma did not differ (10/182 (10%) in the aspirin group vs 7/83 (7%) in the placebo group; NS). Conclusion Daily low-dose aspirin decreased adenoma recurrence significantly at 1 year but not at year 4. This discrepancy might be explained by a differential effect of aspirin according to the natural history of the polyp. Trial Registration Number NCT 00224679.

Hydrolyzed dietary casein as compared with the intact protein reduces postprandial peripheral, but not whole-body, uptake of nitrogen in humans

BACKGROUND Compared with slow proteins, fast proteins are more completely extracted in the splanchnic bed but contribute less to peripheral protein accretion; however, the independent influence of absorption kinetics and the amino acid (AA) pattern of dietary protein on AA anabolism in individual tissues remains unknown. OBJECTIVE We aimed to compare the postprandial regional utilization of proteins with similar AA profiles but different absorption kinetics by coupling clinical experiments with compartmental modeling. DESIGN Experimental data pertaining to the intestine, blood, and urine for dietary nitrogen kinetics after a 15N-labeled intact (IC) or hydrolyzed (HC) casein meal were obtained in parallel groups of healthy adults (n = 21) and were analyzed by using a 13-compartment model to predict the cascade of dietary nitrogen absorption and regional metabolism. RESULTS IC and HC elicited a similar whole-body postprandial retention of dietary nitrogen, but HC was associated with a faster rate of absorption than was IC, resulting in earlier and stronger hyperaminoacidemia and hyperinsulinemia. An enhancement of both catabolic (26%) and anabolic (37%) utilization of dietary nitrogen occurred in the splanchnic bed at the expense of its further peripheral availability, which reached 18% and 11% of ingested nitrogen 8 h after the IC and HC meals, respectively. CONCLUSIONS The form of delivery of dietary AAs constituted an independent factor of modulation of their postprandial regional metabolism, with a fast supply favoring the splanchnic dietary nitrogen uptake over its peripheral anabolic use. These results question a possible effect of ingestion of protein hydrolysates on tissue nitrogen metabolism and accretion. This trial was registered at clinicaltrials.gov as NCT00873951.

Endoscopist-directed propofol administration versus anesthesiologist assistance for colorectal cancer screening: a cost–effectiveness analysis

BACKGROUND Propofol for colonoscopy is largely administered by anesthesiologists or anesthesiology nurses in the United States (US) and Europe. Endoscopist-directed administration of propofol (EDP) by nonanesthesiologists has recently been proposed, with potential savings of anesthetist reimbursement costs. We aimed to assess potential EDP-related benefit in a screening setting. METHODS In a Markov model the total number of screening and follow-up colonoscopies in a cohort of 100 000 US subjects were estimated. Anesthetist-assisted colonoscopy was compared with an EDP strategy. Model outputs were projected onto the 50 - 80-year-old US population, assuming 27 % as the current uptake for colonoscopy screening. Anesthetist costs were estimated using the mean reimbursement for the corresponding Medicare code (≥ 65-year-olds) and from commercial insurance information (50 - 64-year-olds). The proportion of colonoscopies with anesthesiologist assistance was estimated from the Medicare database. Mean nurse salary was used to estimate the cost of a 2-week EDP training. The absolute number of US endoscopists was estimated by inflating by 33 % the number of board-certified gastroenterologists. No EDP mortality was assumed in the reference scenario, and 0.0008 % mortality in the sensitivity analysis. US census data were adopted. Analogous inputs were used for France to assess EDP-related benefit in a European country. RESULTS EDP training for 17 166 nurses (one for each US endoscopist) showed a cost of