Mo1018 Probe-Based Confocal Laser Endomicroscopy for In Vivo Detection of Gastric Intestinal Metaplasia, Intraepithelial Neoplasia, and Carcinoma: A Multicenter, Randomized, Controlled Trial

Abstract Background and study aims Owing to the indistinctive endoscopic appearance of gastric intestinal metaplasia (GIM), gastric intraepithelial neoplasia (GIN), and early gastric cancer (EGC), a significant number of such lesions may be missed during surveillance endoscopy. The aim of this clinical trial was to assess the value of combined computed virtual chromoendoscopy (flexible spectral imaging color enhancement [FICE]) and probe-based confocal laser endomicroscopy (pCLE) for in vivo detection of GIM, GIN, and EGC. Patients and methods This was a multicenter, randomized controlled trial performed in 238 patients at four tertiary centers. Patients were randomized to FICE-guided pCLE with targeted biopsies (group A) or FICE with standard biopsies (group B). The diagnostic yield of GIM, GIN, or EGC was compared between the two groups. Results On a per-patient assessment, the diagnostic yield for GIM/GIN/EGC was 73.3 % (88/120) in group A and 63.6 % (75/118) in group B (P = 0.09). On a per-biopsy analysis, FICE-guided pCLE with targeted biopsies significantly increased the diagnostic yield of GIM/GIN/EGC vs. FICE with standard biopsies, from 31.5 % (252/800) to 75.1 % (313/417) (P < 0.001). In addition, pCLE-guided targeted biopsies led to a significant 48.5 % decrease in the number of biopsies per patient vs. FICE with standard biopsies (P < 0.001). Conclusions Real-time pCLE and targeted biopsies after FICE improved the diagnostic yield for the detection of GIM, GIN, and EGC, and only required about half the number of biopsies vs. FICE with standard biopsies. This may allow a better regimen for endoscopic surveillance and subsequent treatment of patients with premalignant and malignant gastric abnormalities.Trial registered at ClinicalTrials.gov (NCT02515721).

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Tryptophan, glutamine, leucine, and micronutrient supplementation improves environmental enteropathy in Zambian adults: a randomized controlled trial

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqz189 ◽

2019 ◽

Vol 110 (5) ◽

pp. 1240-1252 ◽

Cited By ~ 4

Author(s):

John Louis-Auguste ◽

Ellen Besa ◽

Kanekwa Zyambo ◽

Derick Munkombwe ◽

Rosemary Banda ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Controlled Trial ◽

Microbial Translocation ◽

Confocal Laser Endomicroscopy ◽

Confocal Laser ◽

Residential Areas ◽

Barrier Dysfunction ◽

Randomized Controlled ◽

Environmental Enteropathy

ABSTRACT Background Environmental enteropathy (EE) refers to villus blunting, reduced absorption, and microbial translocation in children and adults in tropical or deprived residential areas. In previous work we observed an effect of micronutrients on villus height (VH). Objective We aimed to determine, in a randomized controlled trial, if amino acid (AA) or multiple micronutrient (MM) supplementation can improve intestinal structure or barrier dysfunction in Zambian adults with EE. Methods AA (tryptophan, leucine, and glutamine) and/or MM supplements were given for 16 wk in a 2 × 2 factorial comparison against placebo. Primary outcomes were changes in VH, in vivo small intestinal barrier dysfunction assessed by confocal laser endomicroscopy (CLE), and mechanistic (or mammalian) target of rapamycin complex 1 (MTORC1) nutrient responsiveness in lamina propria CD4+ lymphocytes. Results Over 16 wk AA, but not MM, supplementation increased VH by 16% (34.5 μm) compared with placebo (P = 0.04). Fluorescein leak, measured by CLE, improved only in those allocated to both AA and MM supplementation. No effect was seen on MTORC1 activation, but posttreatment MTORC1 and VH were correlated (ρ = 0.51; P = 0.001), and change in MTORC1 was correlated with change in VH in the placebo group (ρ = 0.63; P = 0.03). In secondary analyses no effect was observed on biomarkers of microbial translocation. Metabolomic analyses suggest alterations in a number of microbial- and host-derived metabolites including the leucine metabolite β-hydroxy-β-methylbutyrate, which was increased by AA supplementation and correlated with VH. Conclusions In this phase 2 trial, AA supplementation protected against a decline in VH over the supplementation period, and improved barrier function when combined with micronutrients. Leucine and MTORC1 metabolism may be involved in the mechanism of effect. This trial was registered at www.pactr.org as PACTR201505001104412.

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