A multicenter validation of an endoscopic classification with narrow band imaging for gastric precancerous and cancerous lesions.

BACKGROUND AND STUDY AIM: The reliability and external validity of narrow band imaging (NBI) in the stomach have not been described consistently. The aim of the current study was to describe and estimate the accuracy and reliability of a simplified classification system for NBI in the diagnosis of gastric lesions. METHODS: Consecutive patients undergoing NBI endoscopy at two reference centers (n=85, 33% with dysplasia) were included in two studies. In total, 224 different areas were biopsied and recorded onto video. In the derivation study, previously described NBI features were analyzed in order to develop a simplified classification. In the validation study the accuracy and reliability of this classification were estimated among three groups of endoscopists with different levels of expertise in NBI. RESULTS: The reliability/accuracy results from the derivation study allowed the creation of a simplified NBI classification. In the validation study, "regular vessels with circular mucosa" (pattern A) was associated with normal histology (accuracy 83%; 95% confidence interval [CI] 75 %-90%); "tubulo-villous mucosa" (pattern B) was associated with intestinal metaplasia (accuracy 84%; 95CI 77%-91%; positive likelihood ratio [LR+]=4.75); and "irregular vessels and mucosa" (pattern C) was associated with dysplasia (accuracy 95%; 95CI 90%-99%; LR+=44.33). The reproducibility of these patterns was high (k=0.62). "Light-blue crest" was moderately reliable (k=0.49) but specific (87%) for intestinal metaplasia. A variable vascular density (additional pattern+) was the best feature for Helicobacter pylori gastritis (accuracy 70%; 95CI 59%-80%) but showed only fair reliability (k=0.38). Non-experienced endoscopists presented lower agreement (k=0.6 vs. k=0.75) and accuracy (74% vs. 86%) than international experts/experienced endoscopists. CONCLUSION: A simplified NBI classification is accurate and reliable for the diagnosis of intestinal metaplasia and dysplasia. The classification should be further assessed and validated on a per-patient assessment of NBI, and by comparing NBI with other imaging technologies.

MSH6 germline mutations in early-onset colorectal cancer patients without family history of the disease.

Germline MLH1 and MSH2 mutations are scarce in young colorectal cancer patients with negative family history of the disease. To evaluate the contribution of germline MSH6 mutations to early-onset colorectal cancer, we have analysed peripheral blood of 38 patients diagnosed with this disease before 45 years of age and who presented no family history of hereditary nonpolyposis colorectal cancer-related cancers. Blood samples from 108 healthy volunteers were analysed for those genetic alterations suspected to affect the function of MSH6. Of the seven (18.4%) MSH6 alterations found, we have identified three novel germline mutations, one 8 bp deletion leading to a truncated protein and two missense mutations resulting in the substitution of amino acids belonging to different polarity groups. High-frequency microsatellite instability was found in the patient with the MSH6 deletion, but not in the other 27 carcinomas analysed. No MLH1 promoter methylation was detected in tumour tissue. Our findings suggest that germline MSH6 mutations contribute to a subset of early-onset colorectal cancer. Further studies are warranted to understand the genetic and environmental factors responsible for the variable penetration of MSH6 germline mutations, as well as to identify other causes of early-onset colorectal cancer.

A follow up model for patients with atrophic chronic gastritis and intestinal metaplasia.

AIM: To devise a follow up model for patients with gastric cancer associated lesions, such as atrophic chronic gastritis (ACG) and intestinal metaplasia (IM). METHODS: Cohort study of 144 patients, followed for a minimum of one year, in whom at least two upper gastrointestinal endoscopic biopsies in flat gastric mucosa provided a diagnosis of ACG, IM, or low grade dysplasia (LGD). RESULTS: Of those diagnosed with ACG at first endoscopic biopsy (entry biopsy), 12% progressed to LGD in outcome biopsy, as did 8% of those with type I IM, 38% with type II or III IM, and 32% with LGD. Type of IM at entry independently predicted progression to LGD and cancer. Type II and III IM had a higher rate of progression to LGD than type I IM, which showed an indolent behaviour similar to ACG. Patients with type II or III IM were at higher risk for development of dysplasia, and 7% of patients with type III IM at first biopsy progressed to high grade dysplasia (HGD), whereas no cases of ACG or type I/II IM progressed to HGD during the first three years. CONCLUSION: Patients with ACG or IM could possibly be allocated to different management schedules, based on differences in rate and proportion of progression to LGD or HGD. Less intensive follow up (two/three yearly with "serological evaluation" (pepsinogen)) may suit those with ACG or type I IM. Patients with type III IM may benefit from six to 12 monthly improved endoscopic examination (magnification chromoendoscopy).