A Possible Link between Gastric Mucosal Atrophy and Gastric Cancer after <i>Helicobacter pylori</i> Eradication

<div><p>Background</p><p>The effect of <i>H</i>. <i>pylori</i> eradication in gastric cancer prevention can be attributed to the improvement of atrophic gastritis, which is a known risk of gastric cancer. However, gastric cancer has also been diagnosed after long-term <i>H</i>. <i>pylori</i> eradication. This study aimed to clarify the association between gastric atrophy and gastric cancer after <i>H</i>. <i>pylori</i> eradication, including its clinicopathological features.</p><p>Methods</p><p>A total of 55 consecutive patients with 64 early gastric cancers (EGCs) diagnosed after <i>H</i>. <i>pylori</i> eradication were enrolled. The degree of endoscopic atrophy and the histological degrees of mononuclear cell infiltration, atrophy, and metaplasia in the corpus and adjacent mucosa of the EGCs were determined and scored.</p><p>Results</p><p>The majority of EGCs (63/64) were located within the endoscopically assessed atrophic mucosa or along the atrophic border. The adjacent mucosa of the EGCs presented significantly higher degrees of all histological parameters than in the corpus (mononuclear cell infiltration, 0.86+/-0.09 <i>vs</i>. 0.51+/-0.11, <i>P</i> = 0.016; atrophy, 1.77+/-0.13 <i>vs</i>. 0.65+/-0.14, <i>P</i><0.0001; metaplasia, 1.68+/-0.13 <i>vs</i>. 0.48+/-0.1, <i>P</i><0.0001). The degree of endoscopic atrophy improved in the patients with longer post-<i>H</i>. <i>pylori</i> eradication periods; however, this trend was not observed for the histological parameters, and high degrees of atrophy and metaplasia were observed in the adjacent mucosa of the EGCs compared with the corpus during all periods (all <i>P</i><0.05). The histological degrees of atrophy and metaplasia in the adjacent mucosa were particularly higher in the patients who underwent eradication due to gastric ulcers.</p><p>Conclusions</p><p>Severe gastric atrophy remained in the adjacent mucosa of the EGCs after <i>H</i>. <i>pylori</i> eradication, which may be linked to gastric carcinogenesis.</p></div

The clinicopathological characteristics of 64 EGCs from 55 patients diagnosed after <i>H</i>. <i>pylori</i> eradication.

<p>The clinicopathological characteristics of 64 EGCs from 55 patients diagnosed after <i>H</i>. <i>pylori</i> eradication.</p

The degree of endoscopic atrophy (a), histological degrees of mononuclear cell infiltration (b), atrophy (c), and metaplasia (d) in the corpus and adjacent mucosa compared to the period after <i>H</i>. <i>pylori</i> eradication.

<p>The statistical analysis was performed using Student's t-test.</p

The histological degrees of mononuclear cell infiltration, atrophy, and metaplasia in the corpus and adjacent (ADJ) mucosa in the EGC patients.

<p>Each factor was scored from 0 (normal) to 3 (marked). The statistical analysis was performed using Student's t-test.</p

A representative case of GC considered to be endoscopic responder.

<p>An ulcerative lesion (type 3 tumor) showed distinct reduction and flattening after two courses of chemotherapy.</p

Primer sequences used in pyrosequencing.

<p>U =  biotin labeled universal primer tag: 5′-biotin-GGGACACCGCTGATCGTTTA.</p><p>Primer sequences used in pyrosequencing.</p

Overall survival (OS, upper) and progression-free survival (PFS, lower) and endoscopy (left) and CT (right) based response evaluations in stage IV cases that have peritoneal dissemination or distant metastasis.

<p>Different two groups was assessed using the Kaplan-Meier method and the Log rank test.</p

Associations between methylation of EMT related genes and subtypes of UC.

<p>Note: Data are expressed as the mean ± SE. n, number of samples.</p><p>Two and three groups were compared using the t-test and Kruskal-Wallis test, respectively.</p>¶<p>? #, , & and *: Data are missing for one, three, one, and one cases, respectively.

: <i>CDH1</i>, <i>p</i> = 0.09, &: <i>CDX1</i>, <i>p</i> = 0.04, <i>miR-1247</i>, <i>p</i> = 0.006, <i>CDH1</i>, <i>p</i> = 0.08.*: <i>miR-1247</i>, <i>p</i> = 0.06.</p><p>Associations between methylation of EMT related genes and subtypes of UC.</p

Methylation of <i>miR-1247</i> (left), <i>CDH1</i> (center) and mean Z score of the two genes (right) in relation to severe clinical phenotype of UC.

<p>The statistical analysis was performed using Student's t-Test.</p

Methylation of <i>CDH1</i> (left), <i>CDH13</i> (center) and mean Z score of the two genes (right) in relation to the age and duration of disease.

<p>Statistical analysis was performed using a Spearman correlation analysis.</p