Previous Helicobacter pylori infection-induced atrophic gastritis: A distinct disease entity in an understudied population without a history of eradication.

Individuals with chronic atrophic gastritis who are negative for active H. pylori infection with no history of eradication therapy have been identified in clinical practice. By excluding false-negative and autoimmune gastritis cases, it can be surmised that most of these patients have experienced unintentional eradication of H. pylori after antibiotic treatment for other infectious disease, unreported successful eradication, or H. pylori that spontaneously disappeared. These patients are considered to have previous H. pylori infection-induced atrophic gastritis. In this work, we define these cases based on the following criteria: absence of previous H. pylori eradication; atrophic changes on endoscopy or histologic confirmation of glandular atrophy; negative for a current H. pylori infection diagnosed in the absence of proton-pump inhibitors or antibiotics; and absence of localized corpus atrophy, positivity for autoantibodies, or characteristic histologic findings suggestive of autoimmune gastritis. The risk of developing gastric cancer depends on the atrophic grade. The reported rate of developing gastric cancer is 0.31%-0.62% per year for successfully eradicated severely atrophic cases (pathophysiologically equal to unintentionally eradicated cases and unreported eradicated cases), and 0.53%-0.87% per year for spontaneously resolved cases due to severe atrophy. Therefore, for previous H. pylori infection-induced atrophic gastritis cases, we recommend endoscopic surveillance every 3 years for high-risk patients, including those with endoscopically severe atrophy or intestinal metaplasia. Because of the difficulty involved in the endoscopic diagnosis of gastric cancer in cases of previous infection, appropriate monitoring of the high-risk subgroup of this understudied population is especially important.

Cutoff Pepsinogen Level for Predicting Unintendedly Eradicated Cases of Helicobacter pylori Infection in Subjects with Seemingly Normal Pepsinogen Levels.

BACKGROUNDS/AIMS: In the ABC method, which is a method for risk stratification of gastric cancer using serum anti-Helicobacter pylori antibody and pepsinogen (PG) test, subjects with normal PG and seronegative for H. pylori are named as "Group A" and are regarded as having a low risk of gastric cancer. These "Group A" subjects include unintentionally eradicated cases at relatively high risk, and this study aimed to identify these subjects. METHODS: Of the 109 subjects, 76 were classified as uninfected Group A subjects with negative histologic H. pylori infection and no histologic and endoscopic atrophy, and 33 subjects were classified serologically as Group A after successful eradication, which are serologically equal to the unintendedly eradicated cases in Group A. The usefulness of measuring PG levels to detect post-eradication cases was validated by using a receiver operating characteristic (ROC) curve analysis. RESULTS: The area under the ROC curve for PGI level was 0.736 ± 0.06 (p < 0.01; cutoff value, 37.0 ng/mL; sensitivity, 77.6%; specificity, 72.7%), and that for the PGI/II ratio was 0.660 ± 0.06 (p < 0.01; cutoff value, 5.1; sensitivity, 84.2%; specificity, 43.4%). CONCLUSION: PGI levels of ≤37 ng/mL and PGI/II ratios of ≤5.1 effectively identified unintendedly eradicated cases in Group A.

Two cases of cystic artery pseudoaneurysm rupture due to acute cholecystitis with gallstone impaction in the neck.

A cystic artery aneurysm is a rare cause of hemobilia. Herein, we report two cases of acute cholecystitis with a ruptured cystic artery pseudoaneurysm. Two patients (a 69-year-old man and an 83-year-old man) were admitted to our hospital because of acute cholecystitis with gallstone impaction in the neck. Percutaneous transhepatic gallbladder drainage (PTGBD) was performed for both patients. After a few days of PTGBD, gallbladder hemorrhage was observed. Abdominal angiography showed cystic artery aneurysm. A transcatheter arterial embolization was therefore performed, followed by an open cholecystectomy.

Gastric Adenocarcinoma in Helicobacter pylori-Negative Autoimmune Gastritis: A Case Report and Literature Review.

Recent studies have suggested that gastric cancer does not occur in patients with Helicobacter pylori-negative autoimmune gastritis (AIG); however, this notion is controversial. We encountered a case of gastric cancer associated with AIG in which H. pylori infection was excluded. A woman in her 70s was referred to our hospital for endoscopic resection of an antral adenoma. An H. pylori antibodies test, stool antigens test, H. pylori culture, and histological analysis using Giemsa staining yielded negative results. AIG was suspected because the antrum was endoscopically normal but the body was severely atrophic, which are typical findings of AIG. Anti-parietal cell antibodies were 40-fold positive, the gastrin level was 2950 pg/ml, and the pepsinogen I level, pepsinogen II level, and pepsinogen I/II ratio were 6.3 ng/ml, 5.7 ng/ml, and 1.1, respectively. A pathological examination of the gastric body revealed severe oxyntic atrophy with hyperplasia of enterochromaffin-like cells, whereas the antrum showed no pyloric gland atrophy or inflammation. These findings indicated that the patient had H. pylori-negative AIG. Four years later, a depressed lesion in the lower body and a flat lesion at the angle were observed; the former was a poorly cohesive carcinoma, and the latter was a differentiated adenocarcinoma. Surgical resection revealed that the lesion in the lower body was a poorly cohesive carcinoma invading the submucosa with vascular involvement, whereas the lesion in the angle was an intramucosal differentiated adenocarcinoma. A review of previous studies of gastric cancer with H. pylori-negative AIG suggested that patients with histologically and serologically advanced gastritis are at high risk for carcinogenesis. Even in H. pylori-negative cases, severe gastric mucosal atrophy in AIG cases may indicate a carcinogenic risk; therefore, surveillance for gastric cancer is especially recommended for these cases. Large cohort studies on the association between H. pylori-negative AIG and gastric cancer are warranted.

Clinical Characteristics of Patients With Previous Helicobacter pylori Infection-Induced Atrophic Gastritis.

AIMS: Patients with atrophic gastritis unrelated to autoimmune gastritis (AIG) and without active Helicobacter pylori (H.pylori) infection or previous eradication therapy are considered to have previous Helicobacter pylori infection-induced atrophic gastritis (PHIG). This study aimed to clarify the clinical characteristics of patients with PHIG. METHODS: Consecutive patients who underwent upper gastrointestinal endoscopy during the study period were enrolled in the study. Pepsinogen and gastrin levels, H. pylori serology, and endoscopic atrophic grade were assessed. Patients were divided into five groups based on their H. pylori status and disease history (PHIG, without H. pylori infection, with active H. pylori infection, with successful H. pylori eradication, and AIG). Their gastric cancer risk status was classified according to the ABC method of serological gastric cancer screening. RESULTS: Of 536 consecutive patients who underwent upper gastrointestinal endoscopy during the study period, 318 were included (31 with PHIG, 77 without H. pylori infection, 101 with active H. pylori infection, 80 with successful H. pylori eradication, and 29 with AIG). Of the 31 patients with PHIG, 21 (68%) were H. pylori-seronegative, and 20 (65%) were classified as group A (normal pepsinogen, H. pylori-seronegative). Patients with PHIG accounted for 90.1% of the patients at high risk for gastric cancer misclassified as group A. The pepsinogen and H. pylori serological profiles of patients with PHIG were similar to those of patients with successful H. pylori eradication more than six years previously. A receiver-operating characteristic curve (ROC) analysis that included 13 patients with AIG and without active H. pylori infection and no previous eradication therapy and 31 patients with PHIG revealed that an endoscopic atrophy grade of O-III or greater according to the Kimura-Takemoto classification can predict AIG. CONCLUSIONS: Two-thirds of the patients with PHIG were misclassified as being at low risk (group A) according to the ABC method, suggesting that endoscopy is necessary for group A patients. The results of the serological evaluation of PHIG indicated that patients with PHIG may have experienced spontaneous H. pylori eradication, possibly because of the use of antibiotics for other conditions. Autoimmune gastritis should be considered in the presence of grade 0-III or greater gastric mucosal atrophy in patients with suspected PHIG, even if the autoantibody and histological findings are not available.

Life-threatening gastrointestinal bleeding caused by perforation of a penetrating atherosclerotic ulcer into the esophagus.

We present a case of life-threatening gastrointestinal bleeding caused by a penetrating atherosclerotic ulcer (PAU) that ruptured into the esophagus. A 65-year-old man presented with pyrexia and nausea. Contrast-enhanced computed tomography (CT) performed on admission revealed a hematoma between the lower esophagus and descending aorta due to a contained rupture of a PAU, which was undiagnosed at that time. Esophagogastroduodenoscopy (EGD) performed on the fifth day of admission revealed a subepithelial lesion in the lower esophagus, further complicated by ulcer formation. Biopsy did not reveal any malignant findings. On the eighth day of admission, the patient experienced substantial hematemesis with vital signs indicative of shock. Emergency EGD was performed, which revealed life-threatening bleeding in the lower esophagus. Contrast-enhanced CT revealed an aortoesophageal fistula with massive hematemesis, after which the patient died. An autopsy revealed perforation of the PAU into the esophagus without aortic dissection or a true aneurysm.Patients with atherosclerosis who develop recent-onset gastrointestinal symptoms, progressive anemia, and/or periaortic lesions should be carefully evaluated using contrast-enhanced CT, and PAU should be considered in the differential diagnosis.

A case of early gastric cancer resembling a subepithelial lesion diagnosed by endoscopic ultrasound-guided fine needle aspiration.

We present a case of early gastric cancer resembling a subepithelial lesion (GCSEL) derived from the submucosal ectopic gastric glands (SEGGs), diagnosed using endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). A 55-year-old woman was referred to our hospital for the investigation of a subepithelial lesion (SEL). Contrast computed tomography and esophagogastroduodenoscopy revealed two SELs in the greater curvature of the fundus and the posterior wall of the upper body of the stomach. EUS revealed a hypoechoic lesion in the submucosa and suggested partial invasion into the muscularis propria of the greater curvature of the fundus, and an anechoic lesion in the submucosa of the posterior wall of the upper body. The different diagnosis for the SEL in the fundus was GCSEL, neuroendocrine tumor, malignant lymphoma, and gastric adenocarcinoma of fundic gland type. EUS-FNA findings suggested adenocarcinoma. The patient underwent a laparoscopic proximal gastrectomy. Pathological findings confirmed a differentiated tubular adenocarcinoma derived from the SEGG, which partially invaded into the submucosa of the surrounding gastric wall without lymphovascular invasion or lymph node metastasis. The patient has been recurrence-free after 10 months of follow-up. EUS should be performed for SELs followed by EUS-FNA for lesions, such as GCSEL, that require early intervention.

Relevance of pepsinogen, gastrin, and endoscopic atrophy in the diagnosis of autoimmune gastritis.

Simple objective modalities are required for evaluating suspected autoimmune gastritis (AIG). This cross-sectional study aimed to examine whether pepsinogen, gastrin, and endoscopic findings can predict AIG. The diagnostic performance of endoscopic findings and serology in distinguishing AIG was evaluated. AIG was diagnosed in patients (N = 31) with anti-parietal cell antibody and/or intrinsic factor antibody positivity and histological findings consistent with AIG. Non-AIG patients (N = 301) were seronegative for anti-parietal cell antibodies. Receiver operating characteristic curve analysis of the entire cohort (N = 332) identified an endoscopic atrophic grade cutoff point of O3 on the Kimura-Takemoto classification (area under the curve [AUC]: 0.909), while those of pepsinogen-I, I/II ratio, and gastrin were 20.1 ng/mL (AUC: 0.932), 1.8 (AUC: 0.913), and 355 pg/mL (AUC: 0.912), respectively. In severe atrophy cases (≥ O3, N = 58, AIG/control; 27/31), the cutoff values of pepsinogen-I, I/II ratio, and gastrin were 9.8 ng/mL (AUC: 0.895), 1.8 (AUC: 0.86), and 355 pg/mL (AUC: 0.897), respectively. In conclusion, endoscopic atrophy is a predictor of AIG. High serum gastrin and low pepsinogen-I and I/II ratio are predictors even in the case of severe atrophy, suggesting their usefulness when the diagnosis of AIG is difficult or as serological screening tests.

Fasting gastric pH of Japanese subjects stratified by IgG concentration against Helicobacter pylori and pepsinogen status.

BACKGROUND: The clinical significance of Helicobacter pylori antibody titer has been controversial, and the association between the extent of gastric atrophy or acid secretion and H. pylori antibody concentration has not been elucidated. MATERIALS AND METHODS: Serum pepsinogen, H. pylori antibody concentration, and fasting gastric pH (as an indicator of acid secretion) were measured in 231 patients undergoing upper gastrointestinal endoscopy. "Atrophic" pepsinogen was defined as pepsinogen-I < 70 ng/mL and pepsinogen-I/II ratio < 3. Other levels of pepsinogen were defined as "normal". Fasting gastric pH was analyzed in subjects stratified by pepsinogen level and by H. pylori antibody concentration. RESULTS: Helicobacter pylori antibody concentration showed no significant relationship with fasting gastric pH when all subjects were analyzed together. In H. pylori-seronegative subjects, fasting gastric pH was within the normal range, irrespective of the extent of mucosal atrophy. In H. pylori-seropositive subjects, H. pylori antibody concentration was positively correlated with fasting gastric pH in subjects with "normal" pepsinogen, but inversely correlated in those with "atrophic" pepsinogen. Particularly in subjects with low H. pylori antibody concentration and atrophic mucosa, a group reportedly at high risk of noncardia cancer, the most impaired acid secretion was shown among subjects with atrophic mucosa. CONCLUSIONS: The relationship between acid secretion and H. pylori antibody concentration differs depending on the presence of mucosal atrophy. Our findings provide a possible rationalization for measuring both serum pepsinogen levels and H. pylori antibody concentration in gastric cancer screening.

Stent placement using dual-channel endoscope for biloma after EUS-guided hepaticogastrostomy.

Highlight Nakamura and colleagues report a case of successful stent placement for biloma through a migrated EUS-guided hepaticogastrostomy stent, using a dual-channel endoscope and the hairpin guidewire technique. This method enables biliary drainage as a potential rescue technique for EUS-guided hepaticogastrostomy stent obstruction with a long metallic stent in the stomach.

Correction: Association between Increased Gastric Juice Acidity and Sliding Hiatal Hernia Development in Humans.

[This corrects the article DOI: 10.1371/journal.pone.0170416.].

Association between Increased Gastric Juice Acidity and Sliding Hiatal Hernia Development in Humans.

OBJECTIVES: Several clinical factors; overweight, male gender and increasing age, have been implicated as the etiology of hiatal hernia. Esophageal shortening due to acid perfusion in the lower esophagus has been suggested as the etiological mechanism. However, little is known about the correlation between gastric acidity and sliding hiatus hernia formation. This study examined whether increased gastric acid secretion is associated with an endoscopic diagnosis of hiatal hernia. METHODS: A total of 286 consecutive asymptomatic patients (64 were diagnosed as having a hiatal hernia) who underwent upper gastrointestinal endoscopy were studied. Clinical findings including fasting gastric juice pH as an indicator of acid secretion, age, sex, body mass index, and Helicobacter pylori infection status determined by both Helicobacter pylori serology and pepsinogen status, were evaluated to identify predictors in subjects with hiatal hernia. RESULTS: Male gender, obesity with a body mass index >25, and fasting gastric juice pH were significantly different between subjects with and without hiatal hernia. The cut-off point of fasting gastric juice pH determined by receiver operating curve analysis was 2.1. Multivariate regression analyses using these variables, and age, which is known to be associated with hiatal hernia, revealed that increased gastric acid secretion with fasting gastric juice pH <2.1 (OR = 2.60, 95% CI: 1.38-4.90) was independently associated with hiatal hernia. Moreover, previously reported risk factors including male gender (OR = 2.32, 95% CI: 1.23-4.35), body mass index >25 (OR = 3.49, 95% CI: 1.77-6.91) and age >65 years (OR = 1.86, 95% CI: 1.00-3.45), were also significantly associated with hiatal hernia. CONCLUSIONS: This study suggests that increased gastric acid secretion independently induces the development of hiatal hernia in humans. These results are in accordance with the previously reported hypothesis that high gastric acid itself induces hiatal hernia development.

Helicobacter pylori Antibody Titer and Gastric Cancer Screening.

The "ABC method" is a serum gastric cancer screening method, and the subjects were divided based on H. pylori serology and atrophic gastritis as detected by serum pepsinogen (PG): Group A [H. pylori (-) PG (-)], Group B [H. pylori (+) PG (-)], Group C [H. pylori (+) PG (+)], and Group D [H. pylori (-) PG (+)]. The risk of gastric cancer is highest in Group D, followed by Groups C, B, and A. Groups B, C, and D are advised to undergo endoscopy, and the recommended surveillance is every three years, every two years, and annually, respectively. In this report, the reported results with respect to further risk stratification by anti-H. pylori antibody titer in each subgroup are reviewed: (1) high-negative antibody titer subjects in Group A, representing posteradicated individuals with high risk for intestinal-type cancer; (2) high-positive antibody titer subjects in Group B, representing active inflammation with high risk for diffuse-type cancer; and (3) low-positive antibody titer subjects in Group C, representing advanced atrophy with increased risk for intestinal-type cancer. In these subjects, careful follow-up with intervals of surveillance of every three years in (1), every two years in (2), and annually in (3) should be considered.

Predictors of Gastric Neoplasia in Cases Negative for Helicobacter pylori Antibody and with Normal Pepsinogen.

BACKGROUND/AIM: Individuals negative for Helicbacter pylori antibody and with a normal pepsinogen test (group A) are regarded as being at low risk in serum gastric cancer screening known as the ABC method, and endoscopy is not recommended; however, this group may include 2-10% of gastric cancer cases. PATIENTS AND METHODS: A total of 345 individuals who underwent upper gastrointestinal endoscopy and were classified by ABC as group A (H. pylori antibody titer <10 U/ml, and pepsinogen-I >70 ng/ml or I/II ratio >3) were enrolled, and predictors of gastric neoplasia were investigated. RESULTS: Ten gastric neoplasia cases (gastric cancer and adenoma) were found to be included. Multiple logistic regression analyses identified H. pylori antibody titer ≥3 U/ml (odds ratio=14.4, 95% confidence interval=2.7-76.9; p<0.01) and pepsinogen-I/II ratio ≤4.3 ng/ml (odds ratio=10.0, 95% confidence interval=2.1-47.9; p<0.01), but not age as independent predictive factors of neoplasia. CONCLUSION: Endoscopy should be considered in individuals with H. pylori antibody titer of ≥3 U/ml and a pepsinogen-I/II ratio of ≤4.3 in those classed as group A by ABC method.

Fundic gland polyps accurately predict a low risk of future gastric carcinogenesis.

OBJECTIVES: Few reports have analyzed the clinical importance of sporadic fundic gland polyps (FGPs). The aim of this study was to investigate the relationship between sporadic FGPs and condition of the gastric mucosa stratified by serum pepsinogen levels and Helicobacter pylori antibody level. METHODS: Three hundred and seventy-five subjects undergoing gastrointestinal endoscopy were enrolled. Subjects on proton pump inhibitors were excluded. Pathologically proven FGPs, and other endoscopic findings (reflux esophagitis, gastric and duodenal ulcer) were examined and serum pepsinogen levels, H. pylori antibody concentration and gastric juice pH were measured simultaneously. Subjects with normal serum pepsinogen and negative H. pylori antibodies were defined as having "low risk" stomachs, suggesting low risk of gastric carcinogenesis. RESULTS: Of the 375 subjects, 44 showed FGPs. The prevalence of "low risk" stomach in subjects with and without FGPs was 98% and 48%, respectively. Multivariable logistic regression analysis indicated three variables as independent factors positively associated with "low risk" stomachs: FGPs (odds ratio [OR] 38.6), reflux esophagitis (OR 4.8), and age<60 years (OR 1.89). Gastric juice pH, which is associated with mucosal atrophy grade and low pH indicates less mucosal atrophy, was significantly lower in subjects with (1.64 ± 0.64) than without FGPs in "low risk" (1.94 ± 1.12) and "high risk" stomachs (3.99 ± 2.31). CONCLUSIONS: Sporadic FGPs tend to be related to the least atrophic mucosa among non-gastric atrophy subjects without H. pylori infection, and can be used as predictors of a low risk of gastric carcinogenesis.