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.

Potential utility of a new ulcerative colitis segmental endoscopic index combining disease severity and the extent of inflammation.

GOAL: To investigate the potential utility of a new scoring system, the Ulcerative Colitis Segmental Endoscopic Index (UCSEI), which combines measures of disease severity and extent of inflammation. BACKGROUND: Intestinal mucosal healing (MH) is a new therapeutic goal for ulcerative colitis (UC). Discontinuous lesions are common in UC and endoscopic observation of the entire colon is important. STUDY: Patients with active mild-to-moderate UC received daily treatment with oral mesalazine (4 g/d) and mesalazine enemas (1 g/d) for 8 weeks. Endoscopic evaluations, using the UCSEI and Mayo Endoscopic Score (MES), were performed in 5 colonic segments at baseline and week 8. The UCSEI criteria included erythema, vascular pattern, friability, and erosion/ulcer. The sum of 5 subscores, determined for each segment, was calculated as the UCSEI. Disease activity was also assessed using the UC Disease Activity Index (UCDAI). MH was defined as MES=0 to 1. RESULTS: Of 58 patients, 51 completed the scheduled endoscopic evaluations. At week 8, the UCDAI score had significantly decreased from 6.63 (baseline) to 2.73 (P<0.001). The remission and MH rates were 35.3% and 55.3%, respectively. Segmental endoscopic evaluation, using UCSEI, showed that baseline inflammation tended to be more severe in the distal colon. The baseline UCSEI increased with the extent of disease, which was not seen in MES. Improvements in UCSEI were observed, even in the patients without decreases in the MES. CONCLUSIONS: UCSEI, reflecting disease severity and extent of inflammation, provides useful information for UC management that is not available with MES.

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.

Transmural pressure loading enhances gastric mucosal cell proliferation.

AIM: Although increased intraluminal pressure in the stomach due to gastric outlet obstruction or functional gastric motor dysfunction, including gastroparesis, may affect gastric mucosal integrity, the direct effect of mechanical pressure on gastric mucosal cells has not yet been fully investigated. The aims of this study were to determine whether exposure to transmural pressure would affect the proliferation of gastric mucosal cells and to elucidate the intracellular signaling pathways involved. METHODS: Cellular proliferation and DNA synthesis were evaluated in rat gastric epithelial cells exposed to high transmural pressures. The levels of activation of 3 MAP kinases, ERK, JNK, and p38, were assessed, and the induction of immediate early gene expression was examined. The activation of nuclear factor activator protein-1 (AP-1) was evaluated by an electrophoretic mobility shift assay. RESULTS: Exposure to high transmural pressure significantly increased DNA synthesis within 24 h, with the most marked increase observed after exposure to a pressure of 80 mmHg, and this increase was inhibited by the MEK1 inhibitor PD98059. Early activation of ERK kinase, but not of JNK or p38 kinase, was detected after pressure loading. Early induction of the c-fos and c-myc genes and activation of the AP-1 transcription factor were also demonstrated within 3 h of exposure to 80 mmHg of pressure. CONCLUSION: Gastric mucosal cell proliferation induced by exposure to high transmural pressure may be related to early activation of ERK, the induction of c-fos and c-myc, and the activation of AP-1.

Successful biliary stent placement using balloon enteroscopy-assisted ERCP in a patient with rare surgically altered anatomy who underwent Roux-en-Y reconstruction twice.

Highlight Nakadai and colleagues report a case of successful endoscopic biliary drainage in a patient with rare surgically altered anatomy after undergoing Roux-en-Y reconstruction twice. Balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography can be the first choice for patients with such complex surgically altered anatomy, especially in those without biliary dilation.

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.

Serum nitrate/nitrite concentration correlates with gastric juice nitrate/nitrite: a possible marker for mutagenesis of the proximal stomach.

BACKGROUND/AIMS: In the normal acid-secreting stomach, luminally generated nitric oxide, which contributes to carcinogenesis in the proximal stomach, is associated with the concentration of nitrate plus nitrite (nitrate/nitrite) in gastric juice. We investigated whether the serum nitrate/nitrite concentration is associated with that of gastric juice and whether it can be used as a serum marker. METHODS: Serum and gastric juice nitrate/nitrite concentration, Helicobacter pylori antibody, and gastric pH were measured in 176 patients undergoing upper endoscopy. RESULTS: Multiple regression analysis revealed that serum nitrate/nitrite concentration was the best independent predictor of gastric juice nitrate/nitrite concentration. On single regression analysis, serum and gastric juice nitrate/nitrite concentration were significantly correlated, according to the following equation: gastric juice nitrate/nitrite concentration (µmol/l) = 3.93 - 0.54 × serum nitrate/nitrite concentration (µmol/l; correlation coefficient = 0.429, p < 0.001). In analyses confined to subjects with gastric pH less than 2.0, and in those with serum markers suggesting normal acid secretion (pepsinogen-I >30 ng/ml and negative H. pylori antibody), the serum nitrate/nitrite concentration was an independent predictor of the gastric juice nitrate/nitrite concentration (p < 0.001). CONCLUSION: Measuring the serum nitrate/nitrite concentration has potential in estimating the gastric juice nitrate/nitrite concentration. The serum nitrate/nitrite concentration could be useful as a marker for mutagenesis in the proximal stomach.

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.