Diagnostic performance of the normal range of gastrin calculated using strict criteria based on a combination of serum markers and pathological evaluation for detecting gastritis: a retrospective study.

BACKGROUND: The ABC method, which combines the pepsinogen method and anti-Helicobacter pylori antibody titers, has been used for risk screening for gastric cancer in Japan. However, it has been reported that there are cases of gastritis and carcinogenesis risk even in group A, which is considered to be a low-risk group based on the ABC method. Currently, in group A, endoscopic examination is needed to strictly discriminate "patients without gastritis" (defined as true A patients) from those "with gastritis." A simple and minimally invasive diagnostic criterion for gastritis using serological markers is desirable. In this study, we aimed to identify the normal serum gastrin concentrations in normal stomach cases based on pathological diagnosis and investigate the usefulness of serum gastrin concentrations in diagnosing gastritis. METHODS: Patients who underwent endoscopy and blood tests at Hiroshima University Hospital were enrolled in the study and categorized into the "pathologically-evaluated group" and "endoscopically-evaluated group," according to the evaluation method of atrophic gastritis. Initially, we measured serum gastrin concentrations in the normal stomach cases in the pathologically-evaluated group and calculated the normal range of serum gastrin concentrations. We used the upper limit of this normal range of serum gastrin concentrations and performed a validation study to determine its usefulness as a diagnostic marker for distinguishing between cases of gastritis and true A in the endoscopically-evaluated group. RESULTS: The 95th percentile of serum gastrin concentrations in pathologically-evaluated normal stomach cases was 34.12-126.03 pg/mL. Using the upper limit of this normal range of serum gastrin concentrations, the sensitivity, specificity, positive predictive value, and negative predictive value for gastritis were 52.8%, 92.6%, 97.0%, and 31.0%, respectively. Additionally, the receiver operating characteristic (ROC) curve for the endoscopically-evaluated group showed an area under the ROC curve of 0.80. CONCLUSION: The gastrin cut-off value of 126 pg/mL has a good positive predictive value (97.0%) for detecting gastritis positing its use as a marker for cases requiring endoscopy. However, the identification of patients with gastritis having normal serum gastrin concentrations due to insufficient sensitivity remains a challenge for the future.

Identification of Helicobacter pylori-related gastric cancer risk using serological gastritis markers and endoscopic findings: a large-scale retrospective cohort study.

BACKGROUND: Gastric cancer remains a severe public health problem worldwide, particularly in Japan. Recent studies have demonstrated that serum markers are beneficial for risk stratification in gastric cancer development. We aimed to evaluate the usefulness of serum markers either alone or in combination (serum markers plus endoscopy) for effective risk stratification of gastric cancer development. METHODS: We enrolled 22,736 patients aged 20-95 years who underwent blood sampling and endoscopic examination at Hiroshima University Hospital in Japan between 1990 and 2014. The serum pepsinogen (PG) levels and anti-Helicobacter pylori antibody (Hp-Ab) titers were evaluated in each patient. The enrolled patients were matched with the database of the Hiroshima Prefecture Regional Cancer Registry. We processed the medical records and excluded patients with possible confounding factors for PG levels, such as proton pump inhibitor use, prior successful eradication therapy, post-gastrectomy, severe hepatorenal dysfunction, Zollinger-Ellison syndrome, and autoimmune gastritis. Among the remaining 5131 patients, we reviewed records of endoscopic examinations and selected 1507 patients (mean age, 62.5 years; 985 men and 522 women) who underwent endoscopic examination more than three months after blood sampling. First, based on the ABC method, patients were classified as follows: High PG levels and negative Hp-Ab, group A, high PG levels and positive Hp-Ab, group B, low PG levels and positive Hp-Ab, group C, and low PG levels and negative Hp-Ab, group D. Group A was further classified into two subgroups using endoscopic findings: true A without atrophic gastritis and pseudo A with atrophic gastritis. All patients underwent annual endoscopy follow-up. RESULTS: Among the 1,507 patients (mean age, 62.5 years; 985 men), 24 were diagnosed with newly developed gastric cancer. No significant difference in cancer development was found between group A (PG negative and Hp-Ab negative) and the other groups. Remarkably, no true A group subjects developed gastric cancer. CONCLUSIONS: The combination of serum markers and endoscopic findings is essential for the risk evaluation of gastric cancer.

Serum Gastrin and Pepsinogen Levels after Administration of Acid Secretion Inhibitors for Ulcers due to Endoscopic Submucosal Dissection in Patients with Early Gastric Cancer.

Acid secretion inhibitors, such as proton pump inhibitors (PPIs) and potassium competitive acid blockers (PCABs), are used to treat ulcers after endoscopic submucosal dissection (ESD) for early gastric cancer. These drugs can influence serum gastrin and pepsinogen (PG) levels; however, their definite effects remain unclear. This open-label, randomized study investigated the effect of acid secretion inhibitors on the serum gastrin and pepsinogen levels. In total, 76 patients were enrolled in the study. They underwent gastric ESD and received a PPI (n = 21) or PCAB (n = 55). Changes in the serum gastrin and PG levels before and 4 weeks after administration were examined. Patient factors associated with the alteration of serum PG or gastrin levels were identified. The median serum levels of gastrin, PGI, and PGII before the administration of the acid secretion inhibitors were 110.5 pg/mL, 36.4 ng/mL, and 8.9 ng/mL, respectively; after administration, the levels increased to 300 pg/mL, 64.7 ng/mL, and 15.8 ng/mL, respectively (P < 0.01). Univariate analysis revealed that PCABs led to a more significant increase in the serum gastrin and PG levels as compared to PPIs. Furthermore, the PG levels were significantly increased in patients with previous Helicobacter pylori infections than in those with current infections. In conclusion, the serum gastrin and PG levels increased after the use of acid secretion inhibitors. This elevation was affected by the type of drug used, whereas the elevation in PGs was affected by the patient's background as well.

Clinical usefulness of combination therapy with polidocanol injection and argon plasma coagulation for gastric antral vascular ectasia.

BACKGROUND AND AIM: Gastric antral vascular ectasia (GAVE) causes gastrointestinal bleeding. The initial treatment for GAVE bleeding is endoscopic hemostasis, and currently, the most performed technique to achieve hemostasis is argon plasma coagulation (APC). However, APC is associated with a high recurrence rate. To overcome this limitation, we examined the outcomes of the combination therapy of APC and polidocanol injection (PDI) for treating GAVE. METHODS: We retrospectively analyzed the outcomes of 15 consecutive GAVE patients treated with PDI + APC at Hiroshima University Hospital between November 2011 and September 2019 with respect to clinical characteristics, hemostatic efficacy, complications related to treatment, and recurrence rate. RESULTS: The mean age of patients (4 men and 11 women) was 74 ± 8.4 years. Patients had comorbidities of liver cirrhosis (seven patients, 47%), chronic renal failure (seven patients, 47%), and autoimmune diseases (seven patients, 47%). Endoscopic hemostasis with PDI + APC was performed in all patients (n = 15). The mean number of PDIs attempted to stop bleeding was 1.5 ± 0.8 (1-4), and the mean number of APCs attempted was 2.1 ± 1.2 (1-5). Complications related to treatment occurred in two patients (14%): ulceration in one patient and hematoma in another patient, both of whom were treated conservatively. Two patients (13%) had recurrences during the follow-up period (average period, 42 months). Both were cured with additional treatment of PDI only. CONCLUSION: The combination therapy of PDI and APC is effective for GAVE with a low recurrence rate.

Preceding endoscopic submucosal dissection in submucosal invasive gastric cancer patients does not impact clinical outcomes.

Submucosal deep invasion of gastric cancer (T1b2; depth of submucosal invasion ≥ 500 µm) is a risk factor for lymph node metastasis and, thus, is one of the criteria for curative treatment. Our aim was to evaluate the specific influence of endoscopic submucosal dissection (ESD) on the prognosis of patients with T1b2 gastric cancer. This was a retrospective analysis of 248 consecutive patients, with 252 pT1b2 gastric cancer lesions, who underwent ESD prior to additional surgery (Group A, n = 101) or surgery only (Group B, n = 147). After propensity score-matching (for sex, age, tumor diameter and gross type), we compared pathological characteristics between the 2 groups and the prognosis over a follow-up period ≥ 60 months. Compared to Group B, patients in Group A were older, with a higher proportion of men. The proportion of depressed and undifferentiated type tumors was greater in Group B than A, with larger tumor size and depth of submucosal invasion as well. There was no incidence of local recurrence, but distant metastasis was identified in 5% of cases in Group A and 3% in Group B. After propensity score-matching, there were no difference in the 5-year overall survival rate between Group A and B (87.5% vs. 91.2%, respectively), nor in the 5-year disease-specific survival rate (96.3% vs. 96.4%, respectively). ESD prior to surgery for T1b2 gastric cancer did not adversely affect clinical outcomes after additional surgery.

Usefulness of linked color imaging in the early detection of superficial esophageal squamous cell carcinomas.

BACKGROUND AND AIMS: Linked color imaging (LCI) improved the visibility of gastric cancer and colorectal flat lesions. This study aimed to investigate the usefulness of LCI in detecting superficial esophageal squamous cell carcinomas (SESCC). METHODS: We enrolled 37 consecutive SESCC patients (46 SESCCs) diagnosed using LCI and blue laser imaging bright mode (BLI-BRT) and treated in Hiroshima University Hospital between April 2018 and November 2018. Eight professional endoscopists compared images obtained on non-magnifying BLI-BRT and LCI versus conventional white light imaging (WLI). Identification and boundary diagnosis of SESCC with LCI and BLI-BRT were compared with WLI. Changes in lesion visibility were clarified. Interobserver agreement was assessed. Clinicopathological features of lesion that influence visibility with LCI were assessed. RESULTS: In LCI, 37% (17/46) of cases had improved visibility and 63% (29/46) had unchanged visibility (interobserver agreement = 0.74). Among cases with multiple lugol voiding lesions (LVLs), ΔE between the lesion and background mucosa was significantly higher in LCI than in WLI (20.8 ± 7.9 vs 9.2 ± 6.1, P < 0.05). No significant differences were found in tumor size, morphological type, color, depth, and smoking or drinking history. However, multiple LVLs were significantly higher among cases with improved versus unchanged visibility. On BLI-BRT, 39% (18/46) of cases had improved visibility and 61% (28/46) had unchanged visibility (interobserver agreement = 0.60). CONCLUSION: Almost the same as BLI-BRT, LCI improves SESCC visibility compared with WLI. This is useful for cases with multiple LVLs. In cases without background coloration (BGC), LCI may make SESCC more visible than BLI-BRT.

Clinical significance of endoscopic ultrasonography in diagnosing invasion depth of early gastric cancer prior to endoscopic submucosal dissection.

BACKGROUND AND AIM: Endoscopic ultrasonography is a reliable diagnostic modality for determining indications of endoscopic submucosal dissection for early gastric cancer. We aimed to clarify the clinical significance of endoscopic ultrasonography in the invasion depth diagnosis of early gastric cancer. METHODS: We retrospectively assessed 1598 consecutive patients with 2001 early gastric cancers who underwent EUS before ESD or surgery between October 2010 and April 2019 at our institution. Lesions were classified according to endoscopic ultrasonography-determined invasion depth as EUS-M/SM1 (lesions confined to sonographic layers 1 and 2 or lesions with changes in sonographic layer 3; depth, < 1 mm) and EUS-SM2 (lesions with changes in sonographic layer 3; depth, ≥ 1 mm). We evaluated the invasion depth determination accuracy of endoscopic ultrasonography and analyzed the clinicopathological features of misdiagnosed early gastric cancer cases. RESULTS: The invasion depth determination accuracy was as follows: EUS-M/SM1: pathological T1a/T1b1 early gastric cancer, 97%; EUS-SM2: pathological T1b2 early gastric cancer, 79%. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 95%, 98%, 69%, 97%, and 79%, respectively. In EUS-M/SM1 early gastric cancer, tumor size of ≥ 15 mm, presence of ulceration, and undifferentiated histological type were significantly associated with endoscopic ultrasonography accuracy. In EUS-SM2 early gastric cancer, tumor size of ≥ 30 mm was significantly associated with endoscopic ultrasonography accuracy. CONCLUSIONS: Endoscopic ultrasonography is a useful modality in accurately determining the invasion depth of early gastric cancer before endoscopic submucosal dissection.

Clinical and genomic characteristics of mucosal signet-ring cell carcinoma in Helicobacter pylori-uninfected stomach.

BACKGROUND: Gastric cancer develops even in Helicobacter pylori(H. pylori)-uninfected patients and its typical histological feature is signet ring cell carcinoma (SRCC) within the mucosal layer. However, the biological characteristics of SRCC remain unclear. We aimed to clarify the pathological and genetic features of SRCC in H. pylori-uninfected patients. METHODS: Seventeen H. pylori-uninfected patients with mucosal SRCCs were enrolled and their clinicopathological characteristics were compared with those of H. pylori-infected patients with mucosal SRCCs. Seven SRCCs without H. pylori-infected, including two invasive SRCCs, and seven H. pylori-infected SRCCs were subjected to a genetic analysis using next-generation sequencing. RESULTS: H. pylori-uninfected patients with mucosal SRCCs revealed male dominancy and a significantly higher prevalence of smokers among them as compared with the H. pylori-infected patients with SRCC. A CDH1 mutation (frame shift indel) was detected in one H. pylori-uninfected cancer not only in the mucosal SRCC but also in the invasive portion. A TP53 mutation was detected in one SRCC without H. pylori-infected. In the control group, ARID1A and TP53 mutations were detected in one SRCC each. The C to A mutation, which is a characteristic smoking-induced mutation, was not found in any of the samples. CONCLUSIONS: Some SRCCs in H. pylori-uninfected patients may have a malignant potential similar to that of SRCCs in H. pylori-infected patients. Smoking may not be the main carcinogenic factor for the development of SRCCs among the H. pylori-uninfected patients.

Correction to: Genomic landscape of epithelium with low-grade atypia on gastric cancer after Helicobacter pylori eradication therapy.

In the original publication of the article, the article title was published with typo. The word "eradiation" should be "eradication" in the article title and keywords.

The Evaluation of Esophageal Motility Using Infusion Manometry with a Trans-nasal Endoscope: A Preliminary Study.

Objective The Chicago classification using high-resolution manometry (HRM) has been proposed for the diagnosis of esophageal motility disorders. However, HRM is expensive, and few patients are likely to benefit from this method. We established a method using a raised infusion catheter called "esophageal manometry using a trans-nasal endoscope". In this study, we examined the clinical utility of this new method for the assessment of patients with dysphagia. Methods We enrolled 124 consecutive patients who complained of dysphagia and were suspected of having esophageal motility disorders. Patients underwent manometry using a trans-nasal endoscope at Hiroshima University Hospital from September 2008 to December 2018. An esophageal biopsy was performed during the procedure from the thoracic esophagus to detect eosinophilic esophagitis. In addition, we examined the clinical courses of patients diagnosed with achalasia. Results The diagnostic ability of manometry using a trans-nasal endoscope was 98%, and no major complications associated with the procedure were recorded. About 30% of patients were diagnosed with achalasia, and most (77%) were well controlled by medications or balloon dilation. One patient was diagnosed with eosinophilic esophagitis. Conclusion Manometry using a trans-nasal endoscope is beneficial and can be used for the clinical management of patients with dysphagia.

Clinical Usefulness of Dual Red Imaging in Gastric Endoscopic Submucosal Dissection: A Pilot Study.

BACKGROUND/AIMS: Dual red imaging (DRI) is a new, image-enhanced endoscopy technique. There are few reports about the usefulness of DRI during gastric endoscopic submucosal dissection (ESD). We aimed to examine the usefulness of DRI in endoscopic hemostasis during gastric ESD. METHODS: We enrolled a total of 20 consecutive patients who underwent gastric ESD. Five endoscopists compared DRI with white light imaging (WLI) for the visibility of blood vessels and bleeding points while performing endoscopic hemostasis. RESULTS: The visibility of blood vessels was increased in 56% (19/34) of the cases, and the visibility of bleeding points was improved in 55% (11/20) of the cases with the use of DRI compared with the use of WLI. CONCLUSION: DRI improved the visibility of blood vessels and bleeding points in cases with oozing bleeding, blood pooling around the bleeding points, and multiple bleeding points.

Genomic landscape of epithelium with low-grade atypia on gastric cancer after Helicobacter pylori eradiation therapy.

BACKGROUND: Gastric cancer may develop after successful eradication of Helicobacter pylori, although the incidence is lower than in non-eradicated individuals. We previously reported the appearance of characteristic epithelium with low-grade atypia (ELA) on the surface of gastric cancer after H. pylori eradication. However, whether ELA originates from cancer after re-differentiation or from the non-cancerous surrounding mucosa is unknown. METHODS: We isolated ELA regions from 10 early gastric cancer patients and analyzed the nucleotide sequences for 90 oncogenes and 35 fusion oncogenes, comparing them with counterpart cancer tissue, normal gastric mucosa, and blood cell-derived DNA. Somatic mutations in each tissue were identified by comparing them with the sequences from whole blood-derived DNA. RESULT: Gene alterations were observed in nine of the ten patients, and up to 42 and 70 somatic mutations were seen in cancer and ELA samples, respectively. Common mutations shared between cancer and ELA tissues were found in eight of these nine patients. In contrast, common mutations between non-cancer mucosa and ELA were only detected in one patient, who also had common mutation between cancer and ELA. ELA-specific nucleotide substitutions were seen in seven patients. In contrast, cancer-specific substitutions were only found in two patients. 18 out of 19 amino acid substitutions present in cancer tissue were also identified in ELA. These results suggest that ELA originated from cancer tissue and accumulated further nucleotide substitutions. CONCLUSIONS: Differential diagnosis of ELA and normal mucosa should be carefully performed to prevent misdiagnosis of ELA as normal mucosa with atypia.

Potential of Helicobacter pylori-uninfected signet ring cell carcinoma to invade the submucosal layer.

BACKGROUND AND AIM: The typical histology of Helicobacter pylori-uninfected gastric cancer is signet ring cell carcinoma (SRCC) localized in the mucosal layer, but the potential of these SRCCs to invade the submucosal layer is unclear. This study aimed to investigate the clinicopathological characteristics of SRCC in H. pylori-uninfected patient and its prevalence in diffuse-type gastric cancer (DGC) within Japan. METHODS: We enrolled consecutive pure DGC patients diagnosed with the disease either localized in the mucosal layer or with submucosal invasion. H. pylori infection was investigated, and the patients were divided into three groups according to histological types: pure SRCC, SRCC with poorly differentiated adenocarcinoma (PDA), and pure PDA. RESULTS: Of the 345 pure DGC patients, 132 (38%), 127 (37%), and 86 (25%) had pure SRCC, SRCC with PDA, and pure PDA histologies, respectively. The prevalence of H. pylori infection and the SM ratio were significantly lower in the pure SRCC group than other groups (P < 0.01). Twenty-two (6.4%) patients, including two with submucosal invasion, were negative for H. pylori and had mucosal SRCC component in the cancer lesions. Of the 259 SRCC cases (pure SRCC or SRCC + PDA), H. pylori-uninfected cases had different clinicopathological characteristics compared with H. pylori-positive cases. Particularly, the ratio of patients with submucosal invasive SRCC was significantly lower in the H. pylori-uninfected gastric cancer group than in those with H. pylori infection. CONCLUSION: Helicobacter pylori-uninfected gastric cancer is not rare among pure DGC patients in Japan. SRCC in patients without H. pylori infection is less likely to be invasive.

A case of primary malignant melanoma of the esophagus with a widely expanded surface area.

Primary malignant melanoma of the esophagus (PMME) is rare but aggressive. PMME accounts for approximately 0. 1% of all malignant esophageal neoplasms occurring worldwide, and is usually diagnosed during the advanced stage. A 67-year-old man underwent an esophagogastroduodenoscopy (EGD) at our hospital and confirmed 20 mm of black pigmentation in the lower esophagus in the chest area. Pathological biopsy findings of the black-pigmented epithelial tissue revealed the presence of tumor cells with brown granules, leading to the diagnosis of malignant melanoma. Owing to difficulty in accurately diagnosing the range in this PMME case, we performed thoracoscopic esophagectomy. Pathological organisation test results were pT1a-LPM, INFb, pN0, and pM0, which were diagnosed at pStage I. The lesion expanded extensively, measuring > 10 cm in diameter. The tumor cells, which were centrally located in the black-pigmented area, were observed to have proliferated beyond the surrounding brownish area into the mucosa, but no findings were found in the endoscopic examination. As in this case, because PMME may diffusely spread along the basal layer outside the range of pigmentation, endoscopic diagnosis of the extent of disease spread may be impossible; hence, it is important to keep this phenomenon in mind while performing resection to treat PMME.

Gastric Cancer with Submucosal Invasion after Successful Helicobacter pylori Eradication: A Propensity Score-Matched Analysis of Patients with Annual Patient Endoscopic Survey.

BACKGROUND AND AIM: The incidence of gastric cancer occurring after successful Helicobacter pylori eradication has been increasing. We aimed to clarify the influence of eradication therapy on the ability to diagnose early gastric cancer after successful H. pylori eradication in patients who underwent annual endoscopic screening. METHODS: A total of 220 patients (179 men; mean age 71.0 years) had differentiated-type early gastric cancer that was discovered through annual endoscopic screening. Patients were categorized into 2 groups: the H. pylori-eradicated group (n = 81) and the non-eradicated control group (n = 139). After matching patients by propensity scores, we retrospectively analyzed the clinicopathological characteristics of 162 patients (81 patients in each group). Furthermore, we compared the characteristics of gastric cancer with submucosal invasion between the 2 groups. RESULTS: The prevalence of early gastric cancer with submucosal invasion was significantly higher in the eradicated group than in the control group, both before propensity score matching (16.0 vs. 7.2%, respectively; p = 0.038) and after propensity score matching of 81 pairs (16.0 vs. 4.9%, respectively; p = 0.021). In the comparative analysis of gastric cancer with submucosal invasion, there was no difference between the 2 groups with respect to factors influencing the ability to diagnose its presence endoscopically. CONCLUSION: H. pylori eradication therapy increased the prevalence of differentiated-type gastric cancer with submucosal invasion despite patients' completion of annual endoscopic screening after eradication.

Clinical Significance of Reddish Depressed Lesions Observed in the Gastric Mucosa after Helicobacter pylori Eradication.

BACKGROUND AND AIM: Reddish depressed lesions (RDLs) frequently observed in patients following Helicobacter pylori eradication are indistinguishable from gastric cancer. We examined the clinical and histological feature of RDLs and its relevant endoscopic diagnosis including magnifying narrow-band imaging (M-NBI). METHODS: We enrolled 301 consecutive patients with H. pylori eradication who underwent endoscopy using white light imaging (WLI). We examined the prevalence and host factors contributing to the presence of RDLs. Next, we used M-NBI in 90 patients (104 RDLs), and compared the diagnostic efficacy between M-NBI and WLI groups using propensity-score matching analysis. RESULTS: In 301 patients after eradication, 117 (39%) showed RDLs. Male, open-type atrophy, and gastric cancer history were risk factors for RDLs. A gastric biopsy was needed in 83 (71%) during WLI observation and only 2 were diagnosed with adenocarcinoma. In M-NBI group, a biopsy was performed in 21 (20%), and 9 were diagnosed with adenocarcinoma. A biopsy was required in fewer patients, and the positive predictive value of a biopsy was statistically higher in M-NBI than in the WLI group (p < 0.01). CONCLUSIONS: RDLs are frequently observed in high-risk patients for gastric cancer after eradication. M-NBI demonstrated significantly superior diagnostic efficacy with respect to RDL.

Serological Evaluation of Gastric Cancer Risk Based on Pepsinogen and Helicobacter pylori Antibody: Relationship to Endoscopic Findings.

BACKGROUNDS AND AIMS: The serological risk-prediction system combined the pepsinogen (PG) test, and anti-Helicobacter pylori antibody is available for evaluation of gastric cancer risk. In this system, chronic atrophic gastritis (CAG) or H. pylori infection is diagnosed. Subjects with H. pylori negative and PG test negative (group A) are supposed to be those who have never been infected with H. pylori and are at extremely low risk for gastric cancer. However, a certain proportion of patients with CAG has been identified as the extremely low-risk group (group A). Here we examined endoscopic atrophy and investigated its relationship with the ABC classification system. METHODS: We examined 540 patients. All patients underwent an endoscopic examination for evaluating corpus atrophy. Fasting sera were collected and serum PGs and anti-H. pylori antibody (Hp-Ab) titer (E-plate Eiken) were evaluated. RESULTS: Of the 540 patients, 306 were classified into group A. However, 136 of them showed signs of endoscopic atrophy (group A with CAG). Group A with CAG frequently comprised the elderly. A new titer cut-off (<3 U/mL) of the Hp-Ab improved the discrimination of group A with CAG by 8%. CONCLUSION: The prevalence of group A with CAG patients is a critical problem, especially in elderly subjects.

Endoscopic findings of the gastric mucosa during long-term use of proton pump inhibitor - a multicenter study.

BACKGROUND AND AIM: It is clinically important to diagnose drug-induced gastric lesions correctly. Recently, the use of proton pump inhibitors (PPI) has increased worldwide. The histological features induced by PPI have been reported; however, few reports have described endoscopic findings induced by PPI. Therefore, we aimed to clarify the characteristic endoscopic features in PPI users and associated pathogenic factors. METHODS: We prospectively registered 1007 consecutive participants (70 PPI users and 937 nonusers) who underwent endoscopic examination for cancer screening in three hospitals/clinics. Clinical data and endoscopic findings were recorded in the registration forms. We compared the endoscopic features between the two groups and evaluated contributing factors via univariate and multivariate analyses. RESULTS: Multiple white elevated lesions (MWEL) and cobblestone-like mucosa (CLM) were more commonly observed in PPI users compared with nonusers (p < .01). Foveolar hyperplastic polyps were also frequently observed in PPI users but were not statistically significantly different (p = .06). MWEL and CLM were more frequently observed in older patients than in younger patients. MWEL was more frequently observed in female patients than in male patients; however, CLM was predominantly observed in male patients. CONCLUSION: MWEL and CLM are characteristic endoscopic features in PPI users. A gender-associated difference was noted in terms of the frequency of these lesions.

Characteristics of gastric cancer in negative test of serum anti-Helicobacter pylori antibody and pepsinogen test: a multicenter study.

BACKGROUND AND AIM: The serological risk prediction system combines the pepsinogen test and anti-Helicobacter pylori (H. pylori) antibody determination. In this system, chronic atrophic gastritis (CAG) is diagnosed using the pepsinogen test. Patients who are H. pylori negative and pepsinogen negative are classified into group A, are assumed to be H. pylori uninfected, and are at an extremely low risk for gastric cancer. However, gastric cancers are detected in this group. The aim of this study is to clarify the clinicopathological status of group A patients with gastric cancer. METHODS: A total of 109 gastric cancer patients classified as group A were enrolled in a multicenter study. Group A patients were divided into two subgroups: group AN (H. pylori uninfected) and group AP (H. pylori infected). They were compared to 183 H. pylori-infected gastric cancer patients who were not in group A. RESULTS: Of the 109 patients, only 7 were classified as group AN; the other 102 were classified as group AP. The clinicopathological features of group AP included older age, predominantly differentiated type cancer, endoscopically visualized CAG, and pepsinogen (PG) I/II ratio lower than that of group AN. In group AN, the depressed type was dominant, and the PG I/II ratio was higher than in those gastric cancer patients who were infected with H. pylori. CONCLUSION: Patients in group AP had CAG, and their gastric cancers were similar to those of H. pylori-eradicated patients. Concerning the recent ABC classification system, advanced decision criteria should be proposed to decrease the false-negative evaluation of gastric cancer risk.

Diagnosis of Helicobacter pylori-induced gastritis by serum pepsinogen levels.

BACKGROUND AND AIM: Gastric cancer develops due to atrophic gastritis induced by Helicobacter pylori (H. pylori) infection. Serum levels of pepsinogen (PG) are known to be excellent markers for evaluating the degree of atrophic gastritis. We investigated whether chronic gastritis could be diagnosed by evaluating serum PG levels. METHODS: A total of 4483 patients (average age, 49.7 years; 2879 men) were included in this study. Fasting serum samples were collected and anti-H. pylori antibody and PG levels were evaluated. We evaluated the endoscopic atrophy grade or histological extent of gastritis, and calculated the diagnostic capability of this serum marker. RESULTS: A total of 4483 patients, were diagnosed as being positive (4160) or negative (323) for H. pylori-induced gastritis. In patients with H. pylori-induced gastritis, the PG II levels were higher and the PG I/II ratios were lower than among those without H. pylori gastritis. A cut-off values of (i) PG I/II ≤ 5; (ii) PG II ≥ 10 or PG I/II ≤ 5; (iii) PG II ≥ 12 or PG I/II ≤ 4.5 showed high sensitivity and accuracy (over 90%) for diagnosing H. pylori-induced gastritis. Moreover, in a mass screening of healthy subjects, a cut-off value of PG I/II ≤ 4.5 might be better for diagnosing the presence of gastritis because of a sensitivity and specificity > 80%. CONCLUSIONS: The presence of H. pylori-induced gastritis can be evaluated using serum PG levels.