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.

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 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.

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.

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.

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.