Helicobacter fennelliae Localization to Diffuse Areas of Human Intestine, Japan.

The site of enterohepatic Helicobacter colonization/infection in humans is still unknown. We report microbiologically and histopathologically confirmed H. fennelliae localization in the large intestine in an immunocompromised patient in Japan. This case contributes to better understanding of the life cycle of enterohepatic Helicobacter species.

Potential for expanding indications and curability criteria of endoscopic resection for early gastric cancer in elderly patients: results from a Japanese multicenter prospective cohort study.

BACKGROUND AND AIMS: Evidence for endoscopic resection (ER) in elderly patients with early gastric cancer (EGC) is limited. We assessed its clinical outcomes and explored new indications and curability criteria. METHODS: We analyzed data from a Japanese multicenter, prospective cohort study. Patients aged ≥75 years with EGC treated with ER were included. We classified eCuraC-2 (corresponding to noncurative ER, defined in the Japanese gastric cancer treatment guidelines) into elderly-high (>10% estimated metastatic risk) and elderly-low (EL-L) (≤10% estimated metastatic risk). RESULTS: In total, 3371 patients with 3821 EGCs were included; endoscopic submucosal dissection was the prominent treatment choice. Among them, 3586 lesions met the guidelines' ER indications, and 235 did not. The proportions of en bloc and R0 resections and perforations were 98.9%, 94.4%, and 0.8%, respectively, in EGCs within the indications. In EGCs beyond the indications, they were 99.5%, 85.4%, and 5.9%, respectively, for lesions diagnosed as ≤3 cm and 96.0%, 64.0%, and 18.0%, respectively, for those >3 cm. Curative ER and EL-L were observed in 83.6% and 6.2% of lesions within the indications, respectively, and in 44.2% and 16.8% of lesions <3 cm beyond the indications, respectively. The 5-year cumulative gastric cancer death rates after curative ER and elderly-high were 0.3% (95% confidence interval [CI], 0.2-0.6) and 3.5% (95% CI, 2.0-5.7), respectively. After EL-L, the rate was 0.9% (95% CI, 0.2-3.5) even without subsequent treatment. CONCLUSIONS: The usefulness of endoscopic submucosal dissection for elderly EGC patients was confirmed by their clinical outcomes. Lesions of ≤3 cm and EL-L emerged as new ER indication and curability criteria, respectively. (Clinical trial registration number: UMIN000005871.).

Clinicopathological Features of Early Gastric Cancer Complicated by Autoimmune Gastritis.

INTRODUCTION: In the post-Helicobacter pylori era, autoimmune gastritis (AIG) is attracting increasing attention as an origin of gastric cancer. Here, we performed clinicopathological examination of gastric cancer complicating AIG treated in our hospital. METHODS: Eighty-six early gastric cancer lesions complicating AIG in 50 patients were treated by endoscopic submucosal dissection (ESD) at our hospital in 2008-2022. Their clinicopathological characteristics were compared with those of a control group comprising 2,978 early gastric cancer lesions (excluding lesions in the remnant stomach after surgery) in 2,278 patients treated by ESD during the same period. RESULTS: Mean age was significantly higher in the AIG group than in the control group (74.7 years vs. 70.9 years; p < 0.01). In the respective groups, the occurrence rate of synchronous/metachronous lesions was 38.0% and 20.4% (p < 0.01), the ratio of longitudinal cancer locations (upper/middle/lower third [U/M/L]) was 27/32/27 and 518/993/1,467 (p < 0.01), the ratio of circumferential cancer locations (lesser curvature/greater curvature/anterior wall/posterior wall) was 25/31/12/18 and 1,259/587/475/657 (p < 0.01), the ratio of major macroscopic types (I/IIa/IIb/IIc) was 13/38/5/30 and 65/881/220/1,812 (p < 0.01). The rates of multiple gastric cancer and cancers in the U region, at the greater curvature, and of protruding types were significantly higher in the AIG group. CONCLUSION: The occurrence rate of multiple gastric cancer was significantly higher in gastric cancer complicating AIG (approximately 40%), and compared with the control group, the proportions of cancers at the U region, at the greater curvature, and of protruding types were significantly higher.

Antacids and reflux esophagitis as a risk factor for gastric neoplasm of fundic-gland type: A retrospective, matched case-control study.

BACKGROUND AND AIM: Since the first report of gastric adenocarcinoma of the fundic-gland type in 2010, the clinicopathological characteristics of gastric neoplasm of the fundic-gland type (GNFG) have become clearer; however, their risk factors remain unclear. This exploratory study aimed to identify the risk factors for GNFG. METHODS: We conducted a single-center, retrospective, matched case-control study using medical information recorded at our health management center from January 2014 to July 2023. During this period, 39 240 people underwent upper gastrointestinal endoscopy. GNFG were extracted as cases and matched to controls, according to age and sex, in a 1:8 ratio, excluding those with a history of gastrointestinal surgery and those with a history or comorbidity of cancer. Univariate analysis was used to compare patient background and endoscopic findings. Multivariable analysis was performed, adjusting for factors with P values < 0.1 and antacid use. RESULTS: A total of 20 GNFG cases and 160 matched healthy controls were included. In the univariate analysis, only reflux esophagitis was significantly more common in GNFG (40.0% vs 18.1%; P = 0.036). Factors antacids and duodenitis had P values < 0.1. Logistic regression analysis was performed, adjusting for antacids, reflux esophagitis, and duodenitis. Antacids and reflux esophagitis were the independent risk factors for GNFG (odds ratio = 3.68 [95% confidence interval: 1.04-11.91] and 3.25 [95% confidence interval: 1.11-9.35]). CONCLUSIONS: Although the sample of patients with GNFG was small, antacids and reflux esophagitis were identified as a risk factor. The pathogenesis of antacids and reflux esophagitis may be involved in the development of GNFG.

Risk factors for intraoperative and delayed perforation related with gastric endoscopic submucosal dissection.

BACKGROUND AND AIM: Perforation is one of the most important complications of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). Several studies have examined risk factors for intraoperative and delayed perforations, but most were retrospective analyses with small numbers of patients. METHODS: This study represents a secondary analysis of a Japanese multicenter prospective cohort study. We investigated the factors associated with each type of perforation using 9015 patients with 9975 EGCs undergoing ESD between July 2010 and June 2012. RESULTS: Intraoperative perforation occurred in 198 patients (2.2%) with 203 lesions (2.0%), necessitating emergency surgery for four lesions (0.04% [2.0%, 4/203]). Delayed perforation occurred in another 37 patients (0.4%) with 42 lesions (0.4%), requiring emergency surgery for 12 lesions (0.12% [28.6%, 12/42]). Factors showing significant independent correlations with intraoperative perforation were upper or middle third of the stomach; remnant stomach or gastric tube; procedure time ≥100 min; tumor size >35 mm; body mass index (BMI) < 18.5 kg/m2; and ≥72 years. Factors showing significant independent correlations with delayed perforation were procedure time ≥60 min; BMI < 18.5 kg/m2; ≥75 years; ulceration; and tumor size >20 mm. Intraoperative perforation occurred most frequently at the greater curvature in the upper third of the stomach (7.9%), whereas delayed perforation occurred most frequently at the greater curvature in the middle third (1.2%). CONCLUSION: This multicenter prospective cohort study clarified the risk and risk factors of intraoperative and delayed perforation related to ESD for EGCs, providing information to help endoscopists reduce perforation.

Endoscopic Features of Synchronous Multiple Early Gastric Cancers: Findings from a Nationwide Cohort.

INTRODUCTION: We investigated the factors associated with synchronous multiple early gastric cancers and determined their localization. METHODS: We analyzed 8,191 patients who underwent endoscopic submucosal dissection for early gastric cancers at 33 hospitals in Japan from November 2013 to October 2016. Background factors were compared between single-lesion (n = 7,221) and synchronous multi-lesion cases (n = 970) using univariate and multivariate analyses. We extracted cases with two synchronous lesions (n = 832) and evaluated their localization. RESULTS: Significant independent risk factors for synchronous multiple early gastric cancer were older age (≥75 years old) (odds ratio [OR] = 1.257), male sex (OR = 1.385), severe mucosal atrophy (OR = 1.400), tumor localization in the middle (OR = 1.362) or lower region (OR = 1.404), and submucosal invasion (OR = 1.528 [SM1], 1.488 [SM2]). Depressed macroscopic type (OR = 0.679) and pure undifferentiated histology OR = 0.334) were more common in single early gastric cancers. When one lesion was in the upper region, the other was more frequently located in the lesser curvature of the middle region. When one lesion was in the middle region, the other was more frequently located in the middle region or the lesser curvature of the lower region. When one lesion was in the lower region, the other was more frequently located in the lesser curvature of the middle region or the lower region. CONCLUSION: Factors associated with synchronous multiple early gastric cancer included older age, male sex, severe mucosal atrophy, tumor localization in the middle or lower region, and tumor submucosal invasion. Our findings provide useful information regarding specific areas that should be examined carefully when one lesion is detected.

Long-term endoscopic change of gastric polyp associated with administration of vonoprazan.

Vonoprazan (VPZ) has been available in Japan since 2015. Endoscopic features of proton-pump inhibitor (PPI)-related gastric mucosal changes, including fundic gland and hyperplastic polyps, have been observed. However, the relationship between gastric polyps and VPZ remains unclear. A 65-year-old man with reflux esophagitis-associated symptoms refractory to PPI was referred to our hospital. VPZ (20 mg) was administered for 3 weeks, which proved effective. Afterward, VPZ dose was reduced to 10 mg; the reflux symptoms worsened, and 20 mg VPZ was restarted. Afterward, esophagogastroduodenoscopy (EGD) revealed a gradually enlarging gastric polyp in the cardia. After 5 years of VPZ administration, the patient developed a reddish polyp (approximately 10 mm) with a whitish substance in the cardia. Based on the clinical course, the polyp was considered to have enlarged because of the long-term VPZ administration. After being informed of the endoscopic findings, the patient decided to discontinue VPZ. One year after VPZ discontinuation, EGD revealed a shrunken polyp (5 mm). Long-term acid suppression causes hypergastrinemia, which may lead to gastric mucosal changes, including gastric polyps. There are few case reports of a decrease in the number and size of gastric polyps after VPZ discontinuation. Hence, some VPZ-induced endoscopic changes may be reversible.

Symptomatic epiphrenic diverticulum in an older patient successfully treated nonsurgically.

Epiphrenic diverticulum is a rare condition commonly diagnosed in middle-aged adults. Symptoms include dysphagia and regurgitation, which are associated with underlying esophageal motility disorders. We herein report a 93-year-old woman with dysphagia diagnosed with symptomatic epiphrenic diverticulum by computed tomography, esophagogastroduodenoscopy, and esophagography. The patient was successfully treated non-surgically without any complications. This case demonstrates that conservative treatment is an option for older high-risk patients.

Long-term Outcome of Asymptomatic Esophageal Eosinophilia.

Background/Aims: : Asymptomatic esophageal eosinophilia (aEE), characterized by eosinophil infiltration in the esophagus without clinical symptoms, has been reported as a precursor of eosinophilic esophagitis (EoE). Nevertheless, no report exists on the long-term clinical course of the disease. Therefore, this study aimed to investigate the long-term clinical course of aEE over 5 years, including the symptomatic conversion rate and the effect of treatments. Methods: : We reviewed 28 patients with aEE who had been followed up for over 5 years with endoscopic monitoring. The basal characteristics of patients were compared with those of 58 patients diagnosed with EoE during the same period. Patients' clinicopathological findings were collected and examined. Results: : No significant differences in basal characteristics and histopathological findings were observed between the patients with aEE and those with EoE. The median follow-up duration was 64 months. Among the 28 patients with aEE, seven were treated with proton pump inhibitor or potassium-competitive acid blocker and the remaining 21 opted for follow-up with no medication. Among the treated patients, six (85.7%) exhibited endoscopic and pathologic improvements. Among the cases followed up without medication, the findings worsened in two (9.5%), improved spontaneously in seven (33.3%), and were unchanged in 12 (57.1%), and three (14.3%) developed symptoms at a mean time of 40 months. Symptoms developed in cases where endoscopic and pathologic findings remained unchanged or worsened during follow-up. Conclusions: : Some patients with aEE had improved findings without treatment, whereas others developed symptoms, emphasizing the importance of long-term monitoring and individualized treatment decisions.

Traction Devices May Not Affect the Vertical Margin Distance in the Endoscopic Submucosal Dissection of Rectal Neuroendocrine Tumors.

Introduction The usefulness of traction devices (TDs) in endoscopic submucosal dissection (ESD) for rectal neuroendocrine tumors (NETs) has not been reported. The aim of this study was to investigate the impact of using a TD on the vertical margin (VM) distance in the ESD of rectal NETs. Methods In this single-center, retrospective study, we included patients with rectal NETs who were treated with ESD during 2013-2023. They were divided into TD and non-TD groups. One pathologist remeasured the VM distance (primary outcome) and the depth of submucosal invasion (SM depth). Secondary outcomes were margins, resection time, delayed bleeding, and perforation. First, we performed propensity score matching (PSM) to assess the usefulness of TD for VM distance. Then, we used multiple regression analysis to identify factors affecting the VM distance. Results The TD and non-TD groups comprised 24 and 117 lesions, respectively. Patients in the TD group were significantly younger than those in the non-TD group (P = 0.003). In the TD and non-TD groups, the VM distance was 150 µm and 100 µm, respectively (P = 0.70). Only resection time significantly differed between groups, shorter in the TD group (P = 0.005). Twenty-two cases in each group were matched after PSM, yielding no significant differences in VM distance. The use of a TD was not an independent predictor of VM distance (P = 0.65), but age (P < 0.001) and SM depth (P = 0.003) were. Conclusion Using a TD does not seem to affect the VM distance in ESD for rectal NETs.

Comparison of Prognosis and Metachronous Gastric Tumor Rates After Endoscopic Submucosal Dissection Between Gastric Neoplasm of Fundic Gland Type Neoplasms and Conventional Gastric Adenocarcinoma.

INTRODUCTION: Gastric neoplasm of the fundic gland type (GNFG) is a tumor with a good prognosis. However, since it has not been compared with conventional gastric adenocarcinoma (CGA), it is unknown whether it has a good prognosis or requires surveillance after treatment. The purpose of this study was to determine the prognosis and metachronous gastric tumor rates compared with those of CGA. METHODS: We conducted a single-center, retrospective, matched-cohort study using our database from January 2010 to December 2021. We extracted GNFG data from the endoscopic submucosal dissection (ESD) database and matched patients with conventional early gastric cancer as controls in a 1:4 ratio by age and sex. GNFG and CGA were compared for the overall survival (OS), disease-specific survival, progression-free survival, and metachronous gastric tumor rates. RESULTS: Overall, 43 lesions were GNFG and 164 CGAs were matched. There were three deaths in the GNFG group and 11 deaths in the CGA group. There was no significant difference in the OS between the two groups (P=0.81). The five-year OS rates for the GNFG and CGA groups were 90.9% and 92.9%, respectively. No disease-specific deaths or recurrences were observed in either group. There was no significant difference in the cumulative metachronous gastric tumor rate between the two groups (P=0.17). The cumulative five-year metachronous gastric tumor rates for the GNFG and CGA groups were 6.6% and 2.5%, respectively. CONCLUSIONS: The prognosis for GNFG is good, however, not better than that for CGA. The metachronous gastric tumor rate after ESD in GNFG was not lower than that in CGA. Therefore, after ESD, GNFG may need to be managed in the same way as CGA.

Metastatic Gastric Tumors: Clinical and Endoscopic Features.

INTRODUCTION: Stomach metastasis is rare, and there are few reports on its endoscopic features. Herein, we focused on the endoscopic features and discussed and reviewed the clinicopathological characteristics of metastatic gastric tumors. METHODS: We conducted an analysis on the clinicopathological features of individuals with gastric metastases originating from solid organ tumors at the Department of Gastroenterology, Toranomon Hospital, Minato-ku, Tokyo, Japan. Thirty-one cases were identified and evaluated for histology, initial presentation, endoscopic findings, lesion locations, treatment courses, and overall survival of the patients. RESULTS: Endoscopic findings resembling submucosal tumors were present in five cases (16%), and those with a morphology similar to that of primary gastric cancer were present in 26 cases (84%). In addition, seven patients (22%) were diagnosed with gastric metastasis due to a suspected biopsy of early gastric cancer. Solitary metastasis (21 patients, 67.7%) was more common than multiple metastases (10 patients, 32.2%). The median time from primary tumor to diagnosis was 36 months, and survival after metastasis was 19 months. The overall survival (OS) after the diagnosis of the primary tumor was 22 months for esophageal cancer, 25 months for lung cancer, and 100 months for breast cancer, and the OS after the diagnosis of gastric metastasis was almost the same. The average time from the diagnosis of the primary tumor to the diagnosis of gastric metastasis (*timespan) was more than seven years for breast and kidney cancers. CONCLUSION: As the prognosis of patients with cancer gradually improves, they develop metastases more frequently. Understanding the endoscopic findings and information about a patient's clinical history is useful to correctly diagnose gastric metastases.

Multicenter study of invasive gastric cancer detected after 10 years of Helicobacter pylori eradication in Japan: Clinical, endoscopic, and histopathologic characteristics.

Objectives: Gastric cancer can be diagnosed even in patients long after Helicobacter pylori eradication. Most cases involve intramucosal lesions; however, some are invasive and require surgery. To clarify appropriate long-term surveillance methods, this study compared invasive gastric cancer diagnosed ≥10 and <10 years after eradication. Methods: This retrospective multicenter study included 14 institutions. We included 377 patients with gastric cancer with submucosal or deep invasion after surgical or endoscopic resection. Ordered logistic regression analysis was used to explore the factors contributing to the pathological stage and histological type. Results: Invasive gastric cancer was detected in 84 patients (Group L) and 293 patients (Group S) ≥10 and <10 years after H. pylori eradication, respectively. Endoscopic mucosal atrophy at the time of cancer detection was similar in both groups; 50% of the patients had severe atrophy. Annual endoscopy correlated with early pathological stage (odds ratio [OR] 0.28, 95% confidence interval [CI] 0.14-0.54, p < 0.001). Group L exhibited an independent correlation with the advanced pathological stage (OR 2.27, 95% CI 1.06-4.88, p = 0.035) and the undifferentiated type (OR 2.12, 95% CI 1.16-3.90, p = 0.015). The pure differentiated type and early pathological stage significantly (p = 0.001) correlated with severe mucosal atrophy in Group S but not in Group L. Conclusions: Invasive cancers diagnosed ≥10 years after H. pylori eradication were likely to be more malignant in histological type and pathological stage. Gastric cancer surveillance should continue regardless of endoscopic atrophy, particularly ≥10 years after eradication.