Novel Endoscopic Findings of Lesions with a Short White Hair-like Appearance in the Lower Esophagus.

Objective The presence of a short white hair-like appearance in the lower esophagus has recently been noted during esophagogastroduodenoscopy (EGD) at our institution. Histological findings showed that this formation was a spiked protrusion of the esophageal papilla. The results regarding the prevalence of such lesions in individuals who underwent EGD examinations as part of medical checkup procedures are herein presented. Methods The EGD results of 14,338 individuals (9,225 males, 5,113 females; mean age 54.0±9.8 years) were examined. The findings related to the presence of multiple lesions with a short white hair-like appearance in the lower esophagus of patients with reflux esophagitis, esophageal squamous papilloma, or gastric mucosal atrophy (GMA), as well as the hiatal hernia width, were investigated. Results Endoscopic findings indicating short white hair-like appendages in the lower esophagus were noted in 167 patients, with a prevalence rate of 1.2%. A female sex, younger age, lower body mass index, lower percentages of habitual smoking and drinking, and the presence of esophageal squamous papilloma were characteristic features of cases with such findings. In addition, a significantly lower prevalence of reflux esophagitis and a smaller diaphragmatic hiatus size were observed. A multiple logistic regression analysis indicated that a female sex, absence of reflux esophagitis, presence of esophageal squamous papilloma, and a smaller diaphragmatic hiatus were factors significantly related to the presence of these short white hair-like appendages. An analysis of circumferential localization revealed the main location to be the left-posterior wall. Conclusion This study is the first to report the prevalence of multiple short white hair-like appendages in the lower esophagus. The occurrence of such lesions is inversely associated with the presence of reflux esophagitis.

Prevalence of Gastric Epithelial Tumors in Helicobacter pylori-uninfected Individuals Undergoing a Medical Checkup.

Objective This study investigated the prevalence of gastric epithelial tumor in Helicobacter pylori-uninfected subjects who underwent esophagogastroduodenoscopy (EGD) as part of an annual checkup. Methods A total of 20,540 EGD examinations of H. pylori-uninfected individuals (12,917 men, 7,623 women; mean age 51.5±9.2 years old) were performed between April 2016 and March 2023. The prevalence of gastric epithelial tumor discovery and the size and location of each lesion type were analyzed. Results According to 20,540 examinations, 61 gastric epithelial tumors were endoscopically and histologically diagnosed in 58 of the subjects, with a prevalence rate of 0.28%. These tumors included signet-ring carcinoma (n=10, 0.05%), gastric adenocarcinoma of fundic-gland type (n=10, 0.05%), intestinal-type well-differentiated adenocarcinoma (n=2, 0.01%), and raspberry-type gastric foveolar tumors (n=36, 0.18%). One subject had two intestinal-type well-differentiated adenocarcinomas, and two each had two raspberry-type gastric foveolar tumors. The mean sizes of the signet-ring carcinomas, gastric adenocarcinoma of fundic-gland type, intestinal-type well-differentiated adenocarcinomas, and raspberry-type gastric foveolar tumors were 6.4, 4.7, 5.0, and 3.4 mm, respectively. Each lesion was located at a specific site in the stomach characteristic of its type. Conclusion In the present H. pylori-uninfected subjects, the prevalence of gastric epithelial tumors found on an EGD examination was 0.28%. Endoscopic examination should be performed in H. pylori-uninfected individuals to detect such tumors in characteristic locations.

Gastric Flat Elevated Undifferentiated Signet-ring Cell Mucosal Cancer Lesion Detected in a Case without Helicobacter pylori Infection.

Protruded signet-ring cell carcinoma (SRCC) is extremely rare. We herein report a rare case of flat elevated gastric SRCC in a patient without Helicobacter pylori infection. Esophagogastroduodenoscopy of a woman in her 50s revealed a flat, whitish lesion in the gastric body with elevation. Histological results of an endoscopically biopsied specimen led to a diagnosis of SRCC. Resection using endoscopic submucosal dissection was performed, and histology results revealed that the tumor was localized in the lamina propria. The size was 10×6 mm, and a protrusion had been formed by SRCC enlargement without destruction of the surface epithelium structure.

Prevalence of Raspberry-type Gastric Foveolar-type Tumor in Individuals Undergoing Medical Checkups.

Objective This study was performed to clarify the prevalence of raspberry-type gastric foveolar-type tumors, along with the time-course changes in the size and clinical course. Methods The subjects were 10,663 consecutive patients who underwent a medical checkup between April 2016 and March 2022, including an esophagogastroduodenoscopy (EGD) examination and determination of Helicobacter pylori infection status (uninfected, positive, post-eradication). The presence of characteristic reddish polypoid lesions in the stomach was investigated, and a diagnosis of raspberry-type gastric foveolar-type tumor was made based on histological findings. Results Thirty-eight cases had gastric polyps with a raspberry-like appearance on endoscopy, with 29 lesions in 28 cases endoscopically and histologically diagnosed as a raspberry-type gastric foveolar-type tumor. All of the affected subjects were determined to be H. pylori-uninfected. The prevalence of this type of lesion in all subjects was 0.26%, while that in the 6,635 H. pylori-uninfected subjects was 0.42%. An older age and the presence of a fundic gland polyp were found to be significant risk factors associated with the occurrence of the tumor. The mean size was 3.8±1.9 (range: 2-10) mm, and the location was in a fundic gland area in all affected subjects. Furthermore, examinations of previous EGD images revealed that two-thirds of the lesions had not changed in size, while follow-up EGD findings showed that lesions ≤5 mm in size had disappeared after a biopsy procedure. Conclusion The prevalence of raspberry-type gastric foveolar-type tumors was 0.42% in H. pylori-uninfected subjects. More than half of the lesions were too small to be removed by an endoscopic biopsy.

Application of Convolutional Neural Networks for Diagnosis of Eosinophilic Esophagitis Based on Endoscopic Imaging.

Subjective symptoms associated with eosinophilic esophagitis (EoE), such as dysphagia, are not specific, thus the endoscopic identification of suggestive EoE findings is quite important for facilitating endoscopic biopsy sampling. However, poor inter-observer agreement among endoscopists regarding diagnosis has become a complicated issue, especially with inexperienced practitioners. Therefore, we constructed a computer-assisted diagnosis (CAD) system using a convolutional neural network (CNN) and evaluated its performance as a diagnostic utility. A CNN-based CAD system was developed based on ResNet50 architecture. The CNN was trained using a total of 1192 characteristic endoscopic images of 108 patients histologically proven to be in an active phase of EoE (≥15 eosinophils per high power field) as well as 1192 normal esophagus images. To evaluate diagnostic accuracy, an independent test set of 756 endoscopic images from 35 patients with EoE and 96 subjects with a normal esophagus was examined with the constructed CNN. The CNN correctly diagnosed EoE in 94.7% using a diagnosis per image analysis, with an overall sensitivity of 90.8% and specificity of 96.6%. For each case, the CNN correctly diagnosed 37 of 39 EoE cases with overall sensitivity and specificity of 94.9% and 99.0%, respectively. These findings indicate the usefulness of CNN for diagnosing EoE, especially for aiding inexperienced endoscopists during medical check-up screening.

Endoscopic diagnosis and screening of Barrett's esophagus: Inconsistency of diagnostic criteria between Japan and Western countries.

Barrett's esophagus (BE) is an endoscopically identifiable premalignant condition for esophageal adenocarcinoma (EAC). To diagnose BE precisely, careful inspection of the anatomic landmarks, including the esophagogastric junction and the squamocolumnar junction is important. The distal end of the palisade vessels and the proximal end of the gastric folds are used as the landmark of the esophagogastric junction in endoscopic diagnosis, with the latter solely used internationally, except in some Asian countries, including Japan. In addition, the diagnostic criteria adopted internationally for BE are inconsistent, particularly between Japan and Western countries. Recently updated guidelines in Western countries have included length criteria, with a 1-cm threshold of columnar epithelium by endoscopic observation and/or histologic confirmation of the presence of specialized intestinal metaplasia. Since BE is endoscopically diagnosed at any length without histologic assessment in Japan, the reported prevalence of short-segment BE is very high in Japan compared with that in Western countries. Although guidelines on screening exist for BE, the current strategies based on the presence of chronic gastroesophageal reflux disease with multiple risk factors may miss the opportunity for early detection of EAC. Indeed, up to 40% of patients with EAC have no history of chronic gastroesophageal reflux disease. To discuss BE on the same footing worldwide, standardization of diagnostic criteria, screening indication, and establishment of effective techniques for detecting dysplastic lesions are eagerly awaited. Japanese guidelines for BE should be revised regarding the length criteria, including the minimum length and long-segment BE, in line with the recently updated Western guidelines.

Heterotopic Gastric Mucosa in Middle Esophagus Complicated with Esophageal Ulcers.

Heterotopic gastric mucosa (HGM) of esophagus, primarily occurring in cervical esophagus, is usually asymptomatic. A healthy woman (mid-40s) with postprandial heartburn was diagnosed with middle esophageal HGM and esophageal ulcers by esophagogastroduodenoscopy. Using 8-channel pH monitoring, a sensor near the HGM area detected postprandial acid phase (pH 3-4), while areas adjacent to the proximal and distal sensors were neutral, suggesting acid secretion from the HGM. A biopsy showed fundic gland tissue expressing H+/K+-ATPase and pepsinogen-I. Oral vonoprazan improved the clinical symptoms and endoscopic findings. This is the first report using 8-channel pH monitoring to diagnose extremely rare middle esophageal HGM.

The Simultaneous Onset of Pancreatitis and Colitis as Immune-related Adverse Events in a Patient Receiving Nivolumab Treatment for Renal Cell Carcinoma.

Immune checkpoint inhibitors (ICIs), which have anti-tumor effects, are currently approved for treatment of several kinds of advanced malignancies. However, with their increasing use, a variety of immune-related adverse events (irAEs) in administered patients have been reported. We herein report a rare case of the simultaneous onset of acute pancreatitis and colitis as irAEs during nivolumab treatment given to a patient with renal cell carcinoma, who then shown marked improvement with corticosteroid therapy.

Primary Extragastrointestinal Stromal Tumor of Greater Omentum with Intraperitoneal Bleeding.

Gastrointestinal stromal tumors (GISTs) develop in the digestive tract, mainly in the stomach, small intestine, colon, or esophagus. However, primary tumors with the same pathologic features as GISTs have been reported to occur outside of the digestive tract and are called extragastrointestinal stromal tumor (EGIST). We herein report a rare case of EGIST arising from the greater omentum in a patient with abdominal pain caused by intraperitoneal bleeding from the tumor.

Eosinophilic Granulomatosis with Polyangiitis Initially Diagnosed as Eosinophilic Gastroenteritis.

We herein report two cases of eosinophilic granulomatosis with polyangiitis (EGPA) initially diagnosed as eosinophilic gastroenteritis (EGE) based solely on endoscopic biopsy results. One year after the EGE diagnosis, one patient presented with multiple purpura, and skin biopsy findings resulted in a change of the diagnosis to EGPA. In another patient, multiple skin and colonic ulcerations emerged eight years after the diagnosis of EGE, at which time histological examinations of endoscopic biopsy specimens revealed vasculitis, and the diagnosis was changed to EGPA. Physicians should be aware of the possible existence of EGPA in cases diagnosed as EGE.

Is Asymptomatic Esophageal Eosinophilia the Same Disease Entity as Eosinophilic Esophagitis?

Eosinophilic esophagitis (EoE) is an allergic inflammatory disorder that is characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation.1,2 Its prevalence has been increasing rapidly in both Western and Asian countries. In Japan, most of the cases of esophageal eosinophilia (EE) are found in an upper endoscopy examination for gastric cancer screening performed during a comprehensive health check-up.3,4 Indeed, we frequently encounter patients with asymptomatic EE showing typical endoscopic findings, such as linear furrows, as well as histologic findings compatible with EoE. However, the current clinical guidelines for EoE diagnosis include symptoms related to esophageal dysfunction, thus patients without symptoms do not fulfill the diagnostic criteria.1,2 The clinical characteristics remain to be fully elucidated,5 thus we aimed to clarify clinical features of asymptomatic EE as compared with those of EoE.

Circumferential distribution and clinical characteristics of esophageal cancer in lower esophagus: differences related to histological subtype.

BACKGROUND: Esophageal adenocarcinoma (EAC) is frequently found on the right-anterior wall of the distal esophagus in short-segment Barrett's esophagus (SSBE) patients. However, the endoscopic characteristics of EAC in cases with long-segment BE (LSBE) and squamous cell carcinoma (ESCC) in the lower esophagus remain to be fully evaluated. Here, we determined the circumferential distribution and clinical characteristics of esophageal cancer occurring in the lower esophagus based on histological subtype. METHODS: We retrospectively reviewed the medical records of 150 patients with esophageal cancer (ESCC, n = 100; EAC, n = 50) diagnosed at our hospital or a related facility between January 2002 and June 2017, including information regarding endoscopic findings, etiology, and clinical parameters. RESULTS: Of the 100 patients with ESCC, 28 lesions were located in the lower esophagus, though characteristic circumferential distribution was not seen regardless of location. Those showed a greater frequency of smoking and drinking habit and gastric mucosal atrophy as compared to patients with EAC. Consistent with the previous reports, EAC in SSBE (n = 41) was frequently located on the right-anterior wall. Likewise, EAC at the esophagogastric junction (EGJ) in LSBE was frequently located on the right-anterior wall, while EAC distant from the EGJ showed no characteristic circumferential distribution. CONCLUSION: Our results showed no circumferential predilection for ESCC in the lower esophagus, suggesting that development of this type of lesion may be less affected by gastroesophageal reflux. In addition, EAC at the EGJ was frequently found on the right-anterior wall irrespective of BE length.

Distinction between Chronic Enteropathy Associated with the SLCO2A1 Gene and Crohn's Disease.

Background/Aims: We recently identified recessive mutations in the solute carrier organic anion transporter family member 2A1 gene (SLCO2A1) as causative variants of chronic nonspecific multiple ulcers of the small intestine (chronic enteropathy associated with SLCO2A1, CEAS). The aim of this study was to investigate the gastroduodenal expression of the SLCO2A1 protein in patients with CEAS and Crohn's disease (CD). Methods: Immunohistochemical staining for SLCO2A1 was performed with a polyclonal antibody, HPA013742, on gastroduodenal tissues obtained by endoscopic biopsy from four patients with CEAS and 29 patients with CD. Results: The expression of SLCO2A1 was observed in one of four patients (25%) with CEAS and in all 29 patients (100%) with CD (p<0.001). The three patients with CEAS without SLCO2A1 expression had a homozygous splice-site mutation in SLCO2A1, c.1461+1G>C (exon 7) or c.940+1G>A (exon 10). The remaining one CEAS patient with positive expression of SLCO2A1 had compound heterozygous c.664G>A and c.1807C>T mutations. Conclusions: Immunohistochemical staining for SLCO2A1 in gastroduodenal tissues obtained by endoscopic biopsy is considered useful for the distinction of CEAS from CD.

Influence of the Degree of Gastric Mucosal Atrophy on the Serum Lipid Levels Before and After the Eradication of Helicobacter pylori Infection.

Objective To clarify the influence of the degree of gastric mucosal atrophy on the serum lipid levels before and after the eradication of Helicobacter pylori infection. Methods The subjects were individuals who underwent an annual detailed medical checkup. Serum anti-H. pylori IgG antibody detection and upper endoscopic examinations were performed in all subjects. Gastric mucosal atrophy was evaluated by the classification of Kimura and Takemoto. The serum levels of total cholesterol, high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC), LDLC/HDLC ratio, and triglycerides were compared among the different degrees of gastric mucosal atrophy in H. pylori-positive subjects. In addition, changes in those serum lipid levels during a two-year period were compared among H. pylori post-eradication cases that showed different degrees of gastric mucosal atrophy prior to eradication. Results In subjects with higher degrees of gastric mucosal atrophy, the serum levels of total cholesterol, LDLC, and triglycerides were elevated. Furthermore, the LDLC/HDLC ratio in subjects with moderate and severe grades of gastric mucosal atrophy was significantly higher than in subjects with mild atrophy. In subjects with higher degrees of gastric mucosal atrophy, the serum level of LDLC and the LDLC/HDLC ratio were decreased following eradication of H. pylori. Conclusion Lipid metabolism is influenced by the degree of gastric mucosal atrophy present before the eradication of H. pylori, and the favorable effects of such eradication are significant in patients with higher degrees of atrophy.

Serum Biomarkers for the Diagnosis of Eosinophilic Esophagitis and Eosinophilic Gastroenteritis.

Objective Clinically useful serum biomarkers for the diagnosis and monitoring of eosinophilic gastrointestinal diseases are not available. This study was conducted to examine the possible value of eosinophil-related proteins as serum biomarkers. Methods The serum concentrations of 49 cytokines, chemokines, and other proteins were measured in 29 patients with eosinophilic gastrointestinal diseases and 80 controls. Results The levels of interleukin (IL)-5, IL-33, eotaxin-3, and thymic stromal lymphopoietin (TSLP), previously reported as possible biomarkers of eosinophilic esophagitis, were not significantly elevated in the serum. In contrast, the B cell-attracting chemokine (BCA)-1/chemokine (C-X-C motif) ligand (CXCL) 13 and hemofiltrate C-C chemokine (HCC)-1/CC chemokine ligand (CCL) 14α levels were significantly elevated, while the granulocyte chemotactic protein (GCP)-2/CXCL6 levels were suppressed in patients with eosinophilic esophagitis as well as in those with eosinophilic gastroenteritis. The cutaneus T cell-attracting chemokine (CTACK)/CCL27, stromal cell-derived factor (SDF)-1/CXCL12, macrophage inflammatory protein (MIP)-3ß/CCL19, and squamous cell carcinoma antigen (SCCA) 2 levels were elevated only in patients with eosinophilic esophagitis. However, there were large overlaps of data obtained from the patient and control groups, indicating that these serum biomarkers are not adequately sensitive for clinical use with presently available assay systems. Conclusion Of the 49 investigated serum proteins, none were shown to be adequately sensitive for use as biomarkers for the diagnosis or monitoring of eosinophilic gastrointestinal diseases.

Similarities and differences among eosinophilic esophagitis, proton-pump inhibitor-responsive esophageal eosinophilia, and reflux esophagitis: comparisons of clinical, endoscopic, and histopathological findings in Japanese patients.

BACKGROUND: Esophageal eosinophilia is classified as either eosinophilic esophagitis (EoE) or proton-pump inhibitor-responsive esophageal eosinophilia (PPI-REE), depending on the response to PPI treatment. The aim of this study was to compare the clinical, endoscopic, and histopathological findings of EoE and PPI-REE in Japanese patients. In addition, the characteristics of these cases were compared with those of reflux esophagitis (RE) cases. METHODS: Eleven patients diagnosed with EoE, 16 with PPI-REE, and 39 with RE, who were all consecutively examined from 2005 to 2015 at Shimane University Hospital, were enrolled. Clinical, endoscopic, and histopathological esophageal findings in these groups were retrospectively examined and compared. RESULTS: The differences in the clinical characteristics of EoE and PPI-REE were not remarkable, though patients with EoE and PPI-REE were younger, presented a higher prevalence of allergic comorbidities, and complained of symptoms of dysphagia more frequently than those with RE. The only noteworthy differences between EoE and PPI-REE were more frequent reports of asthma (36.4 vs. 2.6 %) and food allergy (27.3 vs. 0 %) by patients with EoE (P < 0.05, P < 0.05, respectively). Endoscopic findings in patients with EoE and PPI-REE were similar, with the presence of esophageal erosions in a small percentage of PPI-REE cases being the only difference. There were no histopathological differences between EoE and PPI-REE. CONCLUSIONS: Comparisons of clinical, endoscopic, and histopathological findings between EoE and PPI-REE showed that these two types have similar characteristics, though EoE patients showed a higher atopic background. Predicting PPI responsiveness in cases with esophageal eosinophilia is difficult and requires further investigation.

Specific locations of linear furrows in patients with esophageal eosinophilia.

BACKGROUND AND AIM: Linear furrows are the most frequently found endoscopic abnormality in patients with esophageal eosinophilia (EE); however, the precise endoscopic features remain to be fully elucidated. Here, we aimed to clarify the endoscopic features of EE, essential for the diagnosis of eosinophilic esophagitis (EoE), by focusing on the specific locations of linear furrows in a Japanese population. METHODS: We enrolled 70 cases with EE (≥15 eosinophils/high-power field) who were diagnosed at our hospital and related facilities. Information regarding endoscopic findings and clinical parameters was retrospectively reviewed. Next, the position of linear furrows in relation to esophageal longitudinal folds (ridge or valley) was evaluated in each case and compared with the position of mucosal breaks in patients with reflux esophagitis. Finally, the relationship between linear furrows and eosinophilic infiltration was evaluated. RESULTS: Of the 70 EE patients, 63 (90%) had linear furrows. Those occurred in a radial pattern and were widespread throughout the lower to upper esophagus, and exclusively found in esophageal longitudinal mucosal fold valleys, not on ridges, which was different from the position of mucosal breaks in patients with reflux esophagitis. Increased eosinophilic infiltration was significantly more frequent in linear furrows in the valleys (93%) as compared to mucosa on adjacent ridges (60%) (P < 0.05). CONCLUSION: Investigation of these endoscopic characteristics, especially by focusing on linear furrows in esophageal mucosal fold valleys, may provide important clues for more accurate diagnosis of EoE.

Evaluation of esophageal intramural pseudo-diverticulosis using high-resolution manometry.

Esophageal intramural pseudo-diverticulosis (EIPD) is a rare disease characterized by multiple small flask-shaped pouches in the esophageal wall, with the predominant symptom of chronic progressive or intermittent dysphagia. However, its etiology and pathogenesis remain unknown. We present a case of EIPD evaluated with high-resolution manometry in a 75-year-old man with food impaction after eating beef, who came to our emergency department. The patient experienced similar episodes three times previously, though the cause was unknown. Computed tomography (CT) findings revealed diffuse wall thickness in the upper intrathoracic esophagus, while esophagogastroduodenoscopy showed multiple small depressions and several white plaque patches, and a barium meal esophagogram showed characteristic multiple small outpouching areas. From these findings, we diagnosed the patient with EIPD. In addition, high-resolution manometry revealed strong contractions in the distal esophagus. We started an administration of isosorbide dinitrate, because abnormal esophageal motility may have been causative of the condition and development of pseudo-diverticulosis. Thereafter, the patient had a good clinical course without food impaction. Elevated intra-esophageal luminal pressure caused by abnormal esophageal motility seems to be an important factor in the pathogenesis of EIPD in some cases.

Successful Endoscopic Management of Non-Healing Perforated Duodenal Ulcer with Polyglycolic Acid Sheet and Fibrin Glue.

In recent years, treatment techniques in which polyglycolic acid sheets are applied to various situations with fibrin glue have exhibited great clinical potential, and previous studies have reported safety and efficacy. We describe closure of a non-healing perforated duodenal ulcer with the use of a polyglycolic acid sheet and fibrin glue in an elderly patient who was not a candidate for surgery.

Clinical features of eosinophilic esophagitis: differences between Asian and Western populations.

The prevalence and incidence of eosinophilic esophagitis (EoE) have been rapidly increasing in Western countries. It is thought to be more common among Caucasians than other racial or ethnic groups, but epidemiological studies have not been fully evaluated in Asian populations, and its clinical manifestation is rarely documented. In this review, recent reports regarding EoE in Asian countries have been collected, and differences in the clinical features, including symptoms and endoscopic findings, between Asian and Western populations have been evaluated. In Asia, EoE is still much less prevalent than in Western countries. Baseline values for average age, male/female ratio, and personal history of allergic disease were comparable to those in Western populations. Predominant symptoms were dysphagia, and food impaction was extremely rare among Asian patients. Although the frequency of abnormal endoscopic findings varies among studies, over 90% of patients with EoE have shown abnormal findings such as linear furrow, which is the most common findings, in recent prospective studies in Asia. There are few reports regarding the treatment of EoE and no prospective studies evaluating drugs or elimination diet in patient with EoE have been reported in Asia. Overall, EoE had similar clinical characteristics in Asian populations. Because the incidence of EoE could increase in the future with the increase in allergic disorders in Asian countries, large-scale, nationwide prospective studies should be performed to more fully understand the epidemiology and pathophysiology of EoE in Asian populations.