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.

Validation of rapid fecal calprotectin assay using particle enhanced turbidimetric immunoassay for inflammatory bowel disease.

Fecal calprotectin (FC) is a promising biomarker for diagnosis and treatment of inflammatory bowel disease, ulcerative colitis (UC), and Crohn's disease. An enzyme immunoassay (EIA) is widely used for FC detection, though the considerable lag time, up to several days, causes clinical management delay. This study was performed to examine the new rapid kit fCAL-turbo, which is based on a particle-enhanced turbidimetric immunoassay (15 min), by comparing FC values with other EIAs (EliA, PhiCal, Bühlmann) and endoscopic scores. Using 94 samples, fCAL-turbo showed strong significant positive correlations with the other kits (Spearman's r = 0.9178-0.9886). Of 74 UC patients, 69 underwent an endoscopy and fCAL-turbo reflected endoscopic activity with a moderate correlation with Mayo endoscopic subscore (MES) (r = 0.6945, others r = 0.6682-0.7013). Receiver operating characteristic analyses based on MES 0 versus 1-3 showed a similar efficacy as compared to the other kits (cut-off and area under the curve: 89.70 µg/g and 0.8592, respectively, others 62.35-138.4 µg/g and 0.8280-0.8611, respectively). Furthermore, multiple regression analysis confirmed that fCAL-turbo results significantly contributed to prediction of MES 0 with a higher t-value as compared to the other biomarkers. fCAL-turbo showed strong correlations with the other kits and also demonstrated excellent performance for predicting endoscopic remission of UC.

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.

Clinicopathologic differences of gastric neoplasms between Helicobacter pylori-infected and -naïve patients: a multicenter retrospective analysis.

BACKGROUND: The incidence of gastric neoplasms in Helicobacter pylori (Hp)-naïve patients has recently increased due to a remarkable decrease in the Hp-infected population in Japan. We investigated the clinicopathologic differences between Hp-infected gastric neoplasms (HpIGNs) and Hp-naïve gastric neoplasms (HpNGNs) that have not been fully elucidated so far. METHODS: This retrospective multicenter study investigated 966 consecutive patients with 1131 gastric dysplasia or cancers who underwent endoscopic or surgical treatment for the recent decade. Clinicopathologic features were compared between HpIGN and HpNGN cases. RESULTS: One thousand and sixty-eight HpIGNs in 916 patients included 877 differentiated types and 191 undifferentiated types. Sixty-three HpNGNs in 50 patients included 57 differentiated types (35 foveolar types, 15 intestinal types, 6 fundic-gland types, and 1 other differentiated type) and 6 undifferentiated types. HpNGNs occurred in younger (59.5 vs. 71.8 years, p < 0.05) and female patients (40.0% vs. 26.5%, p < 0.05), were found more frequently in the proximal compartment (p < 0.05), and had smaller size (median 4.0 vs. 20.0 mm, p < 0.05). Histologically, HpNGNs and HpIGNs both primarily consisted of differentiated type (90.5% vs. 82.1%, p = 0.089) and HpNGNs showed lower prevalence of invasive cancer (11.1% vs. 37.6%, p < 0.05) and lymphovascular invasion (1.6% vs. 31.6%, p < 0.05). Nearly all HpNGNs (62/63, 98.4%) were diagnosed in early pathological stage, while 16.1% (172/1068) of HpIGNs were diagnosed in advanced stage (p < 0.05). CONCLUSIONS: HpNGNs is recently on the increase but shows lower malignant nature regardless of histologic type than HpIGN. Endoscopic gastric cancer screening will be reviewed via cost effectiveness for Hp-naïve individuals in future.

Gastric Metastasis from Salivary Duct Carcinoma Mimicking Scirrhous Gastric Cancer.

A 59-year-old man underwent submandibular gland excision for salivary duct carcinoma (SDC). One year later, esophagogastroduodenoscopy indicated gastric diffuse mucosal thickening with luminal contraction, mimicking scirrhous gastric carcinoma. Biopsy specimens showed dense proliferation of neoplastic cells expressing androgen receptor and human epidermal growth factor 2, indicating SDC. Gastric diffuse infiltrative metastasis is generally characteristic of gastric metastasis from invasive ductal carcinoma, which shows histologic features similar to SDC. This is the first known report of gastric diffusely infiltrating metastasis in an SDC patient. Rapidly progressing, diffuse gastric wall thickening should also be considered indicative of salivary tumor-associated gastric metastasis.

Endoscopic differential diagnosis between foveolar-type gastric adenoma and gastric hyperplastic polyps in Helicobacter pylori-naïve patients.

BACKGROUND: Foveolar-type gastric adenoma (FGA) occurs in Helicobacter pylori (Hp)-naïve individuals and morphologically mimics Hp-naïve gastric hyperplastic polyp (HpN-GHP). FGA is often difficult to distinguish from HpN-GHP even by biopsy, due to its low-grade histologic atypia. We conducted a retrospective study to create an endoscopic diagnostic index. METHODS: We analyzed 51 FGAs in 41 patients and 36 HpN-GHPs in 24 patients. All lesions were photographed by white-light endoscopy (WLE) and narrow-band imaging with magnification endoscopy (NBIME). Three experts and three non-experts reviewed the WLE and WLE+NBIME images to assess six items for lesion diagnosis. We analyzed correlations between the diagnostic items and histologic features and compared the diagnostic accuracy between modalities. We created a composite diagnostic index and calculated its accuracy and consistency. RESULTS: FGAs more frequently showed the following features vs. HpN-GHPs: bright-red color (94.1% vs. 44.4%), peripheral hyperplasia (58.8% vs. 8.3%), papillary/gyrus-like microstructure (96.1% vs. 33.3%), visible capillaries (70.6% vs. 38.9%), and demarcation line (98.0% vs. 41.7%) (P < 0.05). White-zone thickening was seen only in HpN-GHPs (52.8%). Diagnostic accuracy (mean, WLE vs. WLE+NBIME) was 90.8 ± 1.1% vs. 93.5 ± 2.4% (P = 0.15) for experts and 88.5 ± 3.0% vs. 86.6 ± 3.5% (P = 0.51) for non-experts. When satisfying the four criteria (bright-red color, papillary/gyrus-like microstructure, demarcation line, and absent white-zone thickening), sensitivity and specificity for FGA were 90.2% and 94.4%, respectively, with a kappa value of ≥ 0.6 for interobserver diagnostic agreement. CONCLUSIONS: Composite diagnostic index contributes to the reproducible, accurate, preoperative differential diagnosis of FGA and HpN-GHP.

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.

Degree of Gastric Mucosal Atrophy Correlated Well with Gastric Cancer Occurrence in Patients with Helicobacter pylori-eradicated Status.

Objective This study was performed to clarify the association of the degree of gastric mucosal atrophy (GMA) with the occurrence of gastric cancer in patients with Helicobacter pylori-eradicated status. Methods The subjects were 3,058 patients (2,035 men, 1,023 women; mean age 57.9 ± 9.5 years old) with H. pylori eradication who underwent esophago-gastroduodenal endoscopy examinations as part of medical checkups conducted between April 2013 and March 2022. The gender, age at eradication, time since eradication, usage of anti-secretory drugs, degree of endoscopic GMA, and the fundic gland polyp (FGP) prevalence were compared between subjects with and without gastric cancer occurrence. Results Gastric cancer was newly detected in 26 subjects (0.85%) during the study period, with an older age at H. pylori eradication and severe grade of endoscopic GMA being significant risk factors for its occurrence. The gender, smoking history, and usage of anti-secretory drugs were not significantly different between subjects with and without gastric cancer occurrence. A Cox regression analysis showed that an older age at eradication and the degree of GMA were risk factors significantly related to occurrence. Furthermore, the degree of GMA was inversely correlated with FGP development, and gastric cancer was not detected in 467 subjects with FGP prevalence. Conclusion An older age at the time of H. pylori eradication and the degree of GMA are significant risk factors for gastric cancer occurrence in H. pylori-eradicated patients. The FGP prevalence in subjects with H. pylori eradication was inversely associated with GMA, suggesting it was negatively related with gastric cancer occurrence.

KLF4 Mutation Shapes Pathologic Characteristics of Foveolar-Type Gastric Adenoma in Helicobacter pylori-Naive Patients.

Along with a recent remarkable decrease in Helicobacter pylori-infected individuals, reports of gastric neoplasms such as sporadic foveolar-type gastric adenoma (FGA) in H. pylori-naive patients have been increasing. This tumor, with its raspberry-like appearance, is common in H. pylori-naive gastric mucosa. The current study investigated the genomic features of sporadic FGA. Fresh-frozen sporadic FGA tissue samples from H. pylori-naive patients were subjected to whole genome analysis using a next-generation sequencer. Proliferation ability and apoptotic profiles of human gastric epithelial cells, along with plasmid transfection of candidate variants, were examined. A mean of 6.65 × 108 total reads were obtained for each sample. Common genetic abnormalities in well-known proliferation driver genes of conventional gastric dysplasia/cancer were not found. However, a common single-nucleotide variation (SNV) was noted within the DNA-binding domain of the tumor suppressor gene KLF4. This novel SNV was located in the zinc finger 2 region. Additional experiments showed that it significantly suppressed proliferation of gastric epithelial cells compared with wild-type KLF4 plasmid-transfected cells, although suppression was reduced in early apoptotic phase-related genes. A novel SNV in the KLF4 zinc finger 2 region was commonly found in sporadic FGA tissue samples, which may explain the slow-growing properties of this neoplasm.

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.

Oxaliplatin-related Portal Hypertension Complicated with Esophageal Varices and Refractory Massive Ascites.

Oxaliplatin, widely used as a chemotherapy drug for colorectal cancer, is known to cause various adverse reactions. In particular, special attention for the development of portal hypertension associated with porto-sinusoidal vascular disease is necessary, as it is a serious adverse life-threating reaction, although rare. We herein report a case of oxaliplatin-related portal hypertension that developed several years after oxaliplatin administration and led to esophageal varices and refractory massive ascites. Clinical physicians should be aware of the possibility of oxaliplatin-induced portal hypertension and its possible development over a long period after discontinuation of the drug.

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.

Endoscopic findings of cardiac lymphoid hyperplasia and Helicobacter pylori infection status.

Objective: Lymphoid hyperplasia is endoscopically observed as multiple small whitish round nodules or spots. This retrospective study was performed to examine the prevalence of that finding in patients with Barrett's epithelium and its relationship with the status of H. pylori infection. Methods: The study subjects were 3353 patients (males 2186, females 1167; mean age 55.2 ± 9.4 years) in whom the status of H. pylori infection had been determined. The presence of Barrett's epithelium ≥ 5 mm in length was endoscopically determined, and then endoscopic observations with blue laser imaging were used to investigate the presence of lymphoid hyperplasia in those areas. Results: Barrett's epithelium was diagnosed in 1884 (56.2%) of the subjects, and endoscopic findings of lymphoid hyperplasia were observed in 402 (21.3%) of those with Barrett's epithelium. Lymphoid hyperplasia in Barrett's epithelium was not present in any without a current or prior H. pylori infection, while the prevalence of lymphoid hyperplasia in H. pylori-positive and post-eradicated subjects was 48.4% and 30.4%, respectively (p < 0.001). Multiple logistic regression analysis revealed that female gender, younger age, and higher degree of gastric mucosal atrophy were significant factors related to lymphoid hyperplasia positivity. In addition, the duration after H. pylori eradication was negatively correlated with its prevalence. Conclusion: Endoscopic findings of cardiac lymphoid hyperplasia were well correlated with H. pylori infection, although prevalence decreased over time following bacterial eradication.

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.

Intestinal-type gastric dysplasia in Helicobacter pylori-naïve patients.

Gastric dysplasia and gastric cancer in Helicobacter pylori (Hp)-naïve patients usually exhibit a gastric phenotype, reflecting gastric mucosa without intestinal metaplasia (IM). We showed that intestinal-type gastric dysplasia (IGD) rarely occurs in the Hp-naïve stomach. In the last 10 years, we treated 1760 gastric dysplasia and gastric cancer patients, with 3.6% (63/1760) being Hp-naïve. Among these, ten were diagnosed with 14 IGDs and enrolled in this retrospective analysis. All lesions were observed by white-light endoscopy (WLE) and narrow-band imaging with magnification endoscopy (NBIME). We analyzed their endoscopic and microscopic features and patient demographics. Five men and five women aged 64 ± 21 years were included. WLE showed the depressed lesions mimicking a benign raised erosion in the prepyloric compartment. Multiple growths were confirmed in 30% (3/10) of patients. NBIME showed a near-regular microstructure and capillaries in 50% (7/14) of lesions with a gastritis-like appearance. Histologically, background mucosa was non-atrophic pyloric gland tissue, but 40.0% of samples (4/10) contained sporadic IM. Most of the lesions (8/14) were low-grade dysplasia, and others had a high-grade component, with one progressing to intramucosal carcinoma. The neoplastic surface was widely covered with foveolar epithelium in 57.1% (8/14). Immunohistochemically, neoplastic cells expressed CDX2 in all patients (14/14), MUC2 and CD10 in 92.9% (13/14), MUC5AC in 14% (2/14), and no expression of MUC6, showing an intestinal phenotype. Ki-67 was overexpressed with a mean labeling index of 58.3 ± 38.5%, and p-53 was overexpressed in 92.9% (13/14), regardless of the dysplastic grade. The IGD rarely occurs in Hp-naïve patients with distinctive clinicopathologic characteristics.

A New Dawn for the Use of Artificial Intelligence in Gastroenterology, Hepatology and Pancreatology.

Artificial intelligence (AI) is rapidly becoming an essential tool in the medical field as well as in daily life. Recent developments in deep learning, a subfield of AI, have brought remarkable advances in image recognition, which facilitates improvement in the early detection of cancer by endoscopy, ultrasonography, and computed tomography. In addition, AI-assisted big data analysis represents a great step forward for precision medicine. This review provides an overview of AI technology, particularly for gastroenterology, hepatology, and pancreatology, to help clinicians utilize AI in the near future.