Development of an Artificial Intelligence Diagnostic System Using Linked Color Imaging for Barrett's Esophagus.

Background: Barrett's esophagus and esophageal adenocarcinoma cases are increasing as gastroesophageal reflux disease increases. Using artificial intelligence (AI) and linked color imaging (LCI), our aim was to establish a method of diagnosis for short-segment Barrett's esophagus (SSBE). Methods: We retrospectively selected 624 consecutive patients in total at our hospital, treated between May 2017 and March 2020, who experienced an esophagogastroduodenoscopy with white light imaging (WLI) and LCI. Images were randomly chosen as data for learning from WLI: 542 (SSBE+/- 348/194) of 696 (SSBE+/- 444/252); and LCI: 643 (SSBE+/- 446/197) of 805 (SSBE+/- 543/262). Using a Vision Transformer (Vit-B/16-384) to diagnose SSBE, we established two AI systems for WLI and LCI. Finally, 126 WLI (SSBE+/- 77/49) and 137 LCI (SSBE+/- 81/56) images were used for verification purposes. The accuracy of six endoscopists in making diagnoses was compared to that of AI. Results: Study participants were 68.2 ± 12.3 years, M/F 330/294, SSBE+/- 409/215. The accuracy/sensitivity/specificity (%) of AI were 84.1/89.6/75.5 for WLI and 90.5/90.1/91.1/for LCI, and those of experts and trainees were 88.6/88.7/88.4, 85.7/87.0/83.7 for WLI and 93.4/92.6/94.6, 84.7/88.1/79.8 for LCI, respectively. Conclusions: Using AI to diagnose SSBE was similar in accuracy to using a specialist. Our finding may aid the diagnosis of SSBE in the clinic.

Risk Factors for Mucosal Redness in the Duodenal Bulb as Detected via Linked Color Imaging.

Linked color imaging (LCI) for image-enhanced endoscopy (IEE) highlights mucosal color differences. We investigated risk factors associated with mucosal redness of the duodenal bulb using LCI. Consecutive patients were retrospectively selected after their duodenal bulbs were observed via LCI. A symptom questionnaire (Izumo scale) was completed. The LCI of the duodenal bulb was subjectively evaluated on whether redness was present and objectively evaluated based on L* a* b* color values. The clinical characteristics of the 302 study participants were: male/female, 120/182; mean age, 70.9 years. Twenty-one cases (7.0%) were in the redness (+) group. After multiple regression analysis, independent predictors for the red component (a*) of the duodenal bulb using LCI were: age (ß = -0.154, p < 0.01), female (ß = -0.129, p < 0.05), body mass index (BMI; ß = -0.136, p < 0.05), Helicobacter pylori eradication (ß = 0.137, p < 0.05), endoscopic gastric mucosal atrophy score (EGAS; ß = -0.149, p < 0.05), and constipation-related quality of life (QOL) (ß = -0.122, p < 0.05) scores. Lower age, lower BMI, lower EGAS, a constipation-related QOL score, post-H. pylori eradication, and being male were associated with mucosal redness in the duodenal bulb with IEE using LCI.

Endoscopic Diagnosis Strategy of Raspberry-Shaped Gastric Lesion in Helicobacter Pylori-Uninfected Patient.

OBJECTIVES: We aimed to clarify the endoscopic and clinicopathological features of raspberry-shaped gastric lesions (RSGLs) and to establish an endoscopic diagnostic algorithm for RSGLs. METHODS: We collected RSGLs from an endoscopic database at our hospital between May 2009 and August 2021. All RSGLs were histopathologically classified and compared based on their endoscopic and clinicopathological characteristics. RESULTS: Sixty-five RSGLs in 54 patients were classified into five histopathological types: gastric adenocarcinoma of foveolar type (GA-FV, n = 43), gastric adenocarcinoma of fundic-gland type (GA-FG, n = 2), gastric adenocarcinoma of fundic-gland mucosa type (GA-FGM, n = 4), hyperplastic polyp (HP, n = 12), and proton pump inhibitor-related lesion (PPI-L, n = 4). All RSGLs exhibited polygonal or curved marginal crypt epithelium (MCE). GA-FV lesions had homogenously reddish (95%) and an irregular microvascular (MV) pattern (91%). GA-FG lesions were heterogeneously reddish with a submucosal tumor shape (100%) and had a regular MV pattern (50%). GA-FGM lesions were homogen+ously reddish (75%) and occasionally had a submucosal tumor shape (50%) with an irregular MV pattern (75%). HPs and PPI-Ls were homogeneously reddish (93%), with linear or dotted MCE (81%) and a regular MV pattern (100%). CONCLUSION: Our diagnostic algorithm for RSGLs constructed using endoscopic features might be useful for the endoscopic differential diagnosis of RSGLs.

Clinicopathological characteristics of gastric adenocarcinoma with enteroblastic differentiation and gastric adenocarcinoma with enteroblastic marker expression.

Gastric adenocarcinoma (GA) with enteroblastic differentiation (GAED) is an aggressive carcinoma histologically characterized by a glycogen-rich clear cytoplasm and fetal gut-like structures. GAED shows the expression of at least one of the following enteroblastic markers (EMs): glypican-3 (GPC3), spalt-like transcription factor 4 (SALL4), and α-fetoprotein (AFP). Despite the absence of clear cytoplasm, we often encounter GA with EMs expression (GA with EM); however, the clinicopathological characteristics of GA with EM remain unclear. Immunohistochemical (IHC) expression of three EMs (AFP, GPC3, and SALL4) was examined on tissue microarray. According to the status of the clear cytoplasm of tumor cells, GAs showing IHC expression of EMs were classified as either GAED or GA with EM, and this analysis categorized 688 GAs into 94 GAEDs (13.7%), 58 GAs with EM (8.4%), and 536 conventional GAs (CGAs). Both GAED and GA with EM showed frequent lymphovascular invasion, lymph node metastasis, and liver metastasis compared to CGA. However, a higher frequency of venous invasion, but not of lymphatic invasion, was noted for GAED in comparison to CGA. GAED and GA with EM showed similar overall survival. GAED had significantly poorer prognosis than CGA; however, not for GA with EM. Furthermore, GA showing EM expression had a worse prognosis than CGA. Interestingly, GA showing EM-positive group was more aggressive than CGA group as they had frequent venous invasion and liver metastasis despite its smaller tumor size. GAED and GA with EM can be clinically classified as aggressive tumors but pathologically they seem to be slightly different.

Comparison of Texture and Color Enhancement Imaging with White Light Imaging in 52 Patients with Short-Segment Barrett's Esophagus.

BACKGROUND Texture and color enhancement imaging (TXI), a new type of image-enhanced endoscopy, may improve the detection of gastrointestinal lesions. Barrett's esophagus (BE) requires an accurate diagnosis since it may undergo neoplastic transformation. We aimed to evaluate the usefulness of TXI compared with white light imaging (WLI) in BE. MATERIAL AND METHODS In this prospective study at a single hospital from February 2021 to February 2022, we enrolled 52 consecutive patients with BE. Endoscopic images of BE using WLI, TXI mode 1 (TXI-1), TXI mode 2 (TXI-2), and narrow-band imaging (NBI) were compared by 10 endoscopists (5 experts and 5 trainees). Endoscopists scored visibility for the images as follows: 5 (improved), 4 (somewhat improved), 3 (equivalent), 2 (somewhat decreased), and 1 (decreased). Total visibility scores for all 10 endoscopists, and subgroups composed of the 5 expert endoscopists and the 5 trainee endoscopists, were evaluated. Main-group (10 endoscopists) scores of ≥40, 21-39, and ≤20, and subgroup (5 endoscopists) scores of ≥20, 11-19, and ≤10, were considered "improved", "equivalent", and "decreased", respectively. Inter-rater reliability (intra-class correlation coefficient [ICC]) was calculated and images were objectively assessed based on L*a*b* color values and color differences (ΔE*). RESULTS All 52 cases were diagnosed as short-segment BE (SSBE). TXI-1/TXI-2 improved visibility compared with WLI was: 78.8%/32.7% for all endoscopists; 82.7%/40.4% for trainees; and 76.9%/34.6% for experts. NBI did not improve visibility. The ICC for TXI-1 and TXI-2 compared with WLI was "excellent" for all endoscopists. The ΔE* between esophageal and Barrett's mucosae, and between Barrett's and gastric mucosae, was higher for TXI-1 than for WLI (P<0.01, P<0.05, respectively). CONCLUSIONS TXI, especially TXI-1, improves the endoscopic diagnosis of SSBE compared with WLI, regardless of the endoscopist's skill.

Emergency Endoscopic Hemostasis for Gastrointestinal Bleeding Using a Self-Assembling Peptide: A Case Series.

Background and Objectives: A novel synthetic self-assembling peptide, PuraStat, has been introduced as a hemostatic agent. This case series aimed to evaluate the clinical efficacy of PuraStat for gastrointestinal bleeding during emergency endoscopy. Cases: Twenty-five patients with gastrointestinal bleeding who had undergone emergency endoscopy with PuraStat between August 2021 and December 2022 were retrospectively examined. Six patients were receiving antithrombotic agents, and ten patients with refractory gastrointestinal bleeding had undergone at least one endoscopic hemostatic procedure. The breakdown of bleeding was gastroduodenal ulcer/erosion in 12 cases, bleeding after gastroduodenal or colorectal endoscopic resection in 4 cases, rectal ulcer in 2 cases, postoperative anastomotic ulcer in 2 cases, and gastric cancer, diffuse antral vascular ectasia, small intestinal ulcer, colonic diverticular bleeding, and radiation proctitis in each case. The method of hemostasis was only PuraStat application in six cases, and hemostasis in combination with high-frequency hemostatic forceps, hemostatic clip, argon plasma coagulation, and hemostatic agents (i.e., thrombin) in the remaining cases. Rebleeding was observed in three cases. Hemostatic efficiency was observed in 23 cases (92%). Conclusions: PuraStat has the expected hemostatic effect on gastrointestinal bleeding during emergency endoscopy. The use of PuraStat should be considered in emergency endoscopic hemostasis of gastrointestinal bleeding.

Gastric Juvenile Polyposis with Intramucosal Cancer Diagnosed by Magnifying Endoscopy with Narrow-band Imaging.

Although gastric juvenile polyposis (GJP) often coexists with gastric cancer, a preoperative accurate diagnosis is still difficult to obtain. A 70-year-old woman was referred for epigastralgia and anemia. Esophagogastroduodenoscopy with a conventional endoscope showed numerous gastric polyps with no cancerous findings. Magnifying endoscopy with narrow-band imaging (M-NBI) showed cancerous findings, and a target biopsy revealed adenocarcinoma. Histopathological findings after endoscopic resection confirmed a diagnosis of juvenile polyposis with intramucosal adenocarcinoma. Genetic analyses revealed a germline pathogenic variant of SMAD4. A target biopsy using M-NBI and endoscopic resection proved useful for confirming the preoperative diagnosis of coexisting cancerous lesions in GJP.

Successful Treatment of Steroid-resistant Eosinophilic Gastrointestinal Disease with Mepolizumab.

We experienced a case of treatment-resistant eosinophilic gastrointestinal disease (EGID). The patient, a 46-year-old man, presented with a fever, persistent abdominal pain, and an elevated peripheral eosinophil count. Eosinophil infiltration of the intestinal mucosa was also observed, and EGID was diagnosed. Corticosteroid therapy was initiated, but no improvement was seen. However, after mepolizumab (anti-interleukin 5 antibody) was administered, the patient's disease was controlled. Currently, the indications for mepolizumab are limited to bronchial asthma and paraneoplastic eosinophilic polyangiitis, but the experience herein reported suggests its usefulness in the treatment of EGID.

Correlation between Constipation Symptoms and Abdominal CT Imaging: A Cross-Sectional Pilot Study.

Evaluation of chronic constipation is important, although it is often difficult to satisfactorily treat due to the complex interplay of factors. This study aimed to determine whether the volume of intraluminal contents and lateral diameter of the colon measured from computed tomography (CT) images were correlated with the symptoms of chronic constipation and stool consistency. Consecutive patients who underwent the Constipation Scoring System (CSS), Bristol Stool Form Scale (BSFS) questionnaires and simple abdominal CT were selected retrospectively. The intestinal tract diameter at each site was measured, and the amounts of stool and gas in the intestinal tract were evaluated at five levels. Of the 149 study participants, 54 were males and 95 were females and their mean age was 72.1 years. In the right hemi-colon, CSS5 (Time) correlated significantly with gas volume (p < 0.01). In the left hemi-colon, stool volume correlated significantly with CSS2 (Difficulty), CSS3 (Completeness), CSS5 (Time) and CSS total (p < 0.05). The BSFS negatively correlated with gas volume and diameter in the right hemi-colon and with gas volume in the rectum (p < 0.05). CT findings including stool volume, gas volume and diameter correlated with some constipation symptoms and stool consistency. These findings may be useful in evaluating and treating constipation.

Mediastinal Thoracic Duct Cyst Infection after Endoscopic Submucosal Dissection for Early Esophageal Cancer.

A mediastinal thoracic duct cyst that originates from the thoracic duct is a very rare disease in the mediastinum. There have been no reports of mediastinal thoracic duct cyst infection caused by endoscopic treatment. This is the first case of mediastinal thoracic duct cyst infection after endoscopic submucosal dissection for early esophageal cancer. We herein report a 75-year-old man with mediastinal thoracic duct cyst infection caused by esophageal endoscopic submucosal dissection. In cases where a mediastinal thoracic duct cyst is found before performing endoscopic esophageal treatment, we should carefully consider the potential risk of post-treatment cyst infection.

Yersinia enterocolitica Enteritis Diagnosed with Erythema Nodosum.

We herein report a rare case of Yersinia enterocolitica enteritis with a fever and abdominal pain followed by erythema nodosum (EN) a few days later. The diagnosis was confirmed based on characteristic colonoscopy and computed tomography findings, pathology, and mucosal culture. Yersinia enteritis is a curable disease provided a proper diagnosis and treatment are performed. Although EN is a rare clinical course, it should still be considered as a differential diagnosis.

Endoscopic Features of Gastric Epithelial Neoplasm of Fundic Gland Mucosa Lineage.

The endoscopic features of gastric epithelial neoplasms of fundic gland mucosa lineage (GEN-FGML) have not been well investigated. We aimed to clarify the endoscopic features of GEN-FGML and differences between gastric adenocarcinoma of the fundic gland type (GA-FG) and fundic gland mucosa type (GA-FGM). A total of 62 GEN-FGML lesions, including 52 GA-FG and 10 GA-FGM, were retrospectively analyzed using endoscopic and clinicopathological findings to provide information of diagnostic value using white light imaging (WLI) and magnifying endoscopy with narrow-band imaging (M-NBI). GA-FG frequently presented with a whitish, submucosal tumor (SMT) shape with dilated vessels with branching architecture and background mucosa without atrophic change in WLI, an indistinct demarcation line (DL), dilatation of the crypt opening and intervening part (IP), and microvessels without distinct irregularity in M-NBI. GA-FGM frequently presented as a reddish, elevated lesion in WLI, with a distinct DL, dilatation of the IP, and an irregular microvascular pattern in M-NBI. As for an M-NBI diagnosis, five GA-FGM lesions met the diagnostic criteria for cancer, whereas none of the GA-FG lesions met the same criteria. We highlight the endoscopic features of GEN-FGML, and the differentiation between GA-FG and GA-FGM might be possible by combination of lesion color and morphology in WLI and M-NBI diagnoses.

Comparative Study of Helicobacter pylori-Infected Gastritis in Okinawa and Tokyo Based on the Kyoto Classification of Gastritis.

The incidence of gastric cancer in Okinawa Prefecture is the lowest in Japan, which is attributed to differences in strains of Helicobacter pylori in Okinawa and other prefectures in Japan. Our aim was to compare the endoscopic findings of H. pylori-infected gastric mucosa in Okinawa and Tokyo. Patients who underwent upper gastrointestinal endoscopy (UGI) at Northern Okinawa Medical Center (Okinawa group) and Juntendo University Hospital (Tokyo group) from April 2019 to March 2020 were included. Patients diagnosed with H. pylori-infected gastric mucosa were retrospectively compared between the Okinawa and Tokyo groups according to the Kyoto Classification of Gastritis. The numbers of subjects (Okinawa/Tokyo) were 435/352, male/female ratio was 247:188/181:171, and age was 53.3 ± 14.7/64.6 ± 14.3 (mean ± standard deviation) years. Regarding the Kyoto Classification of Gastritis, the prevalence (Okinawa/Tokyo) of the closed type of atrophic gastritis was 73%/37% (p < 0.001), diffuse redness 80%/84% (p = 0.145), mucosal swelling 46%/46% (p = 0.991), enlarged fold 26%/32% (p = 0.048), spotty redness 77%/68% (p = 0.002), sticky mucus 17%/36% (p < 0.001), and intestinal metaplasia 32%/42% (p < 0.001). Age analysis also revealed that closed-type atrophy and spotty redness were more frequent in the Okinawa group than in the Tokyo group. There may be regional differences in endoscopic findings of H. pylori-infected gastric mucosa between Okinawa and Tokyo.

Comparison of the Degree of Gastric Mucosal Injury between Patients Who Are Receiving Dual Antiplatelet Therapy or Single Antiplatelet Therapy.

BACKGROUND: Patients taking low-dose aspirin have a higher incidence of gastroduodenal ulcers and higher risk of upper gastrointestinal bleeding than patients who do not. Thienopyridine antiplatelet agents may similarly cause bleeding gastroduodenal erosions and ulcers. The incidence of gastrointestinal bleeding is reported to be higher when these antithrombotic drugs are used in combination. Until now, most studies have focused on bleeding, and no study has compared the degree of gastric mucosal injury between patients receiving dual antiplatelet therapy (DAPT) and those receiving single antiplatelet therapy (SAPT) in real-world clinical practice. AIM: Our objective was to compare the degree of gastric mucosal injury in patients taking low-dose aspirin in combination with clopidogrel (one of the thienopyridine antiplatelet agents) with that of patients who were taking aspirin or clopidogrel as a single agent. METHODS: Patients who were taking aspirin and/or clopidogrel and who underwent scheduled esophagogastroduodenoscopy between April 2015 and March 2020 were enrolled in this study. Endoscopic images were reviewed retrospectively, and the degree of gastric mucosal injury was assessed with the modified Lanza score (m-Lanza score). The m-Lanza score was compared between DAPT patients taking aspirin and clopidogrel and SAPT patients taking either aspirin alone or clopidogrel alone. RESULTS: The m-Lanza scores of the DAPT group, the aspirin group, and the clopidogrel group were 1.67 ± 1.81 (mean ± standard deviation), 0.95 ± 1.61, and 0.72 ± 1.29, respectively. The m-Lanza score of the DAPT group tended to be higher than that of the aspirin group (p = 0.06) and was significantly higher than that of the clopidogrel group (p = 0.03). CONCLUSION: The degree of gastric mucosal injury in DAPT patients was significantly higher than that in patients using clopidogrel alone and tended to be higher than that in patients using aspirin alone in real-world clinical practice.

Association between bile area in the duodenal bulb and abdominal symptoms: Quantitative analysis using blue laser imaging.

Bile acids are strongly associated with the pathogenesis of functional gastrointestinal diseases. In recent years, blue laser imaging (BLI) endoscopy has emerged as a novel image-enhanced endoscopic method, which illustrates bile as a reddish hue. The present study investigated the factors that affect the area of bile in duodenal bulbs using BLI. For this purpose, patients (356 cases) who underwent upper endoscopy with BLI between April, 2017 and December, 2019, and completed patient background and symptom questionnaires [Constipation Scoring System (CSS), Bristol Stool Form Scale (BSFS) and Frequency Scale for Symptoms of gastroesophageal reflux disease (FSSG)], were retrospectively investigated. Each BLI bile score was calculated as a percentage of bile area in a field of view in the duodenal bulb using a KS400 image analysis system, and the association with abdominal symptoms was examined using multiple regression analysis. The patient characteristics included the following: Age (in years), 69.9±11.3; male/female ratio, 146/210; body mass index, 23.0±3.8; reflux esophagitis (M/A/B/C), 143/19/3/3; atrophic gastritis (C-0/C1-3/O1-3), 132/100/124; proton pump inhibitor potassium competitive acid blocker/aspirin/ursodeoxycholic acid/gall bladder stones/cholecystectomy, 105/27/18/43/18; BLI bile score, 7.10 (±14.34); CSS score, 3.55 (±3.80); BSFS score, 3.91 (±1.02); and FSSG score, 4.80 (±5.76). Correlation coefficients (P<0.05) for the BLI bile score were found for cholecystectomy (Rho=0.137) and aspirin use (Rho=0.118). In multiple regression analysis, independent predictors of the BLI bile score were cholecystectomy [standardized partial regression coefficient (ß)=0.169, P=0.001] and the BSFS score (ß=0.107, P=0.042). On the whole, the present study demonstrates that the duodenal bile area in BLI upper endoscopy is associated with cholecystectomy and fecal characteristics.

Clinicopathological and molecular characterization of early gastric adenocarcinoma in Helicobacter pylori-uninfected patients: emphasis on differentiated gastric adenocarcinoma.

BACKGROUND: Recently, Helicobacter pylori (HP)-uninfected gastric mucosal cancer has been reported; however, the clinicopathological and molecular features of HP-uninfected gastric cancer have not been elucidated. METHODS: We evaluated the clinicopathological, immunohistochemical, and genetic alterations in HP-uninfected early gastric adenocarcinoma using next-generation sequencing (NGS). RESULTS: Among 968 primary early gastric carcinomas, 64 (6.6%) were HP-uninfected gastric adenocarcinoma and were pathologically classified as gastric adenocarcinoma of fundic-gland type (GA-FG, n = 39), differentiated gastric adenocarcinoma (DGA, n = 16), and signet-ring cell carcinoma (SRCC, n = 9). Based on the expression profile of the mucin core protein, DGAs were classified into a gastrointestinal phenotype showing either MUC5AC or MUC6 expression and MUC2 or CD10 expression simultaneously (n = 5), and a gastric phenotype (n = 11) showing either MUC5AC or MUC6 expression. All DGAs with a gastrointestinal phenotype shared similar endoscopic characteristics, such as reddish depressed lesions in the antrum. In contrast, DGAs with a gastric phenotype exhibited several distinct endoscopic features, including a raspberry-shaped appearance and whitish flat-elevated appearance; the former expressed only MUC5AC and the latter exhibited co-expression of MUC5AC and MUC6. Among 16 HP-uninfected DGAs, seven were subjected to NGS. APC was recurrently mutated in DGA (42.9%) and was enriched in DGAs with a gastrointestinal phenotype (75%). CONCLUSIONS: Overall, HP-uninfected gastric adenocarcinomas showed distinct clinicopathologic and endoscopic characteristics. Furthermore, HP-uninfected DGAs, especially those with a gastrointestinal phenotype, may be characterized by recurrent APC mutations.

Molecular and clinicopathological analysis of three cases of gastric juvenile polyposis.

Background and Aim: Juvenile polyposis (JP) is a rare disease known to be associated with mutations either in SMAD4/BMPR1A. JP is known to often develop into malignant tumors, with a reported probability of 9-50%. However, the mechanisms of its carcinogenesis are not fully understood. We tried to elucidate the mechanisms of malignant transformation underlying this condition in three cases of gastric JP. Methods: We selected polyps from each patient displaying varying degrees of atypia and their nearby normal polyps and compared them using immunohistochemistry, Sanger sequencing, and loss of heterozygosity (LOH) analysis of SMAD4, BMPR1A, and TP53. Results: Two of the three cases were suspected of having germline SMAD4 mutations based on their familial medical histories; the remaining case was found to have a SMAD4 germline mutation following preoperative genetic testing. All three cases were shown to present with both SMAD4 positive and negative areas across each lesion, with the neoplastic lesions tending to show stronger nuclear SMAD4 expression. This expression was closely associated with the SMAD4 LOH status; however, we also noted paradoxical SMAD4 expression in the neoplastic lesions despite the biallelic inactivation of SMAD4 revealed in the genetic evaluation. Conclusions: These data suggest that strong nuclear expression of SMAD4, even when seemingly paradoxical, seems to be closely associated with dysplastic polyps in JP. Complete inactivation of SMAD4 was not shown to be essential for the development of dysplastic polyps in gastric JP, and other pathways seemed to be involved in the acquisition of the malignant phenotype.

Diagnosis of histological type of early gastric cancer by magnifying narrow-band imaging: A multicenter prospective study.

Objectives: Distinguishing undifferentiated-type from differentiated-type early gastric cancers (EGC) is crucial for determining the indication of endoscopic resection. We aimed to investigate the diagnostic performance of white-light endoscopy (WLE) and magnifying narrow-band imaging (M-NBI) for the histological type of EGC. Methods: In this multicenter prospective study, patients with histologically proven cT1 EGC, macroscopically depressed or flat type, size ≥5 mm, and without erosion/ulcer, were recruited. The diagnostic criterion of WLE for undifferentiated-type EGC was pale color. The M-NBI algorithm was created based on microsurface and microvascular patterns, and lesions with absent microsurface pattern and opened-loop microvascular patterns were diagnosed as undifferentiated-type. The center of the lesion was defined as the evaluation point and was initially evaluated by WLE, then by M-NBI, and a biopsy specimen was taken as a reference standard. The primary and key secondary endpoints were overall diagnostic accuracy and specificity, respectively. Results: In total, 167 lesions (122 differentiated-type and 45 undifferentiated-type EGCs) in 167 patients were analyzed. The overall accuracy, sensitivity, specificity, and positive likelihood ratio of WLE for undifferentiated-type cancer were 80%, 69%, 84%, and 4.4, respectively, and those of M-NBI were 82%, 53%, 93%, and 7.2, respectively. There was no significant difference in overall accuracy (p = 0.755), but specificity was significantly higher in M-NBI (p = 0.041). Conclusions: The use of M-NBI did not improve the accuracy of WLE for the diagnosis of depressed/flat undifferentiated-type EGCs but improved the specificity. It may reduce surgical overtreatment by preventing misdiagnosis of differentiated-type EGC as undifferentiated-type.

Clinicopathological features of PD-L1 protein expression, EBV positivity, and MSI status in patients with advanced gastric and esophagogastric junction adenocarcinoma in Japan.

This real-world study examined the prevalence of programmed death ligand-1 (PD-L1) expression and assessed the frequency of microsatellite instability-high (MSI-H) status and Epstein-Barr virus (EBV) positivity in Japanese patients with advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma. This multicenter (5 sites), retrospective, observational study (November 2018-March 2019) evaluated Japanese patients with advanced gastric and GEJ adenocarcinoma after surgical resection (Stage II/III at initial diagnosis) or unresectable advanced cancer (Stage IV). The primary objectives were prevalence of PD-L1 expression (combined positive score [CPS] ≥1), MSI status, and EBV positivity. Tumor specimens of 389/391 patients were analyzed (male, 67.1%; mean age, 67.6 ± 12.2 years); 241/389 (62%) were PD-L1 positive, 24/379 (6.3%) had MSI-H tumors, and 13/389 (3.3%) were EBV positive. PD-L1 expression was higher in tumor-infiltrating immune cells than in tumor cells for lower CPS cutoffs. Among patients with MSI-H tumors and EBV-positive tumors, 19/24 (79.2%) and 9/13 (69.2%), respectively, were PD-L1 positive. A greater proportion of patients with MSI-H tumors (83.3% [20/24]) were PD-L1 positive than those with MSI-low/stable tumors (60.8% [216/355]; p = .0297); similarly, an association was observed between history of H pylori infection and PD-L1 expression. A higher proportion of patients with MSI-H tumors demonstrated PD-L1 expression with a CPS ≥10 (66.7% [16/24]) vs those with MSI-low/stable tumors (24.8% [88/355]; p < .0001). The prevalence of PD-L1 positivity among Japanese patients was comparable to that in previous pembrolizumab clinical trials and studies in gastric cancer. Particularly, higher PD-L1 expression was observed in MSI-H tumors.