Search

Background: The effectiveness of esophagogastroduodenoscopy (EGD) screening in cohorts with low Helicobacter pylori prevalence is unknown. This study aimed to develop an optimally efficient EGD screening strategy for detecting H. pylori-naïve gastric neoplasms (HpNGNs)., Methods: EGD data of 12 institutions from 2016 to 2022 were retrospectively analyzed. Age-related HpNGN prevalence, tumor growth rate, missing rate, and detection threshold size were calculated from the databases. Subsequently, using clinical data, a novel mathematical model that simultaneously simulated demographic changes and HpNGN detection was developed. Screening strategies using different starting ages (40/45/50 years) and intervals (2/5/10 years) were also compared. The detection rates of all tumors occurring within the virtual cohort and number-needed-to-test (NNT) were measured as outcomes., Results: Data of 519,368 EGDs and 97 HpNGNs (34 pure signet ring cell carcinomas, 26 gastric adenocarcinomas of the fundic gland type, 30 foveolar gastric adenoma-Raspberry type, and seven undifferentiated-type cancer cases) were analyzed. A virtual cohort with a 70-year time horizon was used to simulate the occurrence, growth, and detection of 346,5836 people. Among the strategies with detection rate > 50%, the screening strategy with a 5-year interval starting at 45 years of age had the lowest NNT. Adopting this strategy, most HpNGNs were detected at < 20 mm in size, and the deep submucosal invasion rate was less than 30%., Conclusions: A mathematical simulation model revealed that screening every 5 years starting at 45 years of age could efficiently assist in identifying HpNGNs at an early stage., (© 2024. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

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.)., Competing Interests: Disclosure All authors disclosed no financial relationships. This study was supported by a grant for Clinical Cancer Research from the Japanese Ministry of Health, Labor, and Welfare (H21-022); a grant from Daiwa Securities Health Foundation (H24-16); and grants for the National Cancer Center Research and Development from the Japanese Ministry of Health, Labor, and Welfare (25-A-12, 28-K-1, 29-A-13, and 2021-A-18)., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Little is known about prognostic factors for patients 85 years or older undergoing endoscopic submucosal dissection for early gastric cancer. Therefore, this study aimed to identify such prognostic factors., Methods: We retrospectively evaluated the long-term outcomes and prognostic factors of 143 patients 85 years or older undergoing endoscopic submucosal dissection for early gastric cancer at a single-center between October 2005 and September 2020. Using the Kaplan-Meier method and a Cox proportional hazards regression model, we examined the relationships of patient characteristics and endoscopic curability (additional gastrectomy recommended [eCuraC-2] or not recommended) with overall survival., Results: The median age of the patients was 86 years, and most patients were men (65%). The eCuraC-2 rate was 14.7%. During the follow-up period, 55 patients died; however, only two patients died due to gastric cancer. The 3-year and 5-year overall survival rates were 91.5% and 74.7%, respectively. Male sex (hazard ratio, 2.23; 95% confidence interval, 1.16-4.30), American Society of Anesthesiologists Physical Status of 3 (hazard ratio, 2.57; 95% confidence interval, 1.32-4.99), body mass index < 18.9 kg/m 2 (hazard ratio, 2.21; 95% confidence interval, 1.11-4.40), and eCuraC-2 (hazard ratio, 3.04; 95% confidence interval, 1.37-6.75) were identified as independent prognostic factors. Moreover, patients with eCuraC-2 had significantly more poor prognostic factors than those who did not., Conclusions: The decision to perform endoscopic submucosal dissection for patients with the aforementioned prognostic factors should be carefully considered because follow-up without endoscopic submucosal dissection is possible., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Accurate tumor localization and resection margin acquisition are essential in gastric cancer surgery. Preoperative placement of marking clips in laparoscopic gastrectomy as well as intraoperative gastroscopy can be used for gastric cancer surgery. However, these procedures are not available at all institutions. We conducted a prospective clinical trial to investigate the diagnostic performance of near-infrared fluorescent clips (ZEOCLIP FS) in laparoscopic gastrectomy., Materials and Methods: Patients with gastric cancer or neuroendocrine tumor in whom laparoscopic distal, pylorus-preserving, or proximal gastrectomy was planned were enrolled (n = 20) in this study. Fluorescent clips were placed proximal and/or distal to the tumor via gastroscopy on the day before surgery. During surgery, the clips were detected using a fluorescent laparoscope, and suturing was performed where fluorescence was detected. The clip locations were then confirmed via gastroscopy, and the stomach was transected. The primary endpoint was the detection rate of the marking clips using fluorescence, and the secondary endpoints were complications and distance between the clips and stitches., Results: Among the 20 patients enrolled, distal and pylorus-preserving gastrectomies were performed in 18 and 2 patients, respectively. All clips were detected in 15 patients, indicating a detection rate of 75.0% (90% confidence interval: 54.4%-89.6%). Furthermore, no complications related to the clips were observed. The median distance between the clips and stitches was 5 (range, 0-10) mm., Conclusions: We report the feasibility and safety of preoperative placement and intraoperative detection of near-infrared fluorescent marking clips in laparoscopic gastrectomy., (Copyright © 2024. Published by Elsevier Inc.)

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/m 2 ; and ≥72 years. Factors showing significant independent correlations with delayed perforation were procedure time ≥60 min; BMI < 18.5 kg/m 2 ; ≥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., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Introduction: Gastric cancer with fusion genes involving the Rho GTPase-activating protein domain (RhoGAP-GC) is mainly included in the genomically stable type of The Cancer Genome Atlas classification. Clinical implications and histological characteristics of RhoGAP-GC in the early phase remain unclear., Methods: We analyzed 878 consecutive pT1b GCs for RhoGAP and its partner genes using fluorescence in situ hybridization assay., Results: RhoGAP fusion was detected in 57 (6.5%) GCs. Univariate analysis revealed that female sex, middle-lower third tumor location, advanced macroscopic type, tumor diameter > 2 cm, pT1b2, lymphatic invasion, venous invasion, negative EBER-ISH, and RhoGAP fusion were significantly associated with lymph node metastasis (LNM). Multivariate analysis presented RhoGAP fusion, lymphatic invasion, tumor diameter > 2 cm, advanced macroscopic type, venous invasion, and middle-lower third tumor location as independent risk factors for LNM. Notably, RhoGAP fusion had the highest odds ratio (3.92) for LNM among analyzed parameters (95% CI 2.12-7.27; p < 0.001). Compared to non-RhoGAP-GCs, RhoGAP-GCs were significantly frequent in younger females and showed the highest incidence of lymphatic invasion (56.2%) and LNM (49.1%) (p < 0.001). Histologically, microtubular architecture with pseudo-trabecular interconnection and small aggregations of tumor cells with a varied amount of cytoplasmic mucin, named "microtubular-mucocellular (MTMC) histology," was found in 93.0% (53 of 57) of RhoGAP-GCs in the intramucosal area. MTMC histology showed high sensitivity and negative predictive value (93.0% and 99.4%, respectively) for RhoGAP fusion, albeit positive predictive value is low (34.9%)., Conclusion: RhoGAP-GC is linked to a characteristic MTMC histology and a high incidence of LNM., (© 2024. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Since the indications for endoscopic submucosal dissection have been expanded to include undifferentiated-type early gastric cancers, improvements in preoperative diagnostic ability have been an area of research. There are also concerns about the impact on the diagnosis of Helicobacter pylori infection. Based on our previous studies, in undifferentiated-type early gastric cancers, magnifying endoscopy with narrow-band imaging is useful for delineating the demarcation regardless of the tumor size. Additionally, inflammatory cell infiltration appears to be a cause of misdiagnosis, suggesting that the resolution of inflammation could contribute to the accurate diagnosis of demarcations. As such, the accuracy of demarcation in eradicated and uninfected cases is higher than that in non-eradicated cases. The common features of the endoscopic findings were discoloration under white-light imaging and a predominance of sites in the lower and middle regions. The uninfected group was characterized by smaller tumor size, flat type, more extended intervening parts in magnifying endoscopy with narrow-band imaging, and pure signet ring cell carcinoma. In contrast, the eradication and non-eradication groups were characterized by larger tumor size, depressed type, and wavy microvessels in magnifying endoscopy with narrow-band imaging. In this comprehensive review, as described above, we discuss the diagnosis of demarcation of undifferentiated-type early gastric cancers, undifferentiated-type early gastric cancers that developed following H. pylori eradication, and H. pylori -uninfected undifferentiated-type early gastric cancers, with a focus on studies with self-examination and endoscopic findings and describe the future direction.

Background: The effect of Helicobacter pylori (H.pylori) eradication therapy on mixed-histological-type gastric cancer remains unclear. This study aimed to clarify the effect of H. pylori eradication therapy on mixed-histological-type early gastric cancer using endoscopic and histological findings., Methods: This single-center, retrospective study included patients with mixed-histological-type gastric cancer who underwent endoscopic submucosal dissection at the Cancer Institute Hospital. We compared detailed magnifying endoscopy with narrow-band imaging findings between eradicated and non-eradicated groups of patients with differentiated-type- and undifferentiated-type-predominant cancers. Subsequently, we performed histological evaluations of the non-cancerous epithelium covering differentiated-type components., Results: A total of 124 patients with mixed-type early gastric cancer were enrolled (eradicated group: 62 differentiated-type-predominant cancer patients and 8 undifferentiated-type-predominant cancer patients; non-eradication group: 40 differentiated-type-predominant cancer patients and 14 undifferentiated-type-predominant cancer patients). Regarding differentiated-type-predominant cancer, differentiated-type findings were detected in all patients in eradicated and non-eradicated groups. The difference in the detection rate of undifferentiated-type findings between both groups was not significant in differentiated-type-predominant cancer patients. In differentiated-type-predominant cancers, the percentage of non-cancerous epithelium covering differentiated-type components was higher in the eradicated group than in the non-eradicated group (median: 60% vs. 40%, p < 0.001)., Conclusions: Although the pathological findings of differentiated-type-predominant cancer were affected by H. pylori eradication, eradication did not affect the diagnosis of differentiated-type-predominant early gastric cancer using magnifying endoscopy with narrow-band imaging. ME-NBI is useful for the early detection of D-MIX EGCs and diagnosis of histological types during endoscopy, regardless of whether H. pylori eradication therapy has been administered., (© 2023. The Author(s).)

Objectives: Endoscopists' abilities to diagnose early gastric cancers (EGCs) vary, especially between specialists and nonspecialists. We developed an artificial intelligence (AI)-based diagnostic support tool "Tango" to differentiate EGCs and compared its performance with that of endoscopists., Methods: The diagnostic performances of Tango and endoscopists (34 specialists, 42 nonspecialists) were compared using still images of 150 neoplastic and 165 non-neoplastic lesions. Neoplastic lesions included EGCs and adenomas. The primary outcome was to show the noninferiority of Tango (based on sensitivity) over specialists. The secondary outcomes were the noninferiority of Tango (based on accuracy) over specialists and the superiority of Tango (based on sensitivity and accuracy) over nonspecialists. The lower limit of the 95% confidence interval (CI) of the difference between Tango and the specialists for sensitivity was calculated, with >-10% defined as noninferiority and >0% defined as superiority in the primary outcome. The comparable differences between Tango and the endoscopists for each performance were calculated, with >10% defined as superiority and >0% defined as noninferiority in the secondary outcomes., Results: Tango achieved superiority over the specialists based on sensitivity (84.7% vs. 65.8%, difference 18.9%, 95% CI 12.3-25.3%) and demonstrated noninferiority based on accuracy (70.8% vs. 67.4%). Tango achieved superiority over the nonspecialists based on sensitivity (84.7% vs. 51.0%) and accuracy (70.8% vs. 58.4%)., Conclusions: The AI-based diagnostic support tool for EGCs demonstrated a robust performance and may be useful to reduce misdiagnosis., (© 2022 Japan Gastroenterological Endoscopy Society.)

Background & Aims: We aimed to clarify the long-term outcomes of endoscopic resection (ER) for early gastric cancers (EGCs) based on pathological curability in a multicenter prospective cohort study., Methods: We analyzed the long-term outcomes of 9054 patients with 10,021 EGCs undergoing ER between July 2010 and June 2012. Primary endpoint was the 5-year overall survival (OS). The hazard ratio for all-cause mortality was calculated using the Cox proportional hazards model. We also compared the 5-year OS with the expected one calculated for the surgically resected patients with EGC. If the lower limit of the 95% confidence interval (CI) of the 5-year OS exceeded the expected 5-year OS minus a margin of 5% (threshold 5-year OS), ER was considered to be effective. Pathological curability was categorized into en bloc resection, negative margins, and negative lymphovascular invasion: differentiated-type, pT1a, ulcer negative, ≤2 cm (Category A1); differentiated-type, pT1a, ulcer negative, >2 cm or ulcer positive, ≤3 cm (Category A2); undifferentiated-type, pT1a, ulcer negative, ≤2 cm (Category A3); differentiated-type, pT1b (SM1), ≤3 cm (Category B); or noncurative resections (Category C)., Results: Overall, the 5-year OS was 89.0% (95% CI, 88.3%-89.6%). In a multivariate analysis, no significant differences were observed when the hazard ratio of Categories A2, A3, and B were compared with that of A1. In all the pathological curability categories, the lower limit of the 95% CI for the 5-year OS exceeded the threshold 5-year OS., Conclusion: ER can be recommended as a standard treatment for patients with EGCs fulfilling Category A2, A3, and B, as well as A1 (UMIN Clinical Trial Registry, UMIN000005871)., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Most gastric neuroendocrine tumors (NETs) develop from enterochromaffin-like (ECL) cells. ECL-cell NETs are classically categorized into three types according to their etiology. A 50-year-old woman presented with submucosal tumor-like lesions in the stomach, which were identified via esophagogastroduodenoscopy. Although esophagogastroduodenoscopy and pathological findings of biopsy specimens showed an absence of mucosal atrophy in the body of the stomach, sticky, adherent, dense mucus was observed. All lesions were diagnosed as ECL-cell NETs based on histological examination findings; however, ECL-cell NETs did not apply to any of the classic types I-III categorization based on laboratory, computed tomography, and 24-h intragastric pH monitoring test findings. Endoscopic submucosal dissection of the tumor was performed. Pathological findings of the excised specimen indicated that parietal cell hyperplasia with a protrusion, dilated fundic glands, and endocrine cell hyperplasia in the background mucosa, and parietal cells were not immunostained for the α-subunits of H + /K + -ATPase. Genetic analysis identified mutation in the ATP4A gene. The patient opted for additional gastric resection due to the risk of lymph node metastasis with deeper submucosal invasion and vascular infiltration. This report describes the first case of ECL-cell NETs caused by parietal cell dysfunction, which was treated via endoscopic submucosal dissection., (© 2022. Japanese Society of Gastroenterology.)

Helicobacter pylori (HP) is a major etiologic driver of diffuse-type gastric cancer (DGC). However, improvements in hygiene have led to an increase in the prevalence of HP-naïve DGC; that is, DGC that occurs independent of HP. Although multiple genomic cohort studies for gastric cancer have been conducted, including studies for DGC, distinctive genomic differences between HP-exposed and HP-naïve DGC remain largely unknown. Here, we employed exome and RNA sequencing with immunohistochemical analyses to perform binary comparisons between 36 HP-exposed and 27 HP-naïve DGCs from sporadic, early-stage, and intramucosal or submucosal tumor samples. Among the samples, 33 HP-exposed and 17 HP-naïve samples had been preserved as fresh-frozen samples. HP infection status was determined using stringent criteria. HP-exposed DGCs exhibited an increased single nucleotide variant burden (HP-exposed DGCs; 1.97 [0.48-7.19] and HP-naïve DGCs; 1.09 [0.38-3.68] per megabase; p = 0.0003) and a higher prevalence of chromosome arm-level aneuploidies (p < 0.0001). CDH1 was mutated at similar frequencies in both groups, whereas the RHOA-ARHGAP pathway misregulation was exclusive to HP-exposed DGCs (p = 0.0167). HP-exposed DGCs showed gains in chromosome arms 8p/8q (p < 0.0001), 7p (p = 0.0035), and 7q (p = 0.0354), and losses in 16q (p = 0.0167). Immunohistochemical analyses revealed a higher expression of intestinal markers such as CD10 (p < 0.0001) and CDX2 (p = 0.0002) and a lower expression of the gastric marker, MUC5AC (p = 0.0305) among HP-exposed DGCs. HP-naïve DGCs, on the other hand, had a purely gastric marker phenotype. This work reveals that HP-naïve and HP-exposed DGCs develop along different molecular pathways, which provide a basis for early detection strategies in high incidence settings. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland., (© 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)

Background: No studies have compared the performance of microvascular and microsurface patterns alone with their combination in patients undergoing magnifying endoscopy with narrow-band imaging for diagnosing gastric cancer. This study aimed to clarify the differences in diagnostic performance among these methods., Methods: Thirty-three participating endoscopists who had received specialized training in magnifying endoscopy evaluated the microvascular and microsurface patterns of images of 106 cancerous and 106 non-cancerous lesions. If classified as "irregular," the lesion was diagnosed as gastric cancer. To evaluate diagnostic performance, we compared the diagnostic accuracy, sensitivity, and specificity of these methods., Results: Performance-related items did not differ significantly between microvascular and microsurface patterns. However, the diagnostic accuracy and sensitivity were significantly higher when using a combination of these methods than when using microvascular (82.1% [76.4-86.7] vs. 76.4% [70.3-81.6] and 69.8% [60.5-77.8] vs. 63.2% [53.7-71.8]; P < 0.001 and P = 0.008, respectively) or microsurface (82.1% [76.4-86.7] vs. 73.6% [67.3-79.1] and 69.8% [60.5-77.8] vs. 52.8% [43.4‒62.1]; both, P < 0.001) patterns alone. The additive effect on diagnostic accuracy and sensitivity was 5.7‒8.6% and 6.6‒17.0%, respectively., Conclusions: We demonstrate the superiority of the combination of microvascular and microsurface patterns over microvascular or microsurface patterns alone for diagnosing gastric cancer. Our data support the use of the former method in clinical practice. Although a major limitation of this study was its retrospective, single-center design, our findings may help to improve the diagnosis of gastric cancer., (© 2022. The Author(s).)

Introduction: Although endocytoscopy (EC) with narrow-band imaging (NBI) is effective in diagnosing gastric cancer, no diagnostic system has been validated. We explored a specific diagnostic system for gastric cancer using EC with NBI., Methods: Equal numbers of images from cancerous and noncancerous areas (114 images each) were assessed by endoscopists with (development group: 33) and without (validation group: 28) specific training in magnifying endoscopy with NBI. Microvascular and microsurface patterns (MS) in each image were evaluated. Lesions were diagnosed as cancerous when patterns were deemed "irregular." The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of a diagnosis according to patterns on EC with NBI (microvascular pattern [MV] alone, MS alone, and both) were evaluated and compared between groups to determine the diagnostic performance., Results: In the development and validation groups, diagnoses based on the MV alone had significantly higher accuracy (91.7% vs. 76.3%, p < 0.0001 and 92.5% vs. 67.5%, p < 0.0001, respectively) and sensitivity (88.6% vs. 68.3%, p < 0.0001 and 89.5% vs. 38.6%, p < 0.0001, respectively) than those based on the MS alone. In both groups, there were no significant differences in diagnostic accuracy between using the MV alone and both patterns., Discussion/conclusion: Evaluation of the MV alone is a simple and accurate diagnostic method for gastric cancer. This system could find widespread applications in clinical practice., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

Background and Aims: Endoscopic submucosal dissection (ESD) has become an important and minimally invasive treatment for early gastric cancer (EGC) with a negligible risk of metastasis not only for differentiated-type (D-type) cancer but also for undifferentiated-type (UD-type) cancer. We aimed to investigate the incidence and characteristics of metachronous cancer after ESD for UD-type cancer, which has not yet been elucidated., Methods: In total, 175 patients who underwent ESD for UD-type EGC were enrolled. For comparison, 350 patients who underwent ESD for D-type EGC during the same period were randomly selected. These patients underwent a follow-up EGD annually. The median observation period was 6.0 years and 5.4 years, respectively., Results: The annual incidence of metachronous cancer after ESD for UD-type and D-type cancer was .9% and 5.3%, respectively. Among the patients who underwent ESD for UD-type cancer, 30.9% of patients were uninfected with Helicobacter pylori, whereas all patients who underwent ESD for D-type cancer were infected with H pylori. All patients who developed metachronous cancer were infected with H pylori. UD-type metachronous cancer developed more frequently in patients after ESD for UD-type cancer than after ESD for D-type cancer, and the curative resection rate of ESD was significantly lower in these cases., Conclusions: Metachronous cancers developed only in H pylori-infected patients in this cohort. Although metachronous cancer incidence was significantly less frequent in patients after ESD for UD-type cancer, the curative resection rate of ESD was significantly lower. Routine surveillance should be conducted more carefully after ESD for UD-type cancer, especially in H pylori-infected patients., (Copyright © 2021 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Gastrectomy with lymphadenectomy is recommended for type 3 gastric neuroendocrine tumors (G-NETs). This study aimed to identify the risk factors for lymph node metastasis (LNM) arising from G-NETs to assess the suitability of endoscopic resection (ER)., Methods: Nationwide clinicopathological data of patients with type 3 G-NETs who underwent surgery or ER were collected. A single pathologist graded the histological tumor specimens., Results: Among 176 cases from 53 institutions, 144 were eligible for analysis (90 NET-G1 and 54 NET-G2 grade, 8-mm median-size tumors). Of these, 63 patients had undergone ER (15 with additional surgeries). Histological data regarding LNM were available for 93 surgical patients. LNM was confirmed in 15 (16%) tumors and was correlated with tumor diameter, invasion depth, and tumor grade. LNM was negative in six tumors ≤5 mm, confined to the mucosa or submucosa, with a grade of G1, and without lymphovascular invasion, but the number of cases was too small to propose ER indications. Among 48 patients treated with ER alone, only one developed recurrence; no mortality was observed at follow-up, although many patients were classified with SM2/NET-G2/tumors >5 mm. This suggests that not all LNMs arising from small G-NETs are fatal., Conclusion: Gastrectomy with lymphadenectomy for type 3 G-NETs is recommended on the basis of LNM. However, ER for type 3 G-NETs ≤10 mm, confined to the mucosa or submucosa, with a grade of G1 has shown excellent survival outcomes despite the risk of LNM, and therefore, could be an alternative treatment option., (© 2020 Japan Gastroenterological Endoscopy Society.)

Background: For diagnosing gastric cancer, differences in the diagnostic performance between endocytoscopy with narrow-band imaging and magnifying endoscopy with narrow-band imaging have not been reported. We aimed to clarify these differences by analyzing diagnoses made by endoscopists in Japan., Methods: This single-center retrospective cohort study used 106 cancerous and 106 non-cancerous images obtained via both modalities (total, 424 images) for diagnosis. Sixty-one endoscopists with varying experience levels from 45 institutions were included. Diagnostic accuracy, sensitivity, specificity, and positive and negative predictive values were evaluated to determine the diagnostic performance of each modality and compared using the Mann-Whitney U test., Results: Among all endoscopists, diagnostic accuracy, sensitivity, positive predictive value, and negative predictive value were higher with endocytoscopy with narrow-band imaging than with magnifying endoscopy with narrow-band imaging (percentage [95% confidence interval]: 78.8% [76.4-83.0%] versus 72.2% [69.3-73.6%], p < 0.0001; 82.1% [78.3-85.9%] versus 64.2% [60.4-69.8%], p < 0.0001; 88.7% [82.6-90.7%] versus 78.5% [75.4-85.1%], p = 0.0023; 79.0% [75.3-80.5%] versus 68.5% [66.4-71.6%], p < 0.0001, respectively). In the magnifying endoscopy with narrow-band imaging-trained group, these values were also higher with endocytoscopy with narrow-band imaging than with magnifying endoscopy with narrow-band imaging (p < 0.0001, p = 0.0001, p = 0.0143, and p < 0.0001, respectively). Diagnostic accuracy, sensitivity, and negative predictive value were higher with endocytoscopy with narrow-band imaging than with magnifying endoscopy with narrow-band imaging in the magnifying endoscopy with narrow-band imaging-untrained group (p = 0.0041, p = 0.0049, and p = 0.0098, respectively)., Conclusions: Diagnostic performance was higher using endocytoscopy with narrow-band imaging than using magnifying endoscopy with narrow-band imaging. Our results may help change the technique used to diagnose gastric cancer.

Introduction: Curative rates of endoscopic treatment for undifferentiated-type early gastric cancer (EGC), particularly mixed poorly differentiated adenocarcinoma (MIXED-POR), are lower than those of endoscopic treatment for the differentiated type. Magnifying endoscopy with narrow-band imaging (ME-NBI) is useful for diagnoses of the histological type. This study aimed to investigate the detection rates of MIXED-POR among undifferentiated-type EGCs using biopsy and ME-NBI in order to improve curative rates through endoscopic treatment., Methods: We analyzed 267 lesions initially subjected to endoscopic submucosal resection (ESD) and histologically diagnosed as undifferentiated-type EGCs between July 2005 and December 2016 at our hospital. We obtained written informed consent from all participants. Biopsy and ME-NBI findings were compared to distinguish pure signet ring cell carcinoma (PURE-SIG) and MIXED-POR. ME-NBI findings were divided into 2 categories depending on the presence of irregular vessels. Results of biopsy and ME-NBI (combination method) were also analyzed, and detection rates of MIXED-POR and PURE-SIG were evaluated in terms of sensitivity, specificity, and accuracy., Results: Overall, 114 lesions were analyzed. Fifty-eight lesions (50.9%) were identified as MIXED-POR. With biopsy, the detection rate of MIXED-POR was significantly lower than that of PURE-SIG (p < 0.0001). ME-NBI detected significantly more MIXED-POR with irregular vessels than PURE-SIG (p < 0.0001). The combination method could detect significantly more MIXED-POR than PURE-SIG (p < 0.0001). The sensitivity and accuracy for MIXED-POR diagnosis were significantly higher with the combination method than with biopsy alone (p < 0.0001)., Discussion/conclusion: Combining biopsy and ME-NBI improved the accuracy of pretreatment diagnosis before ESD in undifferentiated-type cancer., (© 2021 S. Karger AG, Basel.)

Objectives: Detecting early gastric cancer is difficult, and it may even be overlooked by experienced endoscopists. Recently, artificial intelligence based on deep learning through convolutional neural networks (CNNs) has enabled significant advancements in the field of gastroenterology. However, it remains unclear whether a CNN can outperform endoscopists. In this study, we evaluated whether the performance of a CNN in detecting early gastric cancer is better than that of endoscopists., Methods: The CNN was constructed using 13,584 endoscopic images from 2639 lesions of gastric cancer. Subsequently, its diagnostic ability was compared to that of 67 endoscopists using an independent test dataset (2940 images from 140 cases)., Results: The average diagnostic time for analyzing 2940 test endoscopic images by the CNN and endoscopists were 45.5 ± 1.8 s and 173.0 ± 66.0 min, respectively. The sensitivity, specificity, and positive and negative predictive values for the CNN were 58.4%, 87.3%, 26.0%, and 96.5%, respectively. These values for the 67 endoscopists were 31.9%, 97.2%, 46.2%, and 94.9%, respectively. The CNN had a significantly higher sensitivity than the endoscopists (by 26.5%; 95% confidence interval, 14.9-32.5%)., Conclusion: The CNN detected more early gastric cancer cases in a shorter time than the endoscopists. The CNN needs further training to achieve higher diagnostic accuracy. However, a diagnostic support tool for gastric cancer using a CNN will be realized in the near future., (© 2020 The Authors. Digestive Endoscopy published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Image recognition using artificial intelligence (AI) has progressed significantly due to innovative technologies such as machine learning and deep learning. In the field of gastric cancer (GC) management, research on AI-based diagnosis such as anatomical classification of endoscopic images, diagnosis of Helicobacter pylori infection, and detection and qualitative diagnosis of GC is being conducted, and an accuracy equivalent to that of physicians has been reported. It is expected that AI will soon be introduced in the field of endoscopic diagnosis and management of gastric cancer as a supportive tool for physicians, thus improving the quality of medical care., (© 2020 Japan Gastroenterological Endoscopy Society.)

Background: We previously reported for the first time the usefulness of artificial intelligence (AI) systems in detecting gastric cancers. However, the "original convolutional neural network (O-CNN)" employed in the previous study had a relatively low positive predictive value (PPV). Therefore, we aimed to develop an advanced AI-based diagnostic system and evaluate its applicability for the classification of gastric cancers and gastric ulcers., Methods: We constructed an "advanced CNN" (A-CNN) by adding a new training dataset (4453 gastric ulcer images from 1172 lesions) to the O-CNN, which had been trained using 13 584 gastric cancer and 373 gastric ulcer images. The diagnostic performance of the A-CNN in terms of classifying gastric cancers and ulcers was retrospectively evaluated using an independent validation dataset (739 images from 100 early gastric cancers and 720 images from 120 gastric ulcers) and compared with that of the O-CNN by estimating the overall classification accuracy., Results: The sensitivity, specificity, and PPV of the A-CNN in classifying gastric cancer at the lesion level were 99.0 % (95 % confidence interval [CI] 94.6 %-100 %), 93.3 % (95 %CI 87.3 %-97.1 %), and 92.5 % (95 %CI 85.8 %-96.7 %), respectively, and for classifying gastric ulcers were 93.3 % (95 %CI 87.3 %-97.1 %), 99.0 % (95 %CI 94.6 %-100 %), and 99.1 % (95 %CI 95.2 %-100 %), respectively. At the lesion level, the overall accuracies of the O- and A-CNN for classifying gastric cancers and gastric ulcers were 45.9 % (gastric cancers 100 %, gastric ulcers 0.8 %) and 95.9 % (gastric cancers 99.0 %, gastric ulcers 93.3 %), respectively., Conclusion: The newly developed AI-based diagnostic system can effectively classify gastric cancers and gastric ulcers., Competing Interests: Tomohiro Tada is a shareholder of AI Medical Service Inc. The other authors have no conflict of interest to disclose.., (Thieme. All rights reserved.)

Background and Aims: The performance of magnifying endoscopy with narrow-band imaging (ME-NBI) using a computer-aided diagnosis (CAD) system in diagnosing early gastric cancer (EGC) is unclear. Here, we aimed to clarify the differences in the diagnostic performance between expert endoscopists and the CAD system using ME-NBI., Methods: The CAD system was pretrained using 1492 cancerous and 1078 noncancerous images obtained using ME-NBI. One hundred seventy-four videos (87 cancerous and 87 noncancerous videos) were used to evaluate the diagnostic performance of the CAD system using the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). For each item, comparisons were made between the CAD system and 11 experts who were skilled in diagnosing EGC using ME-NBI with clinical experience of more than 1 year at our hospital., Results: The CAD system demonstrated an AUC of 0.8684. The accuracy, sensitivity, specificity, PPV, and NPV were 85.1% (95% confidence interval [95% CI], 79.0-89.6), 87.4% (95% CI, 78.8-92.8), 82.8% (95% CI, 73.5-89.3), 83.5% (95% CI, 74.6-89.7), and 86.7% (95% CI, 77.8-92.4), respectively. The CAD system was significantly more accurate than 2 experts, significantly less accurate than 1 expert, and not significantly different from the remaining 8 experts., Conclusions: The overall performance of the CAD system using ME-NBI videos in diagnosing EGC was considered good and was equivalent to or better than that of several experts. The CAD system may prove useful in the diagnosis of EGC in clinical practice., (Copyright © 2020 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

The Japan Gastroenterological Endoscopy Society developed the Guideline for Endoscopic Diagnosis of Early Gastric Cancer based on scientific methods. Endoscopy for the diagnosis of early gastric cancer has been acknowledged as a useful and highly precise examination, and its use has become increasingly more common in recent years. However, the level of evidence in this field is low, and it is often necessary to determine recommendations based on expert consensus only. This clinical practice guideline consists of the following sections to provide the current guideline: [I] Risk stratification of gastric cancer before endoscopic examination, [II] Detection of early gastric cancer, [III] Qualitative diagnosis of early gastric cancer, [IV] Diagnosis to choose the therapeutic strategy for gastric cancer, [V] Risk stratification after endoscopic examination, and [VI] Surveillance of early gastric cancer., (© 2020 Japan Gastroenterological Endoscopy Society.)

Background: Early detection of early gastric cancer (EGC) allows for less invasive cancer treatment. However, differentiating EGC from gastritis remains challenging. Although magnifying endoscopy with narrow band imaging (ME-NBI) is useful for differentiating EGC from gastritis, this skill takes substantial effort. Since the development of the ability to convolve the image while maintaining the characteristics of the input image (convolution neural network: CNN), allowing the classification of the input image (CNN system), the image recognition ability of CNN has dramatically improved., Aims: To explore the diagnostic ability of the CNN system with ME-NBI for differentiating between EGC and gastritis., Methods: A 22-layer CNN system was pre-trained using 1492 EGC and 1078 gastritis images from ME-NBI. A separate test data set (151 EGC and 107 gastritis images based on ME-NBI) was used to evaluate the diagnostic ability [accuracy, sensitivity, positive predictive value (PPV), and negative predictive value (NPV)] of the CNN system., Results: The accuracy of the CNN system with ME-NBI images was 85.3%, with 220 of the 258 images being correctly diagnosed. The method's sensitivity, specificity, PPV, and NPV were 95.4%, 71.0%, 82.3%, and 91.7%, respectively. Seven of the 151 EGC images were recognized as gastritis, whereas 31 of the 107 gastritis images were recognized as EGC. The overall test speed was 51.83 images/s (0.02 s/image)., Conclusions: The CNN system with ME-NBI can differentiate between EGC and gastritis in a short time with high sensitivity and NPV. Thus, the CNN system may complement current clinical practice of diagnosis with ME-NBI.

Background and Aim: Gastric neoplasms (GN), including gastric adenoma and carcinoma, are well known as extracolonic manifestations of familial adenomatous polyposis (FAP). We aimed to investigate the clinicopathological features of GN in FAP patients and to clarify their relationship with the endoscopic status of the background mucosa., Methods: We analyzed the records of 39 patients who were diagnosed with FAP and underwent esophagogastroduodenoscopy between April 2005 and July 2016. Patients were divided into two groups according to atrophic gastritis (AG) status. Endoscopic findings of GN and background mucosa, and histopathological findings, including phenotypic expression of GN and mutation locus of adenomatous polyposis coli (APC) gene, were evaluated., Results: Gastric neoplasms were more predominant in the AG-positive group than in the AG-negative group (6/9, 66.7% vs 7/30, 23.3%; P = 0.039). Of 36 GN detected in 13 patients, six GN in five patients were followed and 30 GN in eight patients were endoscopically resected and analyzed. GN in the AG-negative group frequently showed whitish color, were located in the proximal stomach, and presented the gastric immunophenotype compared to GN in the AG-positive group. All GN were intramucosal lesions and were curatively resected regardless of AG status. APC germline mutations were identified in 32 patients. In patients with GN, a significantly higher number of mutation loci were among exons 10-15 (codons 564-1465)., Conclusion: Clinicopathological characteristics and phenotypic expressions of GN in FAP patients depend on background mucosa status with or without AG. These findings are useful for detecting GN in FAP patients., (© 2019 Japan Gastroenterological Endoscopy Society.)

We aimed to clarify the differences in therapeutic outcomes of patients with pure undifferentiated-type and mixed undifferentiated-type cancers who underwent endoscopic submucosal dissection (ESD), and whether pre-treatment diagnosis of mixed undifferentiated-type cancer is associated with requiring additional surgery after ESD. Patients subjected to ESD as initial treatment between May 2005 and March 2017 were enrolled. There were 277 undifferentiated-type cancers (265 patients). Histologically, 258 lesions were pure-type and 19 were mixed-type. We compared therapeutic outcomes and pre-treatment factors (tumour diameter, tumour depth, ulcerative findings, tumour location, and the macroscopic, and histological type of the biopsy specimen) between pure-type and mixed-type lesions, and between cases not requiring additional surgeries and cases requiring additional surgeries. Tumour diameter >20 mm, submucosal invasion, and the presence of ulcerative findings made pre-treatment diagnosis more difficult for mixed-type than for pure-type lesions. In cases requiring additional surgery, pre-treatment diagnosis of mixed-type lesions was significantly more likely than pre-treatment diagnosis of pure-type lesions. For mixed-type lesions, pre-treatment histological diagnosis and careful consideration are necessary to determine indications for ESD to avoid additional surgery after ESD.

Background: Based on Japanese guidelines for endoscopic submucosal dissection (ESD) in undifferentiated-type early gastric cancer (UD-EGC), UD-predominant mixed-type (M-UD) EGC is considered high risk for lymph node metastasis (LNM). However, differences in LNM risk between pure UD (P-UD) and M-UD remain unclear. This study assessed risk factors for LNM considering differences between P-UD and M-UD and identified pathological features related to the lowest LNM risk., Methods: This single-center, retrospective study included 1425 patients with UD-EGC treated with surgical resection between April 2005 and May 2017. We divided patients into those with and without LNM and compared background characteristics and post-operative pathological results between groups. Patients were further stratified based on depth, tumor diameter, ulcerative findings, lymphatic invasion, vascular invasion, and histological type to clarify post-operative pathological features associated with the lowest LNM risk., Results: When comparing background characteristics and post-operative pathological results, multivariate analysis showed that, in patients with LNM, tumor diameters were significantly larger, and there were higher rates of submucosal invasion, lymphatic invasion, and M-UD histological type. In patients with absence of ulcerative findings, absence of lymphatic invasion, and absence of vascular invasion, no LNM occurred among those with intramucosal P-UD tumor diameters of 1-40 mm (1-20 mm: 95% confidence interval [CI], 0-5.5%; 21-40 mm: 95% CI, 0-6.1%)., Conclusions: Intramucosal P-UD EGC patients with absence of ulcerative findings, absence of lymphatic invasion, absence of vascular invasion, and tumor diameters of ≤ 40 mm did not show LNM. We suggest expanding indications for ESD to include these patients.

Background: Pretreatment biopsy may not correctly diagnose mixed-type early gastric cancers. Despite reports on the usefulness of magnifying endoscopy with narrow-band imaging in diagnosing early gastric cancers, no reports exist on differences in magnifying endoscopy with narrow-band imaging findings between differentiated-type-predominant mixed-type and undifferentiated-type-predominant mixed-type early gastric cancers., Aim: This study aimed to clarify differences in magnifying endoscopy with narrow-band imaging findings and investigate the additive effect of combining magnifying endoscopy with narrow-band imaging and biopsy findings for pretreatment histological-type diagnosis., Methods: Patients undergoing endoscopic submucosal dissection as initial treatment between April 2005 and March 2017 participated in this retrospective study. There were 156 differentiated-type-predominant mixed-type and 36 undifferentiated-type-predominant mixed-type lesions. We extracted the most significant magnifying endoscopy with narrow-band imaging findings of differentiated-type-predominant mixed-type and undifferentiated-type-predominant mixed-type lesions using multivariate analysis and compared the accuracy, sensitivity, and specificity between pretreatment biopsy alone and a combination of biopsy and magnifying endoscopy with narrow-band imaging findings., Results: Significant magnifying endoscopy with narrow-band imaging findings was fine network pattern in differentiated-type-predominant and corkscrew pattern in undifferentiated-type-predominant mixed-type lesions. Accuracy, sensitivity, and specificity were significantly higher with combined biopsy and magnifying endoscopy with narrow-band imaging findings than with pretreatment biopsy alone., Conclusions: The study results demonstrated the additive effect of magnifying endoscopy with narrow-band imaging with biopsy for diagnosing mixed-type early gastric cancers. This study may be beneficial in routine practice because it indicates a possibility of reducing additional surgery after endoscopic submucosal resection because of incorrect diagnosis of histological type.

This study aimed to clarify the pretreatment factors associated with overtreatment with surgery in patients with differentiated-type early gastric cancer. This single-centre, retrospective study included 781 patients with differentiated-type early gastric cancer treated by surgical resection between April 2005 and May 2017. Postoperative pathological results were used to divide patients into the accurate surgical indication group and overtreatment with surgery group; the groups were compared with respect to accurate diagnosis and misdiagnosis based on tumour diameter (≤30 mm or >30 mm), diagnosis of depth, diagnosis of ulcerative findings, and diagnosis of main histology. There were 224 patients in the overtreatment with surgery group. Multivariate analysis revealed significant differences in misdiagnosis of tumour diameter, misdiagnosis of depth, misdiagnosis of ulcerative findings, and misdiagnosis of main histology between the accurate surgical indication group and overtreatment with surgery group. Significant factors for pretreatment misdiagnosis leading to overtreatment in differentiated-type early gastric cancer were tumour diameter, depth, and main histology. It may be acceptable to perform endoscopic resection for patients with pretreatment tumour diameter ≤30 mm, mucosal invasion of pretreatment depth, and undifferentiated-type cancers containing differentiated-type components of pretreatment histology because this reduces overtreatment with surgery.

Background: Epstein-Barr virus-positive gastric cancer (EBVGC) is associated with a low prevalence of lymph node metastasis (LNM); however, EBV status is not considered in the indication of endoscopic resection (ER). We aimed to clarify the implication of EBV status for ER of pT1b GC., Methods: Consecutive cases of pT1b GCs treated with surgery between 2005 and 2014 were retrospectively analyzed. Clinicopathological factors and LNM status were compared between EBVGC and non-EBVGC groups., Results: EBVGC accounted for 7.9% (71 of 898) cases. Compared to non-EBVGC, EBVGC was more frequent in males (p = 0.0055), the upper third region (p < 0.0001), showed elevated growth features (p = 0.0059), and was associated with a lower frequency of accompanying ulceration (p = 0.002), greater depth of submucosal invasion (p = 0.017), and lower frequency of lymphatic invasion (p < 0.0001). Frequency of LNM was significantly lower in EBVGC than in non-EBVGC (4.2% vs. 21.9%, p < 0.0001). In EBVGC, tumors without lymphovascular invasion showed significantly lower frequency of LNM than those with lymphovascular invasion (0 of 50, 0%; vs 3 of 21, 14.3%; p = 0.023). Histologically, 84.5% (60 of 71) of EBVGC included carcinomas with lymphoid stroma and/or lace pattern components., Conclusions: pT1b EBVGC is a convincing candidate for ER, regardless of risk factors other than lymphovascular invasion.

Background: The double-tracer method has been established for sentinel node (SN) mapping in gastric cancer surgery. However, there remain several unresolved issues that prevent its widespread use in clinical practice. In this study, we aimed to demonstrate the feasibility of single-tracer SN mapping in laparoscopic surgery for gastric cancer, using indocyanine green (ICG) fluorescence imaging with a one-step nucleic acid amplification (OSNA) assay intraoperatively., Methods: Patients with clinical T1N0M0 gastric adenocarcinoma preoperatively were considered for inclusion if they had a single primary lesion 4 cm or less in maximal diameter. Immunohistochemical staining with the anti-cytokeratin 19 antibody was performed on preoperative biopsy specimens, and patients with faint positive reactions were excluded. Intraoperatively, single-tracer SN biopsy with ICG fluorescence imaging was performed, followed by laparoscopic gastrectomy with modified D1+ or D2 lymph node dissection., Results: Twenty eligible patients underwent SN biopsy and laparoscopic gastrectomy. SNs were identified in 17 cases (85%), with a median number of three SNs per patient. The median times for SN mapping and OSNA assay were 19 and 35 min, respectively. OSNA assay detected one metastatic lymph node, but all other nodes were negative. No adverse effects were observed in relation to SN mapping., Conclusions: Single-tracer SN mapping by ICG fluorescence imaging with intraoperative diagnosis by OSNA assay is feasible and safe. SNs can be identified in most patients, without producing false-negative results. Further clinical trial to demonstrate the sensitivity is ongoing.

Background and Aims: The incidence of metachronous gastric cancer (MGC) in patients whose primary gastric neoplasm is discovered after Helicobacter pylori eradication remains unclear. Here, we evaluated the long-term effect of previous H pylori eradication on development of MGC after endoscopic submucosal dissection (ESD)., Methods: We analyzed prospectively collected data of consecutive patients with successful H pylori eradication more than 1 year before (eradicated group, 180 patients) or after (control group, 602 patients) initial curative ESD. These patients were also followed by endoscopy for over 2 years. Propensity score matching and inverse probability of treatment weighting (IPTW) were used to adjust for confounding variables during data analysis. The main outcome was the incidence of MGC after initial ESD., Results: In a propensity-matched analysis of 174 pairs, the incidence of MGC was similar in the 2 cohorts (33.9 per 1000 person-years vs 40.8 per 1000 person-years in the control group, P = .454) at a median follow-up of 4.1 years (interquartile range, 3.0-5.6). Incidences were also similar in the 2 groups when data were analyzed using IPTW, even after exclusion of 123 patients with successful H pylori eradication <5 years before initial ESD. Multiple Cox regression analysis revealed age, differentiated-type histology, and initial multiplicity were predictors of MGC in patients after initial curative ESD., Conclusions: The frequency of follow-up surveillance after initial curative ESD should be kept constant, irrespective of whether H pylori eradication is performed before or after initial curative ESD., (Copyright © 2019. Published by Elsevier Inc.)

Background: Gastric tube cancers (GTCs) are found frequently, even as the surgical outcomes of esophageal cancer improve. Diagnosing and treating early gastric tube cancer endoscopically has therefore become very important., Aims: This study aimed to evaluate the clinical characteristics and outcomes of endoscopic resection for GTC., Methods: We analyzed 29 patients (33 lesions) with metachronous GTC who underwent endoscopic resection from April 2005 to August 2016 and evaluated their clinical characteristics and the short-term outcomes of endoscopic resection., Results: All of the cases were identified by periodic examinations. The lesions were found a median of 6.5 years after surgery (range 9 months-19 years), with six lesions found more than 10 years later. Among the total of 33 lesions, 28 resulted in curative resections (85%), and five were non-curative resections because of lymphovascular invasion, submucosal deep invasion, histological type, and size. None had received additional treatment or had a local recurrence thus far. Regarding the complications, delayed perforation occurred in a case (3%) and precordial skin burn occurred in four cases (12%)., Conclusion: The safety and efficacy of endoscopic resection for gastric tube cancer were evaluated. Additionally, it is important to continue annual endoscopy even 5 years or more after esophageal surgery.

Objectives: A Japanese multicenter prospective cohort study examining endoscopic resection (ER) for early gastric cancer (EGC) has been conducted using a Web registry developed to determine the short-term and long-term outcomes based on absolute and expanded indications. We hereby present the short-term outcomes of this study., Methods: All consecutive patients with EGC or suspected EGC undergoing ER at 41 participating institutions between July 2010 and June 2012 were enrolled and prospectively registered into the Web registry. The baseline characteristics were entered before ER, and the short-term outcomes were collected at 6 months following ER., Results: Nine thousand six hundred and sixteen patients with 10 821 lesions underwent ER (endoscopic submucosal dissection [ESD]: 99.4%). The median procedure time was 76 min, and R0 resections were achieved for 91.6% of the lesions. Postoperative bleeding and intraoperative perforation occurred in 4.4% and 2.3% of the patients, respectively. Significant independent factors correlated with a longer procedure time (120 min or longer) were as follows: tumor size >20 mm, upper-third location, middle-third location, local recurrent lesion, ulcer findings, gastric tube, male gender, and submucosa. Histopathologically, 10 031 lesions were identified as common-type gastric cancers. The median tumor size was 15 mm. Noncurative resections were diagnosed for 18.3% of the lesions. Additional surgery was performed for 48.6% (824 lesions) of the 1695 noncurative ER lesions with a possible risk of lymph node (LN) metastasis. Among them, 64 (7.8%) exhibited LN metastasis., Conclusions: This multicenter prospective study showed favorable short-term outcomes for gastric ESD., (© 2018 Japan Gastroenterological Endoscopy Society.)

Background: It is unknown how the accuracy rate of diagnostic demarcation of undifferentiated-type early gastric cancers (UD-type EGCs) differs between patients uninfected with Helicobacter pylori (H. pylori) and patients with and without H. pylori eradication. This study assessed and compared the diagnostic accuracy rate in the H. pylori-uninfected group and the non-H. pylori eradication and H. pylori eradication groups., Methods: Subjects were 81 patients with 81 lesions who underwent endoscopic submucosal dissection between January 2010 and January 2015. There were 21 lesions in the H. pylori-uninfected group, 27 in the H. pylori eradication group, and 33 in the non-H. pylori eradication group. The rate in the H. pylori-uninfected group was separately compared with the rates in the non-H. pylori eradication and H. pylori eradication groups, as was inflammatory cell infiltration., Results: The diagnostic accuracy rates were 60.6% in the non-H. pylori eradication group, 92.2% in the H. pylori eradication group, and 100% in the H. pylori-uninfected group; the rate was significantly higher in the H. pylori-uninfected group than in the non-H. pylori eradication group, but no significant difference was observed between the H. pylori-uninfected group and the H. pylori eradication group. In addition, the H. pylori-uninfected and H. pylori eradication groups showed no significant differences in neutrophil infiltration and intestinal metaplasia, whereas the state in the H. pylori-uninfected group was significantly milder., Conclusions: Because neutrophil infiltration was classified as mild or none, the accuracy of diagnostic demarcation was high in the H. pylori-uninfected and H. pylori eradication groups.

Background and Aim: Previous studies of surgical specimens have found that the presence of mixed histological components in differentiated-type early gastric cancer (EGC) is a risk factor for lymph node metastasis and indicates greater malignancy. As there have been no reports on its endoscopic treatment, we examined endoscopic curative resection in relation to differentiated-type-predominant mixed-type (MT)., Methods: This was a single-center, retrospective study. Subjects were 2585 differentiated-type EGC in 2551 patients treated with endoscopic submucosal dissection (ESD) in our hospital between March 2005 and January 2016. These lesions comprised 2231 cases of curative resection and 354 cases of non-curative resection. Histologically, 2339 lesions were pure differentiated-type (PDT) and 246 lesions were MT. Rates of curative resection were compared, according to tumor size, between different histological types., Results: When curative and non-curative cases were compared using multivariate analysis among lesions measuring ≤20 mm for factors other than those determining curative resection, significant differences were obtained for tumor diameter, ulcer, and MT. Among lesions measuring 21-30 mm, ulcer and MT were associated with significant differences. Among lesions measuring >30 mm, upper region and MT were associated with significant differences. Curative resection rates, in relation to histological type among lesions measuring ≤20 mm, were 93.4% for PDT and 63.4% for MT, whereas corresponding rates were 85.1% and 60.0%, respectively, among lesions measuring 21-30 mm, and 55.3% and 30.2%, respectively, among lesions measuring >30 mm., Conclusion: We found that MT was a risk factor for non-curative resection irrespective of lesion size., (© 2018 Japan Gastroenterological Endoscopy Society.)

Background: Image recognition using artificial intelligence with deep learning through convolutional neural networks (CNNs) has dramatically improved and been increasingly applied to medical fields for diagnostic imaging. We developed a CNN that can automatically detect gastric cancer in endoscopic images., Methods: A CNN-based diagnostic system was constructed based on Single Shot MultiBox Detector architecture and trained using 13,584 endoscopic images of gastric cancer. To evaluate the diagnostic accuracy, an independent test set of 2296 stomach images collected from 69 consecutive patients with 77 gastric cancer lesions was applied to the constructed CNN., Results: The CNN required 47 s to analyze 2296 test images. The CNN correctly diagnosed 71 of 77 gastric cancer lesions with an overall sensitivity of 92.2%, and 161 non-cancerous lesions were detected as gastric cancer, resulting in a positive predictive value of 30.6%. Seventy of the 71 lesions (98.6%) with a diameter of 6 mm or more as well as all invasive cancers were correctly detected. All missed lesions were superficially depressed and differentiated-type intramucosal cancers that were difficult to distinguish from gastritis even for experienced endoscopists. Nearly half of the false-positive lesions were gastritis with changes in color tone or an irregular mucosal surface., Conclusion: The constructed CNN system for detecting gastric cancer could process numerous stored endoscopic images in a very short time with a clinically relevant diagnostic ability. It may be well applicable to daily clinical practice to reduce the burden of endoscopists.

Background: Comparisons between surgical cases of mixed poorly differentiated adenocarcinoma and pure signet ring cell carcinoma have revealed higher frequencies of lymph node metastasis and submucosal invasion in the former. However, this comparison has not been reported for endoscopically treated cases. Therefore, we compared cases of curative and noncurative resection in patients who underwent endoscopic submucosal dissection to determine what factors could influence the curative resection rate., Methods: We analyzed 268 undifferentiated-type early gastric cancers in 264 patients treated with endoscopic submucosal dissection in our hospital between March 2005 and March 2017, involving 229 and 39 cases of curative and noncurative resection, respectively. Treatment results were compared between 129 lesions of pure signet ring cell carcinoma and 139 lesions of mixed poorly differentiated adenocarcinoma., Results: The overall curative resection rate was 85.4% (229/268). On comparing noncurative and curative resection cases, after excluding factors that determine curative resection (e.g., tumor diameter), we found that the former was associated with older age and significantly more mixed poorly differentiated adenocarcinomas, with odds ratios of 1.052 [95% confidence interval (CI), 1.017-1.089] and 2.746 (95% CI, 1.162-6.485), respectively, on multivariate analysis. The curative resection rate was significantly higher in pure signet ring cell carcinoma than in mixed poorly differentiated adenocarcinoma (93.8% vs. 77.7%, respectively)., Conclusion: Advanced age and mixed poorly differentiated adenocarcinoma predicted endoscopic noncurative resection.

Background and Aims: Endoscopic submucosal dissection (ESD) is a well-established minimally invasive treatment for early gastric cancer. To heal ESD-induced ulcers, we commonly prescribe proton pump inhibitors (PPIs). Vonoprazan is our new choice, which is reported to have a stronger and longer acid inhibitory effect than existing PPIs. Here, we aimed to evaluate the efficacy of vonoprazan for healing ESD-induced ulcers compared with rabeprazole., Methods: We reviewed 190 patients who underwent ESD before and after we switched the acid secretion inhibitor from rabeprazole to vonoprazan. We evaluated scarring and reduction rates at 4 weeks after ESD., Results: Scarring rates were not different between vonoprazan and rabeprazole (31.7 vs. 18.9%; p = 0.07). However, for ulcers ≤35 mm, vonoprazan was superior to rabeprazole (42.2 vs. 19.2%; p < 0.05). Reduction rates were superior for vonoprazan compared with rabeprazole (93.0 vs. 90.4%; p < 0.05). In multivariate analysis, vonoprazan was superior to rabeprazole for ulcer scarring (OR 2.21; p < 0.05), and ulcer location in the lower-third of the stomach had higher risk of incomplete scarring (OR 0.37; p < 0.05)., Conclusion: Vonoprazan was superior to rabeprazole for healing ESD-induced ulcers., (© 2018 S. Karger AG, Basel.)

Background and Aim: In Japan, an increase in the number of routine esophagogastroduodenoscopy procedures is expected because several studies have reported that endoscopy screening has reduced gastric cancer mortality. Magnifying narrow-band imaging has been reported to be effective for accurate diagnosis of gastric abnormalities such as cancers, adenomas, and intestinal metaplasia. However, the efficacy of this method in routine esophagogastroduodenoscopy has not been clarified., Methods: We divided 3763 patients into two groups. The non-magnification group included 1842 patients who underwent endoscopy screening using GIF-H260/LUCERA-SPECTRUM between October 2014 and February 2015, whereas the magnification group included 1921 patients who underwent screening using GIF-H290Z/LUCERA-ELITE between March 2015 and May 2015. In the magnification group, diagnosis of cancer was conducted using the VS classification system. We did not carry out a biopsy when results were confirmed as non-cancer using magnifying narrow-band imaging. If cancer was diagnosed, or when a cancer or non-cancer diagnosis was difficult, we carried out a biopsy. We analyzed and compared the diagnostic performance between the two groups., Results: Gastric biopsy rate was significantly lower in the magnification group (29%) than in the non-magnification group (41%) (P < 0.001). Positive predictive value (PPV) for gastric cancer was significantly higher in the magnification group (5.5%) than in the non-magnification group (2.5%) (P < 0.001). Furthermore, PPV for gastric epithelial neoplasia was significantly higher in the magnification group (7.9%) than in the non-magnification group (3.2%) (P < 0.001)., Conclusion: Magnifying narrow-band imaging improves the diagnostic performance of routine esophagogastroduodenoscopy., (© 2017 Japan Gastroenterological Endoscopy Society.)

Background: The factors associated with the pathogenesis of Helicobacter pylori-uninfected undifferentiated-type early gastric cancer (HPUGC) remain unclear. This study compared patient characteristics, including medical history and alcohol/tobacco use, of HPUGC patients with characteristics of patients with H. pylori-positive undifferentiated-type early gastric cancer (HPPGC) to clarify and gain understanding on those differences that could play a role in the pathogenesis., Methods: This retrospective study included 282 patients who were treated endoscopically from March 2005 to March 2014. This cohort consisted of 232 patients with HPPGC (82.3%) and 50 patients with HPUGC (17.7%). Patient characteristics were analyzed by subgroups of HPUGC vs. HPPGC, with comparisons for age, gender, cancer history, comorbidity of lifestyle diseases requiring medication (hypertension, type 2 diabetes, and dyslipidemia), cumulative amount of alcohol consumption, and smoking history (Brinkman index [BI])., Results: HPUGC patients were typically younger, had less frequent hypertension, and had higher BI values (p < 0.05 for all parameters). In a younger non-hypertensive subgroup, the OR for high BI (BI ≥340) in the HPUGC group vs. HPPGC group was 5.049 (95% CI 2.458-10.373, p < 0.0001)., Conclusions: The investigation of clinical factors identified smoking history as being possibly contributing to the pathogenesis of HPUGC. Future research is necessary at the cellular and genetic levels., (© 2017 S. Karger AG, Basel.)

Background: It is unknown whether Helicobacter pylori (H. pylori) eradication is beneficial when demarcating undifferentiated-type early gastric cancers (UD-type EGCs). This study aimed to determine whether H. pylori eradication is beneficial, and also when benefits become detectable., Methods: Sixty lesions that were detected as a ≤20-mm lesion without metastasis or ulceration on routine examination, diagnosed as UD-type EGC on biopsy, and treated with endoscopic submucosal dissection between January 2010 and January 2015 were studied. Magnifying endoscopy with narrow-band imaging (ME-NBI) was performed to demarcate the lesions. The most oral and most anal sites were marked. After endoscopic therapy, the markings were compared with the pathological examination results to calculate accurate diagnosis rates, which were compared between 27 patients with H. pylori eradication and 33 patients without. Mean intercrypt distance ratio and inflammatory cell infiltration were also compared, as were seven patients who underwent the procedure 1 month after H. pylori eradication and 20 patients who underwent the procedure more than 1 month after H. pylori eradication., Results: Accurate diagnosis rates were 92.2% with eradication and 60.6% without. Mean intercrypt distance ratios were 1.95 and 1.59, respectively. Neutrophil infiltration was mild in the eradication group. Significant differences were observed in each parameter (p < 0.05). No significant difference was observed between the 1-month eradication and >1-month eradication subgroups in terms of accurate diagnosis rate, mean intercrypt distance ratio, or histological grade of any item., Conclusions: This study suggests that H. pylori eradication therapy aids the accurate delineation of UD-type EGC in ME-NBI.

Objectives: Siewert type II esophagogastric junction adenocarcinoma encompasses both gastric cardia adenocarcinoma (GCA) and Barrett's esophageal adenocarcinoma (BEA) due to short-segment Barrett's esophagus. We compared these two types of Siewert type II esophagogastric junction adenocarcinoma in terms of background factors and clinical outcomes of endoscopic submucosal dissection (ESD)., Methods: We enrolled 139 patients (142 lesions) who underwent ESD from 2006 to 2014 at our institution. Background factors evaluated were age, sex, body mass index, hypertension, hyperlipidemia, hyperuricemia, diabetes mellitus, smoking, drinking, double cancer, and endoscopic findings. Clinical outcomes evaluated were procedure time, en bloc resection rate, curative resection rate, and adverse events., Results: There were 87 GCA lesions (61.2%) and 55 BEA lesions. Features of BEA [55 lesions (38.8%)] included a younger age, small diameter, and a protruding type, along with a high frequency of esophageal hiatal hernia and less mucosal atrophy. There were no significant differences in lifestyle-related background factors between the GCA and BEA groups. Curative resection rate was greater for GCA (81%) than for BEA (66%) (P = 0.01). There were no serious adverse events in either group. Among the factors for noncurative resection, lymphovascular invasion and depth of invasion were greater for BEA (33.3 vs. 7 and 20.7 vs. 8.2%, respectively (P < 0.01). Of the noncured patients, 70% underwent additional surgery and none had postoperative lymph node metastasis., Conclusions: Siewert type II adenocarcinoma encompasses two types of cancers with different etiologies: GCA and BEA. Although there are no significant differences in lifestyle-related background factors between GCA and BEA, BEA is a risk factor for noncurative resection via ESD.

Background and Aim: The usefulness of magnifying endoscopy with narrow-band imaging (ME-NBI) in undifferentiated-type early gastric cancers (UD-type EGCs) is unclear. This study investigated the accuracy of ME-NBI in the diagnostic demarcation., Methods: Among UD-type EGCs that were initially surgically resected between June 2011 and August 2014 in this hospital, 74 lesions were studied that were preoperatively diagnosed with white-light imaging (WLI) or endoscopic ultrasonography as lesions for which endoscopic treatment was not indicated and found to be early gastric cancers by postoperative pathology. The demarcation line was marked on the most oral and anal sides with argon plasma coagulation using WLI and ME-NBI, and the diagnostic demarcation of cancer was defined as correct, if consistent with the results of postoperative pathology. The length of extension into the proliferative zone, distance between crypts and inflammatory cell infiltration (updated Sydney classification: USC) were compared between the correctly diagnosed and the misdiagnosed cases., Results: The diagnosis was correct in 62 cases (83.8 %). The average distance between crypts in correctly diagnosed and misdiagnosed cases was approximately 1.9 and 1.3 times, respectively, that in normal mucosa (p < 0.0001). The accuracy of diagnosis was higher when atrophy and neutrophil and monocyte infiltration were mild according to the USC (p < 0.05). The additional use of ME-NBI improved the accuracy of diagnosis by 36.5 % compared with the use of WLI alone., Conclusion: The use of ME-NBI in the preoperative diagnosis of the demarcation of cancer is useful to prevent postoperative positive surgical margins.

Background and Aims: Laparoscopic gastric resection is widely used for gastric submucosal tumors (SMTs). However, determining an appropriate resection line using only the laparoscopic approach is difficult. We developed a laparoscopic and endoscopic cooperative surgery (LECS) technique by combining laparoscopic gastric resection with endoscopic submucosal dissection, and we have used this procedure to resect gastric SMTs. In this study, the procedure is presented and its safety and feasibility for resecting gastric SMTs are evaluated., Methods: This retrospective study included 100 patients who underwent LECS for SMTs at the Department of Gastroenterological Surgery, Cancer Institute, between June 2006 and November 2014. The demographics, tumor histopathologic characteristics, and operative and follow-up data were reviewed., Results: Complete resection with negative surgical margins was achieved in all patients, and LECS was performed regardless of tumor location. The mean operation time was 174.3 minutes, with an estimated blood loss of 16.3 mL. In addition, the mean time until the initiation of oral intake was 1.4 days, and the mean postoperative hospital stay was 8.4 days. Moreover, no local or distant tumor recurrence was observed. The only severe adverse event was leakage, which was observed in 1 patient., Conclusions: LECS was performed with a reasonable operation time, low blood loss, and minimal adverse events. Therefore LECS is safe and feasible for resecting gastric SMTs., (Copyright © 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background and Aim: The mortality rate of gastric cancer (GC) is close to the incidence rate worldwide. However, in Korea and Japan, the mortality rate of GC is less than half of the incidence rate. We hypothesized that good-quality routine esophagogastroduodenoscopy (EGD) contributes to a high detection rate for early GC (EGC) and improves mortality in these countries., Methods: To clarify the differences in routine EGD, a questionnaire survey was conducted in 98 Japanese and 53 international institutions., Results: Prevalence of screening examination among routine EGD was higher in Japanese than in international institutions. Japanese endoscopists noted that endoscopic mucosal atrophy was the most significant risk factor for GC, whereas international endoscopists paid more attention to clinical information such as age, symptoms and family history. Antispasmodics, mucolytics and defoaming agents were used more frequently in Japanese institutions. The examination time was similar (mostly 5-10 min) between Japanese and international institutions. Japanese endoscopists took more pictures (>20 in almost all institutions) than international endoscopists (≤20 in two-thirds of institutions). In Japanese institutions, biopsy specimens were more frequently taken from areas of mucosal discoloration, unevenness or spontaneous bleeding rather than from obvious endoscopic lesions such as ulceration or polyps. In most Japanese institutions, one or two biopsy specimens were taken per lesion, compared with ≥three in international institutions., Conclusion: There were some discrepancies between Japanese and international institutions for routine EGD. Thus, standardization is required for adequate risk assessment, proper techniques, and knowledge of endoscopic diagnosis of EGC., (© 2016 The Authors Digestive Endoscopy © 2016 Japan Gastroenterological Endoscopy Society.)