Japanese Classification of Esophageal Cancer, 12th Edition: Part I.

This is the first half of English edition of Japanese Classification of Esophageal Cancer, 12th Edition that was published by the Japan Esophageal Society in 2022.

Japanese Classification of Esophageal Cancer, 12th Edition: Part II.

This is the second half of English edition of Japanese Classification of Esophageal Cancer, 12th Edition that was published by the Japan Esophageal Society in 2022.

Treatment Decision for Locally Resected T1 Colorectal Carcinoma-Verification of the Japanese Guideline Criteria for Additional Surgery Based on Long-Term Clinical Outcomes.

INTRODUCTION: To verify the value of the pathological criteria for additional treatment in locally resected pT1 colorectal carcinoma (CRC) which have been used in the Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines since 2009. METHODS: We enrolled 4,719 patients with pT1 CRC treated at 27 institutions between July 2009 and December 2016 (1,259 patients with local resection alone [group A], 1,508 patients with additional surgery after local resection [group B], and 1,952 patients with surgery alone [group C]). All 5 factors of the JSCCR guidelines (submucosal resection margin, tumor histologic grade, submucosal invasion depth, lymphovascular invasion, and tumor budding) for lymph node metastasis (LNM) had been diagnosed prospectively. RESULTS: Any of the risk factors were present in 3,801 patients. The LNM incidence was 10.3% (95% confidence interval 9.3-11.4) in group B/C patients with risk factors, whereas it was 1.8% (95% confidence interval 0.4-5.2) in those without risk factors ( P < 0.01). In group A, the incidence of recurrence was 3.4% in patients with risk factors, but it was only 0.1% in patients without risk factors ( P < 0.01). The disease-free survival rate of group A patients classified as risk positive was significantly worse than those of groups B and C patients. However, the 5-year disease-free survival rate in group A patients with no risk was 99.2%. DISCUSSION: Our large-scale real-world multicenter study demonstrated the validity of the JSCCR criteria for pT1 CRC after local resection, especially regarding favorable outcomes in patients with low risk of LNM.

The impact of staple transection of the dorsal venous complex and urethra on intraoperative blood loss in cooperative laparoscopic and transperineal endoscopic pelvic exenteration.

PURPOSE: While laparoscopic pelvic exenteration reduces intraoperative blood loss, dorsal venous complex bleeding during this procedure causes issues. We previously introduced a method to transect the dorsal venous complex and urethra using a linear stapler during cooperative laparoscopic and transperineal endoscopic (two-team) pelvic exenteration. The present study assessed its effectiveness in reducing intraoperative blood loss by comparing it with conventional laparoscopic pelvic exenteration. METHODS: This retrospective cohort study was conducted at a Japanese tertiary referral center. Eleven cases of two-team laparoscopic pelvic exenteration with staple transection of the dorsal venous complex (T-PE group) were compared to 25 cases of conventional laparoscopic pelvic exenteration (C-PE group). The primary outcome measure was intraoperative blood loss. RESULTS: There were no significant between-group differences in patient background. The mean intraoperative blood loss was significantly lower in the T-PE group than in the C-PE group (200 vs. 850 mL, p = 0.01). The respective mean operation time, postoperative complication rate, and R0 resection rate were similar between the T-PE and C-PE groups (636 min vs. 688 min, p = 0.36; 36% vs. 44%, p = 0.65; 100% vs. 100%, p = 1.00). CONCLUSIONS: Two-team laparoscopic pelvic exenteration with staple transection of the dorsal venous complex reduced intraoperative blood loss from the dorsal venous complex in a technically safe and oncologically feasible manner.

Prediction of the invasion depth of superficial nonampullary duodenal adenocarcinoma.

OBJECTIVES: Distinguishing between intramucosal cancer and submucosal invasive cancer is vital for optimal treatment selection for patients with superficial nonampullary duodenal adenocarcinoma (SNADAC); however, standard diagnostic systems for diagnosing invasion depth are as yet undetermined. METHODS: Of 205 patients with SNADAC who underwent treatment at our institution between 2006 and 2022, 188 had intramucosal cancer and 17 had submucosal invasive cancer. The clinical, endoscopic, and pathological features used in the preoperative diagnosis of invasion depth and the diagnostic performance of endoscopic ultrasonography (EUS) were retrospectively analyzed in 85 patients. RESULTS: The oral side of the papilla tumor location, protruded or mixed macroscopic type, and moderately-to-poorly differentiated adenocarcinoma based on biopsy specimens were significantly more frequent in submucosal invasive cancer than in intramucosal cancer (88% vs. 48%; 94% vs. 42%; 47% vs. 0%, respectively). From the relationship between the endoscopic features and the submucosal invasive cancer incidence, submucosal invasion risk was stratified as: (i) low-risk (risk, 2%), all lesions located on the anal side of the papilla and superficial macroscopic type on the oral side of the papilla; and (ii) high-risk (risk, 23%), protruded or mixed macroscopic type on the oral side of the papilla. Based on the biopsy specimens, all eight patients with moderately-to-poorly differentiated adenocarcinoma had submucosal invasive cancer. Furthermore, EUS was not associated with invasion depth's diagnostic accuracy improvements. CONCLUSION: Optimal treatment indications for SNADAC can be selected based on the risk factors of submucosal invasion by tumor location, macroscopic type, and biopsy diagnosis.

Randomized phase II study comparing neoadjuvant 5-fluorouracil/oxaliplatin/docetaxel versus docetaxel/oxaliplatin/S-1 for patients with type 4 or large type 3 gastric cancer.

Macroscopic type 4 and large type 3 gastric cancer, mostly overlapping with scirrhous or linitis plastica type, exhibit a highly invasive nature and show unfavorable prognosis after curative surgery, even with adjuvant chemotherapy. A randomized phase III trial (JCOG0501) failed to demonstrate a survival advantage of neoadjuvant chemotherapy with S-1 plus cisplatin for this population. The current authors initiated a randomized phase II study comparing neoadjuvant chemotherapy with 5-fluorouracil/oxaliplatin/docetaxel versus docetaxel/oxaliplatin/S-1 for type 4 and large type 3 gastric cancer. 76 patients are planned to be enrolled over two years. The primary end point is the proportion of patients with a pathological response (grade 1b or higher) and secondary end points include overall survival and adverse events. Clinical Trial Registration: jRCTs031230231 (rctportal.niph.go.jp).

14-3-3 Proteins stabilize actin and vimentin filaments to maintain processes in renal glomerular podocyte.

14-3-3 proteins are a ubiquitously expressed family of adaptor proteins. Despite exhibiting high sequence homology, several 14-3-3 isoforms have isoform-specific binding partners and roles. We reported that 14-3-3ß interacts with FKBP12 and synaptopodin to maintain the structure of actin fibers in podocytes. However, the precise localization and differential role of 14-3-3 isoforms in kidneys are unclear. Herein, we showed that 14-3-3ß in glomeruli was restricted in podocytes, and 14-3-3σ in glomeruli was expressed in podocytes and mesangial cells. Although 14-3-3ß was dominantly co-localized with FKBP12 in the foot processes, a part of 14-3-3ß was co-localized with Par3 at the slit diaphragm. 14-3-3ß interacted with Par3, and FKBP12 bound to 14-3-3ß competitively with Par3. Deletion of 14-3-3ß enhanced the interaction of Par3 with Par6 in podocytes. Gene silencing for 14-3-3ß altered the structure of actin fibers and process formation. 14-3-3ß and synaptopodin expression was decreased in podocyte injury models. In contrast, 14-3-3σ in podocytes was expressed in the primary processes. 14-3-3σ interacted with vimentin but not with the actin-associated proteins FKBP12 and synaptopodin. Gene silencing for 14-3-3σ altered the structure of vimentin fibers and process formation. 14-3-3σ and vimentin expression was increased in the early phase of podocyte injury models but was decreased in the late stage. Together, the localization of 14-3-3ß at actin cytoskeleton plays a role in maintaining the foot processes and the Par complex in podocytes. In contrast, 14-3-3σ at vimentin cytoskeleton is essential for maintaining primary processes.

Prognostic factors of para-aortic lymph node metastasis from colorectal cancer in highly selected patients undergoing para-aortic lymph node dissection.

PURPOSE: We investigated the surgical outcomes of para-aortic lymph node (PALN) dissection in patients with colorectal cancer and assessed the prognostic factors related to the survival. METHODS: This single-center retrospective study included 31 patients with synchronous or metachronous PALN metastasis from colorectal cancer who underwent PALN dissection between January 2006 and December 2018. RESULTS: Twenty-one patients had synchronous PALN metastasis, and 10 had metachronous PALN metastasis. Seven patients had either simultaneous distant metastasis or a history of distant metastasis other than PALN metastasis at the time of PALN dissection. Eighteen patients underwent adjuvant chemotherapy. The 5-year overall and recurrence-free survival rates were 54.2 and 17.2%, respectively. A multivariable analysis revealed that rectal cancer, metachronous PALN metastasis, and three or more pathological PALN metastases were significantly poor prognostic factors for the recurrence-free survival. Among patients with rectal cancer, lower rectal cancer and lateral pelvic lymph node metastasis were poor prognostic factors for the overall survival. CONCLUSION: Curative PALN dissection for PALN metastasis from colorectal cancer is feasible with favorable long-term outcomes. A multidisciplinary approach, including surgery and chemotherapy, is needed for colorectal cancer with PALN metastasis to improve the long-term outcomes.

Optimal resection of gastric bronchogenic cysts based on anatomical continuity with adherent gastric muscular layer: A case report.

BACKGROUND: Bronchogenic cysts are congenital lesions requiring radical resection because of malignant potential. However, a method for the optimal resection of these cysts has not been completely elucidated. CASE SUMMARY: Herein, we presented three patients with bronchogenic cysts that were located adjacent to the gastric wall and resected laparoscopically. The cysts were detected incidentally with no symptoms and the preoperative diagnosis was challenging to obtain via radiological examinations. Based on laparoscopic findings, the cyst was attached firmly to the gastric wall and the boundary between the gastric and cyst walls was difficult to identify. Consequently, resection of cysts alone caused cystic wall injury in Patient 1. Meanwhile, the cyst was resected completely along with a part of the gastric wall in Patient 2. Histopathological examination revealed the final diagnosis of bronchogenic cyst and revealed that the cyst wall shared the muscular layer with the gastric wall in Patients 1 and 2. In Patient 3, the cyst was located adjacent to the gastric wall but histopathologically originated from diaphragm rather than stomach. All the patients were free from recurrence. CONCLUSION: The findings of this study state that a safe and complete resection of bronchogenic cysts required the adherent gastric muscular layer or full-thickness dissection, if bronchogenic cysts are suspected via pre- and/or intraoperative findings.

Intratumoral Budding and CD8-Positive T-cell Density in Pretreatment Biopsies as a Predictor of Response to Neoadjuvant Chemoradiotherapy in Advanced Rectal Cancer.

BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) is the standard treatment for advanced rectal cancer. Yet, the response to CRT varies from complete response to zero tumor regression. MATERIALS AND METHODS: The impact of intratumoral budding (ITB) and intratumoral CD8+ cell density on response to CRT and survival were evaluated in biopsy samples from 266 patients with advanced rectal cancer who were treated with long-course neoadjuvant CRT. The expression of epithelial-mesenchymal transition (EMT) markers was compared between patients with high and low ITB, using data from 174 patients with RNA sequencing. RESULTS: High ITB was observed in 62 patients (23.3%). There was no association between ITB and CD8+ cell density. The multivariable logistic regression analysis showed that high CD8+ cell density (OR, 2.69; 95% CI, 1.45-4.98; P = .002) was associated with good response to CRT, whereas high ITB (OR, 0.33; 95% CI, 0.14-0.80; P = .014) was associated with poor response. Multivariable Cox regression analysis for survival showed that high CD8+ cell density was associated with better recurrence-free survival (HR, 0.41; 95% CI, 0.24-0.72; P = .002) and overall survival (HR, 0.36; 95% CI, 0.17-0.74; P = .005), but significance values for ITB were marginal (P = .104 for recurrence-free survival and P = .163 for overall survival). The expression of EMT-related genes was not significantly different between patients with high and low ITB. CONCLUSION: ITB and CD8+ cell density in biopsy samples may serve as useful biomarkers to predict therapy response in patients with rectal cancer treated with neoadjuvant CRT.

Concurrent chemoradiotherapy using proton beams can reduce cardiopulmonary morbidity in esophageal cancer patients: a systematic review.

This systematic review was performed to investigate the superiority of proton beam therapy (PBT) to photon-based radiotherapy (RT) in treating esophageal cancer patients, especially those with poor cardiopulmonary function. The MEDLINE (PubMed) and ICHUSHI (Japana Centra Revuo Medicina) databases were searched from January 2000 to August 2020 for studies evaluating one end point at least as follows; overall survival, progression-free survival, grade ≥ 3 cardiopulmonary toxicities, dose-volume histograms, or lymphopenia or absolute lymphocyte counts (ALCs) in esophageal cancer patients treated with PBT or photon-based RT. Of 286 selected studies, 23 including 1 randomized control study, 2 propensity matched analyses, and 20 cohort studies were eligible for qualitative review. Overall survival and progression-free survival were better after PBT than after photon-based RT, but the difference was significant in only one of seven studies. The rate of grade 3 cardiopulmonary toxicities was lower after PBT (0-13%) than after photon-based RT (7.1-30.3%). Dose-volume histograms revealed better results for PBT than photon-based RT. Three of four reports evaluating the ALC demonstrated a significantly higher ALC after PBT than after photon-based RT. Our review found that PBT resulted in a favorable trend in the survival rate and had an excellent dose distribution, contributing to reduced cardiopulmonary toxicities and a maintained number of lymphocytes. These results warrant novel prospective trials to validate the clinical evidence.

Geriatric nutritional risk index after neoadjuvant chemoradiotherapy and survival in older patients with advanced rectal cancer.

PURPOSE: To investigate the clinical impact of malnutrition on the survival of older patients with advanced rectal cancer who underwent neoadjuvant chemoradiotherapy. METHODS: We investigated the clinical significance of the geriatric nutritional risk index (GNRI) in 237 patients aged over 60 years with clinical stage II/III rectal adenocarcinoma who were treated with neoadjuvant long-course chemoradiotherapy or total neoadjuvant therapy followed by radical resection from 2004 to 2017. Pre-treatment and post-treatment GNRI were evaluated, with patients split into low (< 98) and high (≥ 98) GNRI groups. The prognostic impact of pre-treatment and post-treatment GNRI levels on overall survival (OS), post-recurrence survival (PRS), and disease-free survival (DFS) was evaluated using univariate and multivariate analyses. RESULTS: Fifty-seven patients (24.1%) before neoadjuvant treatment and 94 patients (39.7%) after neoadjuvant treatment were categorized with low GNRI. Pre-treatment GNRI levels were not associated with OS (p = 0.80) or DFS (p = 0.70). Patients in the post-treatment low GNRI group had significantly poorer OS than those in the post-treatment high GNRI group (p = 0.0005). The multivariate analysis showed that post-treatment low GNRI levels were independently associated with poorer OS (hazard ratio, 3.06; 95% confidence interval, 1.55-6.05; p = 0.001). Although post-treatment GNRI levels were not associated with DFS (p = 0.24), among the 50 patients with recurrence, post-treatment low GNRI levels were associated with poorer PRS (p = 0.02). CONCLUSION: Post-treatment GNRI is a promising nutritional score associated with OS and PRS in patients over 60 years with advanced rectal cancer treated with neoadjuvant chemoradiotherapy.

Diagnostic criteria and endoscopic and histological findings of autoimmune gastritis in Japan.

The Japanese diagnostic criteria for autoimmune gastritis (AIG) were established by the "Study Group on the establishment of diagnostic criteria for type A gastritis," which is related to a workshop associated with the Japan Gastroenterological Endoscopy Society (JGES) and the Committee of AIG Research Group (CARP). The criteria were set as follows: the cases of confirmed diagnosis are patients in whom either the endoscopic or histological findings, or both, meet the requirements for AIG and who are confirmed to be positive for gastric autoantibodies (either anti-parietal cell or anti-intrinsic factor antibodies, or both). The presentation of endoscopic findings of early-stage AIG in the diagnostic criteria was withheld owing to the need for further accumulation and characterization of endoscopic clinical data. Therefore, diagnosis of early-stage AIG only requires histological confirmation and gastric autoantibody positivity. Suspected cases are patients in whom either the endoscopic or histological findings, or both, meet only the requirements for AIG. Histological findings only meet the requirements for early stage. AIG has been underdiagnosed in the past, but our study group's newly proposed diagnostic criteria will enable a more accurate and early diagnosis of AIG. The criteria can be used to stratify patients into various high-risk groups for gastric tumors and pernicious anemia. They would allow the establishment of an appropriate surveillance system in the coming years. Nevertheless, issues such as establishing the endoscopic findings of early-stage AIG and obtaining Japanese insurance coverage for gastric autoantibody tests require attention.

Estrogen Receptor-ß Gene Cytosine-Adenine (ESR2-CA) Repeat Polymorphism in Postmenopausal Colon Cancer.

The pathobiological role of estrogen is controversial in colorectal cancer. Cytosine-adenine (CA) repeat in the estrogen receptor (ER)-ß gene (ESR2-CA) is a microsatellite, as well as representative of ESR2 polymorphism. Though its function is unknown, we previously showed that a shorter allele (germline) increased the risk of colon cancer in older women, whereas it decreased it in younger postmenopausal women. ESR2-CA and ER-ß expressions were examined in cancerous (Ca) and non-cancerous (NonCa) tissue pairs from 114 postmenopausal women, and comparisons were made considering tissue types, age/locus, and the mismatch repair protein (MMR) status. ESR2-CA repeats <22/≥22 were designated as 'S'/'L', respectively, resulting in genotypes SS/nSS (=SL&LL). In NonCa, the rate of the SS genotype and ER-ß expression level were significantly higher in right-sided cases of women ≥70 (≥70Rt) than in those in the others. A decreased ER-ß expression in Ca compared with NonCa was observed in proficient-MMR, but not in deficient-MMR. In NonCa, but not in Ca, ER-ß expression was significantly higher in SS than in nSS. ≥70Rt cases were characterized by NonCa with a high rate of SS genotype or high ER-ß expression. The germline ESR2-CA genotype and resulting ER-ß expression were considered to affect the clinical characteristics (age/locus/MMR status) of colon cancer, supporting our previous findings.

Transcriptomic Analyses of Pretreatment Tumor Biopsy Samples, Response to Neoadjuvant Chemoradiotherapy, and Survival in Patients With Advanced Rectal Cancer.

Importance: Neoadjuvant chemoradiotherapy (CRT) is the standard of care for advanced rectal cancer. Yet, estimating response to CRT remains an unmet clinical challenge. Objective: To investigate and better understand the transcriptomic factors associated with response to neoadjuvant CRT and survival in patients with advanced rectal cancer. Design, Setting, and Participants: A single-center, retrospective, case series was conducted at a comprehensive cancer center. Pretreatment biopsies from 298 patients with rectal cancer who were later treated with neoadjuvant CRT between April 1, 2004, and September 30, 2020, were analyzed by RNA sequencing. Data analysis was performed from July 1, 2021, to May 31, 2022. Exposures: Chemoradiotherapy followed by total mesorectal excision or watch-and-wait management. Main Outcomes and Measures: Transcriptional subtyping was performed by consensus molecular subtype (CMS) classification. Immune cell infiltration was assessed using microenvironment cell populations-counter (MCP-counter) scores and single-sample gene set enrichment analysis (ssGSEA). Patients with surgical specimens of tumor regression grade 3 to 4 or whose care was managed by the watch-and-wait approach for more than 3 years were defined as good responders. Results: Of the 298 patients in the study, 205 patients (68.8%) were men, and the median age was 61 (IQR, 52-67) years. Patients classified as CMS1 (6.4%) had a significantly higher rate of good response, albeit survival was comparable among the 4 subtypes. Good responders exhibited an enrichment in various immune-related pathways, as determined by ssGSEA. Microenvironment cell populations-counter scores for cytotoxic lymphocytes were significantly higher for good responders than nonresponders (median, 0.76 [IQR, 0.53-1.01] vs 0.58 [IQR, 0.43-0.83]; P < .001). Cytotoxic lymphocyte MCP-counter score was independently associated with response to CRT, as determined in the multivariable analysis (odds ratio, 3.81; 95% CI, 1.82-7.97; P < .001). Multivariable Cox proportional hazards regression analysis, including postoperative pathologic factors, revealed the cytotoxic lymphocyte MCP-counter score to be independently associated with recurrence-free survival (hazard ratio [HR], 0.38; 95% CI, 0.16-0.92; P = .03) and overall survival (HR, 0.16; 95% CI, 0.03-0.83; P = .03). Conclusions and Relevance: In this case series of patients with rectal cancer treated with neoadjuvant CRT, the cytotoxic lymphocyte score in pretreatment biopsy samples, as computed by RNA sequencing, was associated with response to CRT and survival. This finding suggests that the cytotoxic lymphocyte score might serve as a biomarker in personalized multimodal rectal cancer treatment.

Clinical Evaluation of Computer-Aided Colorectal Neoplasia Detection Using a Novel Endoscopic Artificial Intelligence: A Single-Center Randomized Controlled Trial.

INTRODUCTION: Computer-aided diagnostic systems are emerging in the field of gastrointestinal endoscopy. In this study, we assessed the clinical performance of the computer-aided detection (CADe) of colonic adenomas using a new endoscopic artificial intelligence system. METHODS: This was a single-center prospective randomized study including 415 participants allocated into the CADe group (n = 207) and control group (n = 208). All endoscopic examinations were performed by experienced endoscopists. The performance of the CADe was assessed based on the adenoma detection rate (ADR). Additionally, we compared the adenoma miss rate for the rectosigmoid colon (AMRrs) between the groups. RESULTS: The basic demographic and procedural characteristics of the CADe and control groups were as follows: mean age, 54.9 and 55.9 years; male sex, 73.9% and 69.7% of participants; and mean withdrawal time, 411.8 and 399.0 s, respectively. The ADR was 59.4% in the CADe group and 47.6% in the control group (p = 0.018). The AMRrs was 11.9% in the CADe group and 26.0% in the control group (p = 0.037). CONCLUSION: The colonoscopy with the CADe system yielded an 11.8% higher ADR than that performed by experienced endoscopists alone. Moreover, there was no need to extend the examination time or request the assistance of additional medical staff to achieve this improved effectiveness. We believe that the novel CADe system can lead to considerable advances in colorectal cancer diagnosis.

Nomogram as a novel predictive tool for lymph node metastasis in T1 colorectal cancer treated with endoscopic resection: a nationwide, multicenter study.

BACKGROUND AND AIMS: Since 2009, the Japanese Society for Cancer of the Colon and Rectum guidelines have recommended that tumor budding and submucosal invasion depth, in addition to lymphovascular invasion and tumor grade, be included as risk factors for lymph node metastasis (LNM) in patients with T1 colorectal cancer (CRC). In this study, a novel nomogram was developed and validated by usirge-scale, real-world data, including the Japanese Society for Cancer of the Colon and Rectum risk factors, to accurately evaluate the risk of LNM in T1 CRC. METHODS: Data from 4673 patients with T1 CRC treated at 27 high-volume institutions between 2009 and 2016 were analyzed for LNM risk. To prepare a nonrandom split sample, the total cohort was divided into development and validation cohorts. Pathologic findings were extracted from the medical records of each participating institution. The discrimination ability was measured by using the concordance index, and the variability in each prediction was evaluated by using calibration curves. RESULTS: Six independent risk factors for LNM, including submucosal invasion depth and tumor budding, were identified in the development cohort and entered into a nomogram. The concordance index was .784 for the clinical calculator in the development cohort and .790 in the validation cohort. The calibration curve approached the 45-degree diagonal in the validation cohort. CONCLUSIONS: This is the first nomogram to include submucosal invasion depth and tumor budding for use in routine pathologic diagnosis based on data from a nationwide multi-institutional study. This nomogram, developed with real-world data, should improve decision-making for an appropriate treatment strategy for T1 CRC.

Performance of an artificial intelligence-based diagnostic support tool for early gastric cancers: Retrospective study.

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.