Background Reliable biomarkers for prognostication and recurrence surveillance in esophageal squamous cell carcinoma (ESCC) remain limited. The authors therefore investigated the potential clinical utility of exosomal DNA, which has emerged as a promising component of liquid biopsy. Methods This study screened 54 patients with ESCC. After exclusions, 210 blood samples from 21 patients underwent mutation-specific droplet digital polymerase chain reaction assays of plasma exosomal DNA (exoDNA) and circulating tumor DNA (ctDNA) before and after treatment. Kaplan-Meier and receiver operating characteristic analyses were performed to examine associations with overall survival (OS), disease-specific survival (DSS), relapse-free survival (RFS), and recurrence. Results Pretreatment exoDNA positivity was significantly associated with shorter DSS (p = 0.035) and shorter RFS (p = 0.048). Post-treatment exoDNA positivity was significantly associated with shorter OS (p = 0.0008), DSS (p = 0.0001), and RFS (p = 0.0001). Post-treatment ctDNA positivity was associated with shorter DSS (p = 0.038). Conclusions In ESCC, exoDNA demonstrated prognostic and predictive value, supporting its potential role as a complementary biomarker for postoperative surveillance.

Abstract Background: The benefits of immune checkpoint inhibitors (ICIs) in gastric cancer (GC) vary according to the Helicobacter pylori (Hp) status. While profiling transcriptomes, intron retention (IR) emerged as a major distinguishing feature in Hp-positive disease, but its immunologic significance remains unclear. Methods: We analyzed 66 RNA-seq tumor samples (39 Hp-positive and 27 Hp-negative) from 24 patients. Alternative splicing (AS) were quantified USING PSIsigma, rMATS. AS-derived neoantigens were predicted (SNAF; strict filters), and a quality-weighted neoantigen burden was calculated. Antigen-presentation machinery (APM) was summarized using a purity-adjusted APM score. Tumor microenvironment (TME) features were profiled using ESTIMATE, Hallmark GSEA, ssGSEA, CIBERSORTx, and a four-class subtype (desert/immune-enriched [IE]/IE fibrotic/fibrotic). High IR was defined as three or more IR events. Statistical analysis was performed using the Mann-Whitney test and Spearman correlation, with BH-FDR correction. Results: Across Hp infection status, Hp-positive tumors harbored more IR/AS events and a higher total neoantigen burden under strict filters; however, IR-specific and quality-weighted burdens were not significantly higher. In Hpnegative tumors, higherquality neoantigen burden correlated with intrinsic APM capacity (ρ≈0.41, p=0.034), indicating preserved antigen-APM coupling. Within Hp-positive tumors, IRhigh (n=12) versus IRlow (n=27) tumors showed higher neoantigen metrics (IRderived 4 vs 1, p=4.6×10-7; weighted 24.1 vs 12.2, p=3.9×10-4), enrichment of G2M/E2F/MYC/mitotic spindle programs (FDR<0.05), higher tumor purity (p=0.022), lower ImmuneScore (p=0.0156) and StromalScore (p=0.017), and uniform classification as the Desert subtype (12/12). NMD and splicing signatures were significantly elevated (p=0.014/0.034), CD8/IFN signatures were reduced (p=0.034), and the APM score favored IRlow tumors ( p=0.050). A Myeloid/mastcell-skewed pattern was also evident (MDSC signature, p = 0.037; activated mast cells, p=0.0077; resting mast cells, p=0.0027). In Hp-positive tumors overall, quality-weighted neoantigen burden correlated positively with NMD/splicing (ρ≈0.63, p=1.9×10-5; ρ≈0.67, p=3.7×10-6), while IR burden correlated negatively with CD8/IFN activity (ρ≈−0.44, p=0.0056). IR events were not enriched in core APM genes. Conclusions: In Hp-positive GC, high IR defines a proliferative, NMD/splicing-stressed, myeloid/mastcell-skewed immunedesert microenvironment characterized by neoantigen-APM uncoupling. This phenotype aligns with limited ICI benefit, identifying high IR as a potential predictive marker of ICI nonresponse, supporting prospective validation and hypothesis-driven evaluation of ICI-based regimens that reprogram myeloid-rich TMEs or modulate splicing/NMD pathways. Citation Format: Daisuke Takayanagi, Junya Kitadani, Masahiro Katsuda, Toshiyasu ojima, Keiji Hayata, Manabu Kawai, Sinichi Hashimoto, Kazuhiko Tagawa, Toru Sugino, Satoshi Wada, Hiroki Yamaue, Takuya Tsunoda. Intron retention marks a myeloid-skewed immune desert and nominates an ICI nonresponse marker in H. pylori-positive gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2885.

BACKGROUND:The prognostic significance of PD-L1 expression in unresectable/recurrent gastric cancer treated by first-line chemotherapy without an immune checkpoint inhibitor (ICI) remains unclear. The phase III trial JCOG1013 demonstrated no overall survival (OS) or progression-free survival (PFS) benefit of docetaxel/cisplatin/S-1 over cisplatin/S-1. This ancillary analysis of JCOG 1013 evaluated the prognostic value of PD-L1 expression. METHODS:PD-L1 expression was assessed in pretreatment tumor specimens using the Dako 28-8 pharmDx assay. Combined positive score (CPS) and tumor proportion score (TPS) were calculated. PD-L1 positivity was defined as CPS ≥ 5 or TPS ≥ 1%. Univariable and multivariable analyses were performed for OS and PFS. RESULTS:Among 741 patients enrolled in JCOG1013, 540 patients were included. In univariable analyses, neither CPS ≥ 5 nor TPS ≥ 1% was significantly associated with OS or PFS. In multivariable analyses, CPS ≥ 5 was not significantly associated with OS (HR 0.86, 95% CI 0.71-1.04; p = 0.127) or PFS (HR 0.92, 95% CI 0.77-1.11; p = 0.392); however, TPS ≥ 1% was significantly associated with longer OS (HR 0.78, 95% CI 0.62-0.97; p = 0.028) and PFS (HR 0.76, 95% CI 0.62-0.94; p = 0.012). CONCLUSIONS:TPS ≥ 1% is an independent favorable prognostic factor for survival in patients with unresectable/recurrent gastric cancer receiving chemotherapy alone. CLINICAL TRIAL REGISTRATION:UMIN000007652.

Background There are two types of methods of creating a gastric conduit after esophagectomy for patients with esophageal cancer: narrow gastric tube reconstruction or whole stomach reconstruction. Whole stomach reconstruction with good blood perfusion was reported in a prospective cohort study to be safe and that it has the possibility to prevent anastomotic leakage (AL). We therefore planned a randomized controlled phase III study to investigate the superiority of whole stomach reconstruction over narrow gastric tube reconstruction after esophagectomy for esophageal cancer. Methods This is a single center, two-arm, open-label, randomized phase III trial. We calculated that 65 patients in each arm of this study and total study population of 130 patients are required according to our historical data on narrow gastric tube reconstruction and prospective data on whole stomach reconstruction. In the narrow gastric tube group, a 3.5-cm-wide gastric tube is made along the greater curvature of the stomach using linear staplers. Otherwise, in the whole stomach group, after the lymphadenectomy of the lesser curvature and No.2, the stomach is cut just below the esophagogastric junction using a linear stapler. The primary endpoint of this study is the incidence of AL. Secondary endpoints are the occurrence rate of anastomotic stenosis, the occurrence rate of pneumonia, the occurrence rate of all postoperative complications, the occurrence rate of reflux esophagitis, quality of life evaluation by EORTC QLQ-C30 and EORTC OES-18, nutritional evaluation, the amount of blood loss, postoperative hospital stays and blood flow evaluation. Complications are evaluated using the Clavien-Dindo classification (Version 2.0), and those of Grade II or higher are considered to be postoperative complications. Discussion If the optimal method for creating a gastric conduit after esophagectomy is clarified, it may be possible to contribute to improving short-term and long-term surgical outcomes for patients undergoing surgery for esophageal cancer. Trial registration: The protocol of ATHLETE trial was registered in the UMIN Clinical Trials Registry as UMIN000050677 (http://www.umin.ac.jp/ctr/index.htm). Date of Registration: March 26, 2023. Date of First Participant Enrollment: March 27, 2023.

2626 Background: Helicobacter pylori (HP) infection, a major risk factor for gastric cancer (GC), modulates tumor immunity. Evidence indicates that H. pylori infection status correlates with the efficacy of immune checkpoint inhibitors (ICI), with varying outcomes in H. pylori -positive ( HPP ) and -negative ( HPN ) patients. This study investigated the impact of HP infection on splicing alterations to elucidate its role in shaping immune responses and the tumor immune microenvironment (TIME), immune checkpoint molecule expression, transcriptional profiles in GC. Methods: Tumors and adjacent normal tissues were collected from 24 patients with GC, comprising 39 tumor samples from HPP patients, 27 samples from HPN patients, and 13 and 10 normal samples of each, respectively. RNA sequencing was performed on these tissues and whole blood RNA from six patients (four HPP and two HPN ) to analyze the alternative splicing (AS) events, the transcriptional profiles, and immune-related gene expression. Differential gene expression (DGE) and enrichment analyses were conducted, and immune cell fractions were evaluated using CIBERSORTx. Results: DGE analysis revealed that HPP tumors were enriched in genes related to cell cycle regulation, whereas HPN tumors were enriched in immune response pathways, including those involved in leukocyte activation, chemokine signaling, and immune effector processes. Additionally, HPN tumors showed higher expression of immune checkpoint molecules, such as CD160 (p = 0.016), PDCD1LG2 (p = 0.0082), and BTLA (p = 0.025). Immune cell profiling demonstrated increased proportions of gamma-delta T cells (p = 0.0077), resting dendritic cells (p = 0.0002), and neutrophils (p = 0.016), reflecting enhanced immune activation and a favorable ICI response. In contrast, HPP tumors were enriched in cell cycle-related pathways, suggesting a proliferative phenotype. HPP tumors also exhibited higher levels of M0 macrophages (p = 0.0039) and CD276 expression (p = 0.0082), indicative of an immunosuppressive TIME. AS analysis identified increased intron retention (IR) events in HPP tumors, particularly in genes associated with RNA processing and extracellular matrix remodeling. These alterations may contribute to immune evasion and tumor progression. In the peripheral blood, HPP samples exhibited upregulation of tripartite motif family genes, which are implicated in immune modulation. Conclusions: This study demonstrated that HP infection significantly affects the TME and gene expression profiles of GC. HPP tumors are characterized by increased M0 macrophage populations, CD276 expression, and IR events that contribute to immunosuppression and tumor progression. In contrast, HPN tumors exhibit greater immune activation and checkpoint molecule diversity. These findings highlight the potential role of HP status in shaping the immune landscape of GC and influencing responsiveness to ICI.

GPR142 is a tryptophan‐sensing receptor that has been implicated in the regulation of inflammation. In this study, we investigated the relationships between inflammatory cytokine and GPR142 expression by using cellular, animal models, and human stomach samples. We found that addition of TNF‐α, IL‐6, and IL‐1β into the culture of ghrelin‐producing cell line, MGN3‐1 cells, increased GPR142 mRNA expression levels. Lipopolysaccharide (LPS) injection to mice significantly increased GPR142 expression in the stomach, confirming the results observed in the cellular model. GPR142 mRNA expression levels in the stomach samples of morbidly obese patients were positively correlated with TNF‐α, IL‐6, and IL‐1β mRNA levels. Taken together our results suggest that GPR142 expression is under the direct control of proinflammatory cytokines and support further investigation of GPR142 potential roles in inflammation.

391 Background: Although high PD-L1 expression predicts a favorable response of advanced solid tumors to immune checkpoint inhibitors (ICIs), its impact on survival in patients with unresectable/recurrent gastric cancer (GC) has remained unclear. We investigated the prognostic value of PD-L1 expression for survival in unresectable/recurrent GC patients receiving first-line chemotherapy without ICIs. Methods: JCOG1013, a phase 3 randomized trial, demonstrated the addition of docetaxel to cisplatin and S-1 as first-line chemotherapy was of no benefit to patients with unresectable/recurrent GC (N=741) either for overall survival (OS) or progression-free survival (PFS). Tumor specimens prior to chemotherapy were collected for assessing PD-L1 expression for this ancillary study. PD-L1 expression was determined using immunohistochemistry (Dako, 28-8 pharmDx) and used to derive the PD-L1 combined positive score (CPS) and PD-L1 tumor proportion score (TPS). As with the CheckMate 649 study, the cutoff values for PD-L1 CPS and PD-L1 TPS were set at 5 and 1%, respectively. Multivariable analyses were performed using Cox proportional hazard models to evaluate the prognostic significance of PD-L1 CPS and PD-L1 TPS as predictors of OS and PFS. All p values were 2-sided; values <0.05 were considered statistically significant. Results: We analyzed 427 patients with unresectable/recurrent GC. The prevalence of PD-L1 CPS≥5, and PD-L1 TPS≥1% was 33% and 24%, respectively. There was no significant difference in OS and PFS between the PD-L1 CPS ≥5 group and the PD-L1 CPS <5 group (Table). The PD-L1 TPS ≥1% group had superior OS and PFS compared to the PD-L1 TPS <1% group (Table). In multivariable analyses for OS, PD-L1 TPS ≥1% was a significant favorable prognostic factor (hazard ratio (HR) = 0.64 [95% CI: 0.50–0.83], p<0.001), but PD-L1 CPS≥5 was not (HR = 0.82 [95% CI: 0.65–1.02], p = 0.073). In multivariable analyses for PFS, PD-L1 TPS ≥1% was a significant favorable prognostic factor (HR = 0.67 [95% CI: 0.52–0.84], p<0.001), but PD-L1 CPS≥5 was not (HR = 0.83 [95% CI: 0.67–1.03], p = 0.090). Conclusions: PD-L1 TPS≥1% is significantly correlated with longer OS and PFS in patients with unresectable/recurrent GC receiving first-line chemotherapy without ICIs. PD-L1 TPS should be considered as a stratification factor in randomized clinical trials for unresectable/recurrent GC. Clinical trial information: UMIN000007652 . [Table: see text]

388 Background: Recently, the usefulness of exosome DNA (exo-DNA) for prognostic analysis of various solid tumors has also been reported. In this study, we investigated the usefulness of ctDNA and exo-DNA as biomarkers for esophageal squamous cell carcinoma. Methods: Patients with esophageal squamous cell carcinoma undergoing standard treatment had ctDNA and exo-DNA collected over time. NGS analysis was performed on biopsy or surgical specimens, and mutated genes in individual cases were followed by ddPCR over time. Results: NGS analysis was performed on 16 patients. 12 of 16 cases showed mutations, In 8 cases, ctDNA and exo-DNA could be measured by ddPCR over time. In one case of Stage IVA. both ctDNA and exo-DNA were useful to determine the efficacy of chemotherapy and radiotherapy, and in one case of Stage II, both ctDNA and exo-DNA were useful to predict postoperative recurrence. Conclusions: In esophageal squamous cell carcinoma, ctDNA and exo-DNA may be useful in determining treatment response and predicting recurrence. We will further investigate the usefulness of ctDNA and exo-DNA in esophageal squamous cell carcinoma, including prognostic prediction. Clinical trial information: UMIN000045311 .

BACKGROUND:The long-term outcomes of gastric tube cancer (GTC) are unclear. This study therefore aimed to clarify clinicopathologic features and the long-term outcomes of patients with GTC. METHODS:The 25 patients who were diagnosed with GTC between April 2003 and December 2022 at our hospital were eligible for inclusion in this retrospective study, and this included 27 lesions. We retrospectively evaluated clinicopathologic factors based on hospital records. RESULTS:In our cohort, 88% of incidences of GTC were located in the middle or lower gastric tube. As the treatment of GTC, we used endoscopic submucosal dissection, gastrectomy, chemoradiotherapy, chemotherapy, and best supportive care for 16 (59%), 6 (22%), 1 (4%), 1 (4%), and 3 (11%) lesions, respectively. Perforation after endoscopic submucosal dissection was observed in 6 of the 16 lesions. Partial gastric tube resection was performed for 3 patients and total gastric tube resection was performed for 3 patients. One patient who underwent total gastric tube resection died due to acute respiratory distress syndrome. In survival analysis, the 3-year overall survival rate was 52% and the 3-year disease-specific survival rate was 74%. Five patients (20%) died of aspiration pneumonia, 2 patients (8%) of another disease, and 1 patient (4%) of another type of cancer. According to multivariate analysis, independent prognostic factors for overall survival were cN status (HR, 18.021; P =0.004) and complication of aspiration pneumonia (HR, 8.373; P =0.004). CONCLUSIONS:The occurrence of aspiration pneumonia and cN status were prognostic factors after the treatment for GTC. Assessment of dysphagia and surveillance after treatment for GTC are important to improve the prognosis.

BACKGROUND:This study aims to prove the feasibility and safety of robotic gastrectomy using the hinotori™ Surgical Robot System (Medicaroid Corporation, Kobe, Japan). METHODS:We retrospectively enrolled the 16 patients who underwent gastrectomy by the hinotori™ Surgical Robot System for gastric cancer at our hospital between June 2023 and January 2024. Console surgeons performed almost all lymphadenectomies, including the clipping of vessels. Assistant surgeons supported the lymphadenectomy using vessel sealing devices and during reconstruction. RESULTS:Thirteen patients were cStage I, one patient was cStage II, and two patients were cStage III. Distal gastrectomy, proximal gastrectomy, and total gastrectomy were performed in 11, 1, and 4 patients, respectively. D1+ and D2 lymphadenectomies were performed in 11 and 5 patients, respectively. Billroth-I, Billroth-II, Roux-en-Y, and esophagogastrostomy were performed in three, six, six, and one patients, respectively. The median operation time was 282 (245-338) min, and the median console time was 226 (185-266) min. The median blood loss was 28 (12-50) mL, and the median amylase levels in drainage fluid were 280 (148-377) U/L on postoperative day 1 and 74 (42-148) U/L on postoperative day 3. There was anastomotic leakage (Clavien-Dindo [CD] IIIa) in one patient who underwent proximal gastrectomy. The median postoperative hospital stay was 12.5 (12-14) days. CONCLUSION:In this initial case series, the hinotori™ Surgical Robot System was found to be safe and feasible for patients with gastric cancer and is suggested to be appropriate for gastrectomy, including distal gastrectomy and total gastrectomy.

Introduction: This study examines whether neoadjuvant docetaxel, cisplatin plus S-1 (DCS) therapy is superior to docetaxel, cisplatin plus 5-fluorouracil (DCF) therapy for resectable advanced esophageal squamous cell carcinoma (ESCC). Methods: Patients diagnosed with resectable advanced ESCC at our hospital between January 2010 and December 2019 underwent either neoadjuvant DCF therapy or DCS therapy, followed by radical esophagectomy. Prior to August 2014, we usually used neoadjuvant DCF therapy; we then completely transitioned to using neoadjuvant DCS therapy. Results: A total of 144 patients received one of these triplet regimens as neoadjuvant chemotherapy: DCF therapy to 67 patients and DCS therapy to 77 patients. After propensity score matching, 55 patients in each group were selected as matched cohorts. There was no significant difference between the groups in complete response (DCF = 7.3%, DCS = 9.1%) or in partial response (DCF = 45.4%, DCS = 52.7%). The pathological response rate was 23.8% for grade 2 and 18.2% for grade 3 in the DCF group, compared with 30.9% and 14.5% in the DCS group. Independent predictive factors for recurrence-free survival were poor clinical response and pathological response ≤1b. Independent prognostic factors for overall survival were poor clinical response, anastomotic leakage, and pathological response ≤1b. Duration of hospital stays in the DCS group was significantly shorter than those of the DCF group (6.0 vs. 15.0 days, p < 0.001). Expenses of drug and hospitalization for the neoadjuvant chemotherapy in the DCS group were also significantly lower than those of the DCF group (265.7 vs. 550.3 USD, p < 0.001). Conclusions: Neoadjuvant DCS therapy for resectable advanced ESCC did not result in significantly higher clinical and pathological response than neoadjuvant DCF therapy. However, neoadjuvant DCS therapy for resectable ESCC required comparatively shorter hospital stays and incurred lower costs, making it an attractive therapeutic option.

TPS422 Background: Fatigue is being increasingly recognized as an important factor in surgical procedures, because it leads to errors in surgeons' decisions and reduced operating efficiency. In comparison to laparoscopic surgery, robot-assisted surgery is expected to reduce surgeon fatigue due to ergonomic adjustments, comfortable sitting positions, minimal restriction of instrument movement, and stable visualization. The aim of this study is to assess surgeon fatigue and explore the superiority of robot-assisted gastrectomy over laparoscopic gastrectomy in surgeon fatigue. Methods: This study is conducted as a prospective observational study ancillary to a randomized controlled phase III trial investigating the superiority in safety of robot-assisted gastrectomy over laparoscopic gastrectomy for clinical stage T1-4aN0-3 gastric cancer (JCOG1907: UMIN000039825). The lead surgeon and the first assistant performing surgeries as protocol treatment in JCOG1907 were included. Surgeon fatigue is quantitatively assessed using multiple assessment tools. The primary endpoint is the average NASA-Task Load Index (NASA-TLX) value for the lead surgeons. Secondary endpoints include six individual parameters of NASA-TLX, visual analog scale assessments for fatigue, advanced trail-making tests, and continuous heart rate variability measurements for lead surgeons and first assistants. The primary analysis compares surgeon fatigue between robot-assisted and laparoscopic surgery. Secondary analyses examine the association between surgeon fatigue and various factors, such as surgeon and patient background, and surgical findings, as well as cross-correlations among measures of surgical fatigue. In addition, the association between surgeon fatigue and postoperative complications and its impact on long-term survival outcomes is also evaluated. The sample size is 500 surgical cases, with a planned accrual period of 2 years. This study was initiated in April 2023 and registered at the University Hospital Medical Information Network as UMIN000052120. As of August 2023, 52 cases (10.4% of the planned accrual) have been enrolled in the study. Clinical trial information: UMIN000052120 .

Background: Anastomotic leakage (AL) is a major complication after esophagectomy and gastric tube reconstruction. This retrospective study aims to reveal the factors in prevention of AL and in reduction of its severity. Methods: Enrolled in this study were the 183 patients diagnosed with esophageal cancer who underwent minimally invasive esophagectomy followed by narrow gastric tube reconstruction at Wakayama Medical University Hospital between January 2018 and March 2023. Evaluation of blood perfusion using indocyanine green began in September 2020. Results: AL occurred in 42 patients (22%) and did not occur in 141 patients (78%). Patient characteristics were not significantly different between patients with and without AL. Evaluation of blood perfusion of the gastric tube was performed in 69 of the 183 patients (37.7%), and after its introduction the rates of AL decreased from 28.0% to 14.4%. Blood perfusion was less evaluated in the AL group than in the non-AL group (23.8% vs. 41.8%, P=0.034). Multivariate analysis demonstrated that non-evaluation of blood perfusion using indocyanine green (odds=3.115) was an independent risk factor for AL. For the patients with AL, active interventions (eg, tube insertion into the gastric tube through the nose or fistula, embolization of cyanoacrylate) were performed significantly more often in the group without evaluation of blood perfusion than in the group with evaluation. Without evaluation of blood perfusion, there was significantly longer time from onset to resumption of diet and significantly longer postoperative hospital stays. Conclusions: Evaluation of qualitative blood perfusion can lead to both risk reduction and prevention of severe AL after narrow gastric tube reconstruction for esophageal cancer.

Purpose The stomach is the most common organ which is used for reconstruction after esophagectomy for esophageal cancer. It is controversial which is better narrow gastric tube reconstruction or whole stomach reconstruction to prevent anastomotic leakage. Methods From August 2022 to March 2023, we started a prospective cohort study of whole stomach reconstruction after esophagectomy. Until then (from January 2018 to July 2022), narrow gastric tube reconstruction was performed as a standard reconstruction. Results Narrow gastric tube reconstruction and whole stomach reconstruction were performed in 183 patients and 20 patients, respectively. The patient’s characteristics were not significantly different between the narrow gastric tube group and the whole stomach group. In particular, for all patients in the whole stomach reconstruction group, retrosternal route and esophagogastrostomy by hand sewn were applied. There were no occurrences of AL through the continuous 20 cases in the whole stomach group, otherwise 42 (22.9%) patients in the narrow gastric group ( P = 0.016). Postoperative hospital stays were significantly shorter in the whole stomach group than in the narrow gastric group (21 days vs. 28 days, P < .001). Blood perfusions were evaluated by indocyanine green for all cases, which had very good blood perfusion in all cases. Additionally, quantitative blood perfusion was examined by SPY-QP (Stryker, USA) for one case. Even the edge of the fornix showed more than 90% blood perfusion levels when the antrum was fixed as the reference point. Conclusion Whole stomach reconstruction with excellent blood perfusion is considered to be safe and has the possibility to prevent from occurring AL after esophagectomy for esophageal cancer patients.

TPS479 Background: The standard treatment for locally advanced proximal gastric cancer invading the greater curvature is “open total gastrectomy combined with splenectomy” (OTG+S) aiming for whole clearance of the splenic hilar lymph nodes. However, its pertinent postoperative severe complication (e.g. pancreatic fistula) is problematic. An objective of this study is to evaluate the safety of “laparoscopic or robotic total gastrectomy with spleen-preserving splenic hilar dissection” (LRSHD) as a new treatment option which has a potential to reduce surgical morbidity, subsequently to replace the current standard treatment, OTG+S. Methods: This is a multicenter single-arm phase II trial. The main eligibility criteria are as follows; clinical T2-4a resectable locally advanced proximal gastric adenocarcinoma that invades the greater curvature; without obvious lymph node metastasis at the splenic hilum nor direct invasion to the spleen/splenogastric ligament. Protocol treatment is laparoscopic or robotic total gastrectomy with splenic hilar lymph node dissection (D2 + No.10 lymphadenectomy according to the Japanese guidelines) in which the spleen is preserved with skeletonizing the splenic vessels. Quality control of surgery is assured by surgeon’s qualification and central peer review of intraoperative photo at the splenic hilum after dissection. The primary endpoint is the proportion of postoperative pancreatic fistula and/or intra-abdominal abscess formation with Clavien-Dindo Grade III or higher (within 30 days after surgery). Secondary endpoints are intraoperative blood loss, operation time, mortality, overall postoperative complication, number of yield splenic hilar nodes, number of metastatic splenic hilar nodes, conversion to splenectomy, conversion to laparotomy, relapse-free survival, and overall survival. Sample size was set as 85 patients to obtain 80% power considering that 15% of patients are judged as unresectable intraoperatively, with the hypothesis that the primary endpoint would have an expected value of 7% and a threshold value of 16% in one-sided alpha of 0.1. Planned accrual period is 5 years. The accrual began in August 2019. As of August 2022, 53 of the planned 85 patients (62.4%) have been enrolled. When the safety of LRSHD is proved by this study, a non-inferiority phase III trial will be consequently launched. Clinical trial registry number: UMIN000037580. Clinical trial information: UMIN000037580 .

346 Background: Upper-third gastric cancer has been increasing in incidence worldwide and performance of laparoscopic proximal gastrectomy has become increasing common. Various reconstructive procedures after laparoscopic proximal gastrectomy have been reported, but the optimal reconstructive procedure is unclear. Methods: This single-center retrospective study included 53 consecutive patients with early gastric cancer in the upper third of the stomach who received laparoscopic proximal gastrectomy at our hospital between September 2013 and November 2019. Of these 53 patients, 39 underwent esophagogastrostomy with fundoplication. In the 14 patients requiring resection of the abdominal esophagus or where the size of the remnant stomach was 50% or less, we performed double-tract reconstruction. We compared the surgical and nutritional outcomes of patients who underwent esophagogastrostomy or double-tract reconstruction after laparoscopic proximal gastrectomy. Results: There was no significant difference between the two groups regarding blood loss, incidence of postoperative complications, occurrence of gastroesophageal reflux disease, food intake, reflux symptoms, or usage of proton pump inhibitors. There was no significant difference in the rate of body weight change at 6 or 12 months, or in biochemical markers (hemoglobin, total protein and albumin) at 12 months. However, eight patients (21%) in the esophagogastrostomy group had extreme body weight loss (≥20%) within 12 months. Conversely, in the double-tract reconstruction group, no patients had any extreme body weight loss ( P = 0.013). Conclusions: Double-tract reconstruction is useful after laparoscopic proximal gastrectomy, especially in terms of preventing extreme body weight loss.

Abstract Background Laparoscopic gastrectomy (LG) is considered a standard treatment for clinical stage I gastric cancer. Nevertheless, LG has some drawbacks, such as motion restriction and difficulties in spatial perception. Robot-assisted gastrectomy (RG) overcomes these drawbacks by using articulated forceps, tremor-filtering capability, and high-resolution three-dimensional imaging, and it is expected to enable more precise and safer procedures than LG for gastric cancer. However, robust evidence based on a large-scale randomized study is lacking. Methods We are performing a randomized controlled phase III study to investigate the superiority of RG over LG for clinical T1-2N0-2 gastric cancer in terms of safety. In total, 1,040 patients are planned to be enrolled from 46 Japanese institutions over 5 years. The primary endpoint is the incidence of postoperative intra-abdominal infectious complications, including anastomotic leakage, pancreatic fistula, and intra-abdominal abscess of Clavien–Dindo (CD) grade ≥ II. The secondary endpoints are the incidence of all CD grade ≥ II and ≥ IIIA postoperative complications, the incidence of CD grade ≥ IIIA postoperative intra-abdominal infectious complications, relapse-free survival, overall survival, the proportion of RG completion, the proportion of LG completion, the proportion of conversion to open surgery, the proportion of operation-related death, and short-term surgical outcomes. The Japan Clinical Oncology Group Protocol Review Committee approved this study protocol in January 2020. Approval from the institutional review board was obtained before starting patient enrollment in each institution. Patient enrollment began in March 2020. We revised the protocol to expand the eligibility criteria to T1-4aN0-3 in July 2022 based on the results of randomized trials of LG demonstrating non-inferiority of LG to open surgery for survival outcomes in advanced gastric cancer. Discussion This is the first multicenter randomized controlled trial to confirm the superiority of RG over LG in terms of safety. This study will demonstrate whether RG is superior for gastric cancer. Trial registration The protocol of JCOG1907 was registered in the UMIN Clinical Trials Registry as UMIN000039825 ( http://www.umin.ac.jp/ctr/index.htm ). Date of Registration: March 16, 2020. Date of First Participant Enrollment: April 1, 2020.

BACKGROUND:This study aimed to investigate the relationship between postoperative atrial fibrillation (POAF) after esophagectomy and pre-existing cardiac substrate. METHODS:We retrospectively analyzed 212 consecutive patients from between July 2010 and December 2022 who were scheduled to undergo esophagectomy for esophageal cancer without previous history of atrial fibrillation. All the patients underwent both echocardiography and contrast-enhanced multi-detector computed tomography (MDCT). RESULTS:POAF occurred in 49 patients (23.1%). Multivariable logistic analysis demonstrated that independent predictors for POAF were age [OR; 1.06 (1.01-1.10), P < 0.01), three-field lymph node dissection [OR; 2.55 (1.25-5.23), P < 0.01), left atrial dilatation (> 35 mm) assessment by echocardiography [OR; 3.05 (1.49-6.25), P < 0.01) and common left pulmonary vein [OR; 3.03 (1.44-6.39), P < 0.01). The correlation coefficient was high for left atrial dimensions assessed by echocardiography and MDCT (r = 0.91, P < 0.01). Combination of left atrial dilatation by echocardiography and common left pulmonary vein had high odds ratio [OR; 8.10 (2.62-25.96), P < 0.01). Instead of echocardiographic assessment, combination of left atrial enlargement (> 35 mm) assessed by MDCT and common left pulmonary vein also showed high odds ratio for POAF [OR; 11.23 [2.19-57.63], P < 0.01). CONCLUSION:Incidence of POAF after esophagectomy was related to both left atrial enlargement and common left pulmonary vein assessed by preoperative MDCT. Additional analysis of atrial size and pulmonary vein variation would facilitate preoperative assessment of the risk of POAF, but future studies must ascertain therapeutic strategy.

Diaphragmatic hernia is a very rare but high-risk complication after esophagectomy. Although there are many studies on the Ivor Lewis esophagectomy procedure for diaphragmatic hernia, there are fewer studies on the McKeown procedure. The present study aimed to estimate the incidence of diaphragmatic hernia after esophagectomy, describing its presentation and management with the McKeown procedure. We retrospectively evaluated the 622 patients who underwent radical esophagectomy between January 2002 and December 2020 at the Wakayama Medical University Hospital. Statistical analyses were performed to evaluate risk factors for diaphragmatic hernia. Emergency surgery for postoperative diaphragmatic hernia was performed in nine of 622 patients (1.45%). Of these nine patients, one developed prolapse of the small intestine into the mediastinum (11.1%). The other eight patients underwent posterior mediastinal route reconstructions (88.9%), one of whom developed prolapse of the gastric conduit, and seven of whom developed transverse colon via the diaphragmatic hiatus. Laparoscopic surgery was identified in multivariate analysis as the only independent risk factor for diaphragmatic hernia (odd's ratio [OR] = 9.802, p = 0.034). In all seven cases of transverse colon prolapse into the thoracic cavity, the prolapsed organ had herniated from the left anterior part of gastric conduit. Laparoscopic surgery for esophageal cancer is a risk factor for diaphragmatic hernia. The left anterior surface of gastric conduit and diaphragmatic hiatus should be fixed firmly without compromising blood flow to the gastric conduit.