This study has been approved by the ethics committee of the Affiliated Cancer Hospital of Nanjing Medical University (2021-091-01). All patients will be fully informed of the precautions by a professional physician and provided with a written informed consent form before participation. All research information will be kept strictly at the study site and these data will be anonymized. This information will not be published outside the research without the consent of the patients.

This multicenter prospective study will be conducted at the Affiliated Cancer Hospital of Nanjing Medical University, First Affiliated Hospital of Nanjing Medical University, Affiliated Drum Tower Hospital of Nanjing University Medical School, First Affiliated Hospital of Soochow University, Affiliated Hospital of Nanjing University of Chinese Medicine, and Affiliated Gaochun Hospital of Jiangsu University. Figure 1 illustrates the flow of the study.

The inclusion criteria for this study are as follows: (1) age range of 18 to 80 years, with no sex preference; (2) histopathological confirmation of adenocarcinoma via endoscopic biopsy; (3) tumor located in the upper third of the stomach without esophageal involvement, largest diameter of ≤4 cm, and preoperative clinical stage cT1-4aN0M0; (4) Eastern Cooperative Oncology Group Performance Status score of 0 to 1; (5) no surgical contraindications identified through comprehensive preoperative evaluations; and (6) voluntary and informed consent signed by the patient or their legal representative. The exclusion criteria are as follows: (1) pregnant or lactating women; (2) presence of severe psychiatric disorders; (3) intraoperative findings indicating tumor invasion into the esophagus or unsuitability for proximal gastrectomy as determined by the primary surgeon; (4) preoperative or intraoperative discovery of distant organ metastasis or extensive peritoneal implantation metastasis; (5) presence of concurrent or metachronous malignancies, including other organ tumors; (6) incomplete radical surgery, including patients who underwent palliative tumor resection; (7) a history of gastrointestinal surgery; (8) a history of neoadjuvant radiotherapy or chemotherapy; (9) serious concomitant diseases that may make the survival period <5 years; and (10) cases considered unsuitable by the investigator.

Patients can withdraw from this study at any time. For patients who withdraw, the information collected before withdrawal will be used for the final analysis unless they request that their information be deleted.

Before surgery, all patients will be required to undergo an endoscopic examination with biopsy, endoscopic ultrasonography, a plain scan and a contrast-enhanced scan of the whole abdomen, and an upper gastrointestinal series. This comprehensive assessment aims to evaluate the gastric cancer lesion and abdominal lymph nodes thoroughly, with the objective of obtaining an accurate preoperative clinical diagnosis and tumor staging.

Patients can only be randomized into different groups once they have signed the informed consent form, completed baseline assessments, and been confirmed as fully meeting the inclusion criteria. Eligible patients will be randomly assigned to 1 of the following 2 groups at a 1:1 ratio: the tunnel anastomosis group or the double-tract jejunal interposition reconstruction group. The randomization process will use a stratified block randomization method, with disease stage (categorized as early stage or advanced stage) serving as the stratification factor. Patient group assignment will be determined based on random numbers generated by the R software program (version 4.0.2; R Foundation for Statistical Computing).

Follow-up will be conducted by dedicated follow-up staff. All patients will undergo follow-up visits at 3 months, 6 months, and 1 year postoperatively. At these visits, hematological examinations and postoperative quality of life assessments (using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 [EORTC QLQ-C30] and 36-Item Short Form Health Survey) will be performed. Nutritional status will be assessed based on hematological test results, changes in body weight, and the prognostic nutritional index (PNI). In addition, reflux symptoms will be assessed via the Visick score. At the 1-year follow-up, gastroscopy will be performed to assess reflux esophagitis according to the Los Angeles (LA) classification.

This study is designed as a prospective randomized controlled trial with a noninferiority objective. It comprises 2 groups: the experimental group (tunnel anastomosis group) and the control group (double-tract jejunal interposition reconstruction group).

The reported incidence of reflux esophagitis for DTJIR in the literature varies widely, ranging from 1.7% to 25%. However, most contemporary studies report rates concentrated at approximately 10% [22-24]. On the basis of retrospective data from our center, the incidence of reflux esophagitis for TA is approximately 5%. Therefore, the estimated incidence of reflux esophagitis was 10% in the DTJIR group and 5% in the TA group. With a significance level set at α=.025 (one sided), a power of 1 – β of 0.80, a noninferiority margin of 0.05 (given the reported incidence of reflux esophagitis with the current surgical options, a noninferiority margin of ≤5% was deemed clinically acceptable as such a difference would not offset the significant benefits associated with the new technique), a 1:1 ratio between the experimental and control groups, and an anticipated dropout rate of 10%, the sample size was calculated via the PASS software (NCSS, LLC). The resulting sample sizes for both groups were 120 patients each.

Therefore, a total of 240 patients will be included in this study, with 120 patients in the experimental group and 120 patients in the control group.

Basic patient information and clinical data will be collected before discharge, including identity card number; gender; age; contact information; date of operation; surgical approach; duration of surgery; intraoperative blood loss; pathological tumor, node, metastasis staging; number of lymph nodes dissected; number of positive lymph nodes; length of postoperative hospital stay; and postoperative complications. Each patient will be followed up on at the 3rd, 6th, and 12th months postoperatively, and the following data will be collected regarding their postoperative quality of life: daily meal frequency, Visick score, and postoperative quality of life score (using the EORTC QLQ-C30), as well as data on their postoperative nutritional status, including weight change, hemoglobin level, total protein level, albumin level, total lymphocyte count, and PNI.

The basic information and clinical data for each patient collected before discharge will be classified, stored, and entered into the database. The results of each follow-up will be meticulously recorded and entered into the database alongside the other data. All electronic data will be backed up to prevent loss.

Data analysis will be conducted by professional statisticians. In addition to the overall comparative analysis conducted between the TA and DTJIR groups, we will further perform subgroup analyses stratified by disease stage and surgical approach.

Intention-to-treat and per-protocol approaches will be applied for efficacy analysis. An as-treated approach will be used for safety analysis. For continuous variables, a normality test will be performed first. For those that conform to a normal distribution, the 2-tailed t test will be used for statistical analysis (all continuous values will be expressed as means and SDs). Those not conforming to a normal distribution will be presented as quartiles and rank means, and the Mann-Whitney U test will be used to calculate the P value to compare differences between groups. For categorical variables, the chi-square test will be used for statistical analysis. Repeated-measure data will be analyzed using a mixed-effects model. Subgroup analyses will be conducted by disease stage (early vs advanced); surgical approach (open, laparoscopic, or robot-assisted); age; macroscopic types; and tumor, node, metastasis stage. All P values calculated in the analysis will be 2-sided, and P<.05 will be considered statistically significant. If missing data constitute more than 5%, multiple imputations will be conducted. Statistical analyses will be performed via SPSS (IBM Corp), Prism (GraphPad Software), or PASS.