Study design and patients
This single-center retrospective cohort study enrolled 662 patients who underwent gastrectomy for primary gastric adenocarcinoma from January 2011 to December 2019. All patients preoperatively underwent esophagogastroduodenoscopy, computed tomography and/or positron emission tomography. The diagnosis was based on the Japanese Classification of Gastric Carcinoma [October 2017 (The 15th Edition)], Japanese Gastric Cancer Association [7]. Eligibility criteria included age of 20 years old or older, cT1-4 and cN0/+, and partial or total gastrectomy. Patients who had remnant gastric cancer (n = 34) and underwent preoperative chemotherapy or chemoradiotherapy (n = 40), robot-assisted surgery (n = 17), and composite resection of the lower part of the esophagus (n = 23) were excluded.
This study was approved by the Ethics Committee of Kobe University and the institutional review board (No. B200365). Informed consent was obtained from all patients who satisfied the inclusion criteria.
Anticoagulant and antithrombotic therapy
Patients receiving antithrombotic therapy were defined as those who had received antithrombotic agents for prophylaxis of acute coronary artery disease or brain infarction or treatment of DVT/PE. Antithrombotic agents included anticoagulants, such as warfarin and non-vitamin K antagonist direct oral anticoagulants (DOACs) (e.g., rivaroxaban, apixaban, edoxaban, and betrixaban), and antiplatelets, such as aspirin and others (e.g., clopidogrel, dipyridamole, prasugrel, ticlopidine, cilostazol, and ethyl icosapentate). All patients receiving antithrombotic therapy were referred to cardiologists regarding indications for continuation or discontinuation during surgery. In general, heparin bridging was needed for patients treated with DVT/PE or dual antiplatelet therapy within 6 months after percutaneous coronary intervention for acute coronary syndrome. The use of a single aspirin for prophylaxis of acute coronary artery disease was continued during surgery. Single DOAC or antiplatelet agents, excluding aspirin for prophylaxis, were discontinued during surgery and resumed within 24–72 h after surgery if possible.
Outcomes
Data regarding age, sex, body mass index, comorbidities, laboratory findings, operative data, and postoperative clinical course were extracted from medical records. Operative time, intraoperative blood loss, and transfusion were then compared between patients who did and did not receive antithrombotic therapy. Postoperative complications based on the Clavien–Dindo (C-D) classification were also analyzed. Postoperative complications included postoperative hemorrhage, thrombosis, surgical site infection (SSI), anastomotic leakage, pancreatic leakage, postoperative pneumonia, and arrhythmia. We thought clinically significant postoperative complications were two or more grade of the C-D classification.
Statistical analysis
To remove any bias from all observed covariates, two groups of patients were established using propensity score (PS) matching. PSs for individuals were calculated using age, sex, tumor invasion depth, lymph node metastasis, surgical approach (open or laparoscopic), and procedures as covariates. Accordingly, one group patient was sequentially matched to another group patient using the PSs with a 1:1 nearest neighbor matching algorithm without replacement. To prevent low matches, a caliper equal to 0.20 of the standard deviation of the logit of the PS was used. The χ2 test, Student’s t-test, or Mann–Whitney U test were performed to determine statistical differences between both groups as appropriate, with P values < 0.05 indicating statistical significance.
All statistical computations, including PS matching, were performed using JMP® 14 (SAS Institute, Cary, NC, USA).