Participants
This is a retrospective study performed at the Department of Gastroenterology, the First Affiliated Hospital of Nanchang University in China. Patients who underwent ESD for gastric lesions at our department between January 2014 and January 2019 were enrolled. Informed consent was obtained from every patient. The exclusion criteria were as follows: (1) did not have a body temperature exceeding 37.5 °C after ESD (regardless of the duration of the fever period); (2) age younger than 18 years or older than 85 years; (3) the use of antibiotics within 2 weeks before ESD; (4) immunodeficiency status; (5) serious cardiovascular, cerebrovascular, or hepatorenal diseases; (6) fever (temperature＞37.5 ℃) before the procedure; (7) patients with incomplete demographic data. This study was approved by the Ethics Committee of the First Affiliated Hospital of Nanchang University.
Relevant definitions
Intraoperative bleeding refers to any bleeding in which haemoglobin is diluted from preoperative level to a level > 2G/dl the day after ESD. Perforation is defined as other organs, extraluminal fat, or extraluminal space outside the muscle layer that can be seen through endoscopy during the ESD operation, regardless of air accumulation in the abdominal cavity, retroperitoneum or mediastinum[13]. En bloc resection is defined as the endoscopic removal of a lesion in one piece and the acquisition of a single specimen. ESD operation time is defined as the period from intraoperative marking time to withdrawal time. Fever is defined as a temperature >37.5 °C after the ESD procedure (regardless of the duration of the fever period). Because the fever time could not be accurately recorded in minutes, we recorded fever duration < 1 day, >1 day ≤ 2 days, >2 days ≤ 3 days, >3 days ≤ 4 days, and >4 days ≤ 5 days as 1, 2, 3, 4, and 5 days, respectively.
Gastric ESD procedure
Before the ESD procedure, patients underwent an endoscopic ultrasound (EUS) test with a radial-scanning echo endoscopy unit (UM240; Olympus Co., Ltd., Tokyo, Japan) or a 12-Fr catheter probe (UM-3R, 12 MHz; Olympus Co., Ltd., Tokyo, Japan) to identify the size, shape and layer of origin of the tumour. In addition, abdominal computerized tomography (CT) was performed to evaluate the tumour location, growth pattern (intra/extraluminal) and the possibility of lateral growth or distant metastasis. All ESD procedures were performed by experienced endoscopists with more than 10 years of experience. A single-channel endoscope (GIF-Q260J; Olympus Co. Ltd, Tokyo, Japan) was used in this procedure. After intravenous anaesthesia with propofol, routine vital sign monitoring was performed. After identifying the gastric lesions through endoscopy, dots were marked around them with argon plasma coagulation (APC, 40 W soft coagulation). Then, 250 ml glycerol fructose, 2—3 ml indigo carmine and 1 ml 1:10,000 epinephrine were injected into the submucosal layer to elevate the lesion. The superficial mucosa was incised along the outer edge of the marker point by endoscopists using a hook knife (KD 620LR, Olympus). Subsequently, an IT knife-2 (KD 611L, Olympus) was used to gradually separate the submucosal layer and lesion, and a snare (SD-230U-20; Olympus) was used to help with the removal of the lesion if necessary. If the gastric lesions originating from submucosal layer or superficial muscularis propria (MP) layer endoscopic submucosal excavation (ESE) was used. ESE is the derivative technology of ESD. On the basis of ESD technology, continue to gradually peel off the submucosa and part of the muscularis propria at the base of the tumor. If the tumor was located in deep MP layer with extraluminal growth pattern or closely adhered to serosal layer, endoscopic full-thickness resection (EFTR) was chosen for safe and complete tumor removal. The difference between EFTR and ESE was the need for active perforation. In order to achieve complete resection, the tumor, the adjacent MP and serosa were removed. Hot biopsy forceps (FD-410LR; Olympus) or argon plasma coagulation (APC 300, ERBE) were used for intraoperative haemostasis. If there was active perforation caused by tumour excavation, titanium clips (HX-610-135; Aomori Olympus) or an over-the-scope clip system (OTSCs, Ovesco Endoscopy AG, Tübingen, Germany) were used to close the perforation. After removing the lesions, a stomach tube was placed based on the experience of endoscopists to reduce gastric pressure for at least 24 h. All specimens were measured and immersed in formalin and were sent to the pathology department for immediate identification of the nature of the lesion.
Postoperative management
Patients were sent to our ward after recovery from anaesthesia and were asked to fast for 2-5 days. All of the patients received infusions (electrolytes, etc.), gastric mucosal protective agents and proton pump inhibitors (PPIs). The stomach tube was removed according to each patient’s condition. If patients had a fever after ESD, they were treated according to the experience of the doctors (either physical cooling, observation treatment, or use of second-generation antibiotics for three consecutive days depending on the situation), and their temperature was recorded once a day until their temperature returned to normal. If they did not have any complications after ESD, they were permitted to return to a normal diet gradually.
Statistical analysis
We divided the patients into two groups according to whether antibiotics were used. The variables are presented as the mean ± standard deviation (SD), the median and interquartile range (IQR) or proportion, as appropriate. Propensity score (PS) analysis was performed as a nonrandomized sensitivity analysis to control and reduce the selection bias of each group. PS was estimated by using a multivariable logistic regression model with the following covariates: age, sex, diabetes, hypertension, previous abdominal surgery, lesion location, tumour size, pathology, intraoperative bleeding, perforation, operation time, en bloc resection, maximum body temperature, and stomach tube. The match ratio was 1:1, and the “nearest neighbour matching” method was used (calliper width=0.02). The absolute standardized difference (ASD) was used to assess the balance of covariates between the two groups. An ASD ＜0.1 signifies a good balance for a particular covariate. Then, we compared the fever days and hospitalization days between the two groups after matching.
The differences in baseline characteristics between the antibiotic and non-antibiotic groups were assessed using Student’s t-test for continuous variables of a normal distribution, the chi-square test or Fisher’s exact test for categorical variables, and the Wilcoxon rank-sum test for rank variables and continuous variables of a abnormally distributed, as appropriate. P<0.05 was considered to be statistically significant. Statistical analyses were performed using R statistical software 3.6.1 (www.r-project.org) and IBM SPSS Statistics for Windows (V. 23.0).