Inclusion and exclusion criteria
Patients with resectable or potentially resectable AGC who received chemotherapy plus immunotherapy or chemotherapy before surgical treatment were included in this study. All included patients were treated at Peking University Cancer Hospital and Institute Gastrointestinal Cancer Center I between January 2019 and June 2021. Patients aged between 18 and 80 years old with a Karnofsky performance scale score higher than 70 were eligible. In addition, patients were excluded if they had (1) other malignancies, (2) a history of upper abdomen operation other than laparoscopic cholecystectomy, (3) medical conditions requiring emergency surgeries, (4) a history of receiving any radiotherapy or antiangiogenesis treatment before surgery, or (5) a history of thoracotomy. The study was approved by the Ethics Committee of Beijing Cancer Hospital (No. 2017XJS07), and all eligible participants provided written informed consent.
Preoperative treatment strategies
The determination of treatment routines was managed by the multidisciplinary team (MDT). The choice of treatment strategy, including PCIT or PCT, was decided through shared decision-making between patients and doctors, with consideration of gastroscopic biopsy pathological immunohistochemical results, such as microsatellite status, tumor mutational burden (TMB), EBER status, programmed death-ligand 1 combined positive score (PD-L1 CPS) and other results. The doctors informed patients that PCT was the standard treatment. If the patients had one or more of the following indicators, such as microsatellite instability-high (MSI-H), TMB-high, EBER-positive, or PD-L1 CPS ≥ 5, PCIT was strongly recommended. If the patients and their relatives agreed, PCIT was employed; otherwise, PCT was employed. The surgical approach, either open gastrectomy or laparoscopic gastrectomy, was chosen according to the preferences of each patient after sufficient explanation of the advantages and risks of both approaches. If a patient could not decide on the surgical approach, the chief surgeon decided based on actual operative circumstances. In each group, the range of gastrectomy and the extent of lymphadenectomy were both chosen based on the Japanese Gastric Cancer Treatment Guidelines 2018 (5th edition) [24] and the Japanese Classification of Gastric Carcinoma: 3rd English Edition guidelines [25]. Laparoscopic exploration was performed to determine whether there was adjacent organ invasion and peritoneal dissemination prior to the operation.
Surgical techniques
An incision of approximately 20–25 cm in length was made from the falciform process to the periumbilical area in patients who chose open approaches. Laparoscopic surgery was performed using five trocars, including one 12-mm trocar below the umbilicus for the camera, two five-mm trocars that were placed in the right anterior axillary below the costal margin level and the left clavicular midline at the umbilical level, and two additional 12-mm trocars that were placed in the right clavicular midline at the umbilical level and the left anterior axillary below the costal margin. The main reconstruction methods included esophagogastrostomy, double-tract reconstruction, Roux-en-Y, uncut Roux-en-Y, and standard Billroth I or Billroth II gastrojejunal anastomosis with Braun’s anastomosis. The chief surgeon chose a suitable reconstruction method depending on the actual operative conditions. These procedures were performed by a single surgical team with extensive experience in both open and laparoscopic procedures to treat GC. Conversion to open surgery was performed when the surgeon considered an open approach to be necessary for a particular surgical situation, such as in the case of dense peritoneal adhesions, pneumoperitoneum intolerance, severe hemorrhaging during operation, and extensive tumor invasion. During the perioperative periods, all the patients were managed by a standard clinical scheme. Discharge was recommended when the patient tolerated more than two days of a soft diet without abdominal pain or fever.
Data collection and outcome measurements
Demographic characteristics, including age, sex, weight, height, comorbidities, American Society of Anesthesiology (ASA) scores, and pathological characteristics, were collected from all included patients. Body mass index (BMI) was calculated from weight and height for each patient. Enhanced abdominal computed tomography (CT) was conducted before and after preoperative treatment in each patient to evaluate the preoperative treatment response according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [26]. The overall response rate (ORR) was defined as the percentage of patients who achieved complete response (CR) or partial response (PR). The disease control rate (DCR) was defined as the ORR plus the rate of stable disease (SD). Pathological and clinical stages were determined according to the 8th edition of the International Union Against Cancer (UICC) TNM classification [27]. In addition, tumor regression grade (TRG) was also used to evaluate the response to preoperative therapy based on the NCCN Clinical Practice Guidelines in Oncology for Gastric Cancer (version v3.2015) [28].
The length of incision, operation time, and estimated blood loss were collected. Postoperative recovery-relevant indices, including time to first aerofluxus, time to first defecation time, time to liquid diet, time to drainage removal, and length of hospital stay after surgery, were also recorded. Furthermore, the number of retrieved and metastatic lymph nodes, long and short tumor diameters, proximal margin length of the tumor, and distal margin length of the tumor, which were measured on fresh surgical tissue specimens, were recorded. The visual analog scale (VAS) [29, 30] was used to assess postoperative pain intensity at 24, 48, and 72 h after surgery. The duration of intravenous patient-controlled analgesia (IV-PCA) use and the supplementary analgesic dose were recorded in each patient. The supplemental analgesic dose after surgery was converted to oral morphine equivalents (OMEs) [31]. Postoperative complications were defined as conditions that occurred during the hospital stay following surgery and were graded using the Clavien‒Dindo classification system [32, 33]. Severe complications were defined as Clavien‒Dindo grade III or greater. Postoperative mortality was defined as death that occurred within 30 days after initial surgery, regardless of cause.
Statistical analysis
In the case of continuous variables, the data are displayed as the means and standard deviations, and in the case of categorical variables, the data are displayed as proportions. For high-skew data, the results are presented as the medians (interquartile ranges, IQRs). Independent t tests, Mann‒Whitney U tests, chi-square tests, and Fisher’s exact tests were used to determine differences between the two groups’ baseline data and outcomes. The correlation analyses were performed using Pearson correlation. All p values were two-sided, and a p value < 0.05 was considered statistically significant. All the above statistical analyses were conducted by the SPSS version 24.0 software package (IBM Corp., Armonk, NY, USA).
