General information and criteria for patient selection
This cohort study was performed using clinical data that were retrospectively retrieved from the medical charts of patients diagnosed with gastric cancer who underwent cancer treatment at our hospital during the period from January 2016 to June 2019. All the patients recruited for this study were further divided into ERAS and ERAS + NAC groups.
The inclusion criteria for patient selection for this study were as follows: (1) patients with complete clinical and pathological data, (2) postoperative pathological examination confirmed the diagnosis of gastric cancer, (3) patients who underwent radical gastric cancer resection, and (4) patients who were compliant with the ERAS perioperative protocol.
To improve the study design, the following exclusion criteria were applied: (1) patients who underwent exploratory laparotomy or reductive surgery, (2) patients who developed synchronous and metachronous malignancies, (3) patients who had emergency surgery, (4) intraoperative exploration revealed tumor invasion of adjacent organs requiring combined organ resection, (5) patients who were converted from laparoscopy to laparotomy, (6) patients who were transferred to the intensive care unit after surgery, (7) patients who failed to complete NAC or were found to have disease progression, and (8) patients who had multiple severe comorbidities.
The ERAS protocol
Patients in the ERAS group followed the preoperative ERAS protocol and underwent a series of preparatory procedures including preoperative admission education, functional exercise, and nutritional support if they were old and malnourished with insufficient cardiopulmonary functions. Gastrointestinal preparation and nil per os were not required for all patients before surgery. Patients without obstruction drank 1000 ml of 10% glucose solution 12 hours before surgery and sipped another 500 ml within 2 hours before surgery. A key procedure to be avoided was the routine placement of a nasogastric decompression tube before surgery.
In accordance with the intraoperative portion of the ERAS protocol, the patients received general anesthesia combined with epidural anesthesia and warm water irrigation to the abdominal cavity. They were also resuscitated with the target-directed fluid-giving approach. Routine placement of an abdominal drainage tube was not performed and the incision was sutured intradermally with absorbable sutures. Afterward, the patients were administered a 0.2% Ropivacaine injection to enhance postoperative pain control at the incision sites.
Postoperatively, the ERAS protocol is mainly focused on multimodal analgesia, which combines thoracic epidural analgesia with intravenous or oral cyclooxygenase (COX) enzyme inhibitors to improve the effectiveness of analgesia. We started a clear liquid diet for all patients approximately 4 hours after Postanesthesia Care Unit stay without a rigid requirement of flatus first. The patients were encouraged to ambulate early and fluid replacement was stopped after the resumption of a full liquid diet.
Chemotherapy regimen
The XELOX regimen is the standard choice for neoadjuvant and postoperative chemotherapy in our Department. The regimen consists of a 3-week cycle of oral Capecitabine (1000 mg/m² twice daily from days 1-14 of each cycle) plus intravenous Oxaliplatin (130 mg/m² on day 1 of each cycle). Patients in the ERAS + NAC group were underwent at least two rounds of NAC. In the 6th week following the first dose of Oxaliplatin, the patients received a work-up through ultrasonic gastroscopy and contrast-enhanced computed tomography of the whole abdomen to assess the degradation of the original malignancy.
The responses to NAC were classified into complete response, partial response, stable disease, and disease progression according to the Response Evaluation Criteria in Solid Tumors (RECIST). The response was calculated with the following equation: clinical response rate = [(number of cases with complete response + number of cases with a partial response)/number of measurable cases] × 100% and disease control rate = [(number of cases with complete response + number of cases with partial response + number of cases with stable disease)/number of measurable cases] × 100%. Blood routine and serum biochemistry were monitored before and after chemotherapy, and cancer surgery was performed in the 2nd week after the completion of NAC.
For postoperative chemotherapy, the patients were prescribed six cycles of chemotherapy with the XELOX regimen immediately after recovering from the trauma of surgery and after adverse complications related to the surgical operation were ruled out. Postoperative chemotherapy was performed with 1-day periodic admissions for intravenous Oxaliplatin.
Preoperative nutritional support
Nutrition-depleted patients were managed with nutritional support. For patients without obvious obstructive symptoms, oral enteral nutrition powder was given in addition to the normal diet due to the gastrointestinal upset and loss of appetite related to chemotherapy and cancer cachexia. For patients with incomplete obstruction, enteral feeding was performed either through a transnasal feeding tube by endoscope-guided insertion or a percutaneous feeding tube through endoscopic gastrostomy and jejunostomy (PEG-J). Enteral nutrition preparations consisted of Nutrison Liquid or Nutrison from Nutricia Co.
Surgical operations
All laparoscopic and open procedures were performed by the same surgical team. Based on the tumor site and preoperative workup, the procedure of distal, proximal, or total gastrectomy was selected for R0 resection. Regarding the laparoscopic approach, the continuation of the digestive tract was reconstructed extracorporeally through a small abdominal incision, which was made after laparoscopic perigastric lymph node dissection. In general, Billroth I and II anastomoses were fashioned after proximal and distal gastrectomy, respectively, and Roux-en-Y anastomosis was installed after total gastrectomy. Six cycles of XELOX chemotherapy were carried out after surgery.
Discharge criteria
The patients were discharged upon the restoration of a regular oral diet and normal ambulation without the restrictions of a urinary catheter, drainage tube, and intravenous lines with no complaints of postoperative pain, which was well controlled by oral pain-relieving medication. Most importantly, the patients were discharged after they autonomously agreed to the discharge.
Outcome measures
The parameters for evaluating the effectiveness of the ERAS protocol were TNM staging, the choice of surgical approach, estimated blood loss (EBL), operating time (OT), placement of drainage and catheter, the volume of fluid resuscitation in surgery (VFRIS), the volume of fluid resuscitation on the first postoperative day (VFRFPD), time to postoperative ambulation (TTPA), time to first postoperative flatulence (TTPF), time to first clear liquid diet (TTFCLD), time to puree and soft food diet (TTPSFD), time of catheter removal (TOCR), length of hospitalization after surgery (LOHAS), length of hospitalization (LOH), complications, mortality, and 30-day readmission rate.
Statistical processing
The data following a normal distribution were expressed as the mean ± SD, and the student’s t-test was used for comparison of the data. Data with a skewed distribution were expressed as M (range) and compared using the Mann–Whitney U test. The enumeration data were expressed as an absolute number or percentage and the χ² test was used for comparison. P < 0.05 was considered statistically significant. IBM SPSS Statistics 26.0 software was used for analysis.