Ethics Approval and Trial Registration
Ethical approval was given by local ethics regional board: Shanghai Changhai Hospital Ethics Committee (No. CHEC 2019-087). Registration with approved clinical trials registry, Chinese Clinical Trials Register, was undertaken (ChiCTR 1900024826). Ethics approval and registration were performed before trial commencement.
Patients
From Jan 2019 to June 2019, a total of 25 cases diagnosed with early AEG were preoperatively performed DTR at Shanghai Changhai Hospital, China, which is a tertiary teaching hospital with more than 2,500 beds serving 40,000 inpatients and 1,800,000 outpatients and emergencies each year. The case volumes for gastric carcinoma reach more than 1500 per year. And we retrospectively collected the data of another 25 early AEG patients performed TG by propensity score matching analysis from Jan 2018 to Dec 2018 as control group.
Preoperative assessments were carried out by endoscopy and biopsy, endoscopic ultrasound and computed tomography (CT) or magnetic resonance imaging (MRI) if necessary. And the eligibility criteria of patients were as follows: (1) gastric cancer was confined within muscularis propria layer by echogastroscopy (T1), (2) no lymph nodes and organs metastases in CT or MRI (N0M0), (3) the diameter of tumor was less than 3cm. Additional inclusion criteria were age 18 to 80 years, life expectancy >1 year, and adequate organ functions (leukocyte count >3,500/μl, platelet count >100,000/μl, hemoglobin >10.0 g/dl, serum creatinine <1.25 times upper limit of normal [ULN], transaminases and alkaline phosphatase <2.5 times ULN or <5 times ULN in patients with liver metastasis, bilirubin <1.5 times ULN, and prothrombin time <12.0 s).
The exclusion criteria of patients were as follows: (1) patients with previous history of abdominal surgery and endoscopic submucosal dissection (ESD), (2) patients with central nervous system involvement or other significant medical conditions, (3) patients chose ESD instead of operation.
Procedures for double-tract reconstruction after PG and conventional alimentary reconstruction after TG
Double-tract reconstruction after PG The decision to perform laparoscopic operation or open procedure is a judgment decision made by surgeons either before or during the operation.The basic range of surgical resection included the distal esophagus and proximal 1/3 to 1/2 stomach with D1+ dissection of lymph nodes (No. 1, 2, 3a, 4sa, 4sb, 7, 8a, 9 and 11p). Intraoperative frozen section examinations were performed to confirm the tumor-negative resection margins. The right gastroepiploic vessels, right gastri cartery and suprapyloric veins were preserved.
Gastrointestinal continuity was restored by double-tract method. The jejunum was divided about 15-20 cm below the Treitz ligament and esophagojejunostomy was performed with the distal jejunum by a circular stapler. Jejunojejunostomy was performed about 45 cm below the esophagojejunostomy and gastrojejunostomy was performed 10 cm below the esophagojejunostomy.
Alimentary reconstruction after TG The basic range of surgical resection included the distal esophagus and total stomach with D2 dissection of lymph nodes (No. 1, 2, 3, 4, 5, 6, 7, 8a, 9 and 11p). Intraoperative frozen section examinations were performed to confirm the tumor-negative resection margins. The jejunum was divided about 15-20 cm below the Treitz ligament and esophagojejunostomy was performed with the distal jejunum by a circular stapler. Jejunojejunostomy was performed about 40 cm below the esophagojejunostomy.
Modification in alimentary tract reconstruction in DTR
- Shorten the distance between esophagojejunostomy and gastrojejunostomy, which was set within 10cm.
- Gastrojejunostomy was performed on the anterior gastric wall.
- Retrocolic gastrojejunostomy were adopted.
- Preserve all pyloric vessels and nerves. (Including: right gastric artery (RGA), right gastric vein (RGV), right gastro-epiploic artery (RGEA), right gastro-epiploic vein (RGEV), infra-pyloric vein (IPV) and pyloric branches of vagal nerve. (Figure 1)
Enhanced Recovery After Surgery (ERAS) program post-operation
All patients underwent an ERAS program which was initially developed through a consensus meeting involving surgeons, oncologists, anesthesiologists and nutritionists. Details are as follows: Preoperative care included counseling before and after admission, avoidance of mechanical bowel preparation, a normal diet until the evening meal of the day before surgery and 1000ml oral rehydration salts intake 3h before surgery. Intraoperative care included transversus abdominis plane block (TAP-block), warming set for all intravenous infusions during operation. Postoperative care included patient controlled analgesia (PCA) in 48 hours after surgery, high flow oxygen for at least 12 hours, analgesia and antiemetic drug use if necessary (no motility agents or opioid antagonists). On postoperative day (POD) 1, nasogastric tube and urinary catheter were usually removed and patients were encouraged to get out of bed for more than 4 hours and drink water or clear soup 50ml per time. From POD 2, patients were encouraged to walk for more than 4 hours and start nutritious powder supplement 100ml per time. From POD 4, patients were encouraged to try semi-liquid diet and stepwise to normal diet. The frequency of food intake was at the patients’ discretion. Drainage tube was evaluated and removed from POD 5. Patients were discharged if they had achieved adequate pain relief and semi-liquid food tolerance, free walking ability, and exhibited normal vital signs and laboratory data. The completion of ERAS program included two categories, the first was that patient followed the aforesaid schedule and discharged within 8 days and the second was one or two days delay due to patients’ personal reason [10].
Clinical Analysis, Surgical Outcomes and Nutritional Status
The indicators of clinicopathological characteristics gathered were age, sex, BMI, ASA score, cancer stage, and tumor size. The surgical characteristics were operation time, estimated blood loss, proximal and distal resection margins, and number of retrieved LNs. The surgical outcomes were recovery of gut function which was measured by time to first flatus and first bowel motion, postoperative daily intake, the severity of gastroesophageal reflux symptoms (Visick score), remnant gastritis, surgical complications, and length of stay (LOS). The degrees and extent of Remnant gastritis and severity of reflux esophagitis (Los Angeles Classification) were evaluated by one same doctor by gastroscope, and the severity of early or late postopertative adverse events was classified according to Clavien-Dindo Classification System.
Follow up
All the patients enrolled were followed up 3, 6, and 12 months post-operation in outpatient department. The characteristics of the patients and their outcomes were obtained by reviewing the electronic medical records and the picture archiving and communication system.
Statistical Analysis
To minimize the influence of other confounders on outcome, we used propensity score analysis to match early AEG patients performed DTR with patients performed TG. Enrolled patients performed DTR were matched in a 1:1 ratio with patients performed TG using the nearest neighbor matching and based on gender (male or female), Siewert Type (Type Ⅰ, Ⅱ, Ⅲ), tumor Grade (well-differentiated, moderately differentiated, poorly differentiated) and TNM stage (Ⅰa, Ⅰb, Ⅱ).
Statistical analysis was performed using SPSS software (18th version, SPSS, Chicago, IL, USA). Enumeration data was presented in percentage, measurement data was presented in average number and standard deviation, abnormal distribution data was displayed by median and quartile. Continuous variables were expressed as mean±SD and compared using the t test or Mann-Whitney test. Categorical variables were compared by the χ2 test or Fisher’s exact test. A probability (P) value <0.05 was considered to indicate statistical significance. All tests were two-sided.