Effect of Pre-habilitation Combined With Enhanced Recovery After Surgery (ERAS) Versus ERAS Perioperative Management on Clinical Outcomes of Laparoscopic (Robotic) Gastrectomy in Patients With Gastric Cancer Receiving Neoadjuvant Chemotherapy: A Single-center Randomized Controlled Trial
Phase: NA
Conditions: Gastric Cancer (GC)
Sponsor: The Affiliated Hospital of Qingdao University

Prehabilitation for Gastric Cancer Patients Receiving Neoadjuvant Chemotherapy: A 
Randomized Trial 
 
Study Protocol  
 
 
 
Research Sponsor: The Affiliated Hospital of Qingdao University 
 
Date: 2024.7.27 
 
QYFYEC2025-08 
 
 
 
 
 
 
 

Table of Contents 
 
Study Protocol Abstract 
Study Protocol 
1.Research Background 
1.1 Epidemiology of Gastric Cancer 
1.2 Application of Neoadjuvant Therapy 
 1.3 Overview of Enhanced Recovery After Surgery (ERAS) 
 1.4 Preoperative Prehabilitation 
2.Study Objectives 
3.Study Design 
 3.1 Study Population 
 3.2 Neoadjuvant Treatment Regimen and Efficacy Evaluation 
 3.3 Intervention 
 3.4 Surgical Procedure 
 3.5 Postoperative Adjuvant Chemotherapy 
4.Study Endpoints and Endpoint Measurements 
5.Sample Size Estimation 
6.Permissible Treatments and Medications During the Study 
7.Measurements and Recorded Indicators 
 7.1 Outpatient Enrollment Assessment 
 7.2 Preoperative Assessment 
 7.3 Intraoperative Details 
 7.4 Postoperative Status and Short-Term Clinical Outcomes 
 7.5 Adverse Events and Evaluation 
 7.6 Postoperative Follow-Up Plan 
8.Statistical Analysis 
 8.1 Data Collection, Monitoring, Review, and Interim Analysis 
 8.2 Statistical Analysis Plan 
   8.2.1 Enrollment and Withdrawal Analysis 
   8.2.2 Demographic and Baseline Characteristic Analysis 
8.2.3 Primary Outcome Measure Analysis 
8.2.4 Secondary Outcome Measure Analysis 
8.3 Data Storage Plan 
9.Informed Consent 
Attachments 
References 
Appendix Prehabilitation Manual 
Protocol Signature Page 
 
 

Study Protocol Abstract: 
Protocol 
Number 
1.0 
Protocol Title 
Effect of Prehabilitation Combined with ERAS versus ERAS 
Perioperative Management on Clinical Outcomes of Laparoscopic 
(Robotic) Gastrectomy in Patients with Gastric Cancer Receiving 
Neoadjuvant 
Chemotherapy: 
A 
Single-Center 
Randomized 
Controlled Trial 
Study 
Population 
Patients aged 18-75 years receiving neoadjuvant therapy scheduled 
for laparoscopic (robotic) radical gastrectomy for gastric cancer. 
Study Objective 
To investigate the impact of prehabilitation combined with 
perioperative ERAS pathway management versus perioperative 
ERAS pathway management alone on short-term and long-term 
clinical outcomes in gastric cancer patients receiving neoadjuvant 
therapy undergoing laparoscopic (robotic) radical gastrectomy. 
Study Design 
This is a prospective, single-center, randomized, open-label, 
controlled clinical trial. It compares the effects of a 4-week tri-modal 
prehabilitation 
(exercise, 
nutrition, 
psychological 
intervention) 
combined with perioperative ERAS pathway management versus 
perioperative ERAS management alone on short-term and long-term 
clinical outcomes in gastric cancer patients receiving neoadjuvant 
chemotherapy undergoing laparoscopic (robotic) surgery. It also 
observes the safety, feasibility, and efficacy of the combined 
prehabilitation and ERAS pathway management in patients receiving 
neoadjuvant chemotherapy. The trial is designed with a 1:1 allocation 
ratio for the target number of effective cases between the 
experimental and control groups. The experimental group receives 4 
weeks of tri-modal prehabilitation combined with perioperative ERAS 
pathway management, while the control group receives perioperative 
ERAS management alone until discharge. Relevant indicators and 
adverse events are recorded. Patients are followed up in the 
outpatient clinic until 3 years postoperatively or death. 
Sample Size 
Total sample size is 136 cases, 68 in each group. The sample size 
calculation is based on the following assumptions. According to our 
center's data and previous study results [2-4], the 30-day 
postoperative 
complication 
rate 
in 
neoadjuvant 
patients is 
approximately 25%. It is expected to decrease to 15% after combined 
multimodal prehabilitation and ERAS intervention. Assuming a 9-
month recruitment period, a superiority margin of 0.3, a 1:1 
randomization ratio, a significance level α=0.05 (one-sided), a test 
power (1-β=80%), and a dropout rate=10% in either group, a total 
sample size of at least 136 patients (68 in the experimental group, 68 
in the control group) is required. 
Randomization 
All participants will be randomized to the experimental or control 

Method 
group using a random number table method, with a 1:1 allocation 
ratio. 
Planned Study 
Period 
Recruitment Start Date: December 2024 
Planned Study 
Period 
Inclusion 
Criteria 
Recruitment End Date: November 2025 
Follow-up End Date: December 2025 
Preliminary Analysis Date: February 2026 
1. 18 years ≤ Age ≤ 75 years. 
Inclusion 
Criteria 
Exclusion 
Criteria 
2. ECOG score 0-2. 
3. ASA classification I-III. 
4. Pathologically confirmed gastric adenocarcinoma (cT3-4N-M0) by 
endoscopy before neoadjuvant therapy, deemed suitable for radical 
resection by MDT discussion. 
5. Negative pregnancy test within one month, not pregnant or 
breastfeeding. 
6. Informed consent and ability to comply with the study protocol. 
1. Severe cardiac insufficiency (preoperative LVEF <30% or NYHA 
class IV). 
Exclusion 
Criteria 
Withdrawal 
Criteria 
2. Severe hepatic or renal insufficiency (Child-Pugh ≥10; creatinine 
clearance <25 ml/min). 
3. History of cerebral hemorrhage, cerebral infarction, TIA within six 
months, or presence of central nervous system diseases/psychiatric 
illnesses preventing completion of neoadjuvant therapy. 
4. Synchronous tumors or other diseases requiring simultaneous 
surgery (except laparoscopic cholecystectomy). 
5. Tumor complications (e.g., bleeding, perforation, obstruction) 
requiring emergency surgery. 
6. Severe infection or other severe comorbidities. 
7. Participation in other clinical trials. 
1. Participant requests to withdraw or discontinue the trial. 
Withdrawal 
Criteria 
Outcome 
Measures 
2. After enrollment, the patient's condition changes, and the attending 
physician confirms the need for emergency surgery. 
3. Violation of the trial protocol. 
Primary Endpoint: 
Outcome 
Measures 
Safety 
Indicators 
1.Incidence of 30-day postoperative complications. 
Non-surgical complications: Respiratory complications, urinary 
tract infection, pulmonary embolism, cerebrovascular accident, 
impaired liver/kidney function, etc. 
Surgical complications: Bleeding, anastomotic leak, anastomotic 
stenosis, intestinal obstruction, delayed gastric emptying, abdominal 
infection, surgical site infection, pancreatic leak, etc. 
Complication severity assessed using Clavien-Dindo classification (I-
V). 

Secondary Endpoints: 
1. Pathological data: Type, size, location, stage, etc. 
2. Surgical operation and short-term clinical outcomes. 
3. Patient-Reported Outcomes (PRO). 
4. 6-Minute Walk Test (6MWT). 
Adverse Events/Adverse Reactions/Serious Adverse Events/Serious 
Adverse Reactions: All adverse events during the trial intervention 
phase will be recorded. The investigator is responsible for ensuring 
all adverse events are accurately documented in the participant's 
medical records. 
Statistical 
Analysis 
All statistical analyses will be performed using SPSS version 26.0 or 
later. Unless otherwise specified, all statistical tests will use a two-
sided test with α=0.05, and confidence intervals will be two-sided 
95%. Descriptive statistics (mean, median, standard deviation, min, 
max) will summarize continuous variables; counts and percentages 
for categorical variables. 
Enrollment/Withdrawal 
Analysis: 
Counts/percentages 
enrolled, 
completed, withdrawn. 
Demographics/Baseline Analysis: Descriptive statistics per group; t-
test, χ² test, or rank-sum test for group comparability. 
Primary Outcome Analysis: χ² test for complication rates, etc. 
Secondary Outcomes Analysis: t-test, χ² test, rank-sum test; log-rank 
test for survival curves. 
Follow-up 
Prehabilitation patients will be followed during the prehabilitation 
period. All participants will be followed up at 30 days postoperatively. 
Outpatient follow-up every 2-3 months until 1 year postoperatively, 
recording disease information. 
 
 
 
 
 

Study Protocol: 
 
Title: Prehabilitation for Gastric Cancer Patients Receiving Neoadjuvant Chemotherapy: A 
Randomized Trial 
 
1. Research Background 
1.1 Epidemiology of Gastric Cancer 
Gastric cancer is one of the most common malignancies worldwide. WHO and 
GLOBOCAN statistics show it ranks 5th in incidence and 4th in mortality [5]. China has 
about 400,000 new cases and 290,000 deaths annually [6], posing a significant disease 
burden. Data from the Chinese Gastrointestinal Cancer Surgery Alliance indicates that 
early gastric cancer accounts for only 20%, while locally advanced and advanced stages 
account for 70% and 10%, respectively [7]. Unlike Japan and Korea, where early detection 
and treatment are common, diagnosis in China often occurs at advanced stages, causing 
significant distress. The efficacy of treatment for advanced gastric cancer is inferior to early 
stages, with less than 50% achieving R0 resection, and over 50% of those having poor 
prognosis post-resection [8]. Neoadjuvant therapy offers hope, playing a vital role in 
treating advanced gastric cancer. 
1.2 Application of Neoadjuvant Therapy 
Neoadjuvant chemotherapy (NACT) for gastric cancer aims to reduce tumor stage and 
eliminate occult micrometastases, thereby increasing the rate of radical resection and the 
chance of cure. First proposed by Frei et al. [9] in 1982, it was first applied to gastric cancer 
by Wilke et al. [10] in 1989. NACT can reduce tumor size and stage, improving overall 
survival (OS) and progression-free survival (PFS). Japanese studies JCOG001 [11], 
JCOG0405 [12], JCOG1002 [13] showed promising results. JCOG0405 using cisplatin+S-
1 reported 3-year and 5-year OS of 59% and 53%, superior to JCOG0001. JCOG1002 
adding docetaxel showed no additional benefit. In Europe and the US, neoadjuvant therapy 
is standard for locally advanced gastric cancer. The European MAGIC trial [14] (ECF 
regimen) and the French FNCLCC/FFCD9703 trial [15] (PF regimen) showed similar 
benefits (tumor downstaging, increased R0 resection, prolonged OS). Our center 
participated in the RESOLVE study [16], confirming the non-inferiority of the SOX regimen 
to Capox, providing good RFS and increased R0 resection rates. 
Although guidelines vary slightly, the combined modality of surgery plus NACT is firmly 
established as first-line treatment for advanced gastric cancer. However, while improving 
clinical outcomes, NACT also induces physiological and pathological changes. The tumor 
itself reduces tolerance to treatment, and chemotherapy decreases functional capacity and 
worsens malnutrition. This impaired state reduces the ability to cope with surgical stress, 
potentially increasing complications, worsening outcomes, and impairing prognosis. Jack 
et al. [17] first used CPET to show NACT is associated with reduced physical fitness and 
shortened 1-year OS. Sinclair et al. [18] and West et al. [19] found decreased 
cardiopulmonary function in gastroesophageal adenocarcinoma and rectal cancer patients, 
respectively, linked to perioperative complications. Cognitive impairment and neurotoxicity 
from chemotherapy also reduce quality of life [20]. This poorer health status is linked to 
reduced NACT tolerance, increased drug toxicity, nutritional risk, and clinical prognosis. 

Therefore, robust perioperative management is needed to improve physical state or reduce 
functional decline. Preoperative prehabilitation is a crucial component. 
1.3 Overview of Enhanced Recovery After Surgery (ERAS) 
The ERAS concept, first proposed by Danish surgeon Kehlet [21], is a major milestone in 
surgery. Its core is the use of optimized, evidence-based perioperative measures to reduce 
physiological and psychological surgical stress, accelerating recovery. Unlike traditional 
care, ERAS integrates anesthesiology, pain control, nutrition, psychological adjustment, 
and surgery, combining interventions to enhance postoperative recovery and improve 
clinical endpoints. In China, Professor Jieshou Li first applied ERAS to gastrointestinal 
surgery in 2007 [22]. Our center published the first RCT on ERAS in gastric cancer surgery, 
showing its safety and feasibility, with advantages over traditional care: reduced stress, 
shorter hospital stay, improved quality of life, without increased complications [23]. 
Compared to conventional care, the ERAS group had significantly shorter postoperative 
stay (7.09d vs 8.67d, P<0.001), earlier first flatus, oral intake, and ambulation (2.50d vs 
3.40d, P<0.001; 1.02d vs 3.64d, P<0.001; 1.47d vs 2.99d, P<0.001), and lower costs 
($7621.75 vs $7814.16, P=0.009). Complication rates were higher in the conventional 
group (18.1% vs 12.3%, P=0.030). Inflammatory markers (CRP, PCT) differed significantly 
on POD 3/4 (P<0.001, P=0.025). ERAS also significantly improved 5-year OS and cancer-
specific survival (P=0.013 and P=0.032), particularly in stage III patients (P=0.044). 
Adherence to ERAS improves short-term outcomes, 5-year OS, and cancer-specific 
survival after laparoscopic gastrectomy. 
However, many ERAS studies exclude neoadjuvant therapy patients. We aim to evaluate 
whether these patients benefit from prehabilitation combined with ERAS. 
1.4 Prehabilitation 
Facing the challenges of NACT, prehabilitation has been integrated into clinical practice. 
Prehabilitation involves preoperative interventions to improve physiological and 
psychological state, enhancing the response to surgical stress. Introduced in the early 21st 
century, Carli [24] proposed a multimodal intervention centered on exercise (aerobic, 
resistance, breathing). Topp [25] introduced prehabilitation in ICU. Given the impact of 
cancer on quality of life, prehabilitation is needed in oncology. Since Kehlet's Fast-Track 
surgery [26] was introduced to surgical oncology, evolving into ERAS, it has become 
essential for improving outcomes in cancer patients [27]. 
However, ERAS primarily focuses on intra- and post-operative periods, lacking effective 
preoperative intervention. Prehabilitation, as a key preoperative component of ERAS, 
includes nutrition, exercise, and psychological interventions. Key elements include: ① 
Correcting preoperative anemia. ② Preventive analgesia (e.g., NSAIDs, COX-2 inhibitors) 
[28]. ③ Preoperative frailty assessment (e.g., Clinical Frailty Scale, CFS) and intervention 
[29]. ④ Preoperative exercise: Assess tolerance and create a plan to improve functional 
capacity [30]. ⑤ Preoperative cognitive assessment (e.g., MMSE, MoCA) and intervention 
if needed [31]. ⑥ Preoperative inflammation control: Consider steroids to reduce pain, 
inflammation, fatigue [32]. ⑦ Preoperative psychological intervention: Assess with HADS, 
provide support [33]. ⑧ Preoperative nutritional support: Screen with NRS2002. Provide 
support if: >10% weight loss in 6 months, NRS2002≥5, BMI<18.5 with poor condition, 
albumin<30g/L. Prefer oral/enteral route. Duration typically 7-10 days [34]. 

Francesco Carli et al. found prehabilitation increased 6-minute walk distance (6MWD) 
preoperatively (+36.9m vs -22.8m in controls) and postoperatively (+15.4m vs -81.8m in 
controls, P<.001), indicating improved cardiopulmonary function [35]. Prehabilitation 
improves preoperative and postoperative functional capacity, prevents decline in 
physical/nutritional status, and impacts cancer care continuity. 
Current evidence lacks high-quality multicenter studies supporting prehabilitation. 
There's no standardized intervention duration. There's a need for patient-centered, 
multidisciplinary, individualized prehabilitation programs and determining the optimal 
duration to provide theoretical guidance and evidence for perioperative management. 
 
2. Study Objectives 
This study aims to compare the effects of prehabilitation combined with perioperative 
ERAS pathway management versus perioperative ERAS pathway management alone on 
short-term outcomes and long-term prognosis in gastric cancer patients receiving 
neoadjuvant chemotherapy undergoing laparoscopic (robotic) radical gastrectomy, and to 
explore its feasibility, safety, and clinical application prospects. 
 
3. Study Design 
3.1 Study Population 
Eligible patients providing informed consent will be randomized using a SAS 9.4 generated 
random list by a staff member. The trial uses a 1:1 allocation ratio. The experimental group 
receives prehabilitation combined with ERAS management; the control group receives 
ERAS management alone. Both groups receive standard management from admission 
until discharge, with relevant indicators and adverse events recorded. Outpatient follow-up 
continues until 1 year postoperatively or death/recurrence. 
3.2 Neoadjuvant Treatment Regimen and Efficacy Evaluation 
All patients undergo Multidisciplinary Team (MDT) discussion (including rehabilitation, 
clinical nutrition, psychiatry, oncology, gastrointestinal surgery, radiology, pathology) to 
decide on NACT and determine the regimen. Regimens are primarily fluorouracil-based 
combined with other drugs (targeted therapy, immunotherapy, etc.), given for 2-4 cycles 
preoperatively. Options include: (1) SOX [36]: Oxaliplatin 130mg/m² iv d1 + S-1 40-
60mg/m² po d1-14. (2) DOS [37]: Docetaxel 40mg/m² iv d1, Oxaliplatin 85mg/m² iv d1 + S-
1 40-60mg/m² po bid d1-14. (3) FLOT [38]: Docetaxel 50 mg/m², Oxaliplatin 80 mg/m², 
Leucovorin 200 mg/m², Fluorouracil 2600 mg/m² 24h infusion, d1. (4) XELOX [39]: 
Oxaliplatin 130mg/m² iv d1 + Capecitabine 850-1000mg/m² po bid d1-14. HER-2, MMR, 
MSI, EBV testing determines use of trastuzumab, immunotherapy, etc. 
Patients undergo regular imaging, endoscopy, pathology, tumor markers post-NACT to 
evaluate response. MDT reassesses after 2-4 cycles using imaging (RECIST 1.1: CR, PR, 
PD, SD) and postoperative pathology (CAP-TRG: 0-3). If CR/PR, radical surgery within 1 
month (at least 1 week post-NACT). If SD, MDT decides surgery, continue 1-2 cycles, or 
switch regimen. If PD, MDT assesses resectability. 
3.3 Intervention 
Intervention Plan: 
The study flowchart is shown in Figure 1. Enrollment occurs at the gastrointestinal 

surgery outpatient clinic. The intervention period is from the end of NACT until surgery (4 
weeks total). This is a prospective RCT with two groups: Multimodal Prehabilitation + 
Standard ERAS Management (Prehabilitation Group) and Standard ERAS Management 
alone (Control Group). At baseline (decision for NACT), comprehensive assessment is 
performed (cardiopulmonary function, 6MWD, nutrition, labs, CT, etc.). The Prehabilitation 
Group receives individualized prehabilitation guidance (exercise, breathing, nutrition, 
psychology) plus standard preoperative ERAS guidance. The Control Group receives 
standard preoperative ERAS guidance. Involvement includes hospital team and 
family/patient, monitored via wearable devices, WeChat, phone. NACT is 2-4 cycles, 
decided by MDT based on condition, fitness, response. 
 
 
Figure 1. Flowchart for Multimodal Prehabilitation in Neoadjuvant Gastric Cancer Patients 
 
The prehabilitation content, based on previous studies and local practice, is developed by 
GI surgery, rehabilitation, nutrition, and psychology. It includes exercise, nutrition, and 
psychology. After individual assessment, patients receive one-on-one counseling and 
education, the Prehabilitation Manual, and Prehabilitation Diary. Weekly follow-up 
assesses adherence. At admission, the diary is collected, and a questionnaire on 
prehabilitation strategies is completed. The manual and guidance include: 
Group 
Intervention Modality 
Specific Measures 
Prehabilitation 
Group 
Exercise 
Physical 
fitness 
training 
Resistance & Endurance: At 
least 3 days/week, 2 
sessions/day (aerobic & 
resistance alternating), 
30min/session. Includes: 5min 
warm-up, 25min aerobic (stairs, 
jogging, brisk walking) OR 25min 
resistance (seated leg raises, 
wall push-ups, standing lateral 

raises, half-squats, sit-ups; 3-4 
exercises/session, 3-4 
sets/exercise, 12-15 reps/set 
optimal), 5min cool-
down/stretching. 
Breathing 
Breathing Training: Must quit 
smoking. Includes: 
• Balloon blowing: Start small, 
slow exhalation until breathless, 
hold 3-5s. 
• Back patting/coughing: Sit 
leaning forward, deep breath, 
immediately perform forceful 
cough. 
• Chest breathing: Hands on ribs, 
inspire against resistance, 
expand chest, hold 2-3s, I:E=1:3, 
15 reps/set, 3 sets/time, 3 
times/day. 
• Incentive spirometer: Use 
correctly, slow exhalation, hold 2-
3s at target. 3 sets/time, 3 
times/day. 
Nutrition Intervention 
Advise healthy diet: avoid high-
energy/fat; increase vegetables, 
fruit, fiber, micronutrients, high-
quality protein. Aim for 1.5g 
protein/kg/day. If nutritional 
risk/malnutrition, provide 
ONS/EN (≥400kcal/day). If 
ONS/EN inadequate <3 days or 
<50% needs >1 week, use PN. 
Combine PN+EN for gastric 
outlet obstruction. Refer to 
nutrition clinic. Supplement iron, 
Vitamin D, multivitamins as 
needed. 
Psychological Intervention 
Assess anxiety with HADS. 
Mild/moderate: Guided imagery, 
meditation, pleasant music with 
family help. Severe: Refer to 
psychology clinic. 

Control Group 
Traditional 
ERAS Preop 
Management 
Preop 
Exercise 
Quit smoking/limit alcohol; deep 
breathing exercises; appropriate 
activity. 
Preop 
Nutrition 
Screen/assess nutritional status; 
dietary guidance, small frequent 
meals; supplemental PN/EN if 
needed for ≥1 week. 
Preop 
Psychological 
Care 
Assess psychological state, 
family support, finances; 
communicate concerns, increase 
communication. 
 
Assessment: 
(1) Exercise Intensity: The intensity of exercise is evaluated through two aspects: the 
subjective fatigue rating (rating of perceived exertion, RPE), also known as the Borg scale, 
and the target heart rate.  
The intensity of endurance training should be set within the modified Borg scale range 
of 13-16 points, that is, the subjective fatigue sensation is slightly strenuous or strenuous. 
If the patient feels that the exercise can be completed easily, the intensity can be 
appropriately increased. When the patient feels severe fatigue or slight shortness of breath, 
the intensity can be reduced. It is not recommended to exercise too intensely [40]. The 
target heart rate is calculated based on the patient's age, that is, target heart rate = (220 - 
age) * (70% - 80%). For example: for a 60-year-old patient, their target heart rate = (220 - 
60) * (70% - 80%) = 112 - 128 beats.  
During resistance training and endurance training, it is important to take breaks between 
groups to prevent muscle soreness and affect compliance. 
(2) Pulmonary Function: Prehabilitation group assessed pre- and post-training; control 
group preoperatively. Best of 3 attempts recorded (FEV1, FVC, FEV1/FVC, MVV, PEF). 
(3) 6-Minute Walk Test (6MWT) [41]: Prehabilitation group pre- and post-training; control 
group preoperatively. Conducted in a 15m corridor. Instructions given. Distance in 6 
minutes recorded. Monitor for symptoms. BP, HR, SpO₂ pre/post. Interpretation: <150m 
severe cardiac impairment; 150-425m moderate; 426-550m mild. 
 
Control Group Intervention: 
Patients managed per center's gastric cancer ERAS pathway. Preop: smoking/alcohol 
cessation, 
coughing 
exercises, 
DVT 
prophylaxis, 
nutrition 
screening/support, 
communication. Surgery: laparoscopic/robotic. Anesthesia: epidural + general. Goal-
directed fluid therapy. Postop: early ambulation, early tube removal, multimodal analgesia. 
See Table 1 for ERAS pathway details. 
 
 
(Table 1) Gastric Cancer Perioperative ERAS Pathway Management Plan 

Intervention Measure 
Whether to execute 
PRE-ADMISSION 
Preoperative organ function/risk 
assessment & clinical decision 
Yes 
Instruct patient to quit 
smoking/alcohol 
Yes 
Encourage patient/family 
participation 
Ye 
PREOPERATIVE MANAGEMENT 
MDT-led consultation, explain 
ERAS 
Yes 
Preoperative education, 
expectation management, 
discharge planning 
Yes 
Mental state assessment & 
intervention 
No 
Bowel preparation 
Not routine, case-by-case 
Fasting (solids 6h, clear liquids 
until 2h pre-op) 
Yes 
INTRAOPERATIVE MANAGEMENT 
Nasogastric tube 
Not routine, case-by-case 
Surgical incision 
Minimize size for exposure 
Anesthesia method 
Epidural (Th7-11) + General Anesthesia 
Intraoperative warming 
Warming blanket, fluid warmer 
Antibiotic prophylaxis 
30min pre-incision, re-dose if >3h 
Abdominal drain 
Remove 24h postop 
Wound closure 
Absorbable suture 
Pain management 
Urinary catheter 
Remove 24h postop 

IV fluids 
Goal-directed therapy 
Patient mobilization 
Encourage; bedside day of surgery, ambulate 
POD1 
Thromboprophylaxis plan 
MDT assess/screen/intervene; risk assessment, 
TED stockings, IPC, mobilize (>6h), massage, 
prophylactic heparin 
Nasogastric tube 
Not routine, case-by-case 
Surgical incision 
Minimize size for exposure 
POSTOPERATIVE MANAGEMENT 
Planned discharge, MD/nutritionist 
discharge instructions, 24h post-
discharge call 
Yes 
Treatment review & summary 
Yes 
30-day post-discharge follow-up & 
management 
Yes 
ERAS: ENHANCED RECOVERY OF SURGERY; NSAIDS: NON-STEROIDAL 
ANTIINFLAMMATORY DRUGS; DVT: DEEP VENOUS THROMBOSIS 
 
3.4 Surgical Procedure 
Surgeons: Must have performed ≥50 laparoscopic-assisted gastrectomies with D2 
lymphadenectomy. 
Requirements: Minimally invasive approach. Laparoscopic access follows Chinese expert 
consensus. D2 radical lymphadenectomy per Japanese Gastric Cancer Association 
guidelines. Lymph node processing per Chinese expert consensus. Surgery type: Da Vinci 
robotic / Laparoscopic. Procedure: Total / Proximal / Distal Gastrectomy. Reconstruction: 
Billroth I / Billroth II / Roux-en-Y / Billroth II+Braun / Esophagojejunostomy Roux-en-Y. 
Postop complications graded by Clavien-Dindo. 
 
3.5 Postoperative Adjuvant Chemotherapy 
Both groups are reviewed ~1 month post-discharge. Decision for adjuvant chemotherapy 
based on pathology. If indicated, use SOX, XELOX, DOS, etc., based on 
tolerance/assessment. 
 
4. Study Endpoints and Endpoint Measurements 
Primary Endpoint: Incidence of 30-day postoperative complications (recorded during 1-
month follow-up). Includes non-surgical (respiratory, UTI, PE, CVA, hepatic/renal 

impairment) and surgical (bleeding, leak, stenosis, obstruction, delayed emptying, infection, 
pancreatic leak) complications. Severity by Clavien-Dindo. 
Secondary Endpoints: 
1.Pathological data. 
2.Surgical operation & short-term outcomes. 
3.Patient-Reported Outcomes (PRO). 
4.6MWT. 
 
5. Sample Size Estimation 
Total sample size 136 (68/group). Based on assumed complication rate of 25% (control) 
vs 15% (intervention), 1:1 ratio, α=0.05 (one-sided), power=80%, dropout=10%, superiority 
margin=0.3. 
 
6. Permissible Treatments and Medications During the Study 
Treatments/medications for adverse events should be recorded in CRF. Includes: 
antipyretics/NSAIDs for fever; antibiotics for infection; PPIs; antidiarrheals; antiemetics 
(ondansetron); sedatives for insomnia; antihistamines for allergy; somatostatin for bloating; 
hemostatics/transfusions for bleeding; G-CSF for leukopenia; TPO for thrombocytopenia. 
 
7. Measurements and Recorded Indicators 
Data recorded in CRF for outpatient, preop, intraop, postop phases. Data entry into 
EpiData by two independent staff, quality monitored by a third. 
7.1 Outpatient Enrollment Assessment: Demographics, medical history, personal history, 
labs, imaging (CT, CTA), echo, PFTs, tumor markers, NRS2002, HADS, 6MWD, QLQ-C30. 
7.2 Preoperative Assessment: BMI, smoking status, ASA, NYHA, labs, echo, PFTs, 
NRS2002, HADS, 6MWD, VTE risk, ACS risk, education, consent. 
7.3 Intraoperative Details: Surgery info, events (hypotension, hypertension, hypoxia), 
inputs/outputs, anesthesia/surgery times. 
7.4 Postoperative Status & Short-term Outcomes: ICU admission, pain, drain removal 
time, 
flatus/defecation, 
first 
liquid 
intake, 
30-day 
complications/mortality/reoperation/readmission, LOS, cost, pathology, PROs (nutrition, 
inflammation, fitness, psychology), HADS, 6MWD, QLQ-C30 at 30 days. 
7.5 Adverse Events & Evaluation: Nausea, vomiting, bloating, postop complications are 
main AEs. Record all changes/reactions. Severity per NCI CTCAE v5.0. 
7.6 Postoperative Follow-up Plan: For life guidance, complication treatment, detecting 
recurrence/second cancer. Follow-up at our center preferred. Schedule: In-hospital daily; 
weekly phone/WeChat first 30 days; outpatient at 30 days. Phone follow-up to reduce loss. 
 
8. Statistical Analysis 
8.1 Data Collection, Monitoring, Review, Interim Analysis: Hospital ethics committee 
reviews data semi-annually. Interim analysis by independent statistician when 50% 
randomized. Trial stops if intervention shows significant harm. 
8.2 Statistical Analysis Plan: Use SPSS 26.0+. Two-sided α=0.05, 95% CIs unless 
specified. Descriptive stats for continuous (n, mean, median, SD, min, max) and 

categorical (n, %) variables. 
8.2.1 Enrollment/Withdrawal Analysis: Counts/percentages. 
8.2.2 Demographics/Baseline Analysis: Descriptive stats per group; t-test, χ², rank-
sum for comparability. 
8.2.3 Primary Outcome Analysis: χ² test for complication rates. 
8.2.4 Secondary Outcome Analysis: t-test, χ², rank-sum test; log-rank test for survival 
analysis. 
8.3 Data Storage Plan: Electronic data backed up multiple times. Original records kept 
by investigator; uploaded to clinical trial registry. 
 
9. Informed Consent 
The investigator must fully explain the study purpose, potential side effects, and risks, 
ensuring patients understand their rights, risks, and benefits before participation. 
Participants must sign the informed consent form. 
 
 
 

Reference: 
1. Zhang Shuze, Li Fan, Yang Hanteng, et al. Selection of neoadjuvant chemotherapy 
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