A Multicenter Randomized Prospective Study on Establishing an ERAS Program and Optimized Clinical Protocol for Patients Undergoing Minimally Invasive Pancreatoduodenectomy (MIPD)
Phase: NA
Conditions: Pancreaticoduodenectomy, ERAS, Minimally Invasive Surgery
Sponsor: Seoul National University Hospital

1 
 
 
A Multicenter Randomized Prospective Study 
on Establishing an ERAS Program and 
Optimized Clinical Protocol for Patients 
Undergoing Minimally Invasive 
Pancreatoduodenectomy (MIPD) 
 
 
 
 
ClinicalTrials.gov Identifier (NCT): pending 
Document Date: 03 June, 2025 
 
 
 
 
 
 
 
 
 
 
 
Principal Investigator Affiliation: 
 Department of Surgery, Seoul National University Hostpial 
Principal Investigator:  
Wooil Kwon 

2 
Study Overview 
 
Title 
A Multicenter Randomized Prospective Study on Establishing an ERAS 
Program and Optimized Clinical Protocol for Patients Undergoing Minimally 
Invasive Pancreatoduodenectomy (MIPD) 
Principal 
Investigator 
Wooil Kwon 
Department of Surgery, Seoul National University Hospital 
Funding 
Korea Health Industry Development Institute (KHIDI) 
 
Objective 
To evaluate the impact of an Enhanced Recovery After Surgery (ERAS) 
program on postoperative recovery in patients undergoing minimally 
invasive pancreatoduodenectomy (MIPD) 
Study Design 
A multicenter prospective open-labeled randomized study 
Study Period 
IRB approval ~ 2027-12-31 
Study Population 
Patients aged 19 years or older with pancreatic or periampullary tumors 
scheduled for standard minimally invasive (robotic or laparoscopic) 
pancreatoduodenectomy 
Sample Size 
Total N = 140 (ERAS group: 70; Control group: 70) 
Vulnerable  
Subjects 
None 
Study Methods 
Patients scheduled for standard minimally invasive (robotic or laparoscopic) 
pancreatoduodenectomy for periampullary lesions will be randomized to 
either the ERAS protocol (ERAS group) or the conventional perioperative 
protocol (control group). The primary comparison will be the rate of 
meeting discharge criteria on the afternoon of postoperative day 5. 
Secondary comparisons include length of hospital stay and incidence of 
major complications within 30 days postoperatively. Overall operation-
related morbidity (Clavien–Dindo classification), postoperative length of stay, 
and total medical costs (including inpatient, outpatient, and emergency 
charges from admission through 30 days post-discharge) will also be 
analyzed. 
Efficacy 
Evaluation  
- Primary efficacy analysis: Rate of meeting discharge criteria by the 
afternoon of POD 5; overall operation-related morbidity (< 30 days)  
- Secondary efficacy analysis: Length of hospital stay; incidence of major 
complications within 30 days; medical costs (KRW) 
Safety 
Assessment 
All adverse events occurring during the study will be recorded, including 
assessment of causality with study procedures. Severity, duration, 

3 
management, and relationship to the interventions will be evaluated. 
Expected 
Outcomes 
Development of clinical practice guidelines for perioperative management in 
minimally invasive pancreatoduodenectomy in Korea, demonstrating the 
effectiveness of the ERAS protocol and establishing a new standard of care. 
Compared with the conventional protocol, we anticipate improved short-
term clinical outcomes and reduced medical costs. 
 

4 
Protocol 
 
1. Title 
A Multicenter Randomized Prospective Study on Establishing an ERAS Program and 
Optimized 
Clinical 
Protocol 
for 
Patients 
Undergoing 
Minimally 
Invasive 
Pancreatoduodenectomy (MIPD) 
Affiliation 
1) 
Seoul National University Hospital: 101, Daehak-ro, Jongno-gu, Seoul 
2) 
SMG-SNU Boramae Medical Center: 20, Boramae-ro 5-gil, Dongjak-gu, Seoul 07061 
3) 
Korea University Anam Hospital: 73 Goryeodae-ro Seongbuk-gu, Seoul 02841 
 
2. Names and Titles of the Principal Investigator and Co-Investigators 
1)  Principal Investigator 
Associate Professor, Wooil Kwon 
Department of Surgery, Seoul National University Hospital 
 
2) Co-Investigators 
Associate Professor, Ho-Jin Lee 
Department of Anesthesiology and Pain Medicine, Seoul National University Hospital 
 
Clinical Assistant Professor, Soo-Hyuk Yoon 
Department of Anesthesiology and Pain Medicine, Seoul National University Hospital 
 
Clinical Assistant Professor, Hye-Sol Jung 
Department of Surgery, Seoul National University Hospital 
 
Clinical Instructor, Young Jae Cho 
Department of Surgery, Seoul National University Hospital 
 

5 
Research Nurse, Youngmin Han 
Department of Surgery, Seoul National University Hospital 
 
Research Nurse, Hyo-Jin Lee 
Department of Surgery, Seoul National University Hospital 
 
Research Nurse, Seulah Park 
Department of Surgery, Seoul National University Hospital 
 
Associate Professor, Chang-Sup Lim 
Department of Surgery, Seoul National University Boramae Medical Center 
 
Associate Professor, Jung-Man Lee 
Department of Anesthesiology and Pain Medicine, Seoul National University 
Boramae Medical Center 
 
Associate Professor, Young-Dong Yu 
Department of Surgery, Korea University Anam Hospital 
 
Clinical Assistant Professor, Yoo Jin Choi 
Department of Surgery, Korea University Anam Hospital 
 
Clinical Assistant Professor, Hyunyoung Seong 
Department of Anesthesiology and Pain Medicine, Korea University Anam Hospital 
 
3) Study Coordinator 
Clinical Instructor, Young Jae Cho 
Department of Surgery, Seoul National University Hospital 
 
 
4) Pharmacist for Investigational Medicinal Products / Device Manager 

6 
Not applicable 
 
3. Sponsor Institution 
1) Name and Address of Sponsor Institution 
Department of Surgery, Seoul National University Hospital 
101 Daehak-ro, Jongno-gu, Seoul, Republic of Korea 03080 
 
2) Monitoring Staff Name and Title 
Research Nurse Hyo-Jin Lee, Department of Surgical Education, Seoul National University 
Hospital 
 
4. Funding Source 
Korea Health Industry Development Institute (KHIDI)  
- 
Grant number has not yet been assigned. 
 
5. Estimated Study Period 
Date of IRB approval ~ December 13, 2027 
 
6. Target Disease/Condition 
Disease scheduled for minimally invasive pancreaticoduodenectomy 
 
7. Background and Objectives 
1) Background 
Since Codivilla first reported pancreatoduodenectomy in 1898, the procedure has 
evolved, and mortality has decreased to as low as 2%1. However, it remains a complex, 
high-risk operation with postoperative complication rates approaching 40–60%, 
which impede recovery and drive up healthcare costs. To reduce complications, 
improved perioperative care protocols were needed2. In recent years, numerous 
studies have explored ways to minimize surgical stress and enhance patient recovery. 
These efforts led to the development of the Enhanced Recovery After Surgery (ERAS) 

7 
protocol, a multimodal pathway designed to reduce postoperative stress, maintain 
homeostasis, and expedite recovery3. Since its introduction, ERAS has demonstrated 
favorable outcomes across various major surgeries, and the first ERAS guidelines for 
pancreatoduodenectomy were published in 20124,5. 
Several studies of ERAS in pancreaticoduodenectomy have shown reductions in 
postoperative complications, length of stay, and costs2,3,5-8. However, research 
specifically focused on minimally invasive pancreatoduodenectomy remains limited, 
and evidence for ERAS efficacy in this setting is lacking2,9,10. Moreover, no domestic 
studies have yet addressed ERAS in minimally invasive pancreatoduodenectomy, 
underscoring the urgent need for a protocol tailored to the Korean context. Therefore, 
this study aims to evaluate the impact of an evidence-based ERAS protocol on 
postoperative 
recovery 
in 
patients 
undergoing 
minimally 
invasive 
pancreatoduodenectomy. 
 
2) Hypothesis and Objectives 
A. Hypothesis: 
In 
patients 
undergoing 
standard 
minimally 
invasive 
pancreatoduodenectomy, those managed with our ERAS protocol will have a 
significantly higher rate of meeting discharge criteria on the afternoon of 
postoperative day 5 compared to those managed with the conventional protocol. 
B. Objective: To demonstrate the effectiveness of the new ERAS protocol in 
minimally invasive pancreatoduodenectomy and establish it as the standard 
perioperative care guideline. 
 
8. Investigational Medicinal Product Code Name, Generic Name, Raw Material and 
Quantity, Formulation 
Not applicable 
 
9. Selection Criteria, Exclusion Criteria, Target Sample Size and Rationale, and 
Recruitment Plan 
1) Inclusion Criteria: Participants must meet all of the following to be eligible: 
A. Age ≥ 19 years, scheduled for standard minimally invasive (robotic or 
laparoscopic) pancreatoduodenectomy for periampullary tumors 

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B. ECOG performance status of 0 or 1 at screening 
C. Able to provide written informed consent, understand study 
procedures, and complete patient-reported questionnaires 
D. ASA physical status classification I-III 
 
2) 
Exclusion Criteria: Participants meeting any of the following will be excluded: 
A. Hypersensitivity to fentanyl or ropivacaine 
B. Cognitive impairment preventing independent use of patient-
controlled analgesia or completion of questionnaires 
C.  Major internal medical or psychiatric disorders affecting treatment 
response 
D. Severe hepatic or renal dysfunction 
E. Any condition deemed inappropriate for study participation by the 
investigator 
 
3) 
Target Sample Size and Rationale 
Sample size was calculated using the StatTools sample size calculator 
(Stattools.crab.org). Based on previous literature and our clinical experience, we 
assumed a 30% rate of meeting discharge criteria on the afternoon of postoperative 
day 5 in the conventional protocol group and a 60% rate in the ERAS group. Using 
a two-sided test with 80% power, α = 0.05, no continuity correction, and accounting 
for a 10% dropout rate, we determined that 70 patients per arm (total N = 140) are 
required11.  
 
4) 
Recruitment Plan 
At Seoul National University Hospital, eligible patients aged ≥ 19 years with 
pancreatic or periampullary tumors scheduled for standard minimally invasive 
pancreatoduodenectomy who meet inclusion and do not meet exclusion criteria will 
be informed about the study. Those who voluntarily consent in writing will be 
enrolled. 
 
10. Study Methods 

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1) Specific Research Methods 
A. Screening (Outpatients): When surgery is scheduled in the outpatient clinic, the study 
coordinator or co-investigator will explain the attached information sheet and informed 
consent form to the patient and obtain written consent. During screening, the following 
assessments and investigations will be performed: 
i. 
Evaluation of inclusion and exclusion criteria 
ii. 
Demographic data (sex, age, height, weight, BMI) 
iii. 
Pancreatic cancer staging 
iv. 
Medical/surgical history and concomitant medications relevant to exclusion 
criteria 
v. 
Randomization immediately after screening. Patients assigned to the ERAS 
group will receive education using a pre-prepared ERAS protocol leaflet. 
vi. 
Both groups will complete the following patient-reported outcome 
questionnaires: 
a. Korean-EORTC QLQ C-3015 
b. Korean version of Hospital Anxiety and Depression Scale Anxiety 
Subscale 
B. 
Perioperative Protocol Details: 
The specific perioperative care protocols for each group are as follows. 
C. 
Perioperative Fasting: 
i. 
ERAS group: Per ESPEN guidelines, patients without signs of aspiration risk may 
consume clear fluids until 2 hours and solid foods until 6 hours prior to anesthesia 
induction. 
ii. 
Conventional group: Normal regular diet (NRD) on the evening before surgery, with 
sips of water (SOW) maintained until midnight; then nothing by mouth (NPO) from 
midnight. 
iii. 
ERAS group: NRD on the evening before surgery; fasting from solid foods starting 
at midnight. Water is allowed until 3 hours before surgery, and one carbohydrate 
drink (CarboEn 50, 300 mL, HK Innoen) is taken 2–4 hours pre-operatively. 
iv. 
ERAS group only: On the day of surgery, when consuming CarboEn, patients also 
receive preemptive analgesia with acetaminophen 650 mg and zaltoprofen 80 mg. 
The conventional group does not receive preemptive analgesia. 
D. Intraoperative Management: 
i. 
 Both 
groups 
follow 
Seoul 
National 
University 
Hospital’s 
standard 
pancreatoduodenectomy protocol. 
ii. 
ERAS group: 8 mg IV dexamethasone at anesthesia induction; ~1 hour before end 

10 
of surgery, IV acetaminophen 1000 mg + ibuprofen 300 mg combination and 
nefopam 20 mg. 
iii. 
Conventional group: 5 mg IV dexamethasone at induction; IV acetaminophen 1000 
mg ~1 hour before end of surgery. 
 
 
E. 
Postoperative Nutritional Protocol: 
i. 
The ERAS protocol recommends early oral intake. Colorectal ERAS guides diet from 
4 hours post-op without increased complications,12 and gastrectomy ERAS from 
POD 1.13 Based on these and our experience, the conventional group currently 
follows: 
ii. 
Conventional group: Remove Levin tube in the OR immediately after surgery. Begin 
SOW on the morning of POD 1. After an upright abdominal radiograph on POD 3 
morning, if no abnormalities, start soft fluid diet (SFD) on POD 3 evening. After 
pancreatobiliary CT on POD 4, if no abnormalities, begin soft bland fluid (SBD) at 
lunch. 
iii. 
ERAS group: Remove Levin tube in the OR. Begin SOW on POD 1 morning. After 
upright abdominal radiograph on POD 2 morning, if no abnormalities, start SFD 
on POD 2 evening. After pancreatobiliary CT on POD 3, if no abnormalities, begin 
SBD at lunch. 
F. Postoperative Perianastomotic Drain Management: 
i. 
Numerous studies have examined perianastomotic drainage.14-18 ERAS 
recommends drain removal within 72 hours if POD 1 fluid amylase < 5000 
U/L.4 At our center, considering published data, local CT cost/access, and 
experience, we maintain the following—adopting an ERAS-based removal 
protocol for the ERAS group: 
ii. 
Conventional group: Two drains placed at hepaticojejunostomy and 
pancreaticojejunostomy sites. Measure drain fluid amylase on POD 1, 3, 
and 5; perform pancreatobiliary CT on POD 4. If no issues, remove drains 
from POD 5 at the surgeon’s discretion (based on findings, drain output, 
fever, pain, etc.). 
iii. 
ERAS group: Same drain placement. Measure amylase on POD 1 and 3; CT 
on POD 3. If POD 1 amylase ≤ 5000 U/L, amylase is trending down, and 
CT is clear, remove drains from POD 4. If amylase > 5000 U/L, remove per 
surgeon’s discretion as in conventional group. 

11 
iv. 
In both groups, remove the urinary catheter on POD 2.  
G. Postoperative Pain Management Protocol: 
1. 
Both groups use intravenous patient-controlled analgesia (IV-PCA). 
2. 
PACU: If NRS ≥ 5 without nausea/vomiting, give fentanyl 50 µg IV as rescue. 
If NRS ≥ 5 with nausea/vomiting, give ketorolac 30 mg IV plus 
metoclopramide 10 mg IV. 
3. 
Ward: 
1. 
For NRS ≥ 3, patients in both groups are instructed to use the PCA 
button. 
2. 
ERAS group: From surgery day through morning of POD 1, IV 
acetaminophen 1000 mg + ibuprofen 300 mg every 8 hours; from 
POD 1 morning onward, oral selective COX-2 inhibitor and 
acetaminophen every 8 hours. 
3. 
Conventional group: From POD 3 onward, oral acetaminophen 650 
mg q8h. 
4. 
If NRS ≥ 7 persists and no opioid side effects, IV fentanyl 50 µg as 
first-line rescue. If side effects occur, IV nefopam 20 mg in 50 mL 
saline over 30 minutes as second-line rescue (only as needed, not 
exceeding max dose). Failure to control pain leads to study 
withdrawal. 
5. 
If nausea/vomiting occurs within 6 hours of prophylactic ramosetron 
0.3 mg IV (Nasea®, Astellas), give metoclopramide 10 mg IV; after 
6 hours, give ramosetron 0.3 mg IV. 
6. 
Prohibited: fentanyl patches and non-rescue opioids (nalbuphine, 
morphine) until POD 3. 
7. 
Discontinue IV-PCA at lunch on POD 2 in both groups. 
 
Table 1. Key Differences in Perioperative Management Between Groups 
Aspect 
Conventional Protocol 
ERAS Protocol 
Preoperative 
Fasting 
NPO (nothing by mouth) of solids 
and fluids from midnight the day 
before surgery. 
NPO of solids from midnight the day 
before surgery; clear fluids allowed 
until 
3 
hours 
pre-op; 
one 

12 
carbohydrate 
drink 
(300 
mL) 
consumed 2–4 hours before surgery. 
Preemptive 
Analgesia 
Not applied. 
With the pre-op carbohydrate drink, 
patients take acetaminophen 650 mg 
and zaltoprofen 80 mg orally 2–4 
hours before surgery. 
Intraoperative 
Management 
– IV dexamethasone 5 mg at 
anesthesia 
induction– 
IV 
acetaminophen 1 g ~1 hour before 
end of surgery 
– IV dexamethasone 8 mg at 
anesthesia 
induction– 
IV 
acetaminophen 1 g + ibuprofen 300 
mg + nefopam 20 mg ~1 hour before 
end of surgery 
Postoperative 
Nutrition 
– Remove Levin tube in the OR 
immediately after surgery– POD 1 
morning: begin sips of water (SOW)– 
POD 3 morning: upright abdominal 
X-ray; if no abnormalities, start soft 
fluid diet (SFD) on POD 3 evening– 
POD 4: pancreatobiliary CT; if no 
findings, start soft bland diet (SBD) at 
lunch 
– Remove Levin tube in the OR 
immediately after surgery– POD 1 
morning: 
begin 
SOW– 
POD 
2 
morning: upright abdominal X-ray; if 
no abnormalities, start SFD on POD 2 
evening– POD 3: pancreatobiliary CT; 
if no findings, start SBD at lunch 
Postoperative 
Drain 
Management 
– 
Two 
drains 
placed 
at 
hepaticojejunostomy 
and 
pancreaticojejunostomy 
sites– 
Measure drain fluid amylase on POD 
1, 3, and 5– POD 4: pancreatobiliary 
CT; if no abnormalities, remove drains 
from POD 5 per surgeon’s discretion 
(based on drain output, fever, pain, 
etc.) 
– 
Same 
drain 
placement 
as 
conventional– Measure amylase on 
POD 
1 
and 
3– 
POD 
4: 
pancreatobiliary 
CT; 
if 
no 
abnormalities and POD 1 amylase ≤ 
5000 U/L and POD 3 amylase 
trending down, remove drains on 
POD 4– If amylase > 5000 U/L, 
remove per surgeon’s discretion as in 
conventional group 
Postoperative Pain 
Control 
– IV-PCA until ~POD 3– From POD 3 
morning: PO acetaminophen 650 mg 
q8h 
– IV-PCA until ~POD 3– Until POD 1 
morning: IV acetaminophen 1 g + 
ibuprofen 300 mg every 8 hr– From 
POD 1 morning until POD 5: PO 
acetaminophen 650 mg + zaltoprofen 
80 mg q8h 
Abbreviations: NPO = nothing by mouth; POD = postoperative day; SOW = sips of water; SFD = soft 
fluid diet; SBD = soft bland diet; IV-PCA = intravenous patient-controlled analgesia. 
 

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2) Allocation and Randomization 
1. 
Allocation Strategy 
Randomization will be performed by an independent researcher not 
involved in the trial, using R software (version 3.5.1, R Foundation for 
Statistical Computing, Vienna, Austria). For each participating site, a block‐
randomization list with block size 4—containing two control and two ERAS 
assignments—will be generated and the blocks will be randomly permuted. 
At each center, subjects will be allocated to control or ERAS in the order 
specified by this list. The seed number required to reproduce the random 
sequence will be recorded and kept confidential. 
2. 
Allocation Concealment 
The randomization list will be prepared and maintained by a third party 
not involved in subject enrollment or assessment, ensuring that 
investigators cannot foresee assignments. Randomization results will then 
be communicated to the treating team. This is an open‐label (non‐blinded) 
study. 
 
3) Investigational Product Administration 
Not applicable 
 
4) Observations, Clinical Assessments, and Measurement Methods 
A.  Baseline and Demographic Data 
 • Age, sex, height, weight, BMI 
 • Smoking status 
 • ASA physical status 
 • ECOG performance status 
 • Comorbidities and concomitant medications 
 • History of prior surgery 
 • Preoperative neoadjuvant chemotherapy or radiotherapy 
 • Presence and type of synchronous malignancy 

14 
 • Dates of hospital admission and planned surgery 
 
B. Intraoperative Data 
 • Procedure name and duration 
 • Vascular resection performed (yes/no) 
 • Estimated blood loss 
 • Intraoperative fluids and blood products administered 
 • Use of continuous vasopressor infusion 
 • Intraoperative adverse events 
 
C. Postoperative Pain Scores 
At 4 PM (± 1 hour) on postoperative days (POD) 1–5, pain at rest and on 
movement will be assessed using the 11-point Numeric Rating Scale (NRS). 
 
D. Total Narcotic Consumption 
Cumulative opioid use (morphine‐equivalent dose) recorded through POD 
5. 
 
E. 
Time to First Flatus 
Hours elapsing from end of surgery to first passage of gas. 
 
F. 
Postoperative Nausea and Vomiting 
On POD 0–5, nausea graded 0 = none, 1 = mild, 2 = requiring antiemetic; 
record any vomiting episodes. 
 
G. Quality of Recovery 
On POD 1–5 at 4 PM (± 1 hour), patient‐reported recovery quality via the 
Korean EQ-5D-5L instrument. 
 
H. Postoperative Complications 
All events within 30 days classified by the revised Clavien–Dindo system 

15 
and the Comprehensive Complication Index19,20 
 
I. 
Postoperative Pancreatic Fistula (POPF) 
Incidence and grade of POPF according to ISGPS definitions21 
 
J. 
Readmission Within 30 Days 
Any unplanned hospital readmission within 30 days of discharge. 
 
K. Mortality Within 30 Days 
Any death occurring within 30 days of surgery. 
 
L. 
Discharge‐Criteria Fulfillment 
At 4 PM (± 1 hour) on POD 5, the proportion of patients who 
simultaneously meet all of the following: 
 • Tolerate a soft blended diet for 24 hours 
 • Ambulate safely without assistance 
 • Adequate pain control (NRS ≤ 3) on oral non-opioid analgesics only 
 • Afebrile (< 37.2 °C) without major complications 
 • No clinically concerning laboratory abnormalities (e.g., WBC, CRP) 
 
5) Novelty and Differentiation from Existing Studies 
To date, no studies have exclusively evaluated ERAS in minimally invasive 
pancreatoduodenectomy. This trial will develop and assess an ERAS pathway tailored 
for the increasing application of minimally invasive PD. 
  
6) Subject Benefits and Risks 
 • Control Group: Standard care as practiced at Seoul National University Hospital; no 
additional risk beyond routine treatment. 
 • ERAS Group: Expected to experience shorter length of stay and fewer complications, 
as reported in other ERAS studies. Risks associated with the ERAS interventions are 
minimal. 

16 
 • Any serious adverse event (SAE) will be managed immediately by the principal 
investigator and reported to the IRB within 24 hours of occurrence. 
7) Discontinuation and Withdrawal Criteria 
Subjects may withdraw at any time at their own request. The investigator may also 
discontinue a subject for safety, protocol compliance, or administrative reasons. 
Upon withdrawal, no further assessments or data collection will occur, though data 
collected prior to withdrawal will remain in the study database. 
 
8) Safety Evaluation 
A. Overview 
All ERAS interventions are guideline-recommended and widely used; 
complication risk is very low. 
B. Serious Adverse Events (SAEs) 
Defined as Clavien–Dindo grade ≥ 3. SAEs must be reported to the principal 
investigator within 24 hours and to the IRB within 48 hours. 
C. Adverse Event Monitoring 
• Record every AE, assess causality with study procedures, and document severity, 
duration, management, and outcome. 
• Monitor planned assessments and any additional testing prompted by clinical 
findings. 
D. Severity Grading 
• Mild: Transient, does not interfere with daily activities 
• Moderate: Causes some discomfort or interferes with daily activities 
• Severe: Prevents performance of daily activities 
E. 
Causality Assessment 
Classified as “Unrelated,” “Possibly Related,” “Likely Related,” “Clearly Related,” or 
“Indeterminate,” separately for drugs and procedures, based on investigator 
judgment. 
 
9) Efficacy Endpoints, Analysis Methods, and Interpretation 
A. Efficacy Endpoints 
1. 
Primary Outcome: Proportion of patients meeting all discharge criteria on 
POD 5 afternoon; comparison by chi-square test. 
2. 
Secondary Outcomes: 

17 
1. Pain Scores: NRS at rest and on movement from POD 1 to POD 5, 
analyzed by linear mixed-effects modeling. 
2. Nausea/Vomiting Rate: Incidence from POD 0 to POD 5, compared by 
chi-square test. 
3. Total Opioid Use: Compared by Student’s t-test or Mann–Whitney U test, 
depending on distribution. 
4. Comprehensive Complication Index: Compared by t-test or Mann–
Whitney U test. 
5. Clinically Relevant POPF (Grade B+): Incidence compared by chi-square 
test. 
6. Length of Stay (days): Compared by t-test or Mann–Whitney U test. 
 
B. Analysis Populations 
1. All Enrolled (Full Analysis Set): All randomized subjects excluding 
duplicates and ineligible registrations. 
2. Modified Intent-to-Treat (mITT): Subjects who underwent the planned 
minimally invasive surgery after randomization. 
3. Per-Protocol (PP): mITT subjects who fully adhered to their assigned 
perioperative protocol. 
The primary analysis will be performed on the mITT set; sensitivity analyses will 
use the PP set. 
 
C. Definition of Complications 
Complications occurring within 30 days post-operatively. They include 
complications of the carbohydrate drink (e.g., aspiration pneumonia), analgesic 
agents (e.g., acetaminophen, ketorolac, nefopam, opioids), and surgical 
complications. Intraoperative AEs will be graded per CTCAE v4.0; postoperative 
AEs per Clavien–Dindo classification. 

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1. 
Clavien-Dindo Classification of Surgical Outcomes 
2. 
Clinically Relevant Postoperative Pancreatic Fistula (CR-POPF; ISGPS Criteria 
as Grade B or C) 
 
3. 
Delayed Gastric Emptying (DGE; ISGPS consensus guidelines) 
4. 
Post-Pancreatectomy Hemorrhage (PPH; ISGPS consensus guidlines) 
 
10) Post-Trial Patient Care and Treatment Standards 
All subjects in both the Conventional and ERAS groups will be closely monitored for 
adverse events during their hospital stay. If pain control is inadequate, “rescue 
medications” will be administered in-hospital, and upon discharge patients will 
continue to receive pain management prescriptions at their scheduled surgical 
outpatient visits as needed. 
 
11) Study Schedule 

19 
  
PreOP 
IntraOP 
PostOP 
During 
Admission 
PostOP 
Outpatie
nts 
Pre-
registratio
n 
Post-
registration 
PreOP 
#1 
OP 
Day 
POD 
#1 
POD 
#2 
POD 
#3 
POD 
#4 
POD 
#5 
Informed 
Consent 
Explanation 
● 
 
 
 
 
 
 
 
 
 
 
 
Eligibility 
Assessment & 
Study 
Registration 
● 
 
 
 
 
 
 
 
 
 
 
 
Baseline 
Patient 
Characteristics 
● 
● 
 
 
 
 
 
 
 
 
 
 
EORTC QLQ C-
30 
 
● 
 
 
 
 
 
 
 
 
 
● 
Surgery & 
Anesthesia 
Data 
 
 
 
● 
 
 
 
 
 
 
 
 
Discharge-
Criteria 
Assessment 
 
 
 
 
 
 
 
 
 
● 
 
 
EQ-5D-5L 
 
 
● 
 
 
● 
● 
● 
● 
● 
 
 
Postoperative 
Pain (NRS) 
 
 
 
 
 
● 
● 
● 
● 
● 
 
 
Postoperative 
Nausea/Vomiti
ng 
 
 
 
 
● 
● 
● 
● 
● 
● 
 
 
Total Opioid 
Consumption 
 
 
 
 
 
 
 
 
 
 
● 
 
Time to First 
Flatus 
 
 
 
 
● 
● 
● 
● 
● 
● 
● 
 
Urinary 
Catheter 
Removal 
 
 
 
 
 
● 
● 
 
 
 
 
 
Oral Diet 
Initiation 
 
 
 
 
 
 
 
● 
● 
 
 
 
Drain Removal 
 
 
 
 
 
 
 
 
● 
● 
● 
 
IV-PCA 
Removal 
 
 
 
 
 
 
● 
 
 
 
 
 
CT/MRI 
● 
 
 
 
 
 
 
● 
● 
 
 
 
Follow-up for 
Postoperative 
Complication 
 
 
 
 
 
 
 
 
 
 
 
 
 
 1. 
Registration must occur within 28 days prior to surgery. 
 2. 
The day of surgery is defined as Day 0. 

20 
 3. 
IV-PCA is discontinued in both groups on POD 2. 
 4. 
Oral soft fluid diet begins on POD 3 evening in the Conventional group and 
POD 2 evening in the ERAS group, provided no fever, pain, or distension, even if first 
flatus has not occurred. 
 5. 
Soft bland diet begins after CT if no abnormalities—on POD 4 lunch in the 
Conventional group; POD 3 lunch in the ERAS group. 
 
11. Data and Safety Monitoring Plan 
1) Monitoring Leadership 
• Monitoring Officer: Associate Professor Wooil Kwon  
Department of Surgery, Seoul Natinoal University Hospital 
 
• Monitoring Staff: Research Nurse Hyo-Jin Lee 
Department of Surgery, Seoul Natinoal University Hospital 
2) Monitored Items 
⚫ Study Accruals 
A. Baseline Data: age, sex, BMI, ECOG status, neoadjuvant therapy, comorbidities, 
alcohol history, medication history, preoperative biliary drainage 
B. Intraoperative Data: operation name, operation time, vascular resection, 
estimated blood loss, fluid, transfusion, vasopressor use, intraoperative events 
C. Postoperative Analgesics: types and doses of medications (e.g., fentanyl, NSAIDs, 
acetaminophen) 
D. POD 1-5 Pain Scores 
E. POD 0-5 Nausea/Vomiting 
F. 30-Day Complications (including POPF) 
G. 30-Day Readmissions & Mortality 
⚫ Safety Signals: consent process, adverse effects from additional 
analgesics, aspiration risk from carbohydrate loading 
⚫  
3) Monitoring Methods & Frequency 
A. Safety monitoring for analgesic‐related and aspiration events every six months. 
B. 
Periodic review of case report forms for protocol adherence and safety. 

21 
C. 
Monitoring items include: 
i. 
Study progress 
ii. 
Compliance with inclusion/exclusion criteria 
iii. 
Serious adverse events (SAEs) 
iv. 
Protocol deviations 
v. 
Reasons for treatment discontinuation 
vi. 
Integrity of baseline characteristics 
vii. 
Other safety concerns 
4) Adverse Event Reporting & Non-Compliance 
A. AE Grading: Intraoperative AEs per CTCAE v4.0; postoperative AEs per Clavien-
Dindo Classifications. 
a. AE Definition: Any unintended sign, symptom, or disease occurring within 
one week of protocol procedures, unrelated to expected physiological 
fluctuations. Data collection extends to 1 month post-op. 
b. Permitted Co-Interventions: Antibiotics, plasma extenders, blood 
products, H2 blockers, PPIs, etc., without restriction. 
B. 
Monitoring & Reporting: Bi-monthly reviews of enrollment, data quality, 
protocol/GCP compliance. IRB notified of SAEs, unexpected issues, or significant 
deviations. Immediate action and potential trial suspension if patient safety is 
at risk. 
5) Study Suspension Criteria 
A. Investigator judgment that continuation contradicts participant welfare, failure 
to meet enrollment targets, or emergence of concerning efficacy/safety data. 
B. 
Upon suspension, the PI must notify the IRB and all investigators within two 
weeks; investigators must inform participants promptly. 
 
 
12. Protections for Research Participants 
1) Ethical Safeguards 
All personnel will comply with the 2024 Declaration of Helsinki and ICH-GCP 
guidelines. Study begins only after IRB approval. 
2) Informed Consent Process 
 
A. Personnel obtaining consent: PI or delegated co-investigator 

22 
B. 
Consent provider: the participant 
C. 
Waiting period between explanation and signing: 10 minutes to 2 days 
D. Minimizing undue influence: Participation is voluntary; refusal incurs no penalty 
E. 
Language used by investigators: Korean 
F. 
Language understood by participants: Korean 
G. Consent materials include study purpose, procedures, risks/benefits, contact 
information, data use, new findings disclosure, confidentiality protections, and a 
copy of the signed form. 
3) Participant Compensation 
In the event of trial-related AEs, appropriate medical care will be provided, and any 
hospitalization costs due to surgical complications will be minimized for the 
participant. Compensation is not provided for AEs arising from non-protocol 
treatments, unapproved procedures, participant negligence, or progression of 
underlying disease. 
4) Privacy and Confidentiality 
Personal identifiers will be coded and accessible only to the PI and designated staff. 
Documents (e.g., consent forms) will be kept under lock for three years post-study 
per local regulations, after which identifying data will be securely destroyed. 
5) Vulnerable Populations 
Not applicable 
 
13. Handling and Disposal of Human-Derived Materials 
Not applicable 
 
 
 
 
 
 
 
14. References 

23 
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2. 
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4. 
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Gustafsson UO, Scott MJ, Hubner M, et al. Guidelines for Perioperative Care in 
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J Surg. Sep 2014;101(10):1209-29. doi:10.1002/bjs.9582 
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