RISE Ileocecal Valve Functional Reconstruction for the Prevention of Postoperative Intestinal Dysfunction After Robotic/Laparoscopic Right Hemicolectomy: a Single-blind, Two-arm, Multicenter Randomized Controlled Clinical Study
Phase: NA
Conditions: Right-sided Colon Cancer
Sponsor: Army Medical University, China

A clinical study conducted by researchers at the Second Affiliated Hospital of the
Army Military Medical University
RISE ileocecal valve functional reconstruction for the
prevention of postoperative intestinal dysfunction after
robotic/laparoscopic right hemicolectomy: a single-blind,
two-arm, multicenter randomized controlled clinical study
(Interventional Clinical Study Protocol)
administrative or
technical offices ：
General Surgery
Lead researcher:
Xiao Weidong
contact number ：
13996390860
version number ：
1.0
Version date:
21 May 2025

The Second Affiliated Hospital of Army Military Medical University IIT Version: 1.0
29
I. RESEARCH CONTEXT
Colorectal cancer, a prevalent tumor in the digestive tract, has shown an
increasing incidence rate year by year. Laparoscopic right hemicolectomy serves as
the standard surgical approach for tumors involving the ascending colon, cecum, and
partial transverse colon, with its conventional resection scope encompassing portions
of the ileum, ileocecal valve, cecum, ascending colon, and transverse colon [1]. The
ileocecal valve—a semilunar fold formed by thickened muscular tissue and mucosal
lining at the terminal ileum's junction with the cecum—functions as a sphincter-like
structure that separates the small intestine from the large intestine. This anatomical
feature plays a crucial role in regulating nutrient absorption through intestinal
contents [2-3]. However, current right hemicolectomy procedures routinely omit
ileocecal valve preservation, neglecting this critical physiological structure. This
omission may lead to two major complications: (1) Loss of the ileocecal valve's "gate
mechanism": As a bidirectional valve, the ileocecal valve restricts intestinal contents
from rapidly flowing into the cecum, thereby maintaining nutrient absorption
efficiency. Valve absence allows excessive intestinal contents to enter the colon,
disrupting bile acid reabsorption and potentially causing both bile acid malabsorption
(BAM) and bile acid diarrhea (BAD)[4]. (2) Disruption of the ileocecal valve's
"anti-reflux defense": When colonic bacteria infiltrate the ileum and proximal small
intestine, they compromise the intestinal microbiota barrier, triggering severe bacterial
overgrowth (SIBO). This condition frequently causes recurrent abdominal bloating,
diarrhea, and other chronic gastrointestinal symptoms. In severe cases, it may impair
nutrient absorption including vitamin B12 and fatty acid processing – a common
complication
in
right
hemicolectomy
patients
that
significantly
compromises
postoperative recovery outcomes[5].
According to the existing research, there are two ways to preserve the function of
the ileocecal valve: one is to reduce the scope of surgical resection and directly retain
the ileocecal valve; the other is to reconstruct the corresponding function after the
removal of the ileocecal valve as far as possible. However, there are the following

The Second Affiliated Hospital of Army Military Medical University IIT Version: 1.0
29
problems in clinical application:
1. For patients with ileocecal valve retention, studies have reported that ileostomy
with ileocecal valve preservation in ulcerative colitis can reduce high-volume fluid
loss during the stoma. Additionally, solid food intake leads to firmer stools within one
week after resuming solid diet post-surgery, with over 10% weight gain observed
within one year. This approach also improves quality of life for patients undergoing
total colectomy [10]. Current research on right hemicolectomy with ileocecal valve
preservation for tumors in the hepatic flexure and transverse colon has demonstrated
feasibility and surgical safety. Postoperative recovery shows significant advantages:
patients in the valve-preserving group pass gas earlier and resume bowel movements
sooner than non-preserved groups [11]. However, due to the extremely low incidence
of hepatic flexure and transverse colon cancers (2%-4% for transverse colon,
0.7%-3% for hepatic flexure), this procedure faces practical limitations. For instance,
its application to tumors in other colonic regions may result in insufficient resection
margins. Consequently, many right hemicolectomy patients still face the necessity of
removing the ileocecal valve along with tumor removal.
2. The concept of reconstructing the ileocecal valve was first proposed by Kellogg in
1918 [6]. Later, Itzhak Vinograd applied the concept of reintegrating the ureter into
submucosal tubular valves for reconstructing the ileocecal valve, with results showing
that the time for intestinal contents to pass through in the reconstructed group was
significantly longer than the control group (16.2±1.5min vs 4.1±1.0 min), meaning
the submucosal tunnel method quadrupled transit time [7]. Chardavoyn et al.
employed a papillary flap technique, where a segment of the distal small intestine was
grafted into the colon to form an embedded papilla approximately 4cm in diameter. To
stabilize the ileocecal valve and prevent slippage, non-absorbable sutures were
reinforced between the opposing serosal surfaces in a circular pattern before
implantation. Postoperative analysis of intestinal microbiota revealed significantly
reduced bacterial reflux in the papillary flap group compared to conventional
anastomosis groups [8]. These methods have achieved satisfactory outcomes in

The Second Affiliated Hospital of Army Military Medical University IIT Version: 1.0
29
treating children with congenital ileocecal valve atresia and patients requiring
combined resection due to non-neoplastic causes [9], indicating potential clinical
benefits of ileocecal valve reconstruction. However, these approaches also present
notable limitations: (1) The relatively thin colon wall makes submucosal tunnel
reconstruction prone to bowel perforation; (2) The complex procedural steps hinder
clinical application and promotion.
Building on these findings, this study proposes an innovative ileocolonic
anastomosis approach based on the integrated reconstruction concept of mucosal folds
within the ileocecal valve and the annular muscle outside the valve. The "Revolute
Insert Side-End ileocecal valve reconstruction (RISE)" method combines "revolute
insertion of the ileocecal valve" with "sleeve embedding reconstruction of the colonic
muscle" in the ileal pouch. Preliminary small-sample clinical data demonstrate that
this RISE-based ileocecal valve reconstruction technique features simple operation
and a distinct "gate effect". Compared to conventional ileocolonic side-to-side
anastomosis, patients with RISE anastomosis exhibit faster postoperative intestinal
function recovery and significantly improved bowel function quality, highlighting the
unique advantages of RISE. Notably, there was no significant difference in short-term
complications between RISE and conventional anastomosis groups, indicating good
surgical safety. This study plans to conduct a multicenter clinical comparative trial
combining complete laparoscopic/robot-assisted right hemicolectomy with RISE
anastomosis, observing its effects on short-term and long-term complication rates,
quality of life, bowel function, gut microbiota, nutrient absorption, and long-term
oncological outcomes.
II. RESEARCH OBJECTIVES
1. Main objectives:
To evaluate the efficacy of total laparoscopic/robot-assisted right hemicolectomy
combined
with
ileocolonic
RISE
anastomosis
(intervention)
in
improving
postoperative stool formation time (primary outcome) in patients with right
hemicolectomy
for
colorectal
cancer
compared
with
traditional
side-to-side

The Second Affiliated Hospital of Army Military Medical University IIT Version: 1.0
29
anastomosis.
2. Secondary purposes:
(1) Compare the surgical safety of the two groups (RISE anastomosis group vs.
traditional anastomosis group), including intraoperative bleeding, anastomotic leakage
rate (Clavien-Dindo classification), and complication rate within 30 days after
surgery;
(2) To evaluate the effects of RISE anastomosis on postoperative nutritional and
metabolic disorders, including serum albumin, vitamin B12, bile acid levels, and body
composition analysis (body fat percentage, muscle mass);
(3) To analyze the improvement effect of RISE anastomosis on postoperative
quality of life, and evaluate it by EORTC QLQ-C30 and QLQ-CR29 scale scores;
(4) To explore the long-term effects of RISE anastomosis on overall survival (OS)
and progression-free survival (PFS);
(5) Detect the dynamic changes of intestinal flora abundance (such as Proteus,
streptococcus, obligate anaerobic bacteria, etc.) and metabolites (such as short chain
fatty acids) in the two groups after surgery to clarify the regulatory effect of RISE
anastomosis on intestinal microecology.
III. RESEARCH DESIGN
1. Research on the overall design
This prospective, single-blind, double-arm, multicenter, randomized controlled
clinical trial with superiority design aims to compare postoperative intestinal function
recovery
between
complete
laparoscopic/robot-assisted
right
hemicolectomy
combined with RISE anastomosis and traditional side-to-side anastomosis in patients
with right-sided colon cancer. Eligible participants will be randomly assigned into
RISE anastomosis and conventional anastomosis groups through zonal randomization,
with evaluation of key outcomes including postoperative bowel function recovery
(primary endpoint), complications, nutritional metabolism, quality of life, and
oncological prognosis. Patients must provide informed consent prior to surgery, and
all procedures are performed by senior physicians with extensive experience at each

The Second Affiliated Hospital of Army Military Medical University IIT Version: 1.0
29
center to ensure standardized protocols.
1.1 Random grouping method-block randomization
Randomized design: Block Randomization was used, and computer-generated
random sequences (SAS 9.4) were used to assign subjects to either RISE or traditional
groups on a 1:1 basis.
Group setting: The size of the fixed group is 4 cases (2 cases per group) to ensure
balanced number of cases between groups. The order of the groups is randomly
arranged (e.g., AABB, ABAB, BAAB, etc.) to prevent prediction of the distribution
pattern.
Blind assignment: The random results are sealed in an opaque envelope, which
only indicates the research center and the subject enrollment number. After signing
the informed consent form, the independent research assistant of the sub-center
unpacks the envelope to carry out the grouping, ensuring that the assignment process
is irreversible and cannot be traced back.
Implementation process:
The random sequence is generated uniformly by the statisticians of the leading
unit;
The groups were assigned according to the order of case reception in the
sub-center;
If the number of cases in a sub-center is less than one group (4 cases), the
remaining quota will be filled according to the random sequence.
1.2 Blinding-single-blind
Blind subjects: Patients were not informed of the specific anastomosis method,
and postoperative care and follow-up procedures were kept consistent to avoid
inter-group exposure differences.
2. Selection and withdrawal of participants
Research site: General Surgery, Second Affiliated Hospital of Army Medical
University
Patients who meet the diagnostic criteria for right-sided colon cancer in the

The Second Affiliated Hospital of Army Military Medical University IIT Version: 1.0
29
NCCN Colon Cancer Guidelines and are candidates for radical surgical resection.
Inclusion criteria:
a. The study was conducted with subjects aged 18 to 80;
b. ASA score is less than 3 points;
c. Patients with a first diagnosis of tumor located in the appendix, ileocecal
region, ascending colon, hepatic flexure of colon and right 1/3 of transverse colon, or
patients who plan to undergo laparoscopic radical resection of the right half of colon;
d. No other history of digestive tract disease (except intestinal polyps and
gallstones)
e. Willing to participate in this study and sign the informed consent form;
f. Clinical data is complete.
Exclusion criteria:
a. Patients with other malignant tumors of organs;
b. Tumors invade local surrounding organs;
c. Patients with other infectious or autoimmune diseases (e.g., Crohn's disease);
d. Patients have congenital or acquired metabolic diseases;
e. Have taken antibiotics and other drugs that interfere with the flora within one
month before being selected for research;
f. The plan of the operation was changed, and the resection did not include the
ileocecal valve;
Exit criteria:
a. Subjective withdrawal: the patient explicitly refuses to continue to participate
in the study or adopts the anastomosis method of reconstructing the ileocecal valve.
b. Withdrawal by the investigator:

During or after the operation, complicated conditions (such as severe
abdominal adhesion, more difficult than expected) are found, which
make it impossible to complete the operation according to the
established plan.

The
patient's
postoperative
condition
changes
(such
as
severe
complications,
infection,
etc.)
are
not
suitable
for
continued
participation in the study after evaluation by the investigator.
c. Missing follow-up: the patient is unable to complete the follow-up (e.g., lost

The Second Affiliated Hospital of Army Military Medical University IIT Version: 1.0
29
contact, refusal to further examination).
d. Protocol deviation: the subject did not receive the intervention or follow-up as
required by the study protocol, affecting the validity of the data.
Termination criteria:
a. Study intervention-related risks: serious safety problems were found during
the study (such as significantly higher incidence of serious complications such as
anastomotic leakage and massive hemorrhage than expected), and the study was
terminated after evaluation by the ethics committee.
b. Ineffective: The interim analysis showed that the intervention (RISE
anastomosis) did not achieve the predefined superiority and efficacy goals, and
continued study was clinically meaningless.
c. External request for termination:
The ethics committee or regulatory authorities require the termination of the
study due to safety or ethical issues. The research funds or resources are insufficient
to sustain the study.
d. Force Majeure: The research cannot be continued due to force majeure such as
natural disaster or epidemic.
3. Sample size:
This prospective, double-arm, single-blind, multicenter randomized controlled
trial
evaluated
the
effectiveness
of
RISE
anastomosis
with
ileocecal
valve
reconstruction. The postoperative stool formation time served as the primary endpoint
for sample size calculation. Based on our prior trial results, the stool formation rate
was approximately 65% in the RISE group and 33.3% in the control group on day 2
postoperatively. With a two-tailed test level α=0.05 and a 1:1 group ratio, PASS11.0
software estimated minimum sample sizes of 85 cases per group. Considering a 10%
dropout rate, each group required 94 additional cases (85 + 85 × 10%), totaling 188
cases combined. The study employed block randomization with minimum blocks of 4
samples. Subsequently, sample allocation was determined based on regional average
patient intake levels to match block sizes.

The Second Affiliated Hospital of Army Military Medical University IIT Version: 1.0
29
According to the number of patients with right-sided colon cancer admitted by
each center per year, the number of cases was allocated proportionally among the
research centers,
Table 1 Sample size allocation of each sub-center
Center units
Sample size allocation
Second Affiliated Hospital of Army Military Medical
University
108
The
First Affiliated
Hospital
of
Chongqing
Medical
University
20
Affiliated Hospital of North Sichuan Medical College
20
Guangan People's Hospital, Sichuan Province
20
Third People's Hospital of Yibin City, Sichuan Province
20
Figure 1 PASS11.0 software interface-sample size calculation results

The Second Affiliated Hospital of Army Military Medical University IIT Version: 1.0
29
4. Research process
The research process is divided into screening period, treatment period and
follow-up period, the details of which are as follows:
1. Screening period
Time point: preoperative
Research content and items to be collected/detected:
(1) Audit the inclusion and exclusion criteria (according to the inclusion and
exclusion criteria);
(2) Sign the informed consent form;
(3) Registration of demographic statistics (age, gender, occupation, contact
information);
(4) Record the past medical history (digestive tract disease, tumor history,
metabolic diseases) and treatment history (surgery, radiotherapy, chemotherapy,
antibiotic use);
(5) Disease diagnosis (tumor location, stage and pathological type);
(6) Physical examination (height, weight, BMI, abdominal palpation);
(7) Vital sign monitoring (blood pressure, heart rate, respiratory rate, body
temperature);
(8) Imaging examination:
CT scan of upper and lower abdomen and pelvis with plain and enhanced (to
evaluate the extent and metastasis of tumors);
Chest CT scan (excluding lung metastasis);
(9) Laboratory test:
Blood routine, blood biochemical (liver function, kidney function, electrolyte,
blood sugar, blood lipid);
(10) Quality of life assessment: EORTC QLQ-C30 and QLQ-CR29 scales;
(11) Collect baseline biological specimens:
biological
specimen
Method
of
collection
Collection
volume
use
Method
of
preservation
Blood samples
Clinical
Fasting
Subsequent
Centrifuge
and

The Second Affiliated Hospital of Army Military Medical University IIT Version: 1.0
29
additional
collection
venous blood
10mL
metabolites
and molecular
mechanism
analysis
separate
plasma/saliva
for-80℃storage
Stool samples
Clinical
additional
collection
5g
Fungal
profiling
After
sterile
collection, it was
directly
frozen
and stored at-80℃
2. Treatment
Time node: from intraoperative to 7 days after surgery
Research content and items to be collected/detected:
(1) Operation implementation:
In this study, the intervention group and the control group only differ in the
digestive tract reconstruction method:
a.
RISE anastomosis group (intervention group)
All procedures were performed under general anesthesia with the patient in
lithotomy position. In accordance with established principles of laparoscopic right
hemicolectomy, five cannulation needles were inserted to facilitate D2 lymph node
dissection from inside out.
Step 1: Measurement and Dissection: Mark a 2 cm mark along the mesocolon at
the terminal transverse colon, and mark the ileal distal end approximately 10 cm and
12 cm from the ileocecal junction. Use an endoscopic linear stapler to dissect the right
half of the transverse colon. Perform mesenteric trimming on the ileal distal segment,
ligate the ileum at marked points with 4-0 silk sutures, then dissect it using an
ultrasonic scalpel. Carefully inspect both ends and disinfect with alcohol swabs.
Step 2: Intestinal End Inversion and Colon Insertion: Using an ultrasonic scalpel,
make a horizontal incision 2 cm from the colon's distal end. Divide the proximal
ileum into three equal segments, then suture them to the muscularis 浆膜layer with
3-0 silk sutures, creating a 1.5 cm mucosal flap to form a simulated ileocecal valve.
Perform an interrupted suture of three stitches at the midpoint of the inverted ileal
segment using 3-0 silk sutures. Insert the intact ileal segment into the colon without

The Second Affiliated Hospital of Army Military Medical University IIT Version: 1.0
29
torsion, ensuring adjacent mesenteric vessels are free from torsion and tension.
Step 3: Intestinal Colon End-to-End Anastomosis. When there is no intestinal
volvulus, fix three sutures at the transverse colon opening, one-third of the distance
from the mid-point of the small bowel eversion line, to ensure precise fixation of the
small intestine on the transverse colon. Close the anastomosis with 3-0 catgut suture
(with barbs) using a tight stitch. If the closure is inadequate, perform interrupted
suturing. After confirming no significant fistula formation, encase the anastomosis
with seromuscular layer. Continuously suture the gap between the ileum and colonic
mesentery with 3-0 catgut suture (with barbs). Finally, manually assess the
anastomosis's size and patency.
Figure 2 Schematic of RISE anastomosis steps. A-B: Identify and mark the transection sites on the
transverse colon stump and terminal ileum. C-D: Evert the terminal ileum to mimic the anatomical
structure of the ileocecal valve. E-F: Place fixation sutures at the transverse colon opening. G-H:
Complete the RISE anastomosis of the terminal ileum with colon.
b. Conventional lateral side anastomosis group (control group)
After inserting the same cannula, ligating blood vessels, and making a 10 cm
distal transection at the transverse colon mass along with a 15 cm proximal
transection at the ileocecal valve, the specimen was extracted through a small midline
incision. A linear stapler was used in vitro for the side-to-side ileocolonic anastomosis,
followed by closure of the common intestinal incision with a second stapler. The
anastomotic site was reinforced with 3-0 catgut sutures using reverse-staple
technique.
(2) Intraoperative index recording:

The Second Affiliated Hospital of Army Military Medical University IIT Version: 1.0
29

Total operation time (min);

Surgical duration of anastomosis (min);

Blood loss during operation (mL);

Blood transfusion volume (mL);

(3) Immediate postoperative monitoring:

Blood pressure, heart rate, respiration and body temperature at 24h,48h and
72h after surgery;

Daily postoperative physical examination (abdominal signs, resumption of
bowel sounds);

Bristol stool score (recorded daily for 7 consecutive days);
(4) Laboratory test:
Blood routine and blood biochemistry (monitoring inflammatory indicators and
metabolic status) at 24h and 72h after surgery;
(5) Postoperative complication records (according to Clavien-Dindo grading
system):
Table 1. Clavien-Dindo grading system for surgical complications
I
①Abnormal conditions that do not require medication or surgery, endoscopy
and radiation therapy.
②
Antispasmodic, antipyretic, analgesic, diuretic, electrolyte and other drug
therapy and physical therapy.
③Open infected wounds at the bedside
II
①Complications requiring the use of medications other than those described above
for treatment of grade I complications.
②Blood transfusion, total parenteral nutrition
III
Complications requiring surgery, endoscopy or radiation therapy
IIIa
No general anesthesia is required
IIIb
Need general anesthesia
IV
Life-threatening complications (including central nervous system complications, such
as cerebral hemorrhage, ischemic stroke, subarachnoid hemorrhage, but not transient

The Second Affiliated Hospital of Army Military Medical University IIT Version: 1.0
29
ischemic attack) require IC/ICU management
IVa
Single organ dysfunction (including dialysis)
IVb
Multiple organ dysfunction
V
die
“d”
If a patient has complications at discharge (see example in Table 2), the corresponding
complication grade should be followed by the suffix "d". This label indicates that
follow-up is required to fully assess the complication.
(6) Biological specimen collection:
biological
specimen
Method
of
collection
Collection
volume
use
Method of preservation
Organizing
samples
Clinical
additional
collection
About 10g
Pathological
analysis
Molecular
mechanism
studies
Some were fixed in 10%
formalin (for pathological
analysis) and some were
rapidly frozen
in liquid
nitrogen
and
transferred
to-80 ℃
(for molecular
mechanism studies)
3. Follow-up period
Time nodes: 1 month, 3 months, 6 months and 1 year after surgery
Research content and items to be collected/tested:
(1) 1 month (±1 week) after surgery:

Intestinal function evaluation: barium contrast (observation of intestinal
passage time and anastomosis morphology);

Colonoscopy
(to
assess
mucosal
healing
and
inflammation
at
the
anastomosis).

Laboratory tests: blood routine, blood biochemistry, serum vitamin B12 test,
tumor markers (CEA, CA19-9);

Imaging examination: chest X-ray, abdominal CT enhancement (to assess
anastomosis healing and tumor recurrence);

The Second Affiliated Hospital of Army Military Medical University IIT Version: 1.0
29

Human body composition analysis (assessment of patient nutrition);

Quality of life assessment: EORTC QLQ-C30 and QLQ-CR29 scales;

Collection of biological specimens:
biological
specimen
Method
of
collection
Collection
volume
use
Method
of
preservation
Blood samples
Clinical
additional
collection
Fasting
venous blood
10mL
Subsequent
metabolites
and molecular
mechanism
analysis
Centrifuge
and
separate
plasma/saliva
for-80℃storage
Stool samples
Clinical
additional
collection
5g
Fungal
profiling
After
sterile
collection, it was
directly
frozen
and stored at-80℃
(2) 3 months, 6 months and 1 year (±1 week) after surgery:

Laboratory tests: blood routine, blood biochemistry, serum vitamin B12 test;
tumor markers (CEA, CA19-9);

Imaging examination: chest X-ray, abdominal enhanced CT (to assess
anastomosis healing and tumor recurrence);

Human body composition analysis (assessment of patient nutrition);

Collection of biological specimens:
biological
specimen
Method
of
collection
Collection
volume
use
Method
of
preservation
Blood samples
Clinical
additional
collection
Fasting
venous blood
10mL
Subsequent
metabolites
and molecular
mechanism
analysis
Centrifuge
and
separate
plasma/serum
for-80℃storage
Stool samples
Clinical
additional
collection
5g
Fungal
profiling
After
sterile
collection, it was
directly
frozen
and stored at-80℃

The Second Affiliated Hospital of Army Military Medical University IIT Version: 1.0
29
Research process table
search
procedure
Screenin
g period
stage of therapy
follow-up period
Postoperati
ve 24h
Postoperati
ve 48h
Postoperati
ve 72h
Postoperati
ve 1 month
Postoperati
ve 3
months
Postoperati
ve 6
months
Postoperati
ve 1 year
Sign the
informed
consent form
√
Review
selection/exclusi
on criteria
√
General
information
√
medical history
√
check-up
√
√
√
√
vital sign
√
√
√
√
Full abdominal
scan with
enhanced CT
√
√
√
√
√
Chest X-ray
√
√
√
√
√
routine blood
test
√
√
√
√
√
√
√
Blood Biochemistry 1
√
√
√
√
√
√
√
Surgery time
√
amount of
bleeding
√
mRS grade
√
NIHSS grade
√
Therapeutic
medication
√
√
√
complication
√
√
√
√
√
√
√
adverse event
√
√
√
√
√
√
√
enteroscopy
√
Barium contrast
√
Bristol Fecal
Score
√
√
√
√
√
√
√
√
Stool samples
√
√
√
√
√
Blood samples
√
√
√
√
√
Organizing
samples
√
remarks ：
1: Blood biochemistry includes liver function, kidney function, blood electrolyte, blood sugar, blood lipid

The Second Affiliated Hospital of Army Military Medical University IIT Version: 1.0
29
5. End-point indicators
Key endpoint indicator: Time to first stool formation post-surgery (Bristol Stool
Score <4): The Bristol Stool Scale categorizes stool into seven grades. As stool shape
correlates with retention time in the colon, this score helps assess both intestinal
transit time and anastomotic function. Scoring criteria:>5 indicates diarrhea, 6
represents mild diarrhea, and 7 signifies severe diarrhea. (Detailed scoring guidelines
are provided in the appendix)
Secondary endpoints:
a. Surgical safety:
The operation was successful and the treatment effect was accurate, without
anastomosis fistula, bleeding, stenosis-related symptoms; no serious complications
occurred.
Indicators during operation: operation time, anastomosis time, intraoperative
blood loss;
Postoperative indicators: complications within 30 days after surgery and
postoperative inflammatory indicators.
Follow-up
indicators:
anastomosis
healing,
gastrointestinal
iodine
water
radiography, upper gastrointestinal barium meal, colonoscopy, blood glucose, blood
lipid and glycosylated hemoglobin and physiological related indicators.
b. Nutrient metabolism disorder:
Due
to
the
corresponding
nutritional
complications
such
as
bile
acid
malabsorption (BAM) after right hemicolectomy, the patients' albumin level, total
protein, VitB12, bile acid and body composition analysis were tested on 3 days, 1
month, 3 months, 6 months and 1 year after surgery.
c. Improvement of quality of life after surgery:
The EORTCQLQ-C30 and EORTCQLQ-CR2930 scales were completed one
month before and after surgery.
d. Total survival and tumor-free survival:
The total survival and tumor-free survival of patients after surgery. One year after
surgery, imaging examination, endoscopy and tumor marker detection were used to

The Second Affiliated Hospital of Army Military Medical University IIT Version: 1.0
29
evaluate the recurrence and distant metastasis of tumors.
e. Changes in gut microbiota and metabolites:
Following diarrhea onset, significant taxonomic shifts occur in the gut microbiota,
favoring the proliferation of fast-growing facultative anaerobes. Proteus species
(primarily Enterobacteriaceae/Escherichia coli) and Streptococcus species (mainly
Streptococcus salivarius and Streptococcus gallolyticus) show the most pronounced
enrichment during early stages, with relative abundance potentially reaching 80% in
fecal microbiota. The dramatic decline of obligate anaerobic gut symbionts and the
oxidative changes in intestinal environment during diarrhea further promote their
proliferation, as evidenced by elevated expression of genes encoding low-affinity
cytochrome
oxidases.
This
abundance
increase
coincides
with
the
abrupt
disappearance
of
obligate
anaerobic
gut
symbionts
(Blautia,
Prevotella,
Faecalibacterium, Lachnospiraceae, Ruminococcaceae, etc.), leading to depletion of
related metabolites such as short-chain fatty acids. Differential analysis was
conducted by detecting changes in abundance and metabolites of these associated
bacterial groups.
Exploratory endpoints:
Potential organ cross-talk and molecular mechanisms of nutritional and metabolic
disorders
caused
by RISE
anastomosis. Based
on the changes
in
patients'
postoperative metabolism and stool habits, the corresponding metabolites and
molecular changes in blood, stool and bile were detected to speculate the potential
mechanism.
6. Data management and statistical analysis
The clinical departments utilize the institution's electronic medical record system
to compile relevant patient data. Clinical outcomes are systematically analyzed by
designated personnel using SPSS 22.0 statistical software. Categorical data are
presented as [count (%)], analyzed through χ2-tests. Quantitative data, validated by
S-W method testing for normal distribution, are expressed as (x ±s) and evaluated
using t-tests. Statistical significance is defined as P <0.05.

The Second Affiliated Hospital of Army Military Medical University IIT Version: 1.0
29
Follow-up processing: The lost cases were included in the intention-to-treat (ITT)
analysis, and multiple interpolation was used to fill in the missing data.
IV. Observation, recording and disposal of adverse events
Safety was evaluated by detecting or observing various vital signs, adverse
events and laboratory indicators. Adverse event evaluation was based on the
Clavien-Dindo Complication Scoring System (score details are shown in the
appendix).
All adverse events, whether reported by patients or identified through physical
examinations, laboratory tests, or other methods by investigators, will be documented
in the original medical records with appropriate follow-up. Postoperative anastomotic
leakage occurs when intestinal wall defects at the anastomosis site create a
communication between the intestinal lumen and external environment. The presence
of bleeding near the anastomosis or pelvic abscesses — even without obvious
connection to the intestinal lumen — should raise suspicion for leakage. Clinical
manifestations include sudden severe abdominal pain, high fever, chills, significantly
elevated inflammatory markers, and changes in drainage fluid characteristics
(cloudiness or bloody discharge). Immediate symptomatic treatment including fasting,
anti-infective therapy, and hemostasis should be initiated upon symptom onset. Close
monitoring of vital signs is required, with potential consideration for endoscopic
hemostasis or repair. Emergency surgery may be considered if endoscopic treatment
proves ineffective. The research team assigns dedicated personnel to document all
adverse events during the trial period (from informed consent to 30 days post-surgery)
in original medical records. Adverse events will be reported in detail using
standardized medical record forms, with thorough evaluation of their correlation to
study interventions. When necessary, senior physicians will provide guidance to
ensure effective medical care and minimize adverse reaction risks.
V. Quality control

The Second Affiliated Hospital of Army Military Medical University IIT Version: 1.0
29
1. Development of study protocol and standard operating procedures (SOPs)
Unified research plan: clarify the research design, inclusion and exclusion
criteria, intervention measures, evaluation indicators, data collection methods, etc.
Operation manual: covers sample collection, testing methods, equipment
calibration, adverse event recording, etc.
Data entry specification: unified filling rules of electronic case report form
(eCRF).
2. Personnel training and qualification certification
Unified training: Researchers, coordinators and data administrators are required
to pass centralized training (online/offline) and pass the assessment and certification.
Training content: research protocol, SOPs, ethics, use of data entry system.
Regular retraining: retraining for process updates or problem feedback.
Authorization list: records the qualifications and operation rights of personnel in
each center.
3. Data management
Use a unified EDC system (e.g., REDCap, Medidata) to set up logical checks
(e.g., numerical ranges, required items).
Real-time monitoring of data entry progress and quality.
Data verification and cleanup:
Centralized data monitoring: periodic sampling of data and source documents
(Source Data Verification, SDV).
Abnormal value automatic alarm (such as laboratory indicators beyond the
normal range).
Central Laboratory and Imaging Center:
Biological samples are sent to the central laboratory for testing to avoid
differences in testing between different laboratories.
The images were evaluated by an independent central laboratory in a blind
manner.
4. Monitoring and auditing (Monitoring & Auditing)
Centralized monitoring: An independent monitoring team will check the

The Second Affiliated Hospital of Army Military Medical University IIT Version: 1.0
29
implementation of each center on a regular basis (frequency: once a month in the
initial stage and once a quarter later).
Key inspection: subject informed consent, consistency of original data with
eCRF, adverse event records.
Risk-based monitoring (RBM): Strengthen monitoring of high-risk centers or
critical data points (e.g., primary endpoints).
Third-party audit: Invite an independent audit team to conduct surprise
inspection on randomly selected centers to ensure compliance.
5. Equipment and materials management
Equipment standardization: all centers use the same brand and model of key
equipment (such as blood pressure monitors, centrifuges); regular calibration and
record calibration certificates.
Unified supply of materials: Research drugs/instruments are uniformly packaged,
coded and distributed by the central pharmacy to avoid label errors.
6. Communication and coordination mechanisms
Regular meetings: kick-off meeting, mid-term analysis meeting and summary
meeting to ensure that all centers update progress and problems simultaneously;
establish a steering committee to resolve disputes.
Problem feedback and correction: set up a central mailbox or online platform to
report problems (such as plan deviation, equipment failure) in real time; formulate the
"plan deviation processing process" to record and analyze the root cause.
7. Statistical analysis and central effect adjustment
Preset statistical plans: How to handle center effects (e.g., stratified analysis,
mixed effects model) is predefined in the Statistical Analysis Plan (SAP).
Sensitivity analysis: compare the consistency of results in different central
subgroups and evaluate the robustness of results.
VI. Ethical principles and requirements for clinical research
Clinical research will adhere to the Helsinki Declaration of the World Medical
Assembly and China's "Measures for Ethical Review of Human Life Science and

The Second Affiliated Hospital of Army Military Medical University IIT Version: 1.0
29
Medical Research", implementing principles including informed consent, privacy
protection, compensation for free participation, risk control, special subject protection,
and liability for related damages. Clinical trials may only commence after obtaining
approval from the ethics committee for the study protocol. Prior to enrollment,
investigators must provide participants or their legal representatives with a
comprehensive explanation of the study's purpose, procedures, and potential risks,
followed by signing written informed consent forms. Participants must be fully aware
that their decision to join is entirely voluntary, and they retain the right to withdraw at
any stage without facing discrimination or retaliation, while maintaining their medical
rights. Investigators shall strictly safeguard participants' personal privacy and data
confidentiality. All research materials will be stored at the Second Affiliated Hospital
of the Army Medical University. Exceptions to privacy protection and personal
information confidentiality may occur under legal/regulatory circumstances, allowing
investigators, research supervisors, and ethics committees to access such materials.
The research team hereby commits: We will make every effort to protect
participants 'personal privacy and information within the bounds of the law. Security
measures include concealing identifiable participant information during data reporting,
restricting access to such information, implementing data anonymization, and
ensuring that all public reports regarding this study's findings will not disclose
participants' personal identities.
VII. PROJECT TEAM MEMBERS
surname and
personal name
unit
administrative
or technical
offices
professional
ranks and
titles
Year and
month of GCP
training
Division of
project work
Xiao Weidong
Newbridge
Hospital
forensic
sursery
botanic
physician
April 2017
Project Overall
Manager
Jiang Enlai
Newbridge
Hospital
forensic
sursery
associate
chief
physician
May 2017
project
implementation
Du Guangsheng
Newbridge
Hospital
forensic
sursery
associate
chief
physician
February 2022
project
implementation

The Second Affiliated Hospital of Army Military Medical University IIT Version: 1.0
29
Qiu Yuan
Newbridge
Hospital
forensic
sursery
associate
chief
physician
March 2023
Head of the
Subcentres
Zheng Daofeng
Newbridge
Hospital
forensic
sursery
physician
May 2025
data statistics
Zihan Wang
Newbridge
Hospital
forensic
sursery
chief
physician
March 2017
project
implementation
VIII. PARTICIPATING ORGANIZATIONS
1. List of sub-centres
name of organization
Department/office
leading
official
divide the work
cell-phone
number
The First Affiliated
Hospital of Chongqing
Medical University
Hong-yu zhang
Medical team
leader
Patient enrollment at
the sub-center
13983055038
Affiliated Hospital of
North Sichuan Medical
College
Wei Shoujiang
head of
department
Patient enrollment at
the sub-center
13990898624
Department of
Gastrointestinal Hernia,
Guang 'an People's
Hospital, Sichuan Province
Li Yang
head of
department
Patient enrollment at
the sub-center
13551950216
Third People's Hospital of
Yibin City, Sichuan
Province
Liu Shicheng
head of
department
Patient enrollment at
the sub-center
18683120314
2. Other units
name
of
organization
Department/office
leading official
divide the work
cell-phone
number
not have
IX. MAIN REFERENCES
1. Strey CW, Wullstein C, Adamina M, Agha A, Aselmann H, Becker T,
Grützmann R, Kneist W, Maak M, Mann B, Moesta KT, Runkel N,
Schafmayer C, Türler A, Wedel T, Benz S. Laparoscopic right hemicolectomy
with CME: standardization using the "critical view" concept. Surg Endosc.
2018 Dec;32(12):5021-5030.
2. Phillips SF, Quigley EM, Kumar D, Kamath PS. Motility of the ileocolonic
junction. Gut. 1988 Mar;29(3):390-406.
3. LASSER EC, RIGLER LG. Observations on the structure and function of the

The Second Affiliated Hospital of Army Military Medical University IIT Version: 1.0
29
ileocecal valve. Radiology. 1954 Aug;63(2):176-83.
4. Larsen HM, Krogh K, Borre M, Gregersen T, Mejlby Hansen M, Arveschoug
AK, Christensen P, Drewes AM, Emmertsen KJ, Laurberg S, Ladefoged
Fassov J. Chronic loose stools following right-sided hemicolectomy for colon
cancer and the association with bile acid malabsorption and small intestinal
bacterial overgrowth. Colorectal Dis. 2023 Apr;25(4):600-607.
5. Roland BC, Ciarleglio MM, Clarke JO, Semler JR, Tomakin E, Mullin GE,
Pasricha PJ. Low ileocecal valve pressure is significantly associated with small
intestinal bacterial overgrowth (SIBO). Dig Dis Sci. 2014 Jun;59(6):1269-77.
6. Kellogg
JH.
TECHNIC
OF
OPERATION
FOR
REPAIR
OF
THE
ILEOCAECAL VALVE: WITH SUMMARY OF THE RESULTS IN A
SERIES OF TWENTY-SIX CASES. Ann Surg. 1918 Jan;67(1):83-93.
7. Vinograd I, Merguerian P, Udassin R, Mogle P, Nissan S. An experimental
model of a submucosally tunnelled valve for the replacement of the ileo-cecal
valve. J Pediatr Surg. 1984 Dec;19(6):726-31.
8. Chardavoyne R, Isenberg HD, Tindel M, Stein TA, Sampson-Scherer J, Wise L.
Microbiologic efficacy of a surgically constructed nipple valve. Am J Surg.
1984 Feb;147(2):230-3.
9. Cacciari A, Mordenti M, Ceccarelli PL, Ruggeri G. Ileocaecal valve atresia:
our surgical approach. Eur J Pediatr Surg. 2004 Dec;14(6):435-9.
10. Nio Y, Itakura M, Yamaguchi K, Hirahara N. Ileocecal valve-preserving
ileostomy after total proctocolectomy--a novel technique for ileostomy. Dig
Surg. 2004;21(1):7-9.
11. Su H, Wu H, Mu B, Bao M, Luo S, Zhao C, Liu Q, Wang X, Zhou Z, Zhou H.
The
feasibility
and
safety
of
complete
laparoscopic
extended
right
hemicolectomy with preservation of the ileocecal junction in right-transverse
colon cancer. World J Surg Oncol. 2020 Jul 7;18(1):159.
ANNOTATIONS
Bristol defecation classification criteria

The Second Affiliated Hospital of Army Military Medical University IIT Version: 1.0
29
grade
expression
1
Hard small particles are difficult to pass and may be accompanied
by constipation.
2
Irregularly shaped, chunky stools are difficult to pass and may be
accompanied by constipation.
3
The stool is similar to a lump but smooth on the outside and easy to
pass.
4
A banana-shaped stool is the standard form of normal bowel
movements.
5
Soft and mushy stool, easy to pass, is a normal range of changes.
6
Fusel stools, relatively loose, may be accompanied by diarrhea.
7
Complete liquid stool is a sign of diarrhea.
Adverse event evaluation was based on the Clavien-Dindo complication scoring
system.

The Second Affiliated Hospital of Army Military Medical University IIT Version: 1.0