A Prospective Non-randomized Controlled Multi-center Study of Laparoscopic Intracorporeal Distal Rectal Transection by Using the Traditional Approach vs. Using Transanterior Obturator Nerve Gateway Approach for Ultralow Rectal Cancers
Phase: NA
Conditions: Rectal Neoplasms Malignant
Sponsor: Peking University First Hospital

 
 
 
Clinical Trial Protocol 
 
 
Title 
A 
Prospective 
Non-randomized 
Controlled Multi-center Study of 
Laparoscopic Intracorporeal Distal Rectal Transection by Using the 
Traditional Approach vs. Using Transanterior Obturator Nerve Gateway 
Approach for Ultralow Rectal Cancers 
 
NCT No. 
Not assigned yet 
 
Date 
2021/9/7 
 
 
 
 
 
 
Principle Investigator Name 
Jianqiang Tang, M.D., Associate Professor (Specialized in GI and colorectal 
surgical oncology) 
Contact: Phone: +86 13661090036; Email: doc_tjq@hotmail.com  

 
Investigator Affiliation 
Peking University First Hospital 
Co-ordinating Investigators 
Hekai Chen (Tianjin Fifth Central Hospital), Xiping Ding (Shengli Oilfield 
Hospital) and Qiuhong Wang (The Second Affiliated Hospital of Baotou 
Medical College).  
Trial sites 
Multi-center 
Methodology 
Prospective, Non-randomized, Interventional, Controlled 
The Biomedical Research Ethics Committee of Peking University First 
Hospital is overseeing the research. (Phone: 010-66119025; Email: 
bdyyll@126.com; Address: Xishiku Street No.8, Xicheng District, 
Beijing,100034, People’s Republic of China) 
 
 
 
Background 
Since 1992 when intersphincteric resection (ISR) for rectal cancer was first proposed by 
Braun et al, ISR has been widely used since it can significantly improve patients’ quality 
of life by preserving the anus, especially for those with low rectal cancer[1-4]. A series of 
studies have demonstrated its safety and feasibility. Standard laparoscopic ISR can not 
only ensure the radical resection of the tumor, but also preserve the anus[5-7]. 
Laparoscopic ISR with double stapling technique (DST) can provide a clearer view of the 
narrow pelvic and intersphincteric space, and the minimally invasive approach can 
relieve postoperative pain, shorten hospital stay, and generate better cosmetic outcomes 
compared with traditional combined abdominal perineal resection[8].  

 
The wide application of ISR and DST has greatly improved the anal preservation rate 
for low rectal cancers, but the technical difficulty has also been obviously increased. In 
addition, for ultralow rectal cancers, because of the limited pelvic space, laparoscopic 
distal rectal transection could only be finished by multiple staplings resulting in an 
overlong stapling line, which could increase the risk for postoperative anastomotic 
leakage rate, which would seriously affect the patient’s recovery and quality of life. Or 
the limited space could make it almost impossible to remove enough rectum to ensure a 
radical resection of the tumor, so distal rectal resection would have to be performed by 
converting to a transanal approach, that would definitely prolong the operative time and 
also increase the risk for anastomotic leakage. Although many scholars have tried to 
solve this problem[9-12], all the methods have failed to fundamentally solve the problem of 
“the oblique dissection” of the distal rectum for ultralow rectal cancers. 
To solve the problem above, on the basis of a large number of ISR-DST performing 
experience, Dr Tang, the director of this clinical trial has explored a new distal rectal 
resection method-- transanterior obturator nerve gateway approach. This approach can 
conspicuously expand the pelvic space and optimize the dissection angle without 
significantly prolonging the operative time, thus reducing the technical difficulty. So, by 
using this method, it would be more likely to preserve the anus and reduce the possibility 
of converting to transanal approach without breach of tumor’s radical resection. The 
purpose of this clinical trial is to prospectively collect and compare data on the patients’ 
perioperative items and postoperative functional and oncological outcomes of this novel 
approach with the traditional approach, so as to confirm the safety and feasibility of this 
novel approach and its advantages over the traditional approach. 
References 
[1] 
Scala D, Niglio A, Pace U, et al. Laparoscopic intersphincteric resection: Indications and results [J]. 
Updates Surg, 2016,68(1):85-91. 
[2] Chi P, Huang SH, Lin HM, et al. Laparoscopic transabdominal approach partial intersphincteric 
resection for low rectal cancer: Surgical feasibility and intermediate-term outcome [J]. Ann Surg 
Oncol, 2015,22(3):944-951. 
[3] Fujimoto Y, Akiyoshi T, Kuroyanagi H, et al. Safety and feasibility of laparoscopic intersphincteric 
resection for very low rectal cancer [J]. J Gastrointest Surg, 2010,14(4):645-650. 
[4] Braun J, Treutner KH, Winkeltau G, et al. Results of intersphincteric resection of the rectum with 
direct coloanal anastomosis for rectal carcinoma [J]. Am J Surg, 1992,163(4):407-412. 
[5] Pai VD, Sugoor P, Patil PS, et al. Laparoscopic versus open approach for intersphincteric resection-
results from a tertiary cancer center in india [J]. Indian J Surg Oncol, 2017,8(4):474-478. 
[6] Mahalingam S, Seshadri RA, Veeraiah S. Long-term functional and oncological outcomes following 

 
intersphincteric resection for low rectal cancers [J]. Indian J Surg Oncol, 2017,8(4):457-461. 
[7] Denost Q, Rullier E. Intersphincteric resection pushing the envelope for sphincter preservation [J]. 
Clin Colon Rectal Surg, 2017,30(5):368-376. 
[8] Park SY, Choi GS, Park JS, et al. Short-term clinical outcome of robot-assisted intersphincteric 
resection for low rectal cancer: A retrospective comparison with conventional laparoscopy [J]. Surg 
Endosc, 2013,27(1):48-55. 
[9] Bi L, Deng X, Meng X, et al. Ligating the rectum with cable tie facilitates rectum transection in 
laparoscopic anterior resection of rectal cancer [J]. Langenbecks Arch Surg, 2020,405(2):233-239. 
[10] Hotta T, Takifuji K, Yokoyama S, et al. Rectal transection by the nelaton catheter pulling method during 
a laparoscopic low anterior resection [J]. Dis Colon Rectum, 2011,54(4):495-500. 
[11] Park SJ, Choi SI, Lee SH, et al. Endo-satinsky clamp for rectal transection during laparoscopic total 
mesorectal excision [J]. Dis Colon Rectum, 2010,53(3):355-359. 
[12] Brannigan AE, De Buck S, Suetens P, et al. Intracorporeal rectal stapling following laparoscopic total 
mesorectal excision: Overcoming a challenge [J]. Surg Endosc, 2006,20(6):952-955. 
 
 
 
Objective 
To confirm the safety, feasibility and advantages by comparing the perioperative variables, 
postoperative functional and oncological outcomes of patients with ultralow rectal cancer 
treated by laparoscopic traditional distal rectal dissection vs. by transanterior obturator 
nerve gateway approach. 
Patients 
Patients with ultralow (≤5cm from the anal verge) rectal cancer who are to undergo 
laparoscopic radical resection (ISR- DST) without any contraindications of general 
anesthesia, surgery or chemotherapy. 
➢ Inclusion criteria 
1) Age: 18-80 years old； 
2) Pathologically diagnosed as rectal cancer with the lower margin of the tumor from the 
anal margin ≤5cm； 
3) CT, MRI or endoscopic ultrasonography: Single tumor, clinical T stage ≤3 or no invasion 
of the internal sphincter, maximum diameter ≤10cm, no distant metastasis; 
4) The patient or the patient-authorized representative completely understands the study 
protocol and voluntarily participates in this study, agrees to sign written informed consent. 
➢ Exclusion criteria 

 
1) The patient had previous abdominal surgery that will significantly infect the 
laparoscopic procedures; 
2) Patients requiring emergency surgery owing to intestinal obstruction, perforation, or 
uncontrolled bleeding caused by tumor; 
3) Patients with poor anal function preoperatively (Wexner score ≥10); 
4) ASA (American Society of Anesthesiologists) grading ≥ IV; 
5) Pregnant patients; 
6) Patients concomitant with severe mental illness; 
7) The patient or the patient-authorized representativecan’t understand the contents and 
objectives of the study. 
➢ Withdraw criteria 
1) ISR cannot be performed by intraoperative evaluation and is replaced by Miles surgery; 
2) Distant metastasis is confirmed intraoperatively or by postoperative pathological 
findings; 
3) Patients had other primary tumors requiring surgical/drug treatment during the study, or 
had other illnesses that prevent the patient from continuing to participate this study;  
4) Patients decide to withdraw from the study for any reason, or who are unable to complete 
the study because of any objective reasons. 
Sample size 
Two groups are designed, patients who are to receive the traditional approach to transect 
the distal rectum are assigned to the control group, patients who are to receive the 
transanterior obturator nerve gateway approach to transect the distal rectum are assigned 
to the experimental group. 100 cases are to be enrolled for the experimental group and 
not less than 100 cases are to be enrolled for the controlled group. 
Treatment 
If the participant matches with the requirements for this study and agrees to take part in it, 
once hospitalized, the participant will complete the established preoperative tests including 
blood routine, the comprehensive metabolic panel, blood coagulation function, tumor 
markers, blood type, infectious disease screening tests, chest, abdominal and pelvic CT 
(Computed Tomography) scan and MRI, colonoscopy, echocardiogram, pulmonary 
function, venous duplex ultrasound of legs. All male patients will be routinely asked to fill 

 
in the IIEF-5 sexual function scoring questionnaire preoperatively.  
The following comprehensive treatment will be depended on the examination results: 
➢ Neoadjuvant therapy 
The treatment plan will be made in accordance with the NCCN (National Comprehensive 
Cancer Network) Guidelines for Diagnosis and Treatment of Colorectal Cancer (Version 
1.2021). 
Neoadjuvant chemoradiotherapy: Pelvis radiotherapy with a total dose of 50 Gy with 25 
courses in 5 weeks. Neoadjuvant chemotherapy include single drug therapy: capecitabine 
(CAP, 1250 mg/m2, BID) or double drug therapy: oxaliplatin combined with capecitabine 
(CapeOX, oxaliplatin 130 mg/m2, day 1, capecitabine 1000mg/ m2, day 1 ~ 14, then rest 
for 7 days, repeated every 3 weeks) or three-drug therapy (mFOLFOX6, oxaliplatin 85 mg/ 
m2 intravenous infusion for 2 hours, leucovorin calcium 400 mg/m2 intravenous infusion 
for 2 hours, 5-FU (fluorouracil) 400 mg/m2 intravenous infusion for 1 day, Then 1200 mg/ 
m2/d×2 days of continuous intravenous infusion with a total of 2400mg/m2 for 46 ~ 48 
hours, repeated every 2 weeks. 
Abdominal and pelvic MRI and contrast enhanced CT will be routinely performed 6 to 
8 weeks after neoadjuvant therapy to confirm the extent of tumor regression without new-
found distant metastasis. Those whose clinical stage after neoadjuvant therapy changes 
from T4 to T3 will be seen as eligible in this study. 
➢ Surgical treatment 
⚫ Preoperative preparation  
1) Patients older than 60 years old or having a smoking history for over 10 years will 
receive lung ventilation training and atomization treatment for 3 days 
2) Intestinal preparation will be done with oral cathartic medications 12-24 hours before 
surgery 
3)  Prophylactic antibiotics will be given once anesthesia is begun, the second antibiotics 
will be given if the operation lasts for over 3 hours  
4）Urethral catheterization will be routinely done preoperatively 
5）If the patient refuses to accept the novel approach before surgery, they will be directly 
enrolled in the traditional group. If both approaches are acceptable to the patient, the 
decision whether to use the novel approach will be made according to the intraoperative 

 
conditions (see operating procedures below).  
⚫ Operating procedures 
General anesthesia; Modified lithotomy position (Fig. 1a); Establishment of 
pneumoperitoneum: Place a trocar 1cm above the umbilicus through which to establish 
pneumoperitoneum and keep the abdominal pressure as 12 mmHg (millimeters of mercury). 
Trocar placement: above the umbilicus (trocar C, 10 mm), upper right and left quadrants 
(trocars B and D, 5 mm), lower right quadrant (trocar A, 12 mm), lower left quadrant (trocar 
E, 5 mm), the midpoint between the pubic symphysis and umbilicus (trocar F, 5 mm).  
 
 
Fig.1 Patient position and trocar placement 
Abdominal exploration: Explore the abdominal cavity in accordance with the principle 
of non-contact, from far to near step by step, explore the tumor finally. 
The mesosigmoid and mesorectum are dissected from the right lateral rectum towards 
the root of the inferior mesenteric artery (IMA). The IMA is transected and ligated, so is 
the inferior mesenteric vein. Posterior space of the descending colon is dissected following 
opening the peritoneum beside the left rectum. The rectum in the pelvis is been mobilized 
from posterior rectal space, anterior rectal space to bilateral rectal space successively. The 
lower edge of the tumor is marked by a clamp. The linear stapler is placed in the pelvis to 
clamp the distal rectum below the tumor to see if the transection can be done more than 
1cm from the lower edge of the tumor. If yes, the distal rectum will be transected by the 
traditional approach (that means the patient will be assigned to the traditional group). The 
proximal bowel is transected through a small midline incision. Then the coloanal 

 
anastomosis will be done intracorporeally. A surgical drain is placed in the pelvis and a 
terminal ileostomy is routinely performed. All incisions are closed. 
If the distal rectal transection cannot be done more than 1cm from the lower edge of the 
tumor, the anterior obturator nerve gateway approach will be used (that means the patient 
will be assigned to the experimental group). The steps are as follows: The peritoneum 
covering the ureter and external iliac artery is opened more than 2 cm across the vas 
deferens (male) or round ligament (female). The Retzius space and vesicohypogastric 
fascia are exposed. The obturator vessels and obturator nerve are properly identified. Care 
should be taken to avoid any injury when using energy devices near the obturator nerve. 
The gateway is then opened through theTME (total mesorectal excision) compartment and 
the lateral compartment. If necessary, an “endoloop” can be placed through the gateway, 
and the bundled S2-4 nerves, ureter and bladder vessels are gently retracted toward the 
cranial direction to widen the gap. The linear stapler is placed in the gateway to vertically 
transect the distal rectum. The following procedures are the same with the traditional group 
as described above. 
During the operation, the following variables will be recorded: the angle between the 
linear stapler and the rectum, distance from the lower edge to the resecting margin, whether 
the operation converted to transanal approach, operative time, bleeding volume, 
anastomotic height from anal verge and the length of the stapling line. 
➢ Postoperative management： 
The following information will be recorded: 
1）Vital signs (body temperature, pulse rate, respiration rate, blood pressure) are 
routinely monitored,  gross volume of fluid input and output will be recorded every 24h, 
blood routine, the comprehensive metabolic panel and coagulation function tests will be 
performed every 3 days.  
2）The time of catheter removal (days after operation), residual urine volume in the 
bladder will be measured by ultrasound examination. Whether there is a request to be re-
catheterized or take oral medication to relive the dysuria. All patients will be asked to fulfil 
the IPSS (International prostate symptom score) questionnaire to assess urinary function. 
Table 1. International prostate symptom score assessing urinary function 
In the past month: 
Not at All 
Less than 
1 in 5 
Less than 
Half the 
About 
Half the 
More 
than Half 
Almost 
Always 

 
Times 
Time 
Time 
the Time 
 
1. Incomplete Emptying 
How often have you had the 
sensation of not emptying 
your bladder? 
0 
1 
2 
3 
4 
5 
2. Frequency 
How often have you had to 
urinate less than every two 
hours? 
0 
1 
2 
3 
4 
5 
3. Intermittency 
How often have you found 
you stopped and started again 
several times when you 
urinated? 
0 
1 
2 
3 
4 
5 
4. Urgency 
How often have you found it 
difficult to postpone 
urination? 
0 
1 
2 
3 
4 
5 
5. Weak Stream 
How often have you had a 
weak urinary stream? 
0 
1 
2 
3 
4 
5 
6. Straining 
How often have you had to 
strain to start urination? 
0 
1 
2 
3 
4 
5 
 
None  
1 Time  
2 Times  
3 Times  
4 Times  
5 Times 
7. Nocturia 
How many times did you 
typically get up at night to 
urinate? 
0 
1 
2 
3 
4 
5 
Total Score 
 
Score: 1-7: Mild 8-19: Moderate 20-35: Severe 
 
3）The time of pelvic drain removal (days after operation)  
4）Whether complicated with anastomotic leakage, ileus and long-lasting (more than 5 
days) pulmonary  or abdominal infection  
5）All information of the pathologic report.  
6）Postoperative hospital stay (days) 
➢ Postoperative chemoradiotherapy 
Radiotherapy program is the same with the neoadjuvant therapy. Chemotherapy will be 
advised for patients with stage II cancer accompanied with the following high-risk factors: 
histologically poorly differentiated with normal mismatched repair or stable microsatellite 
(MSS), pT4 (pathological stage T 4), vascular/nerve invasion, preoperative intestinal 
obstruction or perforation, ≤ 12 lymph nodes retrieved and R1 resection. The chemotherapy 
program is the same with neoadjuvant chemotherapy. If mismatch repair defect (dMMR) 
or high-level microsatellite instability (MSI-H) is confirmed by pathology, chemotherapy 

 
will not be advised. Patients with stage III cancer will routinely receive chemotherapy.  
 
Follow-up 
1) Information on general medical history and physical examination will be collected 
every 3 months for 3 years 
2) Blood tumor markers of CEA (carcinoembryonic antigen) and CA19-9 
(carbohydrate antigen 19-9) will be tested every 3 months for 3 years 
3) Abdominal and pelvic ultrasound and chest X-ray examinations will be carried out 
every 3 months for 3 years 
4) Abdominal and pelvic MRI or contrast enhanced CT scan will be done every year 
for 3 years 
5) Colonoscopy will be performed within 1 year after surgery. If there is any       
abnormity, reexamination will be required within half a year. If no abnormality is found, 
once a year for 3 years. All new-found adenomas by the colonoscopy during follow-up 
are recommended to be resected. 
6) Sexual function score is assessed by filling in the questionnaire (IIEF-5) both 
preoperatively and 1 year later since operation.  
Table 2. International Index of Erectile Function-5 assessing sexual function 
Over the past 6 months: 
 
 
 
 
 
1. How do you rate your confidence 
that you could get and keep an 
erection? 
Very low 
1 
Low  
2 
Moderate 
3 
High  
4 
Very 
high  
5 
2. When you had erections with sexual 
stimulation, how often were your 
erections hard enough for penetration? 
Almost 
never/ne
ver 1 
 
A few 
times 
(much 
less than 
half the 
time) 2 
Sometim
es (about 
half the 
time) 3 
Most 
times 
(much 
more 
than half 
the time) 
4 
Almost 
always/a
lways 5 
3. During sexual intercourse, how 
often were you able to maintain your 
erection after you had penetrated 
(entered) your partner? 
Almost 
never/ne
ver 1 
A few 
times 
(much 
less than 
half the 
time) 2 
Sometim
es (about 
half the 
time) 3 
Most 
times 
(much 
more 
than half 
the 
time)4 
Almost 
always/a
lways 5 
4. During sexual intercourse, how 
difficult was it to maintain your 
erection to completion of intercourse? 
Extremel
y 
difficult 
1 
Very 
difficult 
2 
Difficult 
3 
Slightly 
difficult 
4 
Not 
difficult 
5 

 
5. When you attempted sexual 
intercourse, how often was it 
satisfactory for you? 
Almost 
never/ne
ver 1 
A few 
times 
(much 
less than 
half the 
time) 2 
Sometim
es (about 
half the 
time) 3 
Most 
times 
(much 
more 
than half 
the time) 
4 
Almost 
always/a
lways 5 
IIEF-5 scoring: 
 
The IIEF-5 score is the sum of the ordinal responses to the 5 items. 
22-25: No erectile dysfunction 
17-21: Mild erectile dysfunction 
12-16: Mild to moderate erectile dysfunction 
8-11: Moderate erectile dysfunction 
5-7: Severe erectile dysfunction 
 
7) 3-year tumor-free survival (month): The time from operation to confirmation of 
tumor’s local recurrence or distant metastasis. The end point of the patient lost to follow-
up is the date of loss. 30 days is defined as one month 
8) 3-year overall survival (month): The time from operation to death. The end point of 
the patient lost to follow-up is the date of loss. 30 days is defined as one month 
9) Stoma closure time (months since operation). Anal function is assessed by Wexner  
scale 3 months and12 months after stoma closure, respectively. 
Table 3. Wexner score assessing anal function 
Type of 
Incontinence 
Frequency 
Never 
Rarely 
Sometimes 
Usually 
Always 
Solid 
0 
1 
2 
3 
4 
Liquid 
0 
1 
2 
3 
4 
Gas 
0 
1 
2 
3 
4 
Wear Pad 
0 
1 
2 
3 
4 
Lifestyle 
altered 
0 
1 
2 
3 
4 
Never - 0 
Rarely - Less than once a month 
Sometimes - Less than once a week or once a month 
Usually - Once a day or once a week 
Always - Once a day or more 
Score: 0 Perfect; 20 Complete Incontinence 
 
 (As to possible risks and benefits of participating in this trial, see details in the informed 
consent document.) 
Study start date (actual) 

 
2020-12-01 
Study completion date (anticipated) 
2025-12-01 (All outcomes of the last patient are recorded 3 years postoperatively, death 
or loss to follow-up of the last patient.) 
Primary outcomes  
➢ The degree of Angle denotes the degree of angle between the linear stapler and the 
longitudinal axis of the rectum when transecting the distal rectum. 
➢ The degree of △Angle represents the degree of angle between the simulated 
stapling line with the total mesorectal excision approach and the real stapling line 
with the transanterior obturator nerve gateway approach (this outcome is measured 
only in patients of the experimental group ). 
➢ Length of distal resection margin indicates the shortest distance between the distal 
border of the tumor and the edge of the distal resection. 
➢ Rate of conversion to transanal transection and anastomosis of the rectum: For each 
case, whether there is a conversion to transanal transection and anastomosis of the 
rectum during the operation will be recorded. The gross conversion rate (No. of cases 
undergoing conversion/total No. of cases enrolled *100%) for each group will be 
calculated immediately after the last patient’s surgery . 
➢ Rate of anastomotic leakage: Whether the patient complicates with anastomotic 
leakage postoperatively will be followed up till 6 months after surgery. The gross 
anastomotic leakage rate (No. of cases diagnosed with anastomotic leakage/total No. 
of cases enrolled *100%) for each group will be calculated 6 months after the last 
patient’s surgery. Anastomotic leakage will be diagnosed if the patient has clinically 
apparent leakage signs (such as the emission of gas, pus, or feces from the pelvic 
drain, or peritonitis) or extravasation of endoluminally administered watersoluble 
contrast medium according to CT. 
Statistics 
IBM SPSS (Statistical Package for the Social Sciences) Statistics 25 (IBM, Inc., Armonk, 
NY) will be used to perform statistical analyses. The t test and Mann-Whitney U test 
were used for quantitative data between groups. Qualitative data were compared by c2 or 

 
Fisher’s exact test and survival distributions were analyzed by log-rank test. 
Flow chart of the study 
 
Fund 
This study is supported by Wu Jieping's Foundation Special for Clinical Research 
(320.6750.2021-04-2). 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed Consent Document 
For the study: 
A Prospective Non-randomized Controlled Multi-center Study of 
Laparoscopic Intracorporeal Distal Rectal Transection by Using 
the Traditional Approach vs. Using Transanterior Obturator 
Nerve Gateway Approach for Ultralow Rectal Cancers 
 
NCT No. 
Not assigned yet 

 
 
Date 
2021/9/7 
 
 
 
 
 
 
 
 
 
 
 
 
This study is being conducted by Dr. Jianqiang Tang, MD and associate professor at 
Department of General Surgery, Peking University First Hospital. Other researchers 
include Dr. Hekai Chen (Tianjin Fifth Central Hospital), Dr. Xiping Ding (Shengli Oilfield 
Hospital) and Dr. Qiuhong Wang (The Second Affiliated Hospital of Baotou Medical 
College). The Biomedical Research Ethics Committee of Peking University First Hospital 
is overseeing the research.  
 
Please read this form carefully – it tells you about your rights in this study. Ask questions 
if you want more information about the form or the study. 
 
If you decide to participate in this study you will sign this form – make sure you understand 
it completely before signing. We will give you a copy of this form to keep – it has important 
information like whom to contact if you have questions later. 
 
➢ What is this study about? 

 
Since 1992 when intersphincteric resection (ISR) for rectal cancer was first proposed by 
Braun et al, ISR has been widely used since it can significantly improve patients’ quality 
of life by preserving the anus, especially for those with low rectal cancer. A series of 
studies have demonstrated its safety and feasibility. Standard laparoscopic ISR can not 
only ensure the radical resection of the tumor, but also preserve the anus. Laparoscopic 
ISR with double stapling technique (DST) can provide a clearer view of the narrow 
pelvic and intersphincteric space, and the minimally invasive approach can relieve 
postoperative pain, shorten hospital stay, and generate better cosmetic outcomes 
compared with traditional combined abdominal perineal resection. The wide application 
of ISR and DST has greatly improved the anal preservation rate for low rectal cancers, 
but the technical difficulty has also been obviously increased. In addition, for ultralow 
rectal cancers, because of the limited pelvic space, laparoscopic distal rectal transection 
could only be finished by multiple staplings resulting in an overlong stapling line, which 
could increase the risk for postoperative anastomotic leakage rate, which would seriously 
affect the patient’s recovery and quality of life. Or the limited space could make it almost 
impossible to remove enough rectum to ensure a radical resection of the tumor, so distal 
rectal resection would have to be performed by converting to a transanal approach, that 
would definitely prolong the operative time and also increase the risk for anastomotic 
leakage. Although many scholars have tried to solve this problem, all the methods have 
failed to fundamentally solve the problem of “the oblique dissection” of the distal rectum 
for ultralow rectal cancers. 
To solve the problem above, on the basis of a large number of ISR-DST performing 
experience, Dr Tang, the director of this clinical trial has explored a new distal rectal 
resection method-- transanterior obturator nerve gateway approach. This approach can 
conspicuously expand the pelvic space and optimize the dissection angle without 
significantly prolonging the operative time, thus reducing the technical difficulty. So, by 
using this method, it would be more likely to preserve the anus and reduce the possibility 
of converting to transanal approach without breach of tumor’s radical resection. The 
purpose of this clinical trial is to prospectively collect and compare data on the patients’ 
perioperative items and postoperative functional and oncological outcomes of this novel 
approach with the traditional approach, so as to confirm the safety and feasibility of this 

 
novel approach and its advantages over the traditional approach. 
 
➢ Who are we asking to participate? 
Patients with ultralow rectal cancer (≤5cm from the anal verge) who are to undergo 
laparoscopic radical resection of rectal cancer (ISR-DST) without any contraindications of 
general anesthesia, operation or chemotherapy. 
Inclusion criteria 
1) Age: 18-80 years old； 
2) Pathologically diagnosed as rectal cancer with the lower margin of the tumor from the 
anal margin ≤5cm； 
3) CT (Computed Tomography), MRI (Magnetic Resonance Imaging) or endoscopic 
ultrasonography: Single tumor, clinical T stage ≤3 or no invasion of the internal sphincter, 
maximum diameter ≤10cm, no distant metastasis; 
4) The patient or the patient-authorized representative completely understands the study 
protocol and voluntarily participates in this study, agrees to sign written informed consent. 
Exclusion criteria 
1) The patient had previous abdominal surgery that will significantly infect the 
laparoscopic procedures; 
2) Patients requiring emergency surgery owing to intestinal obstruction, perforation, or 
uncontrolled bleeding caused by tumor; 
3) Patients with poor anal function preoperatively (Wexner score ≥10); 
4) ASA grading ≥ IV; 
5) Pregnant patients; 
6) Patients concomitant with severe mental illness; 
7) The patient or the patient-authorized representative can’t understand the contents and 
objectives of the study. 
Withdraw criteria 
1) ISR cannot be performed by intraoperative evaluation and is replaced by Miles surgery; 
2) Distant metastasis is confirmed intraoperatively or by postoperative pathological 
findings; 

 
3) Patients had other primary tumors requiring surgical/drug treatment during the study, or 
had other illnesses that prevent the patient from continuing to participate this study;  
4) Patients decide to withdraw from the study for any reason, or who are unable to complete 
the study because of any objective reasons. 
 
➢ What will you be asked to do? 
If you match with the requirements for this study and agree to take part in it, once 
hospitalized, you will complete the established preoperative tests including blood routine, 
the comprehensive metabolic panel, blood coagulation function, tumor markers, blood type, 
infectious disease screening tests, chest, abdominal and pelvic CT scan and MRI, 
colonoscopy, echocardiogram, pulmonary function, venous duplex ultrasound of legs. All 
male patients will be routinely asked to fill in the IIEF-5 (International Index of Erectile 
Function-5) sexual function scoring questionnaire preoperatively.  
The following comprehensive treatment will be depended on the examination results: 
Neoadjuvant therapy 
The treatment plan will be made in accordance with the NCCN (National Comprehensive 
Cancer Network) Guidelines for Diagnosis and Treatment of Colorectal Cancer (Version 
1.2021).  
Neoadjuvant chemoradiotherapy: Pelvis radiotherapy with a total dose of 50 Gy with 25 
courses in 5 weeks. Neoadjuvant chemotherapy include single drug therapy: capecitabine 
(CAP, 1250 mg/m2, BID) or double drug therapy: oxaliplatin combined with capecitabine 
(CapeOX, oxaliplatin 130 mg/m2, day 1, capecitabine 1000mg/ m2, day 1 ~ 14, then rest 
for 7 days, repeated every 3 weeks) or three-drug therapy (mFOLFOX6, oxaliplatin 85 mg/ 
m2 intravenous infusion for 2 hours, leucovorin calcium 400 mg/m2 intravenous infusion 
for 2 hours, 5-FU (fluorouracil)  400 mg/m2 intravenous infusion for 1 day, Then 1200 
mg/ m2/d×2 days of continuous intravenous infusion with a total of 2400mg/m2 for 46 ~ 
48 hours, repeated every 2 weeks. 
Abdominal and pelvic MRI and contrast enhanced CT will be routinely performed 6 to 
8 weeks after neoadjuvant therapy to confirm the extent of tumor regression without new-
found distant metastasis. Those whose clinical stage after neoadjuvant therapy changes 
from T4 to T3 will be seen as eligible in this study. 

 
Surgical treatment 
Preoperative preparation  
1) Patients older than 60 years old or having a smoking history for over 10 years will 
receive lung ventilation training and atomization treatment for 3 days 
2) Intestinal preparation will be done with oral cathartic medications 12-24 hours before 
surgery 
3)  Prophylactic antibiotics will be given  once anesthesia is begun, the second 
antibiotics will be given if the operation lasts for over 3 hours  
4）Urethral catheterization will be routinely done preoperatively 
5）If the patient refuses to accept the novel approach before surgery, they will be directly 
enrolled in the traditional group. If both approaches are acceptable to the patient, the 
decision whether to use the novel approach will be made according to the intraoperative 
conditions (see operating procedures below).  
Operating procedures 
General anesthesia; Modified lithotomy position (Fig. 1a); Establishment of 
pneumoperitoneum: Place a trocar 1cm above the umbilicus through which to establish 
pneumoperitoneum and keep the abdominal pressure as 12mmHg (millimeters of mercury). 
Trocar placement (Fig. 1b): above the umbilicus (trocar C, 10 mm), upper right and left 
quadrants (trocars B and D, 5 mm), lower right quadrant (trocar A, 12 mm), lower left 
quadrant (trocar E, 5 mm), the midpoint between the pubic symphysis and umbilicus (trocar 
F, 5 mm).  
 
 

 
Fig.1 Patient position and trocar placement 
Abdominal exploration: Explore the abdominal cavity in accordance with the principle 
of non-contact, from far to near step by step, explore the tumor finally. 
The mesosigmoid and mesorectum are dissected from the right lateral rectum towards 
the root of the inferior mesenteric artery (IMA). The IMA is transected and ligated, so is 
the inferior mesenteric vein. Posterior space of the descending colon is dissected following 
opening the peritoneum beside the left rectum. The rectum in the pelvis is been mobilized 
from posterior rectal space, anterior rectal space to bilateral rectal space successively. The 
lower edge of the tumor is marked by a clamp. The linear stapler is placed in the pelvis to 
clamp the distal rectum below the tumor to see if the transection can be done more than 
1cm from the lower edge of the tumor. If yes, the distal rectum will be transected by the 
traditional approach (that means the patient will be assigned to the traditional group). The 
proximal bowel is transected through a small midline incision. Then the coloanal 
anastomosis will be done intracorporeally. A surgical drain is placed in the pelvis and a 
terminal ileostomy is routinely performed. All incisions are closed. 
If the distal rectal transection cannot be done more than 1cm from the lower edge of the 
tumor, the anterior obturator nerve gateway approach will be used (that means the patient 
will be assigned to the experimental group). The steps are as follows: The peritoneum 
covering the ureter and external iliac artery is opened more than 2 cm across the vas 
deferens (male) or round ligament (female). The Retzius space and vesicohypogastric 
fascia are exposed. The obturator vessels and obturator nerve are properly identified. Care 
should be taken to avoid any injury when using energy devices near the obturator nerve. 
The gateway is then opened through the TME (total mesorectal excision) compartment and 
the lateral compartment. If necessary, an “endoloop” can be placed through the gateway, 
and the bundled S2-4 nerves, ureter and bladder vessels are gently retracted toward the 
cranial direction to widen the gap. The linear stapler is placed in the gateway to vertically 
transect the distal rectum. The following procedures are the same with the traditional group 
as described above. 
During the operation, the following variables will be recorded: the angle between the 
linear stapler and the rectum, distance from the lower edge to the resecting margin, whether 
the operation converted to transanal approach, operative time, bleeding volume, 

 
anastomotic height from anal verge and the length of the stapling line. 
 
Postoperative management 
The following information will be recorded: 
1）Vital signs (body temperature, pulse rate, respiration rate, blood pressure) are 
routinely monitored,  gross volume of fluid input and output will be recorded every 24h, 
blood routine, the comprehensive metabolic panel and coagulation function tests will be 
performed every 3 days.  
2）The time of catheter removal (days after operation), residual urine volume in the 
bladder will be measured by ultrasound examination. Whether there is a request to be re-
catheterized or take oral medication to relive the dysuria. All patients will be asked to fulfil 
the IPSS (International prostate symptom score) questionnaire to assess urinary function. 
 
Table 1. International prostate symptom score assessing urinary function 
In the past month: 
Not at All 
Less than 
1 in 5 
Times 
Less than 
Half the 
Time 
About 
Half the 
Time 
More 
than Half 
the Time 
Almost 
Always 
 
1. Incomplete Emptying 
How often have you had the 
sensation of not emptying your 
bladder? 
0 
1 
2 
3 
4 
5 
2. Frequency 
How often have you had to 
urinate less than every two 
hours? 
0 
1 
2 
3 
4 
5 
3. Intermittency 
How often have you found you 
stopped and started again 
several 
times 
when 
you 
urinated? 
0 
1 
2 
3 
4 
5 
4. Urgency 
How often have you found it 
difficult to postpone urination? 
0 
1 
2 
3 
4 
5 
5. Weak Stream 
How often have you had a 
weak urinary stream? 
0 
1 
2 
3 
4 
5 
6. Straining 
How often have you had to 
strain to start urination? 
0 
1 
2 
3 
4 
5 
 
None  
1 Time  
2 Times  
3 Times  
4 Times  
5 Times 
7. Nocturia 
How many times did you 
typically get up at night to 
urinate? 
0 
1 
2 
3 
4 
5 
Total Score 
 
Score: 1-7: Mild 8-19: Moderate 20-35: Severe 

 
 
3）The time of pelvic drain removal (days after operation)  
4）Whether complicated with anastomotic leakage, ileus and long-lasting (more than 5 
days) pulmonary  or abdominal infection  
5）All information of the pathologic report.  
6）Postoperative hospital stay (days) 
 
Postoperative chemoradiotherapy 
Radiotherapy program is the same with the neoadjuvant therapy. Chemotherapy will be 
advised for patients with stage II cancer accompanied with the following high-risk factors: 
histologically poorly differentiated with normal mismatched repair or stable microsatellite 
(MSS), pT4 (pathological stage T 4), vascular/nerve invasion, preoperative intestinal 
obstruction or perforation, ≤ 12 lymph nodes retrieved and R1 resection. The chemotherapy 
program is the same with neoadjuvant chemotherapy. If mismatch repair defect (dMMR) 
or high-level microsatellite instability (MSI-H) is confirmed by pathology, chemotherapy 
will not be advised. Patients with stage III cancer will routinely receive chemotherapy.  
 
Follow-up 
1) Information on general medical history and physical examination will be collected 
every 3 months for 3 years 
2) Blood tumor markers of CEA (carcinoembryonic antigen)  and CA19-9 
(carbohydrate antigen 19-9) will be tested every 3 months for 3 years 
Abdominal and pelvic ultrasound and chest X-ray examinations will be carried out every 
3 months for 3 years 
3) Abdominal and pelvic MRI or contrast enhanced CT scan will be done every year for 
3 years 
4) Colonoscopy will be performed within 1 year after surgery. If there is any abnormity, 
reexamination will be required within half a year. If no abnormality is found, once a year 
for 3 years. All new-found adenomas by the colonoscopy during follow-up are 
recommended to be resected. 
5) Sexual function score is assessed by filling in the questionnaire (IIEF-5) both 

 
preoperatively and 1 year later since operation.  
 
Table 2. International Index of Erectile Function-5 assessing sexual function 
Over the past 6 months: 
 
 
 
 
 
1. How do you rate your confidence 
that you could get and keep an 
erection? 
Very low 
1 
Low  
2 
Moderate 
3 
High  
4 
Very 
high  
5 
2. When you had erections with sexual 
stimulation, how often were your 
erections hard enough for penetration? 
Almost 
never/ne
ver 1 
 
A 
few 
times 
(much 
less than 
half the 
time) 2 
Sometim
es (about 
half the 
time) 3 
Most 
times 
(much 
more 
than half 
the time) 
4 
Almost 
always/a
lways 5 
3. During sexual intercourse, how often 
were you able to maintain your erection 
after you had penetrated (entered) your 
partner? 
Almost 
never/ne
ver 1 
A 
few 
times 
(much 
less than 
half the 
time) 2 
Sometim
es (about 
half the 
time) 3 
Most 
times 
(much 
more 
than half 
the 
time)4 
Almost 
always/a
lways 5 
4. During sexual intercourse, how 
difficult was it to maintain your 
erection to completion of intercourse? 
Extremel
y 
difficult 
1 
Very 
difficult 
2 
Difficult 
3 
Slightly 
difficult 
4 
Not 
difficult 
5 
5. 
When 
you 
attempted 
sexual 
intercourse, 
how 
often 
was 
it 
satisfactory for you? 
Almost 
never/ne
ver 1 
A 
few 
times 
(much 
less than 
half the 
time) 2 
Sometim
es (about 
half the 
time) 3 
Most 
times 
(much 
more 
than half 
the time) 
4 
Almost 
always/a
lways 5 
IIEF-5 scoring: 
 
The IIEF-5 score is the sum of the ordinal responses to the 5 items. 
22-25: No erectile dysfunction 
17-21: Mild erectile dysfunction 
12-16: Mild to moderate erectile dysfunction 
8-11: Moderate erectile dysfunction 
5-7: Severe erectile dysfunction 
 
6) 3-year tumor-free survival (month): The time from operation to confirmation of 
tumor’s local recurrence or distant metastasis. The end point of the patient lost to follow-
up is the date of loss. 30 days is defined as one month 
7) 3-year overall survival (month): The time from operation to death. The end point of 
the patient lost to follow-up is the date of loss. 30 days is defined as one month 
8) Stoma closure time (months since operation). Anal function is assessed by Wexner 

 
scale 3 months and12 months after stoma closure, respectively. 
 
 
Table 3. Wexner score assessing anal function 
Type of 
Incontinence 
Frequency 
Never 
Rarely 
Sometimes 
Usually 
Always 
Solid 
0 
1 
2 
3 
4 
Liquid 
0 
1 
2 
3 
4 
Gas 
0 
1 
2 
3 
4 
Wear Pad 
0 
1 
2 
3 
4 
Lifestyle altered 0 
1 
2 
3 
4 
Never - 0 
Rarely - Less than once a month 
Sometimes - Less than once a week or once a month 
Usually - Once a day or once a week 
Always - Once a day or more 
Score: 0 Perfect; 20 Complete Incontinence 
 
 
➢ Are there any possible risks to you? 
No matter which group you are assigned into, the treatment program will be in accordance 
with the NCCN guideline, except that the transection of the distal rectum is performed by 
the transanterior obturator nerve gateway approach for patients in the experimental group. 
As this is a novel approach, the long-term affection both on the functional and survival 
outcomes are not clear yet. There are possibly both advantages and disadvantages by using 
this novel approach. Possible disadvantages might include: 
1) When constructing transanterior obturator nerve gateway, the obturator nerve and 
vessels might be damaged resulting in numbness and paraesthesia on the medial aspect 
of the thigh and weakness in adduction of the thigh and intraoperative bleeding. 
2) As the construction of transanterior obturator nerve gateway will anyhow destroy the 
normal local anatomical structure of the pelvis, if the tumor relapses in the pelvis 
postoperatively, the technical difficulty of the second operation might be increased. 
 
➢ Will you benefit from participation? 
As stated above, there are possibly both advantages and disadvantages by using this novel 

 
approach. Possible advantages might include: 
1) Although it will take some time (about 5 minutes) to construct the transanterior 
obturator nerve gateway, the novel approach can also obviously enlarge the pelvic 
space, that will lower the difficulty of the following procedures, thus, the total 
operative time for patients in the experimental group might be shorter. 
2) With a more satisfactory transecting angle, the novel approach can be more likely to 
obtain long-enough distal resection margin, that will help to lower the rate of 
conversion to transanal approach. 
3) With a more satisfactory transecting angle, less stapler firings will be taken to perform 
the distal rectal transection, that will not only reduce the risk for anastomotic leakage, 
but also reduce the hospitalization costs. 
4) With a more satisfactory transecting angle, it will be more likely to preserve the anus. 
 
➢ Will it cost you anything to participate? 
Just the time it takes to complete the questionnaire and the follow-up. 
 
➢ Will you receive anything for participating in the study? 
No. 
 
➢ How will your information be kept private? 
Confidentiality will be provided to the fullest extent possible by law. We will not share any 
information that we collect that can identify you unless we legally have to. Any information 
that could identify you will be deleted. Your answers will be stored in a database protected 
by a password. 
 
➢ What if you don’t want to participate or change your mind partway 
through? 
Participating in this study is completely voluntary. You can refuse to participate or quit at 
any time, for any reason. Your decision to stop participating will not influence the 
relationship you may have with the researchers or study staff or the nature of your 

 
relationship with the hospital you are in, or in the future. In the event you withdraw from 
the study, all associated data collected will be immediately destroyed wherever possible. 
 
➢ Who can you call if you have more questions? 
If you have any questions about the research or your participation in the study, feel free to 
contact Dr. Jianqiang Tang at 010-66119025 or doc_tjq@hotmail.com  
This research is approved by the Biomedical Research Ethics Committee of Peking 
University First Hospital that oversees the ethics of research at Peking University First 
Hospital. If you have any questions about your rights – or if you have concerns about the 
study – you may contact them at 010-66119025 or bdyyll@126.com. 
 
Subject Consent 
I have read this consent form completely. I have been encouraged to ask 
questions, and have received helpful answers. I understand that: 
• My participation is voluntary 
• I may quit at any time without penalty 
 
I do 
I do 
I do not give you permission to record me during this study. 
I do not 
give you permission to share my information – 
with no identifying information – with other researchers for future 
studies. 

 
 
I voluntarily agree to participate in this study. 
 
Participant’s Signature 
Date  
 
 
 
 
Investigator’s Signature 
Date