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. (See details in Eligibility part) 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 match with the requirements for this study and agree 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 (Magnetic Resonance Imaging), 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
- 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; 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: 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).
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. 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
- 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. 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 and 12 months after stoma closure, respectively.
(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.) 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 Chi-square test or
Fisher's exact test and survival distributions were analyzed by log-rank test.
