Clinical trial NCT03013153: Low or High Ligation of the IMA With Apical Lymph Node Dissection in Rectal Cancer Laparoscopic Surgery
Official title: Low or High Ligation of the Inferior Mesenteric Artery With Apical Lymph Node Dissection in Rectal Cancer Laparoscopic Surgery: A Prospective, Multi-Center, Randomized, Open-Label, Parallel Group, Non-Inferiority Clinical Trial (LAND)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Rectal Cancer
Keywords: Rectal Cancer
Inferior Mesenteric Artery
Ligation
Apical Lymph Nodes
Laparoscopy
IMA Types
Lead sponsor: Sixth Affiliated Hospital, Sun Yat-sen University
Sponsor class: OTHER
First posted: 2017-01-06
Enrollment: 748
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Laparoscopy colon surgery is accepted worldwide in the recent years. But there is still argument on the effect of laparoscopy rectal surgery. Laparoscopy has advantages on showing the inferior mesenteric artery (IMA), protection of autonomic nerve, low rectal anastomosis, and total mesorectum excision. However, debate on the level of IMA ligation and debonding of splenic flexure never ends. This study is going to give a clear and definite answer to how and why surgeons should deal with the IMA in laparoscopy rectal surgery，base on the 3D reconstruction of IMA and identification of IMA perfusion types.

Detailed description: According to the report of World Health Organization 2015, the morbility and mortality of colorectal cancer (CRC) are rising all over the world. Although the technique gets great approval in CRC surgical treatment in the recent years, such as TME protocol, neoadjuvant and laparoscopy technique, the complication of anastomosis leakage and nerve damage are still to be solved.

Laparoscopy colon surgery is accepted worldwide in the recent years. But there is still argument on the effect of laparoscopy rectal surgery. Laparoscopy has advantages on showing the inferior mesenteric artery, protection of autonomic nerve, low rectal anastomosis, and total mesorectum excision. However, debate on where is the best level of IMA ligation and whether splenic flexure be debonded never ends. This study is going to give a clear and definite answer to how and why surgeons should deal with the IMA in laparoscopy rectal surgery.

The ligation level of IMA affects on hypogastric and pelvic nerve, leads to disorder of sexual and urination functions. What's more, it also have affection on the apical lymph node (No.253) harvesting and the blood supplement of proximal colon. Former studies have proved that the blood supplement and tension of anastomosis leads to leakage after surgery. Meanwhile, the ligation level of IMA is the key point on it.

The former study comes from the sixth affiliated hospital found that the mistake of ligation level of IMA happened because of the poor touching and explosion with laparoscopy. The distance from the root of IMA to left colic artery (DRL) vary between 19mm and 64mm. When surgeon made mistake during ligation, it led to the insufficient resection of apical lymph node. Further more, affect the long-term survival. Besides, there are 4 different types of IMA according to the relationship between the left colic artery, sigmoid artery and superior rectal artery. These branches will confuse surgeon on how to deal with them. 3D reconstruction of abdominal pelvic CT is able to show the length of DRL, IMA types and apical lymph nodes clearly. With these technique, the investigators can preserve the left colic artery and resect apical lymph nodes precisely.

In the past studies, high or low ligation takes advantage on both side. But none of them comes from retrospective clinical trail. Some author believe that high ligation do better in resection of apical lymph nodes, release the tension of anastomosis, providing precise tumor staging. On the other side, some authors consider that high ligation may cut down blood supplement, rise the incident of anastomosis leakage (AL). so they prefer low ligation to the high. Some studies show that there are no long term survival difference between high and low ligation on IMA in laparoscopy rectal resection. So whether high ligation is necessary, still to be proved.

For local advanced rectal cancer, neoadjuvant chemotherapy can lesson tumor size, reduce recurrence, preserve annual better and rise long-term survival. National Comprehensive Cancer Network command chemotherapy before surgery (Total Mesorectal Excision TME) as the standard for rectal cancer since 2005. Another randomized controlled trial (RCT) named Neoadjuvant FOLFOX6 Chemotherapy With or Without Radiation in Rectal Cancer (FOWARC) NCT01211210 has proved the recent positive result. In those cases, the positive metastasis apical lymph node appeared in less than 5% (5/116) cases. On the other side, the incident of AL was up to 7% (8/116) . This phenomenon discover that maybe low ligation with apical lymph nodes dissection can get the same treatment effect and decrease AL from happening.

Eligibility criteria: Inclusion Criteria:

* Pathology shows rectal or sigmoid adenocarcinoma
* The bottom edge of tumor to anuas is less than 15cm
* The clinical staging of tumor by American Joint Committee on Cancer (AJCC) within T2-4 or N1-2
* Receive or not receive neoadjuvant chemotherapy based on 5-fluorouracil before surgery
* Racial resection in available after neoadjuvant chemotherapy
* No metastasis evidence was found
* Annual preservation surgery is available
* Tolerate to general anesthesia
* Eastern Cooperative Oncology Group (ECOG) status score between 0 and 1
* Patients and general anesthesia can understand the clinical trail well and are willing to take part in

Exclusion Criteria:

* Suffer with other carcinoma synchronous or metachronous in 5 years
* Multiple primary colon carcinoma
* Radiation therapy was performed before surgery
* History of colorectal surgery
* Combine with acute intestinal obstruction, intestinal bleeding, intestinal perforation and emergency surgery is needed
* Multiple organs resection surgery is needed
* Abdominal perineal resection is performed
* American Society of Anesthesiologists score stage IV to V
* Pregnant, suckling period or reject to contraception
* Severe cardiovascular disease, uncontrollable infection or other severe complication
* Severe mental illness
* Unable to go through the treatment because of family, society or regional condition
* Refuse to take part in the trail

Primary outcomes:
measure: 5-years overall survival rate
timeFrame: 5 years
Secondary outcomes:
measure: 5-years disease free survival rate
timeFrame: 5 years
measure: 1-year overall survival rate
timeFrame: 1 year
measure: 1-year disease free survival rate
timeFrame: 1 year
measure: Anastomosis leakage rate
timeFrame: 6 months
measure: Apical Lymph Nodes (LN) Positive Rate
timeFrame: 1 week
measure: Operation Time
timeFrame: 1 day
measure: Blood loss during operation
timeFrame: 1 day
measure: Complication incident rate of surgery
timeFrame: 1 day
measure: conversion rate to laparotomy
timeFrame: 1 day
measure: Identification of IMA perfusion type before surgery
timeFrame: 1 day
measure: Identification of lymph node metastasis by CT
timeFrame: 7 days
measure: Mortality rate in 30 days after surgery
timeFrame: 30 days
measure: Recovery time after surgery
timeFrame: 60 days
measure: White cell level
timeFrame: 7 days
measure: C-reaction protein level
timeFrame: 7 days
measure: Albumin level
timeFrame: 7 days
measure: Anastomosis bleeding rate after surgery
timeFrame: 30 days
measure: Anastomosis stenosis rate after surgery
timeFrame: 30 days
measure: Intestinal dysfunction after stoma closure
timeFrame: 1 year
measure: Anus function after surgery
timeFrame: 1 year
measure: Life quality scoring
timeFrame: 1 year
measure: Bladder residual urine volume
timeFrame: 1 year
measure: Sexual function scoring
timeFrame: 1 year
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The sixth affiliated hospital of Sun Yat-sen University
state: Guangdong
Study officials:
affiliation: The Sixth Affiliated Hospital, Sun Yat-sen University
name: Meijin Huang, MD
role: STUDY_DIRECTOR
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