Low or High Ligation of the IMA With Apical Lymph Node Dissection in Rectal Cancer Laparoscopic Surgery

Rectal Cancer Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03013153
• Other study ID #: LAND
• Status: Recruiting
• Phase: N/A
• First received: December 31, 2016
• Last updated: January 11, 2017
• Start date: December 2016
• Est. completion date: December 2023

Study information

• Verified date: December 2016
• Source: Sixth Affiliated Hospital, Sun Yat-sen University
• Contact: Jiaming Zhou, MD
• Phone: +8613560031075
• Email: cysums03[@]163.com
• Is FDA regulated: No
• Health authority: China: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 748
• Est. completion date: December 2023
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Rectal Cancer
• Rectal Neoplasms

Intervention

Procedure:
• Low ligation with apical lymph node dissection
Low ligation with apical lymph node dissection (LAND). Left colic artery (LCA) is identified according to the CT 3D-reconstruction, tie the sigmoid artery and superior rectal artery, preserved LCA while low ligation of the inferior mesenteric artery is performed. Lymphadenectomy to the apical lymph nodes (No.253)is performed around the IMA until 2 cm from the aorta.
• High ligation
High ligation (HL) Open the peritoneum proceeds cephalad towards the duodenojejunal angle of Treitz, and the mesenteric root is incised 1 cm below the inferior margin of the pancreas. The aortomesenteric window is opened wide and the inferior mesenteric vessels are exposed. The IMA is ligated and divided at 2 cm from its origin. The inferior mesenteric vein (IMV) is divided and ligated below the pancreatic margin.

Locations

Country	Name	City	State
China	The sixth affiliated hospital of Sun Yat-sen University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sixth Affiliated Hospital, Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (23)

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* Note: There are 23 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	5-years overall survival rate	5-years overall survival rate	5 years	Yes
Secondary	5-years disease free survival rate	5-years disease free survival rate	5 years	Yes
Secondary	1-year overall survival rate	1-year overall survival rate	1 year	Yes
Secondary	1-year disease free survival rate	1-year disease free survival rate	1 year	Yes
Secondary	Anastomosis leakage rate	anastomosis leakage rate after surgery, acute or chronic	6 months	Yes
Secondary	Apical Lymph Nodes (LN) Positive Rate	Apical Lymph Nodes Positive Rate, No.253 LN	1 week	No
Secondary	Operation Time		1 day	No
Secondary	Blood loss during operation		1 day	No
Secondary	Complication incident rate of surgery		1 day	Yes
Secondary	conversion rate to laparotomy		1 day	No
Secondary	Identification of IMA perfusion type before surgery		1 day	No
Secondary	Identification of lymph node metastasis by CT		7 days	No
Secondary	Mortality rate in 30 days after surgery		30 days	Yes
Secondary	Recovery time after surgery		60 days	No
Secondary	White cell level		7 days	No
Secondary	C-reaction protein level		7 days	No
Secondary	Albumin level		7 days	No
Secondary	Anastomosis bleeding rate after surgery		30 days	No
Secondary	Anastomosis stenosis rate after surgery		30 days	No
Secondary	Intestinal dysfunction after stoma closure		1 year	No
Secondary	Anus function after surgery		1 year	No
Secondary	Life quality scoring		1 year	No
Secondary	Bladder residual urine volume		1 year	No
Secondary	Sexual function scoring		1 year	No