Complete Mesocolic Excision With Central Vessel Ligation Compared With Conventional Surgery for Colon Cancer

Colon Cancer Clinical Trial

Official title:

Complete Mesocolic Excision (CME) With Central Supplying Vessel Ligation (CVL) Compared With Conventional Surgery for Colon Cancer: a Double-blinded Randomized Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02526836
• Other study ID #: Complete Mesocolic Excision
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: September 2014
• Est. completion date: October 2018

Study information

• Verified date: November 2017
• Source: Mansoura University
• Contact: Mohamed Abdelkhalek, M.Sc
• Phone: +201001850214
• Email: mabdelkhalek[@]mans.edu.eg
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to compare between complete mesocolic excision with central vascular ligation and conventional surgery of colon cancer regarding number of harvested lymph nodes, surgical outcome and complications.

Description:

Colorectal cancer is the third most common human malignant epithelial tumor and still represents the second cause of cancer death in the United States and Europe.

Over the past few decades, there have been significant improvements in the treatment of patients with colonic and rectal cancers. In rectal cancer, the role of earlier diagnosis, improved preoperative staging, neoadjuvant therapy and total mesorectal excision have improved outcomes from oncological and patient recovery perspectives. Of these, arguably the most important for the surgeon was the advent of Total Mesorectal Excision (TME).

Current thinking is that colonic tumors spread via hematogenous, lymphatic, and possibly perineural routes, with the lymphatics anatomically following the arterial supply. Current practice is to excise a proportion of the draining lymphatic bed to accurately stage the cancer and also clear possible lymphatic metastases.

Recently, significant debate has centered on the degree of lymphatic clearance required; several reports have demonstrated improved oncologic outcomes with wider lymphovascular resections compared with current standard practice. Whether these improved outcomes are secondary to improved lymph node yield or an alternative technical effect has not yet been ascertained.

In analogy to total mesorectal excision (TME) for rectal cancer complete mesocolic excision was recently introduced for curative treatment of colon cancer. Like TME, CME aims at complete en bloc clearance of the lymphatic drainage of the tumor enveloped in intact fascias of embryologic origin.

Based on total mesorectal excision experience, further investigations of the importance of complete mesocolic excision and central vascular ligation surgery for colonic cancer were done by comparing a series of complete mesocolic excision and central vascular ligation specimens from Erlangen, Germany to standard excisions from Leeds, United Kingdom. Lymph node yields, tissue morphometry, and grading the plane of surgery were used to investigate differences between the techniques that could potentially explain the relative differences in survival.

The group from Erlangen in Germany have advocated for CME in conjunction with central vascular ligation for colon cancer. Complete mesocolic excision is reported to differ from traditional colon cancer surgery by achieving a far more radical excision of the lymphovascular pedicle and mesocolon. In addition, the complete mesocolic excision technique promotes resection of the specimen with an intact visceral peritoneum together with proximal and distal resection margins of at least 10 cm. Arterial supply to the affected segment of bowel is taken at its origin from the superior mesenteric artery (right and transverse colon) and the aorta (left colon), described as central vascular ligation. Complete mesocolic excision has been shown to lead to increased lymph node harvest and more mesocolic tissue.

In a comparison between the Leeds and Erlangen units, it was shown that complete mesocolic excision led to an almost doubling in both the number of lymph nodes retrieved and area of mesentery resected. However, a Danish study showed only a 9% increase in lymph node yield.

Surgical concept of complete mesocolic excision represents sharp separation of the undamaged visceral fascia of mesocolon from parietal fascia of peritoneum and the end goal is mobilization of mesocolon and the approach to the appropriate vascular bundle. The scope of surgical intervention depends on localization of the tumor itself. In case that the tumor is located in the right colon next to caecum and ascending colon, it also implies the elevation of duodenum and the head of pancreas (Kocher maneuver) and access to the upper mesenteric vein and artery and its branches. For tumors of the left colon, mobilization of sigma and descending colon is necessary, total separation from the parietal peritoneum, urethra, testicular or ovarian blood vessels, as well as separation from the kidney fat tissue.

The apparent improved outcomes with complete mesocolic excision are yet to be confirmed with a formal Randomized Controlled Trial (RCT). Proposed explanations for the apparent improvements are that increasing lymph node yield permits stage migration, that increased lymph node yield removes a source of metastases, and that it has nothing to do with lymphatics but is due to the preservation of an intact peritoneum.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: October 2018
• Est. primary completion date: September 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Pathologically proven adenocarcinoma (including mucinous and signet-ring cell) or adenosquamous carcinoma on endoscopic biopsy.

• Tumor localization at the caecum, ascending colon, transverse colon, descending colon, sigmoid colon or rectosigmoid on preoperative endoscopy and radiographic imaging [barium enema or computed tomography (CT)] without location of the lower border of the tumor at the rectum.

• No history of familial adenomatous polyposis, ulcerative colitis or Crohn's disease.

• Body mass index = 35.

• Sufficient organ function including cardiovascular system and liver.

• Written informed consent.

Exclusion Criteria:

• Contraindications to major surgery and American Society of Anesthesiologists (ASA) Physical Status scoring 4 which means extreme systemic disorders which have already become an eminent threat to life regardless of the type of treatment.

• Infectious disease requiring treatment.

• Body temperature = 38 °C.

• Pregnant women.

• History of psychiatric disease.

• Use of systemic steroids.

• History of myocardial infarction or unstable angina pectoris within 6 months.

• Severe pulmonary emphysema or pulmonary fibrosis

Related Conditions & MeSH terms

• Colon Cancer
• Colonic Neoplasms

Intervention

Procedure:
• Conventional Surgery
removal of the tumor with no ligation of the vessel centrally or removal of the whole mesocolon
• Complete mesocolic excision with central vascular ligation
excision of the whole mesocolon plus ligation of the supplying blood vessel centrally

Locations

Country	Name	City	State
Egypt	Oncology Center Mansoura University (OCMU), Egypt	El Mansura	Dakahlia
Italy	National Cancer Institute "Fond. G. Pascale"	Naples

Sponsors (1)

Lead Sponsor	Collaborator
Mansoura University

Countries where clinical trial is conducted

Egypt,  Italy, 

References & Publications (2)

Bertelsen CA, Neuenschwander AU, Jansen JE, Wilhelmsen M, Kirkegaard-Klitbo A, Tenma JR, Bols B, Ingeholm P, Rasmussen LA, Jepsen LV, Iversen ER, Kristensen B, Gögenur I; Danish Colorectal Cancer Group. Disease-free survival after complete mesocolic excision compared with conventional colon cancer surgery: a retrospective, population-based study. Lancet Oncol. 2015 Feb;16(2):161-8. doi: 10.1016/S1470-2045(14)71168-4. Epub 2014 Dec 31. — View Citation

Hohenberger W, Weber K, Matzel K, Papadopoulos T, Merkel S. Standardized surgery for colonic cancer: complete mesocolic excision and central ligation--technical notes and outcome. Colorectal Dis. 2009 May;11(4):354-64; discussion 364-5. doi: 10.1111/j.1463-1318.2008.01735.x. Epub 2009 Nov 5. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Lymph nodes harvest	Number of retrieved lymph nodes	Day of surgery
Secondary	Oncologic outcome	Number of patients with local or distant recurrence after the surgery.	2 years
Secondary	Operative outcome	A composite outcome of the Operative time, blood loss, blood transfusion, intraoperative morbidities and mortality	Day of suregry
Secondary	Postoperative outcome	A composite outcome of the number of morbidities and mortalities in the postoperative setting	1 month
Secondary	Survival outcome	Number of patients with 2 year free survival	3 Years

External Links

•   Disease-free survival after complete mesocolic excision compared with conventional colon cancer surgery: a retrospective, population-based study