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

NCT ID: NCT02526836

Last Updated: 2018-08-16

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-30
• Study Completion Date: 2018-10-31

Brief 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.

Detailed 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.

Conditions

Colon Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Comparison group

including the number of cases with complete data who underwent surgery using the conventional method.

Conventional surgery

Group Type: OTHER

Conventional Surgery

Intervention Type: PROCEDURE

removal of the tumor with no ligation of the vessel centrally or removal of the whole mesocolon

Intervention group

including a convenient sample of about 20 patients which is expected to be recruited, for whom Complete Mesocolic Excision (CME) and Central Vascular Ligation (CVL) will be done.

Complete mesocolic excision with central vascular ligation

Group Type: ACTIVE_COMPARATOR

Complete mesocolic excision with central vascular ligation

Intervention Type: PROCEDURE

excision of the whole mesocolon plus ligation of the supplying blood vessel centrally

Interventions

Conventional Surgery

removal of the tumor with no ligation of the vessel centrally or removal of the whole mesocolon

Intervention Type: PROCEDURE

Complete mesocolic excision with central vascular ligation

excision of the whole mesocolon plus ligation of the supplying blood vessel centrally

Intervention Type: PROCEDURE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mansoura University

OTHER

Sponsor Role: lead

Responsible Party

Mohamed Abdelkhalek

Assistant Lecturer of Surgical Oncology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mohamed Abdelkhalek, M.Sc

Role: PRINCIPAL_INVESTIGATOR

Oncology Center Mansoura University (OCMU), Egypt

Giovanni Romano, MD

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute "Fond. G. Pascale", Italy

Adel Denewer, MD

Role: STUDY_CHAIR

Oncology Center Mansoura University (OCMU), Egypt

Tamer F Youssef, MD

Role: STUDY_DIRECTOR

Oncology Center Mansoura University (OCMU), Egypt

Locations

Oncology Center Mansoura University (OCMU), Egypt

Al Mansurah, Dakahlia Governorate, Egypt

Site Status: RECRUITING

National Cancer Institute "Fond. G. Pascale"

Naples, , Italy

Site Status: RECRUITING

Countries

Egypt; Italy

Central Contacts

Mohamed Abdelkhalek, M.Sc

Role: CONTACT

mabdelkhalek@mans.edu.eg

+201001850214

Ahmed Setit, MD

Role: CONTACT

asetit@mans.edu.eg

Facility Contacts

Mohamed Abdelkhalek, M.Sc

Role: primary

mabdelkhalek@mans.edu.eg

+201001850214

Ahmed Setit, MD

Role: backup

asetit@mans.edu.eg

Giovanni Romano, MD

Role: primary

gromano53@katamail.com

+39 081 5903 311

References

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.

Reference Type: BACKGROUND

PMID: 19016817 (View on PubMed)

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, Gogenur 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.

Reference Type: BACKGROUND

PMID: 25555421 (View on PubMed)

Other Identifiers

Complete Mesocolic Excision

Identifier Type: -

Identifier Source: org_study_id