Complete Mesocolic Excision in Comparison With Conventional Surgery for the Right Colon Cancer

Study Overview
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Brief Summary
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An Italian randomized controlled trial parallel-group in patients with a malignant tumor of the right or proximal transverse colon requiring right hemicolectomy.

Detailed Description
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This study aims to compare the Complete Mesocolic Excision With Central Vascular Ligation (CME+CVL) with the standard (non-CME) right hemicolectomy in patients with right or proximal transverse colon cancer stage II-IV(AJCC 8th edition) to determine the short and long term outcomes in terms of disease-free survival (DFS) as a primary endpoint, and safety, oncologic outcomes, quality of surgery and quality of life (QoL) as secondary endpoints. Eligible patients will be randomized with a 1:1 ratio between CME + CVL vs standard non-CME right colectomy. The randomization sequence will be generated centrally by a computed algorithm and kept concealed to investigators. The Right colectomy with CME + CVL includes the removal of the accessory lymphovascular supply at their origins by resecting the colon and mesocolon in an intact envelope of visceral peritoneum and mesenteric fascia. Despite the surgical approach and the type of procedure adopted, the operation should be strictly conducted following the general rules for colorectal oncologic resection, particularly as concerns proximal and distal margins length and lymph node retrieval. All surgical approaches (open, laparoscopic, or robotic) will be allowed while the type of anastomosis performed and drain placement will be up to the surgeon's discretion. Demographic, baseline, perioperative and postoperative characteristics will be analyzed as well. The study expected to last six and a half years, of which one and a half years for recruiting 416 patients, 208 each arm, with five years of follow-up. Patients will be followed up at 1, 4, 12, 24, 36, and 60 months postoperatively.

Official Title
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Complete Mesocolic Excision With Central Vascular Ligation in Comparison With Conventional Surgery for the Right Colon Cancer: An Italian Randomized Trial

Conditions
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Colon Cancer

Intervention / Treatment
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* Procedure: Conventional Right hemicolectomy (Non-CME)
* Procedure: Right hemicolectomy with CME+CVL


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: American Society of Anesthesiologists(ASA) grade I-III. Right colon cancer (*The right-sided location of the cancer is defined as the location from the caecum up to the proximal third of the transverse colon), preoperative assessment of tumor stage T2-T4a, any N or T any N+ according to the National Comprehensive Cancer Network(NCCN) clinical practice guidelines in oncology: colon cancer version 2.2015); no distant metastasis. Informed consent Exclusion Criteria: Age > 85 years old. T1, N0 T4b, any N BMI > 30. Metastatic disease (Abdominal and chest CT scan will be mandatory to exclude distant metastasis.) American Society of Anesthesiologists(ASA) grade IV. History of cancer in recent 5 years. Need for Emergency surgery. Infectious disease requiring treatment. Pregnancy. Use of systemic steroids. No history of familial adenomatous polyposis, ulcerative colitis or Crohn's disease.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Conventional Right hemicolectomy (Non-CME)<br>Patients will undergo conventional non-CME procedure. | Procedure: Conventional Right hemicolectomy (Non-CME)<br>* Transecting the Ileocolic Vein and Artery close to the Superior Mesenteric Vessels without clearing the superior mesenteric vein (SMV) from the adipose tissue. Transecting the Right Colic Vein and Artery and superior right colic vein (when present) peripherally. Transecting the Right branches of the Middle Colic Vein (MCV) and the Middle Colic Artery (MCA) peripherally, without clearing the main trunk of the MCV and the MCA. The Right Gastroepiploic Vein and artery are never transacted.<br>|
| Experimental: Right hemicolectomy with CME+CVL<br>Patients will undergo Right hemicolectomy CME+CVL procedure. | Procedure: Right hemicolectomy with CME+CVL<br>* Separation of the visceral fascia from the parietal fascia by sharp dissection leaving intact mesocolon coverage. Transecting the supplying vessels at their origin from the main vessels, particularly: The Ileocolic Vessels, The Right Colic Vessels,The superior right colic vein (when present), The Right branches of the Middle Colic Vein and of the Middle Colic Artery The MCV and MCA at their origin in case of cancer of the hepatic flexure or of the proximal third of the transverse colon, as well as The Right Gastroepiploic Vessels at their origin from the gastrocolic trunk of Henle (GCTH) and the gastroduodenal artery. The SMV should be cleared from all adipose tissue all along its anterior surface until its intrapancreatic entrance.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival at 3 years | The length of time after surgery without any signs or symptoms of local or distant recurrence. | 3 Years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety-Operative time. | Total time from incision to skin closure expressed in minutes. | Intraoperative | 
| Safety-Intraoperative blood loss. | Defined by the volume drained in cm2 into aspiration systems and weight of gauzes, calculated, subtracting the weight of the dry gauzes and volume of saline solution used for irrigation. | Intraoperative | 
| Safety-Intraoperative blood transfusion. | Defined as the number of red blood cells, platelets, or plasma units transfused during the intraoperative time. | Intraoperative | 
| Safety- Intraoperative Complications. | Defined as any deviation from the ideal intraoperative course occurring during the operative time, Using the Classiﬁcation of Intraoperative Complications(CLASSIC). | Intraoperative | 
| Early postoperative complications. | Number of patients with any deviation from the normal postoperative course grading by The Clavien-Dindo classification. | 30 postoperative days. | 
| Late postoperative complications. | The number of patients with any deviation from the normal postoperative course grading by The Clavien-Dindo classification. | From the 31st postoperative days to the end of the study. | 
| Safety- Length of stay. | Defined as the length of an inpatient episode of care, calculated from the day of operation to the first discharge and based on the number of nights spent in the hospital. | 30 Days. | 
| Safety- Postoperative mortality rate. | The all-cause death rate, within 30 days after surgery in or out of the hospital. | 30 Days. | 
| Overall Survival at 3 years | Defined as the time from random assignment to the date of death due to any cause. | 3 Years. | 
| Overall Survival at 5 years. | Defined as the time from random assignment to the date of death due to any cause. | 5 Years. | 
| Disease-free survival. | Defined as the length of time after Surgical treatment (CME+CVL or Conventional non-CME procedure) that the patient survives without any signs or symptoms of colon cancer. | 5 Years. | 
| Other Oncologic outcomes. | The number of positive, negative, and total lymph nodes harvested, Quality of surgery specimen, quality of life by EORTC specific Questionnaires | 30 Days. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CME, colon cancer, Right colon cancer, Complete mesocolic excision, Right Hemicolectomy, Right Colectomy