Laparoscopic Versus Open Right Colectomy for Right Colon Cancer

Sponsor

Larissa University Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05713903

Collaborator

(none)

114

Enrollment

Location

Arms

47.1

Anticipated Duration (Months)

2.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this research protocol is to compare open versus laparoscopic right colectomy (according to the CME technique of complete mesocolic excision) for right colon cancer. This study will be designed as a prospective randomized controlled trial. The comparison of the two techniques will include endpoints regarding the quality characteristics of the specimens and the oncological results. In addition, the effectiveness of the two methods will be evaluated in terms of the early and late postoperative period.

Condition or Disease	Intervention/Treatment	Phase
Colon Cancer	Procedure: Laparoscopic right colectomy Procedure: Open right colectomy	N/A

Detailed Description

Colorectal cancer is the third and second most common malignancy in male and female patients, respectively, with up to 1.8 million new cases and 860,000 deaths per year.

Anterior resection with total mesorectal excision (TME) was first proposed by Heald in 1982 and is currently the gold standard surgical technique for middle and lower rectal cancer. Heald considered that the metastatic spread of the tumor occurs through micro-implantations in the lymph node network of the mesorectum, and much less through horizontal intramural infiltration, and thus defined rectal resection margins at 5cm or even 2cm for well-differentiated neoplasms. Therefore, he suggested that mesorectum displays a greater risk for micro-metastatic disease and should be removed en-bloc with intact resection margins.

Similarly in 2009, Hohenberger proposed the complete mesocolon excision (CME) concept for the treatment of colon cancer, based on the respective embryological development anatomical planes. After analyzing a large cohort of patients, he concluded that this operation type leads to a significant reduction in the local recurrence and an increase in the overall survival rates.

Hohenberger proposed open CME as the optimal surgical technique for colon cancer, under the premise that the following principles are met:

Dissection of Toldt's fascia and mesocolon preservation
Central vascular ligation
Extensive locoregional lymph node dissection CME technique, as described by Hohenberger in 2008, is an extension of Heald's TME and it is based on the sharp dissection and separation of the visceral fascia that surrounds the colon from the parietal fascia. The aim is to fully mobilize the colon and the corresponding mesocolon, which is surrounded bilaterally by sheets of visceral fascia. This ensures the complete resection of the tumor and the corresponding lymph nodes. At the same time, central vascular ligation allows the dissection of the apical lymph nodes.

There are three resection planes: the mesocolic, intramesocolic and muscularis propria plane. The ideal resection plane is the mesocolic, in which the colon is removed, along with the entire mesocolon and all the venous and lymphatic tissue, without violating the visceral fascia. Surgical specimens categorized into either of the other two resection planes are associated with reduced R0 resection rates and with reduced overall survival. Characteristically, the muscularis propria resection plane has been associated with up to 15% reduced survival rate compared to the mesocolic plane.

There are specific morphometric characteristics of surgical specimens that are used to assess their quality. These include tumor and proximal colon high vascular ligation distance, number of lymph nodes, length of resected small bowel and colon, and total area of the mesocolon. These characteristics are directly related to the number of harvested lymph nodes and, therefore, to overall survival.

According to initial results, CME specimens were larger in size, contained a longer length of colon, a larger mesenteric surface and a greater number of lymph nodes compared to the standard colectomy specimens. In addition, a greater distance of the tumor from the resection margins was highlighted. Specifically for right colon cancers, recent publications have shown that CME can achieve better morphometric specimen characteristics and a greater number of lymph nodes. In a recent randomized study, Di Buono et al. compared the completion of CME or not, during laparoscopic right colectomy. A significant difference was found in favor of CME, regarding the specimen length and the lymph node harvest.

Despite these, the literature evidence regarding the morphological and qualitative characteristics of laparoscopic and open CME specimens are still inconclusive. Specifically for right colectomies, in the comparative study by Gouvas et al., it was observed that the percentage of the mesocolic resection level was 100% in open colectomy, in contrast to 85.7% in the laparoscopic approach. However, this difference was not statistically significant. In a retrospective study by Ali Koc et al., no difference was found between open and laparoscopic CME in terms of specimen length, R0 resection rate and number of resected lymph nodes. A recent publication by Ali Zedan et al., argued that open CME is associated with longer specimens, larger mesenteric area, and increased resection margins. Another interesting finding was that the number of lymph nodes and the distance of the ligation site were greater in the laparoscopic CME group. However, the meta-analysis by Anania et al. failed to validate any difference between the two methods in the total number of lymph nodes. Finally, a comparative analysis of our own series of patients did not show superiority of one technique over the other in terms of resection level, specimen length and number of lymph nodes.

Additional qualitative characteristics of a colon cancer operation include operative time, intraoperative blood loss, time of bowel function recovery, length of postoperative hospital stay, postoperative complications, as well as overall survival and local recurrence rate. In a recent meta-analysis by Anania et al. applying the principles of CME to right colectomies did not affect the rates of postoperative leaks, bleeding, overall complications, and reoperations. However, CME right colectomy was associated with optimal results in terms of 3-year overall survival and 5-year disease-free survival.

Regarding the application of laparoscopy principles to CME colectomies, previous studies have confirmed that it is a technique with optimal results, such as faster postoperative recovery, shorter hospital stay, and lower morbidity. There is agreement between studies regarding the perioperative benefits of laparoscopic CME right colectomy versus the open method. According to Huang et al., the length of operative time between the two techniques was comparable. Laparoscopic right colectomy was associated with significantly lower intraoperative blood loss and faster initiation of feeding. In addition, these patients were discharged earlier compared to their counterparts in the open colectomy group. Moreover, no differences were observed in complication and local recurrence rates. These findings were also confirmed by the comparative study of Sheng et al., where the application of the minimally invasive technique resulted in lower levels of postoperative pain, and faster recovery. Accordingly, Shin et al., applying propensity score analysis, to remove possible confounding factors, in a sample of 2249 right colectomies and found that the technique is an independent predictor for 5-year disease-free survival. Pooled data from Anania et al., confirmed the superiority of laparoscopic CME in the rates of postoperative complications, intraoperative bleeding, and length of hospital stay. These are also in accordance with our own experience, where a significant benefit of the laparoscopic approach was shown in the duration of hospitalization and septic complications, at the cost of prolonged surgical time.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

114 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

The study will employ a prospective, parallel randomized-controlled designThe study will employ a prospective, parallel randomized-controlled design

Masking:

None (Open Label)

Masking Description:

There will be no blindness at the level of the patient, the treating physicians (surgeon, anesthesiologist) and the researcher who will record the data.

Primary Purpose:

Treatment

Official Title:

Comparison of Laparoscopic Versus Open Right Colectomy for Right Colon Cancer, According to the Complete Mesocolic Excision (CME) Principles: a Prospective Randomized Controlled Trial

Actual Study Start Date :

Feb 6, 2023

Anticipated Primary Completion Date :

Jan 10, 2026

Anticipated Study Completion Date :

Jan 10, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Laparoscopic right colectomy In laparoscopic right colectomy subgroup, the patient will be placed in a lithotomy position. Entrance in the peritoneal cavity will be completed via the open Hasson method. Overall, 4 ports will be used: 10mm at the umbilicus for optical entry, 12mm in the left midclavicular line below the umbilicus as the main working port, 5mm at the McBurney point, and 5mm between the umbilicus and the xiphoid process. Dissection of the peritoneal fold, under the terminal ileum, will be performed based on the medial to lateral approach. Similar to the open approach, the ileocolic vessels, as well as the right branches of the middle colic will be ligated at their origin for cecal and proximal ascending tumors. For hepatic flexure cancers, the medial colic vessels will be ligated. The ileocolic anastomosis will be completed either intracorporeally or extracorporeally, using staples or sutures.	Procedure: Laparoscopic right colectomy Resection of the ascending colon via a laparoscopic approach, adhering to the CME principles
Active Comparator: Open right colectomy In the open right colectomy group, the operation will start with a midline incision and dissection based on the lateral to medial approach. The lateral peritoneal fold along Toldt's line will be incised and the ascending colon will be mobilized from the retroperitoneum according to the embryological dissection planes. Dissection will continue until the anterior surface of the superior mesenteric vessels at the third duodenal part. Ileocolic and right colic vessels will be ligated at their origins. For hepatic flexure tumors, the middle colic vessels will be also ligated at their origin. The ileocolic anastomosis will be performed using an automatic stapler. The anastomosis will be completed either with staples or sutures.	Procedure: Open right colectomy Resection of the ascending colon via an open approach, adhering to the CME principles

Arm

Intervention/Treatment

Experimental: Laparoscopic right colectomy

In laparoscopic right colectomy subgroup, the patient will be placed in a lithotomy position. Entrance in the peritoneal cavity will be completed via the open Hasson method. Overall, 4 ports will be used: 10mm at the umbilicus for optical entry, 12mm in the left midclavicular line below the umbilicus as the main working port, 5mm at the McBurney point, and 5mm between the umbilicus and the xiphoid process. Dissection of the peritoneal fold, under the terminal ileum, will be performed based on the medial to lateral approach. Similar to the open approach, the ileocolic vessels, as well as the right branches of the middle colic will be ligated at their origin for cecal and proximal ascending tumors. For hepatic flexure cancers, the medial colic vessels will be ligated. The ileocolic anastomosis will be completed either intracorporeally or extracorporeally, using staples or sutures.

Procedure: Laparoscopic right colectomy

Resection of the ascending colon via a laparoscopic approach, adhering to the CME principles

Active Comparator: Open right colectomy

In the open right colectomy group, the operation will start with a midline incision and dissection based on the lateral to medial approach. The lateral peritoneal fold along Toldt's line will be incised and the ascending colon will be mobilized from the retroperitoneum according to the embryological dissection planes. Dissection will continue until the anterior surface of the superior mesenteric vessels at the third duodenal part. Ileocolic and right colic vessels will be ligated at their origins. For hepatic flexure tumors, the middle colic vessels will be also ligated at their origin. The ileocolic anastomosis will be performed using an automatic stapler. The anastomosis will be completed either with staples or sutures.

Procedure: Open right colectomy

Resection of the ascending colon via an open approach, adhering to the CME principles

Outcome Measures

Primary Outcome Measures

Mesocolic Resection Plane [1 month postoperatively]
Occurrence of Mesocolic Resection Plane. If such an episode occurs, then it will be defined as=1 'YES' If such an episode does not occur, then it will be defined as=0 'NO'

Secondary Outcome Measures

Open Conversion [Intraoperative period]
Occurrence of Open Conversion. If such an episode occurs, then it will be defined as=1 'YES' If such an episode does not occur, then it will be defined as=0 'NO'
Operative Time [Intraoperative period]
The total operative time will be recorded. Measurement unit: minutes
Type of Anastomosis [Intraoperative period]
Occurrence of Stapled or Handsewn Anastomosis. If such an episode occurs, then it will be defined as=1 'YES' If such an episode does not occur, then it will be defined as=0 'NO'
Intraoperative Transfusion [Intraoperative period]
Occurrence of Intraoperative Transfusion. If such an episode occurs, then it will be defined as=1 'YES' If such an episode does not occur, then it will be defined as=0 'NO'
Postoperative Complication [1 month postoperatively]
Occurrence of Postoperative Complication. If such an episode occurs, then it will be defined as=1 'YES' If such an episode does not occur, then it will be defined as=0 'NO'
Bowel Function Recovery [7 days postoperatively]
Postoperative time until the recovery of bowel function is achieved. Measurement unit: days
Length of Hospital Stay [Maximum time frame 39 days postoperatively]]
Postoperative time that the patient can be safely discharged. Measurement unit: days. The patient will be discharged, when it is ensured that is medically safe to be released. In particular, as the exit time of the patient, will be regarded the time that the patient will fulfil the Clinical Discharge Criteria
Negative Resection Margin [1 month postoperatively]
Occurrence of Negative Resection Margin. If such an episode occurs, then it will be defined as=1 'YES' If such an episode does not occur, then it will be defined as=0 'NO'
Local Recurrence [5 years postoperatively]
Occurrence of Local Recurrence. If such an episode occurs, then it will be defined as=1 'YES' If such an episode does not occur, then it will be defined as=0 'NO'
Disease Free Survival [5 years postoperatively]
Occurrence of Disease Free Survival. If such an episode occurs, then it will be defined as=1 'YES' If such an episode does not occur, then it will be defined as=0 'NO'
Overall Survival [5 years postoperatively]
Occurrence of Overall Survival. If such an episode occurs, then it will be defined as=1 'YES' If such an episode does not occur, then it will be defined as=0 'NO'

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed right colon cancer (cecum, ascending colon, hepatic flexure)
Surgical resection based on the CME principles
Patient 18 to 90 years old
American Society of Anesthesiologists score ≤III
Τ≤3
Elective operation
Signed informed consent of the patient

Exclusion Criteria:

Non elective operation (hemorrhage, perforation, obstruction)
Locally advanced disease (T4)
Distant metastases (Stage IV)
American Society of Anesthesiologists ≥IV
Previous laparotomy
BMI >35 kg/m2
Active sepsis or systemic infection
Untreated physical and mental disability
Pregnancy or breast-feeding
Lack of compliance with the protocol process
Non-granting of signed informed consent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Surgery, University Hospital of Larissa	Larissa		Greece	41110

Sponsors and Collaborators

Larissa University Hospital

Investigators

Principal Investigator: Konstantinos Perivoliotis, MD, University Hospital of Larissa
Study Chair: George Tzovaras, Prof, University Hospital of Larissa
Study Director: Ioannis Baloyiannis, Prof, University Hospital of Larissa