CME Versus Standard Right Hemicolectomy for Right Sided Cancers

CRC is the third most common cancer in men and second most common in women with almost 55% of these cases occurring in more developed nations Findings from a recent population-based study showed that the oncological outcome was worse for right-sided colon cancers than left-sided colon cancers. The authors also noted that the overall survival after curative surgery for right-sided colon cancer was better in patients whose surgery led to a lymph node yield of 22 or more. Other studies also confirmed these findings of better outcome after more extensive lymph node dissection for colon cancer.

To achieve this strategy of increased lymph node yield, a complete mesocolic excision (CME) of the colonic cancer have been proposed. This concept of CME aims to extrapolate the teaching of total mesorectal excision for rectal cancer to colonic cancer by separating the mesocolic from the parietal plane and true central ('high') ligation of the supplying arteries and draining veins. All the lymph nodes along the tumour supplying vessels are contained in the specimen Hohenberger et al have used this technique in 1329 consecutive cases and have found decreased5-year local recurrences rates of colon cancers (from 6.5% to 3.6%) and increased cancer-related 5-year survival rates (82.1% to 89.1%).

However the CME technique remains controversial as the evidence of increased disease-free survival after CME is mainly based on only two single centre studies Complete mesocolic excision is also a more challenging operation than a standard right hemicolectomy. This is due to the complex vascular anatomy of the right colon, and hence many surgeons and surgical units have refrained from performing right-sided complete mesocolic excision.

Nevertheless a few international centres have started to implement CME surgery for right-sided cancers. In Japan for example, central lymph node dissection similar to complete mesocolic excision is recommended for clinical stage T3-4 or pN1-2 tumours. Berthelsen et al recently published their results of central mesocolic lymph node excision on risk of recurrence after resection for right-sided colon adenocarcinoma. They implemented CME as the standard surgical approach for colon cancer in their hospital since 2008.The authors noted that CME has the potential to reduce the risk of recurrence and improve long-term outcome after resection for all UICC stages I-III of right-sided colon adenocarcinomas.

AIM OF THE STUDY Our aim of this study is to compare the difference in lymph node yield in CME specimens versus those patients having a standard right hemicolectomy for right sided cancer .The secondary aim of this study was to investigate whether there is an interaction between greater lymph node harvest towards increased survival. Another subgroup analysis of this study is to compare the complications and oncological outcome between laparoscopic versus Robotic CME.

Right-sided tumours is defined as any primary adenocarcinoma located in the caecum, the ascending colon, the hepatic flexure, and the right or mid-third of the transverse colon

Minimal invasive operative techniques for CME and Standard right hemicolectomy CME has been performed via laparotomy for many years. Minimal access colorectal surgery has matured steadily over the last decades hence there have been questions asked whether CME can be performed safely and adequately using minimal access techniques.

Continuous progress in technology \[application of high-definition (HD) and three-dimensional (3D) and other camera systems, has led to claims of improved precision in lymph node dissection and vascular sceletonization.

Several studies have now reported that laparoscopic CME resection was feasible and did not compromise patient safety. However theses studies were from single institution and were non-comparative small studies.

Robotic right hemicolectomy (RRHC) has been subject to much interest in recent years from its potential dual learning benefits to the operating colorectal surgeon and clinical benefits to the patients. The potential benefits of robotic systems over conventional laparoscopy include superior three-dimensional vision, seven degrees of freedom of movement replicating the surgeon's hand movements, lack of tremor and potential superior ergonomics, suggesting potential application in both routine and more difficult cases Currently there is little if any literature specifically comparing laparoscopic to robotic CME. Hence we also aim to compare the complications and oncological outcome between laparoscopic versus Robotic versus open CME Intra-corporeal anastomosis Formation With minimally invasive surgery for CME and standard right hemicolectomy there have been an increase in intra-corporeal anastomosis formation. The increased dexterity, third-hand retraction and better visualization at Robotic right hemicolectomy can allow for less colonic dissection, less disturbance of the natural embryological lie of tissue planes, elimination of traction and possible twisting on the remaining transverse colon.

Several studies have revealed conflicting results with some showing significantly fewer conversions for the minimally invasive surgery intra-corporeal anastomosis when compared to the extracorporeal approach and others that show no significant difference.

Hence we aim to do a subset analysis on the anastomotic leak rate between the robotic intra-corporeal anastomosis versus laparoscopic intra-corporeal anastomosis versus minimally invasive surgery extra-corporeal anastomosis.

Anastomosis leak will be defined as sepsis in the post operative period with raised inflammatory markers requiring antibiotics or CT scan confirming free gas around anastomosis or patient return to theatre showing anastomosis breakdown intraoperatively

It will be up to the individual surgeon as to the preferred method of anastomosis they use for each case

5\. OBJECTIVES AND OUTCOME MEASURES Objectives Outcome Measures Timepoint(s) of evaluation of this outcome measure (if applicable) Primary Objective The primary aim of the study is to compare the lymph node yield between CME and standard right hemicolectomy in right sided cancers Number of harvested lymph nodes Within 30 days of operation Secondary Objectives Surgical morbidity/mortality up to 90 days

Pathological quality assessment

Incidence of local recurrence after surgery at 2 and 5 years

Overall survival at 5 and 10 years

Assessment of intraoperative adverse events of the surgery

Health economics assessements

Conversion to open surgery

Evaluation of the operative length of time

For Minimally invasive CME or standard right hemicolectomy - to compare the types of anastomosis (intra-corporeal versus Extra-coporeal )

Completeness of CME will be assessed by the pathologist and is defined as:

* Distal resected margin ≥ 5cm * Lymph node yield * Mesocolic plane of surgery * Central vascular ligation (within 1cm of ileocolic vessels origins) * R0 resection (all margins clear) Local recurrence is defined according to first documented clinical or imaging relapse or the date of death from any cause, whichever occurs first.

To report "near misses" and associated impact upon clinical outcomes

Healthcare resource utilization (costs) including hospital length of stay, ICU hours.

Total OR utilisation time and operative time skin to skin, minutes

Anastomosis leak rate

At 30 and 60 days after surgery

LR is defined as the interval from date of randomisation to the date of first evidence of disease progression wholly within the colon and/or distally. Distant failure or death will be considered as a competing risk.

Defined as sepsis with raised inflammatory markers requiring antibiotics or CT scan confirmed free gas around anastomosis or patient return to theatre showing anastomosis breakdown intraoperatively

6\. TRIAL DESIGN This is an observational prospective, multicentre trial Patients will be having either a minimally invasive (laparoscopic/Robotic) CME versus a standard minimally invasive right hemicolectomy ( laparoscopic/Robotic ) for right sided cancers.

Right-sided tumours is defined as any primary adenocarcinoma located in the caecum, the ascending colon, the hepatic flexure, and the right or mid-third of the transverse colon Distal Transverse colon and splenic flexure tumors will be excluded to minimize misclassification bias The study will include 330 patients from UK and a number of international sites including, but not limited to, Denmark, Germany, Japan , The Netherlands and Australia This study has no impact on staging investigations, timing of surgery or any other aspect of the patients' pre, peri or post-operative care.

All decisions remain with the local clinician multi-disciplinary team including when to discharge from hospital.

7\. PARTICIPANT IDENTIFICATION 7.1. Trial Participants Participants with right sided cancer who are scheduled for initial treatment by either CME or standard right hemicolectomy 7.2. Inclusion Criteria

* Participant is willing and able to give informed consent for participation in the trial. * Male or Female, aged 18 years or above. * Undergoing CME or standard right hemicolectomy surgery for right-sided cancer after MDT discussion. * Cancer must be confirmed by histological, radiological, endoscopic diagnosis * In the Investigator's opinion, is able and willing to comply with all trial requirements. * Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the trial.

7.3. Exclusion Criteria

The participant may not enter the trial if ANY of the following apply:

* Female participant who is pregnant, lactating or planning pregnancy during the course of the trial. * Participant with life expectancy of less than 6 months. * Distal Transverse colon and splenic flexure tumors * Evidence of T4 disease invading adjacent organs * Synchronous surgical procedure planned with CME or right hemicolectomy * Urgent, unplanned or emergency surgery * Neoadjuvant chemotherapy administered to treat this cancer prior to resection * Concurrent or previous abdominal or pelvic malignancy within five years prior to registration irrespective of treatment modality * Known Crohn's disease with active terminal ileal disease * Evidence of systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude surgery, or other severe incapacitating disease, i.e. ASA IV (a patient with severe systemic disease that is a constant threat to life) or ASA V (a moribund patient who is not expected to survive without the operation). * Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial.

• mortality and morbidity [Срок оценки: 90 days]
• Pathological quality assessment [Срок оценки: 90 days]
• Incidence of local recurrence after surgery at 1,3 and 5 years [Срок оценки: 5 years]
• Overall survival at 5 and 10 years [Срок оценки: 10 years]
• Assessment of intraoperative adverse events of the surgery [Срок оценки: 90 days]
• Health economics assessements [Срок оценки: 24 months]
• Health related quality of life [Срок оценки: 1, 3 and 5 years]
• Health related quality of life [Срок оценки: 1,3 and 5 years]
• Health related quality of life [Срок оценки: 1,3 and 5 years]