Laparoscopic Versus Open Right Colectomy for Right Colon Cancer

Colon Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05713903
• Other study ID #: LORC
• Status: Recruiting
• Phase: N/A
• Start date: February 6, 2023
• Est. completion date: January 10, 2027

Study information

• Verified date: March 2024
• Source: Larissa University Hospital
• Contact: Konstantinos Perivoliotis, MD
• Phone: 2413501000
• Email: kperi19[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 114
• Est. completion date: January 10, 2027
• Est. primary completion date: January 10, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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
• ?=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

Related Conditions & MeSH terms

• Colon Cancer
• Colonic Neoplasms

Intervention

Procedure:
• Laparoscopic right colectomy
Resection of the ascending colon via a laparoscopic approach, adhering to the CME principles
• Open right colectomy
Resection of the ascending colon via an open approach, adhering to the CME principles

Locations

Country	Name	City	State
Greece	Department of Surgery, University Hospital of Larissa	Larissa

Sponsors (1)

Lead Sponsor	Collaborator
Larissa University Hospital

Country where clinical trial is conducted

Greece, 

References & Publications (25)

Adamina M, Manwaring ML, Park KJ, Delaney CP. Laparoscopic complete mesocolic excision for right colon cancer. Surg Endosc. 2012 Oct;26(10):2976-80. doi: 10.1007/s00464-012-2294-4. Epub 2012 May 2. — View Citation

Anania G, Arezzo A, Davies RJ, Marchetti F, Zhang S, Di Saverio S, Cirocchi R, Donini A. A global systematic review and meta-analysis on laparoscopic vs open right hemicolectomy with complete mesocolic excision. Int J Colorectal Dis. 2021 Aug;36(8):1609-1620. doi: 10.1007/s00384-021-03891-0. Epub 2021 Mar 1. — View Citation

Anania G, Davies RJ, Bagolini F, Vettoretto N, Randolph J, Cirocchi R, Donini A. Right hemicolectomy with complete mesocolic excision is safe, leads to an increased lymph node yield and to increased survival: results of a systematic review and meta-analysis. Tech Coloproctol. 2021 Oct;25(10):1099-1113. doi: 10.1007/s10151-021-02471-2. Epub 2021 Jun 12. — View Citation

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Di Buono G, Buscemi S, Cocorullo G, Sorce V, Amato G, Bonventre G, Maienza E, Galia M, Gulotta L, Romano G, Agrusa A. Feasibility and Safety of Laparoscopic Complete Mesocolic Excision (CME) for Right-sided Colon Cancer: Short-term Outcomes. A Randomized Clinical Study. Ann Surg. 2021 Jul 1;274(1):57-62. doi: 10.1097/SLA.0000000000004557. — View Citation

Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004 Aug;240(2):205-13. doi: 10.1097/01.sla.0000133083.54934.ae. — View Citation

Feng B, Sun J, Ling TL, Lu AG, Wang ML, Chen XY, Ma JJ, Li JW, Zang L, Han DP, Zheng MH. Laparoscopic complete mesocolic excision (CME) with medial access for right-hemi colon cancer: feasibility and technical strategies. Surg Endosc. 2012 Dec;26(12):3669-75. doi: 10.1007/s00464-012-2435-9. Epub 2012 Jun 26. — View Citation

Gouvas N, Pechlivanides G, Zervakis N, Kafousi M, Xynos E. Complete mesocolic excision in colon cancer surgery: a comparison between open and laparoscopic approach. Colorectal Dis. 2012 Nov;14(11):1357-64. doi: 10.1111/j.1463-1318.2012.03019.x. — View Citation

Gustafsson UO, Scott MJ, Hubner M, Nygren J, Demartines N, Francis N, Rockall TA, Young-Fadok TM, Hill AG, Soop M, de Boer HD, Urman RD, Chang GJ, Fichera A, Kessler H, Grass F, Whang EE, Fawcett WJ, Carli F, Lobo DN, Rollins KE, Balfour A, Baldini G, Riedel B, Ljungqvist O. Guidelines for Perioperative Care in Elective Colorectal Surgery: Enhanced Recovery After Surgery (ERAS(R)) Society Recommendations: 2018. World J Surg. 2019 Mar;43(3):659-695. doi: 10.1007/s00268-018-4844-y. — View Citation

Heald RJ, Husband EM, Ryall RD. The mesorectum in rectal cancer surgery--the clue to pelvic recurrence? Br J Surg. 1982 Oct;69(10):613-6. doi: 10.1002/bjs.1800691019. — 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

Huang JL, Wei HB, Fang JF, Zheng ZH, Chen TF, Wei B, Huang Y, Liu JP. Comparison of laparoscopic versus open complete mesocolic excision for right colon cancer. Int J Surg. 2015 Nov;23(Pt A):12-7. doi: 10.1016/j.ijsu.2015.08.037. Epub 2015 Aug 28. — View Citation

Hurwitz EE, Simon M, Vinta SR, Zehm CF, Shabot SM, Minhajuddin A, Abouleish AE. Adding Examples to the ASA-Physical Status Classification Improves Correct Assignment to Patients. Anesthesiology. 2017 Apr;126(4):614-622. doi: 10.1097/ALN.0000000000001541. — View Citation

Kang J, Kim IK, Kang SI, Sohn SK, Lee KY. Laparoscopic right hemicolectomy with complete mesocolic excision. Surg Endosc. 2014 Sep;28(9):2747-51. doi: 10.1007/s00464-014-3521-y. Epub 2014 Apr 10. — View Citation

Koc MA, Celik SU, Guner V, Akyol C. Laparoscopic vs open complete mesocolic excision with central vascular ligation for right-sided colon cancer. Medicine (Baltimore). 2021 Feb 12;100(6):e24613. doi: 10.1097/MD.0000000000024613. — View Citation

Magouliotis DE, Baloyiannis I, Mamaloudis I, Bompou E, Papacharalampous C, Tzovaras GA. Laparoscopic Versus Open Right Colectomy for Cancer in the Era of Complete Mesocolic Excision with Central Vascular Ligation: Pathology and Short-Term Outcomes. J Laparoendosc Adv Surg Tech A. 2021 Nov;31(11):1303-1308. doi: 10.1089/lap.2020.0508. Epub 2021 Mar 12. — View Citation

Matsuda T, Iwasaki T, Sumi Y, Yamashita K, Hasegawa H, Yamamoto M, Matsuda Y, Kanaji S, Oshikiri T, Nakamura T, Suzuki S, Kakeji Y. Laparoscopic complete mesocolic excision for right-sided colon cancer using a cranial approach: anatomical and embryological consideration. Int J Colorectal Dis. 2017 Jan;32(1):139-141. doi: 10.1007/s00384-016-2673-8. Epub 2016 Oct 6. — View Citation

Sheng QS, Pan Z, Chai J, Cheng XB, Liu FL, Wang JH, Chen WB, Lin JJ. Complete mesocolic excision in right hemicolectomy: comparison between hand-assisted laparoscopic and open approaches. Ann Surg Treat Res. 2017 Feb;92(2):90-96. doi: 10.4174/astr.2017.92.2.90. Epub 2017 Jan 31. — View Citation

Shin JK, Kim HC, Lee WY, Yun SH, Cho YB, Huh JW, Park YA, Chun HK. Laparoscopic modified mesocolic excision with central vascular ligation in right-sided colon cancer shows better short- and long-term outcomes compared with the open approach in propensity score analysis. Surg Endosc. 2018 Jun;32(6):2721-2731. doi: 10.1007/s00464-017-5970-6. Epub 2017 Nov 3. — View Citation

Siani LM, Lucchi A, Berti P, Garulli G. Laparoscopic complete mesocolic excision with central vascular ligation in 600 right total mesocolectomies: Safety, prognostic factors and oncologic outcome. Am J Surg. 2017 Aug;214(2):222-227. doi: 10.1016/j.amjsurg.2016.10.005. Epub 2016 Nov 16. — View Citation

Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC, Cercek A, Smith RA, Jemal A. Colorectal cancer statistics, 2020. CA Cancer J Clin. 2020 May;70(3):145-164. doi: 10.3322/caac.21601. Epub 2020 Mar 5. — View Citation

Strey CW, Wullstein C, Adamina M, Agha A, Aselmann H, Becker T, Grutzmann R, Kneist W, Maak M, Mann B, Moesta KT, Runkel N, Schafmayer C, Turler A, Wedel T, Benz S. Laparoscopic right hemicolectomy with CME: standardization using the "critical view" concept. Surg Endosc. 2018 Dec;32(12):5021-5030. doi: 10.1007/s00464-018-6267-0. Epub 2018 Oct 15. — View Citation

Wang Y, Zhang C, Zhang D, Fu Z, Sun Y. Clinical outcome of laparoscopic complete mesocolic excision in the treatment of right colon cancer. World J Surg Oncol. 2017 Sep 18;15(1):174. doi: 10.1186/s12957-017-1236-y. — View Citation

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* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mesocolic Resection Plane	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'	1 month postoperatively
Secondary	Open Conversion	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'	Intraoperative period
Secondary	Operative Time	The total operative time will be recorded. Measurement unit: minutes	Intraoperative period
Secondary	Type of Anastomosis	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 period
Secondary	Intraoperative Transfusion	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'	Intraoperative period
Secondary	Postoperative Complication	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'	1 month postoperatively
Secondary	Bowel Function Recovery	Postoperative time until the recovery of bowel function is achieved. Measurement unit: days	7 days postoperatively
Secondary	Length of Hospital Stay	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	Maximum time frame 39 days postoperatively]
Secondary	Negative Resection Margin	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'	1 month postoperatively
Secondary	Local Recurrence	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'	5 years postoperatively
Secondary	Disease Free Survival	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'	5 years postoperatively
Secondary	Overall Survival	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'	5 years postoperatively