Complete mesocolic excision for colon cancer: is it worth it?

Introduction

In the past, rectal cancer patients tended to have a poorer disease-free and overall survival than compared to those with colon cancer (1-5). However, since the advent of total mesorectal excision (TME) by Heald and Ryall, oncological outcomes of rectal cancer surgery remarkably improved (6,7). Disease-free and overall survival were comparable, and in some centres, even surpassing the results of colonic tumours (8,9). With colon cancer being the second most common cancer in women and third most in men, the results of TME has increased the interest in the recently proposed complete mesocolic excision (CME).

First described by Hohenberger in 2009, CME adopts similar principles as TME (10,11). CME, along with central vascular ligation (CVL) radically extends the lymphadenectomy.

Hohenberger’s description of CME involves three key components, namely:

• Sharp dissection in the embryologically plane to remove an intact envelope of mesentery together with the corresponding lymphatic drainage;
• CVL to remove apical lymph nodes and;
• Resection of a sufficient length of bowel.

Hohenberger’s description of sharp dissection along embryological planes between the mesocolon and retroperitoneum adheres to Heald’s principle of the “Holy Plane”. This ensures that the resected specimen remains within an intact “envelope of peritoneum” and with this “package”, maximizing the lymph nodes removed. This “intact specimen” also prevents “tumour spillage” and avoid transcoelomic spread of cancer cells during surgery (10,11).

In the west, lymphadenectomy was traditionally performed as an extension of tumour excision. Excising the tumour was regarded as a means of local control while its associated lymphadenectomy was performed more for the purpose of completion of pathological staging and disease-related outcome prognostication (12,13).

A CVL, or “high-tie”, ensures apical lymph nodes are removed. This allows more accurate lymph node staging as we capture all possibility drainage lymphatics within the resected specimen. It is well accepted that colonic lymphatic metastatic spread follows the supplying arteries, however, it does not always obey a stepwise-fashion of spread (14-17). Thus, by including the central or apical lymph nodes within the specimen, afforded by a CVL, there is an increased chance of “stage migration”. This principle is similar to that of an extended lymphadenectomy, or D3 lymphadenectomy, which is practiced in the East, previously for gastric cancer, and increasing recommended for T3 lesions for colon and rectal cancer (12). The difference in lymphatic yield and N-staging may result in whether the patient is offered adjuvant chemotherapy and thus, may improve disease-related or overall outcomes.

In addition, some believes that leaving lymph nodes with disease behind is essentially leaving behind residual disease (14,18,19). This may have implications on local control of disease and may affect the survival. Due to this theory, CVL and extended lymphadenectomy, where apical nodes are removed within the resected specimen, was recommended to minimize the risk of leaving residual disease.

Some recent retrospective studies have demonstrated that increasing the lymph node yield to more than 22 is independently associated with improved 5-year overall survival (14,20-23). Other studies also postulated that the increased ratio of negative to positive lymph nodes is also associated with an improved disease-related survival, especially so in those with stage I-II disease (24-27).

Grading of CME

Grading of TME has been crucial in ensuring quality control (23,28). The importance of quality of resection is highlighted in the corresponding sustained improvement of rectal cancer outcomes over the years.

The accepted grading of the quality of the mesocolic dissection was based on the widely accepted Medical Research Council (MRC) CLASICC trial protocol, which was adopted from the mesorectal grading system used in the MRC CR07 trial (23,28). The colonic grading system classified surgery based on the plane of dissection, namely the muscularis propria plane (“poor”) if there is little bulk to the mesocolon and there are presence of disruptions extending down to the muscularis propria; the intramesocolic plane (“moderate”) if there is moderate bulk with some disruption to the mesocolic fascia but does not reach the muscularis propria; the mesocolic plane (“good”) if there is an intact mesocolon with smooth peritoneal lining; and the mesocolic plane with a high vascular tie close to the aorta.

Benefits of performing CME

The main benefit of CME lies in the increased number of lymph node yield (23,24,27,29-34). With CVL and resection of even the apical lymph nodes, many studies have showed that lymph nodes attained has consistency be significantly higher than that without CME (29,35,36).

Previously, the number of resected lymph nodes was thought to be of prognostic value, however, more recently, some studies have shown that it may also have an impact on survival (14,20-27). Hohenberger demonstrated that a lymph node yield of ≥28 was an independent association with an improved 5-year cancer related survival (96.3% vs. 90.7%, P=0.018) in node negative patients (11). When compared to non-CME resections, about five different studies, between 2007 to 2013, have also showed that local 5-year recurrence rates have almost halved (10,14,37-39). Han et al. reported an improved 5-year overall survival of 70.4% compared to 53.5% for the non-CME patients, these findings were consistently replicated in other studies (38-40). Storli et al. and Le Voyer et al. have shown an increased disease-free survival from 82% to 89% for stage I-II colon cancers (21,41).

In addition, by performing a CVL and yielding more apical or central nodes, we may also have an increased chance of capturing “skipped lesions” which might affect the eventual N-stage (14,42). There will thus, be a higher chance of stage migration or more accurate staging of the colon cancer which would affect the recommendation for adjuvant therapy and thereby positively affecting the disease-free and overall survival. Another explanation could also be that by removing more lymph nodes, including the apical ones, there is a higher chance of completely resecting all “residual disease”, thereby literally preventing the metastasis process from taking place (14,18,19).

Several studies have shown that increasing negative lymph node count also correlates with survival in more advanced staged colon cancer (14,20-23). The ratio of lymph node metastases to the total number of harvested lymph nodes, regards as the lymph node ratio (LNR), has been shown to be a better prognostic indicator than the actual N-stage, with the greater the number of negative nodes relative to metastatic nodes, the better than prognosis (24-27).

By performing CME and having an intact mesocolon with its peritoneal lining, West has shown that this also improves overall survival by 15% (24). This finding may not just be related to an increased lymph node yield, it may also be due to the fact that an intact peritoneum reduces the chance of cancer spillage during the time of surgery.

Another proposed advantage of the adoption of CME is that there will now be standardization of colonic surgery (43). Description of surgical techniques as well as the histological grading of completeness CME, similar to that of TME for rectal cancer, can lead to more accurate audits of surgeons performing colonic oncological surgery. Education or Training programmes has been shown to further improve the quality of the specimen (44-47). However, this has yet to translate to improved surgical and oncological outcomes.

Dangers of CME

CME remains a technically more challenging procedure compared to conventional colectomies. With the need for radical dissection obeying embryological planes and with dissection up to the root of the right branch of the middle colic artery and its accompanying vein, critical structures like the superior mesenteric vein (SMV) have a higher tendency to be damaged, leading to catastrophic outcomes (48,49).

Unlike that of the left colon or rectum, there is a greater anatomical variability in the right colon (50). Arterial and venous configurations within the mesentery are more variable, including different lengths of the gastrocolic trunk of Henle, multiple middle colic arteries, varying venous drainage of the middle colic vein. All these lead to an increased possibility of damaging critical structures during dissection (48,49).

The most feared intra-operative complication during CME is damage to the SMV, the main outflow of the small intestines (51,52). One study reported the incidence of intra-operative SMV damage to be 1.6% of all right hemicolectomies (48). Due to its parallel orientation in relation to the middle colic vein, the SMV can potentially be ligated or damaged either because the surgeon mistakes it for the middle colic vein/artery or due to overzealous traction during the dissection of the middle colic trunk. Excessive retraction of the hepatic flexure medially can also lead to an avulsion of the middle colic vein near its origin along the SMV. A compromised of blood flow through the SMV can lead to congested small bowel, resulting in prolonged ileus, or more disastrous—bowel ischemia.

Other detrimental complications that can occur during CME include genitourinary dysfunction especially for rectosigmoid carcinomas with one study reporting the incidence up to 75.5% with 14.8% having permanent dysfunction (27). Sexual dysfunction is also a commonly reported complication for left sided CME. In addition, due to the more extensive dissection with CVL, there will inevitably be a higher incidence of chyle leak, even though most do not require any intervention and may resolve spontaneously (33,39,53).

Although the duration of hospitalization and healthcare cost can both increase with the occurrence of any morbidities, more worryingly for patients, this also means that time to adjuvant treatment may also be delayed (12). It is already well established that the optimal time for high risk stage II or stage III colon cancer patients to receive adjuvant chemotherapy after surgery is 4–6 weeks. Any morbidity from the surgery may result in the patients requiring a longer time to recuperate and be optimized for chemotherapy. With any delay of adjuvant treatment affecting treatment efficacy, the increased risk of morbidity may also result in an increased risk of worsening disease-related outcomes like survival.

Even with morbidity from the procedure aside, with the procedure being more technically challenging, operation time for CME has been shown to be significantly longer compared with standard colectomy (18,31-34). With a longer operative time, blood and insensible fluid losses would inevitably increase. A challenging procedure would also require a longer learning curve, and with greater usage of laparoscopic surgery for colectomies, this may result in an increased rate of conversion. Many studies on laparoscopic surgery have shown that conversion is an independent risk factor for surgical morbidity. On top of that, with increasing emphasis on healthcare cost, the longer operative time may also affect the efficiency of theatre space usage and impact health economics (12).

Laparoscopic vs. open CME

With CME well acknowledged over the years as a technically challenging procedure, it remains debatable whether the laparoscopic approach should be performed. While Hohenberger described CME with CVL initially as an open procedure, there has been some studies which has evaluated the efficacy of the laparoscopic technique with that of the open, especially for right sided tumours (27,30,32,34,39,41,46,54-57).

Most of these studies has yielded similar operative times, safety profile and oncological as compared to the open procedure (27,30,32,34,39,41,46,54-57). The studies available have also demonstrated that some benefits of laparoscopic surgery are seem in those with CME, such as an improved length of stay (41,55,56). Mesocolon intactness, distance from high tie and lymph node yield has also been generally similar (39,41,55,57). However, some studies show that oncological outcomes like survival favours laparoscopy, which might suggest some form of selection bias between the two techniques.

The only randomized trial comparing laparoscopic and open CME from Yamamoto et al. revealed that the laparoscopic group has a lower complication rate and shorter length of stay which is consistent with that from other retrospective comparative studies (57).

Is it really necessary?

The proponents of CME have displayed anatomical and theoretically logical benefits of CME. The standardization of the technique of colectomies through the principles of CME, as well as the grading of resected specimen would definitely help the quality of surgery performed, which can be extrapolated to an improvement of survival for colon cancer. However, one must question its suitability to be applied to all colectomies.

Distractors of CME would still argue that the role of lymph node yield for colectomies may still be prognostic instead of curative, with the efficacy of chemotherapy and its adjuncts being shown to have improved over the years. There are many authors that question the causal relationship between lymph node yield as well as survival, citing confounding factors like age, tumour characteristics, etc. (12,15,43,58,59). Some studies have also shown that there is minimal survival benefit in patients with more than 12 lymph nodes resected (15).

Radical lymphadenectomy has also been postulated to be much easier in lower BMI, Asian patients, where most D3 lymphadenectomy are performed. Some western surgeons believe that the increased complexity, time and morbidity that CME brings may not be a worthwhile investment for the more obese western patients (12,15,58,59).

In addition to the above, most studies encouraging the uptake of CME are have been retrospective in nature, with all the disadvantages and biases associated with a retrospective study unavoidable. There has yet to be any well-designed prospective randomized controlled trials comparing CME against conventional colectomies.

Conclusions

Whilst the purported benefits of CME remain enticing, more well-designed randomized control trials are necessary to justify the increased risks taken and effort to mount the learning curve for CME. The authors are in the opinion that CME may still benefit a group of carefully selected patients, however, more evidence is required before they will jump onto this bandwagon.

Acknowledgments

None.

Footnote

Conflicts of Interest: The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

References

1. Wibe A, Muller B, Norstein J, et al. Norwegian Rectal Cancer Group. A national strategic change in treatment policy for rectal cancer-implementation of total mesorectal excision as rou- tine treatment in Norway. A national audit. Dis Colon Rectum 2002;45:857-66. [Crossref] [PubMed]
2. Martling AL, Holm T, Rutqvist LE, et al. Effect of a surgical training programme on outcome of rectal cancer in the County of Stockholm. Stockholm Colorectal Cancer Study Group, Basingstoke Bowel Cancer Research Project. Lancet 2000;356:93-6. [Crossref] [PubMed]
3. Kapiteijn E, Putter H, van de Velde CJ, et al. Impact of the introduction and training of total mesorectal excision on recurrence and survival in rectal cancer in The Netherlands. Br J Surg 2002;89:1142-9. [Crossref] [PubMed]
4. Green BL, Marshall HC, Collinson F, et al. Long-term follow- up of the Medical Research Council CLASICC trial of conventional versus laparoscopically assisted resection in colorectal cancer. Br J Surg 2013;100:75-82. [Crossref] [PubMed]
5. Quirke P, Steele R, Monson J, et al. Effect of the plane of surgery achieved on local recurrence in patients with operable rectal cancer: a prospective study using data from the MRC CR07 and NCIC-CTG CO16 randomised clinical trial. Lancet 2009;373:821-8. [Crossref] [PubMed]
6. Heald RJ, Husband EM, Ryall RD. The mesorectum in rectal cancer surgery—the clue to pelvic recurrence? Br J Surg 1982;69:613-6. [Crossref] [PubMed]
7. Heald RJ, Ryall RD. Recurrence and survival after total mesorectal excision for rectal cancer. Lancet 1986;1:1479-82. [Crossref] [PubMed]
8. Birgisson H, Talbäck M, Gunnarsson U, et al. Improved survival in cancer of the colon and rectum in Sweden. Eur J Surg Oncol 2005;31:845-53. [Crossref] [PubMed]
9. Iversen LH, Nørgaard M, Jepsen P, et al. Trends in colorectal cancer survival in northern Denmark: 1985-2004. Colorectal Dis 2007;9:210-7. [Crossref] [PubMed]
10. Hohenberger W, Merkel S, Weber K. Lymphadenectomy with tumors of the lower gastrointestinal tract. Chirurg 2007;78:217-25. [Crossref] [PubMed]
11. Hohenberger W, Weber K, Matzel F. Standardized surgery for colonic cancer: complete mesocolic excision and central ligation—technical notes and outcome. Colorectal Dis 2009;11:354-64. [Crossref] [PubMed]
12. Chow CFK, Kim SH. Laparoscopic complete mesocolic excision: West meets East. World J Gastroenterol 2014;20:14301-7. [Crossref] [PubMed]
13. Nelson H, Petrelli N, Carlin A, et al. Guidelines 2000 for colon and rectal cancer surgery. J Natl Cancer Inst 2001;93:583-96. [Crossref] [PubMed]
14. Liang JT, Huang KC, Lai HS, et al. Oncologic results of laparoscopic D3 lymphadenectomy for male sigmoid and upper rectal cancer with clinically positive lymph nodes. Ann Surg Oncol 2007;14:1980-990. [Crossref] [PubMed]
15. Yao HW, Liu YH. Re-examination of the standardization of colon cancer surgery. Gastroenterol Rep (Oxf) 2013;1:113-8. [Crossref] [PubMed]
16. Liang JT, Lai HS, Huang J, et al. Long-term oncologic results of laparoscopic D3 lymphadenectomy with complete mesocolic excision for right-sided colon cancer with clinically positive lymph nodes. Surg Endosc 2015;29:2394-401. [Crossref] [PubMed]
17. Toyota S, Ohta H, Anazawa S. Rationale for extent of lymph node dissection for right colon cancer. Dis Colon Rectum 1995;38:705-11. [Crossref] [PubMed]
18. Park IJ, Choi GS, Kang BM, et al. Lymph node metastasis patterns in right-sided colon cancers: is segmental resection of these tumors oncologically safe? Ann Surg Oncol 2009;16:1501-6. [Crossref] [PubMed]
19. Hida J, Okuno K, Yasutomi M, et al. Optimal ligation level of the primary feeding artery and bowel resection margin in colon cancer surgery: the influence of the site of the primary feeding artery. Dis Colon Rectum 2005;48:2232-7. [Crossref] [PubMed]
20. Chang GJ, Rodriguez-Bigas MA, Skibber JM, et al. Lymph node evaluation and survival after curative resection of colon cancer: systematic review. J Natl Cancer Inst 2007;99:433-41. [Crossref] [PubMed]
21. Le Voyer TE, Sigurdson ER, Hanlon AL, et al. Colon cancer survival is associated with increasing number of lymph nodes analyzed: a secondary survey of intergroup trial INT-0089. J Clin Oncol 2003;21:2912-9. [Crossref] [PubMed]
22. Kessler H, Hohenberger W. Extended lymphadenectomy in colon cancer is crucial. World J Surg 2013;37:1789-98. [Crossref] [PubMed]
23. West NP, Hohenberger W, Weber K, et al. Complete mesocolic excision with central vascular ligation produces an oncologically superior specimen compared with standard surgery for carcinoma of the colon. J Clin Oncol 2010;28:272-8. [Crossref] [PubMed]
24. West NP, Kobayashi H, Takahashi K, P, et al. Understanding optimal colonic cancer surgery: comparison of Japanese D3 resection and European complete mesocolic excision with central vascular ligation. J Clin Oncol 2012;30:1763-9. [Crossref] [PubMed]
25. Bokey EL, Chapuis PH, Dent OF, et al. Surgical technique and survival in patients having a curative resection for colon cancer. Dis Colon Rectum 2003;46:860-6. [Crossref] [PubMed]
26. Moore J, Hyman N, Callas P, et al. Staging error does not explain the relationship between the number of lymph nodes in a colon cancer specimen and survival. Surgery 2010;147:358-65. [Crossref] [PubMed]
27. Gouvas N, Pechlivanides G, Zervakis N, et al. Complete mesocolic excision in colon cancer surgery: a comparison between open and laparoscopic approach. Colorectal Dis 2012;14:1357-64. [Crossref] [PubMed]
28. West NP, Morris EJ, Rotimi O, et al. Pathology grading of colon cancer surgical resection and its association with survival: a retrospective observational study. Lancet Oncol 2008;9:857-65. [Crossref] [PubMed]
29. Bertelsen CA, Bols B, Ingeholm P, et al. Can the quality of colonic surgery be improved by standardization of surgical technique with complete mesocolic excision? Colorectal Dis 2011;13:1123-9. [Crossref] [PubMed]
30. Park JS, Choi GS, Lim KH, et al. Clinical outcome of laparoscopic right hemicolectomy with transvaginal resection, anastomosis, and retrieval of specimen. Dis Colon Rectum 2010;53:1473-9. [Crossref] [PubMed]
31. Lee SD, Lim SB. D3 lymphadenectomy using a medial to lateral approach for curable right-sided colon cancer. Int J Colorectal Dis 2009;24:295-300. [Crossref] [PubMed]
32. Uematsu D, Akiyama G, Magishi A. Multimedia article. Radical lymphadenectomy for advanced colon cancer via separation of the mesocolon into two layers as in filleting fish. Surg Endosc 2011;25:1659-60. [Crossref] [PubMed]
33. Feng B, Sun J, Ling TL, et al. Laparoscopic complete mesocolic excision (CME) with medial access for right-hemi colon cancer: feasibility and technical strategies. Surg Endosc 2012;26:3669-75. [Crossref] [PubMed]
34. Adamina M, Manwaring ML, Park KJ, et al. Laparoscopic complete mesocolic excision for right colon cancer. Surg Endosc 2012;26:2976-80. [Crossref] [PubMed]
35. Eiholm S, Ovesen H. Total mesocolic excision versus traditional resection in right-sided colon cancer—method and increased lymph node harvest. Dan Med Bull 2010;57:A4224. [PubMed]
36. Galizia G, Lieto E, De Vita F, et al. Is complete mesocolic excision with central vascular ligation safe and effective in the surgical treatment of right-sided colon cancers? A prospective study. Int J Colorectal Dis 2014;29:89-97. [Crossref] [PubMed]
37. Mukai M, Ito I, Mukoyama S, et al. Improvement of 10-year survival by Japanese radical lymph node dissection in patients with Dukes’ B and C colorectal cancer: a 17-year retrospective study. Oncol Rep 2003;10:927-34. [PubMed]
38. Tentes AA, Mirelis C, Karanikiotis C, et al. Radical lymph node resection of the retroperitoneal area for left-sided colon cancer. Langenbecks Arch Surg 2007;392:155-60. [Crossref] [PubMed]
39. Han DP, Lu AG, Feng H, et al. Long-term results of laparoscopy-assisted radical right hemicolectomy with D3 lymphadenectomy: clinical analysis with 177 cases. Int J Colorectal Dis 2013;28:623-9. [Crossref] [PubMed]
40. Ovrebo K, Rokke O. Extended lymph node dissection in colorectal cancer surgery. Reliability and reproducibility in assessments of operative reports. Int J Colorectal Dis 2010;25:213-22. [Crossref] [PubMed]
41. Storli KE, Sondenaa K, Furnes B, et al. Outcome after introduction of complete mesocolic excision for colon cancer is similar for open and laparoscopic surgical treatments. Dig Surg 2013;30:317-27. [Crossref] [PubMed]
42. Check JH, Nowroozi K, Chase JS, et al. False-positive human chorionic gonadotropin levels caused by a heterophile antibody with the immunoradiometric as- say. Am J Obstet Gynecol 1988;158:99-100. [Crossref] [PubMed]
43. Emmanuel A, Haji A. Complete mesocolic excision and extended (D3) lymphadenectomy for colonic cancer: is it worth that extra effort? A review of the literature. Int J Colorectal Dis 2016;31:797-804. [Crossref] [PubMed]
44. West NP, Sutton KM, Ingeholm P, et al. Improving the quality of colon cancer surgery through a surgical education program. Dis Colon Rectum 2010;53:1594-603. [Crossref] [PubMed]
45. Takemasa I, Uemura M, Nishimura J, et al. Feasibility of single-site laparoscopic colectomy with complete mesocolic excision for colon cancer: a prospective case-control comparison. Surg Endosc 2014;28:1110-8. [Crossref] [PubMed]
46. Munkedal DL, West NP, Iversen LH, et al. Implementation of complete mesocolic excision at a university hospital in Denmark: an audit of consecutive, prospectively collected colon cancer specimens. Eur J Surg Oncol 2014;40:1494-501. [Crossref] [PubMed]
47. Nakajima K, Inomata M, Akagi T, et al. Quality control by photo documentation for evaluation of laparoscopic and open colectomy with D3 resection for stage II/III colorectal cancer: Japan Clinical Oncology Group Study JCOG 0404. Jpn J Clin Oncol 2014;44:799-806. [Crossref] [PubMed]
48. Freund MR, Edden Y, Reissman P, et al. Iatrogenic superior mesenteric vein injury: the perils of high ligation. Int J Colorectal Dis 2016;31:1649-51. [Crossref] [PubMed]
49. Wang C, Gao Z, Shen K, et al. Safety, quality and effect of complete mesocolic excision vs non-complete mesocolic excision in patients with colon cancer: a systemic review and meta-analysis. Colorectal Dis 2017;19:962-72. [Crossref] [PubMed]
50. Açar Hİ, Cömert A, Avşar A. Dynamic article surgical anatomical planes for complete mesocolic excision and applied vascular anatomy of the right colon. Dis Colon Rectum 2014;57:1169-75. [Crossref] [PubMed]
51. Wexner S, Rasheid S. Chapter 159: Total colectomy and ileorectal anastomosis. In: Fischer JE. editor. Mastery of Surgery, 6 edition. Philadelphia, USA: Lippincott Williams & Wilkins, a Wolters Kluwer business, 2012:1678-97.
52. Bertelsen CA, Neuenschwander AU, Jansen JE, et al. Short-term outcomes after complete mesocolic excision compared with ‘conventional’ colonic cancer surgery. Br J Surg 2016;103:581-9. [Crossref] [PubMed]
53. Shin JW, Amar AH, Kim SH, et al. Complete mesocolic excision with D3 lymph node dissection in laparoscopic colectomy for stages II and III colon cancer: long-term oncologic outcomes in 168 patients. Tech Coloproctol 2014;18:795-803. [Crossref] [PubMed]
54. Miyajima N, Yamakawa T. Present state and problems of laparoscopic surgery for colon and rectal carcinoma. Nihon Geka Gakkai Zasshi 1997;98:380-4. [PubMed]
55. Bae SU, Saklani AP, Lim DR, et al. Laparoscopic-assisted versus open complete mesocolic excision and central vascular ligation for right-sided colon cancer. Ann Surg Oncol 2014;21:2288-94. [Crossref] [PubMed]
56. Cho MS, Baek SJ, Hur H, et al. Modified complete mesocolic excision with central vascular ligation for the treatment of right-sided colon cancer: long-term outcomes and prognostic factors. Ann Surg 2015;261:708-15. [Crossref] [PubMed]
57. Yamamoto S, Inomata M, Katayama H, et al. Short-term surgical outcomes from a randomized controlled trial to evaluate laparoscopic and open D3 dissection for stage II/III colon cancer: Japan Clinical Oncology Group Study JCOG 0404. Ann Surg 2014;260:23-30. [Crossref] [PubMed]
58. Killeen S, Mannion M, Devaney A, et al. Complete mesocolic resection and extended lymphadenectomy for colon cancer: a systematic review. Colorectal Dis 2014;16:577-94. [Crossref] [PubMed]
59. Alhassan N, Yang M, Wong-Chong N, et al. Comparison between conventional colectomy and complete mesocolic excision for colon cancer: a systematic review and pooled analysis: A review of CME versus conventional colectomies. Surg Endosc 2019;33:8-18. [Crossref] [PubMed]