In colorectal cancers, surgery represents a potentially curative outcome for patients with stage I-III disease. A surgical technique that involves complete removal of mesenteric layers is now a gold standard in rectal cancer surgery, but although it has also led to improved outcomes in colon surgery, its uptake among colon surgeons is slow. But experts now argue that the new technique should be taken up as a standard procedure worldwide.
In rectal cancer, it is has been argued that, from a surgical point of view, the advent of total mesorectal excision (TME), pioneered by Heald (J R Soc Med. 1988;81:503–8), has contributed significantly to improving outcomes for patients with rectal cancer — with local recurrence rates down to 4% from 30% to 40%. Today, the procedure is considered a gold standard in rectal cancer surgery.
Procedures implemented in rectal cancers slowly find their way into colon cancer practices. The operative word is slowly. Analogous to TME in rectal cancer, some colon cancer surgeons have been recommending a similar approach for surgical resection of colon cancers in what is described as complete mesocolic excision (CME), which includes central vascular ligation (CVL) and dissection in the mesocolic plane.
Recently, a Danish study published online December 2014 in Lancet Oncology showed that 4-year disease-free survival (DFS) was significantly higher for patients with stage I-III colon cancer who underwent CME with CVL surgery compared with conventional surgery in Denmark.
Reporting on behalf of the Danish Colorectal Cancer Group (DCCG), Claus Anders Bertelsen, MD, consulting surgeon, Hillerød University Hospital, Denmark, and his colleagues suggest that "the improved outcomes after CME are likely to be related to resection in the mesocolic plane and to high ligation of the tumour-supplying vessels."
They also state: "Although further studies are needed to clarify the potential risks of CME, we suggest that an increased focus should be put on implementation of CME surgery."
"Bertelsen and colleagues have generated strong evidence that improving colonic surgery offers the potential to improve survival to an equivalent or greater extent than adjuvant chemotherapy. This finding cannot be ignored and must be explored further," write Phil Quirke, MD, and Nick West, MD, in an accompanying commentary (Lancet Oncol. Published online December 31, 2014).
Dr Quirke is from the Section of Pathology and Tumour Biology, St James's University Hospital, Leeds, and Dr West is from the Section of Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, School of Medicine, University of Leeds, United Kingdom.
The Danish Study
In the Danish study, Dr Bertelsen and colleagues retrospectively analyzed data for patients who underwent elective surgical resection for stage I-III colon adenocarcinoma in the Capital Region of Denmark.
CME surgery is offered only at a single institution, the Hillerød Hospital; conventional colon resection is offered at three hospitals. Patient data were extracted from the DCCG and medical charts.
Of the 1395 patients eligible for this analysis, 364 patients underwent CME surgery, and 1031 patients underwent conventional surgery.
Significantly Higher DFS for CME Surgery
For all patients in the study, 4-year DFS was significantly higher after CME: 85.8% vs 75.9% for conventional surgery (P = .001). Four-year DFS was as follows for patients across each stage compared with conventional surgery:
For patients with stage I disease: 100% after CME vs 89.8%
For patients with stage II disease: 91.9% after CME vs 77.9%
For patients with stage III disease: 73.5% after CME vs 67.5%
CME was a predictive factor for lower disease recurrence or a higher DFS for patients with stage I, II, and III disease.
Although similar data were reported in another small study and in two single-center studies with historical controls, critics have indicated that only randomized trials may set the debate at rest.
When asked about a randomized clinical study, Dr Bertelsen indicated that this will probably never occur. "Surgeons trained in CME will never go back to doing conventional surgery," he told Medscape Medical News.
In their discussion, Dr Bertelsen and colleagues write: "Randomised controlled trials comparing CME with non-CME surgery would be difficult to undertake because the preferences of CME surgeons would be entrenched and a usable definition of how they should undertake conventional resections would be difficult."
Quality of Surgery Better With CME
So how does CME with CVL differ from conventional surgery? To understand that it is important to understand how the lymphatics drain into the colon. Figure 1 shows a segment of the colon with the draining lymphatics. Reference will be made to this figure in discussing the difference between CME and conventional surgery.
Fig. 1. Colonic segment surrounded by blood vessels. D1, D2, D3 indicate location of lymphatics. (Reproduced by permission of Dr Bertelsen.)
A clear description of what is involved in both CME and conventional surgeries is found in a recent review (Surg Oncol Clin N Am. 2014;23:25-34) by Simon J. A. Buczacki, MRCS, PhD, and R. Justin Davies, MChir, FRCS (Gen Surg), EBSQ (Coloproctology), from the Cambridge University Hospitals, United Kingdom. They explain that conventional surgery involves a complete resection of the primary tumor along with "adequate proximal and distal margins and a clear circumferential resection margin (which may require en bloc resection of the abdominal wall or other viscera) together with an anatomically defined mesenteric lymphovascular pedicle."
This would involve resection of lymphatics in the areas of the vasculature that drain into the colon. The resection of the lymphovascular mesentery is necessary to remove tumor spread to the lymphatics.
With reference to Figure 1, this would involve resection of lymphatics in the D1 and/or D2 areas of the vasculature that drains into the colon. The resection of the lymphovascular mesentery is necessary to remove tumor spread to the lymphatics.
Lymph node yield is particularly important for staging I, II, and III cancers, and a high yield is related to increase survival. In this context, it is important to note that understaging, which occurs with an inadequate assessment of lymph nodes, may be associated ultimately with increased mortality, because patients will be undertreated (eg, they might not be offered adjuvant chemotherapy).
CME with CVL has been championed by the Japanese group (Dis Colon Rectum 2010;53:646), the Sidney group, in Australia (Dis Colon Rectum. 2003;46:860–869), and the Erlangen group, in Germany (Colorectal Dis. 2009;11:354-364).
The procedure may be associated with more accurate staging, especially for stage I, II, and III colon cancers, as a consequence of high lymph node yield during surgery. Although this may be possible with conventional surgery with a "high tie" of the vascular pedicle, it is more reproducible in CME with CVL.
With reference to Figure 1, CME with CVL is done with a resection that includes all lymph nodes in the D3 area.
In their review, Dr Buczacki and Dr Davies point out that CME differs from conventional surgery in two major ways. CME achieves a more radical excision of the lymphatic drainage (also known as the lymphovascular pedicle) and the mesocolon, and achieves resection with an intact visceral peritoneum along with near and distal resection margins of at least 10 cm.
The CVL procedure removes the arterial supply to the affected segment at its origin from the superior mesenteric artery and the aorta.
CME with CVL is therefore associated with a high lymph node yield and more mesocolic tissue.
Fig. 2. Specimens after CME and conventional surgery. (A) CME and (B) conventional sigmoid resections. (C) CME and (D) conventional right hemicolectomies for tumor in ascending colon. (E) CME and (F) conventional extended right hemicolectomies for tumor in transverse colon. (Images are from specimens from Bertelsen CA et al. Lancet Oncol. December 31, 2014; West NP et al. Dis Colon Rectum. 2010;53:1594–603. Reproduced with permission of the authors.)
Figure 2 shows specimens from CME and conventional surgeries. Specimens after CME have an envelope of mesocolon containing more lymph nodes as a result of greater distance from bowel/tumor to vascular tie (Figs. A, C, and E). The length of the resected colon segment might in some cases be larger compared with conventional surgery (Figs. A and C). Because the area of the resected mesocolon is a product of the two, the specimen after CME is characterized by a larger amount of resected mesocolon (Figs. A, C, and E). Reproduced with permission of the authors.
The original article by the Erlangen group provides enlightenment on what the surgery involves and discusses the subtleties of surgery as it relates to tumors affecting different regions of the colon (cecum and ascending colon, transverse colon, left colon) (Colorectal Dis. 2009;11:354-365). Indeed, with the procedure, they showed a decrease in local recurrence (from 6.5% to 3.6%) and an increase in 5-year survival (from 82.1% to 89.1%).
So Why Are Surgeons Not Embracing CME With CVL?
Dr Quirke and Dr West bemoan the fact that colon surgeons are not embracing CME. "The rectal cancer story is repeating itself," they write, explaining that "pioneering work by leaders of rectal cancer surgery was initially ignored and it took the independent reproduction of the improved outcomes in single hospital and small regional studies before large-scale regional and national training programmes led to major reductions in local recurrence, significant improvements in survival, and major financial savings occurred around the world."
With respect to colon surgery, they write, "Resection in western countries is unfortunately still viewed as a routine procedure with little concern surrounding these major variations in outcome. Indeed the focus has been on laparoscopic surgery rather than optimisation of the surgery."
Several factors contribute to CME with CVL not being the mainstay of colon cancer surgeries.
Surgeons are more conservative and will not change their practice unless there is overwhelming evidence for making the change, Dr Bertelsen told Medscape Medical News. When implementing CME, it is very important that supervision be provided by someone who is trained in CME in order to avoid the possible pitfalls and have continuous feedback from the pathologist as quality control, he added.
Dr Quirke and Dr West provide an insight into how Dr Bertelsen and his colleagues at the Hillerød Hospital started the process. "By simply visiting and adopting the methods of expert surgeons in Erlangen, led by Werner Hohenberger, and by quality controlling their surgery through mesocolic grading, routine specimen photography, and internal and external pathology audit, the researchers have independently reproduced results from Erlangen and Japan," they wrote in their commentary.
Indeed, Dr Bertelsen and colleagues indicate that their Hillerød Hospital, in Denmark, adopted this procedure in 2008 after a short implementation period. Currently, this hospital predominantly undertakes CME procedures for colon surgeries.
Compared with the other three hospitals that provided patient data for analysis undertaken in this study, specimens from the Hillerød Hospital "had a significantly greater lymph node yield, greater distance between the tumour and vascular high tie, and more intact mesocolic fascia," Dr Bertelsen and colleagues write (see Figure 2).
CME with CVL is easier to perform than conventional surgery once you are trained, Dr Bertelsen told Medscape Medical News.
Dr Buczacki and Dr Davies indicate: "The practice of CME can be standardized, taught, and implemented with reproducible results."
Dr Quirke and Dr West are emphatic in endorsing CME. "What is certain is that we can no longer afford to ignore the variation in surgical quality for colonic cancer. As a first step, standard CME surgery should be routinely implemented worldwide with consistent high-quality pathological assessment and feedback."
They stress that "a strong consideration should be given to routine CVL." They are mindful that this may require "a definitive trial to understand the learning curve and prove that the benefit is generalisable to practice in western countries."
Dr Quirke and Dr West agree that CME with CVL is a radical central dissection and may be associated with potential risk to major vessels, nerves, and organs, especially the pancreas. However, "in Erlangen, Japan, and now in Hillerød, such surgery seems to be safe," they conclude.
The study was funded by Tvergaards Fund and Edgar and Hustru Gilberte Schnohrs Fund. The authors have reported no relevant financial relationships.
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Cite this: Complete Mesocolic Surgery Improves Outcomes in Colon Cancer - Medscape - Jan 22, 2015.