1. Joint Hospital Surgical Grand Round Dr Stewart Chan Kwong Wah Hospital
Should we get more? The concept of complete mesocolic excision + central venous ligation in colorectal cancer surgery
Joint Hospital Surgical Grand Round
Dr Stewart Chan
Kwong Wah Hospital

2. From TME onwards
Total mesorectal excision (TME) is now considered as the standard surgical approach for middle / low rectal cancers
Emphasizes on complete removal of the mesorectum circumferentially and distally
Increased R0 resection rate
Reduced local recurrence
Improved long-term survival
Heald RJ et al. BJS 1982 & Lancet 1984
Quirke P, Eteele R et al. Lancet 2009

3. Can the concept & benefits of TME be applied to colonic cancer?

4. Complete mesocolic excision (CME) + Central venous ligation (CVL)
First described by Hohenberger in 2009 (Erlangen, Germany) as a standardized technique for oncological colonic resection
Aim: removing all lymphatic and vascular tissue in the drainage area of a tumour in a complete and intact mesocolic envelope, and maximizing lymph node yield
Hohenberger W. et al. Colorectal Dis. 2009

5. Concept of CME+CVL
Sharp dissection on the mesocolic plane (Toldt’s line)
 complete removal of mesocolon and all draining lymph nodes within an intact visceral fascia layer
Hohenberger W. et al. Colorectal Dis. 2009

6. Concept of CME+CVL High vascular tie at the origins of blood supply
2. Adequate length of colonic resection
 remove all pericolic (D1) lymph nodes
High vascular tie at the origins of blood supply
 remove all intermediate (D2) + central (D3) lymph nodes
Hohenberger W. et al. Colorectal Dis. 2009

7. Concept of CME+CVL Why is the “mesocolic plane” important?
Retrospective pathological analysis of 399 colonic cancer resection specimen regarding to the plane of resection
15% increase in 5-year overall survival with intact mesocolon (i.e. in mesocolic plane) compared with presence of defects exposing underlying muscularis propria (HR 0·57, p=0·006)
Significant in multivariate analysis for stage III cancers (HR 0·45, p=0·014)
West et al. Lancet oncology 2008

8. Concept of CME+CVL Why should we remove more lymph nodes?
Survival improved if more LN harvested
Benefit: upstaging disease, removing skip lesions, isolated tumour cells / micrometastasis
2000 Guideline: minimum of 12 LN excised
5.8%-11% Central / D3 nodes involvement in right colon cancer
Nelson H et al. J Natl Cancer Inst 2001
LeVoyer et al. J Clin Oncology 2003
Chen SL et al. Ann Surg 2006
Toyota S. et al. Dis Colon Rectum 1995
Park IJ et al. Ann Surg Oncol 2009

9. 5-year OS “improved” from 82% to 89% after CME was implemented, P=0.04
1329 patients who had curative operation for colonic malignancy in the same centre from
Results:
5-year OS “improved” from 82% to 89% after CME was implemented, P=0.04
5-year OS improved if >28 lymph nodes harvested in N0 patients (96% vs 90%, P<=0.018)
5% received adjuvant chemotherapy
Hohenberger W. et al. Colorectal Dis. 2009

10. Question 1: Is CME+CVL better than conventional resections?

11. CME vs conventional resection
Sigmoid colectomy
Right hemicolectomy
Extended right hemicolectomy

12. CME vs conventional resection: on specimen quality
West, et al. Journal of Clinical Oncology (2010):
Macroscopic examination of CME specimens from Erlangen and conventional resection specimens from UK
Results: CME produces a better quality resection specimen
Larger area of mesentery removed: 196cm2 vs 118cm2 (P<0.0001)
Longer bowel segments resected: 31.4cm vs 20.6cm (P<0.0001)
“Higher” vascular tie achieved: 13.1cm vs 9cm (P<0.0001)
More lymph node yielded: 30 vs 18 (P<0.0001)
More mesocolic plane resection 92% vs 40% (P<0.0001)

13. CME vs conventional resection: on short-term outcome
Bertelson, et al. BJS 2016:
4 large centers in Denmark,
529 CME and 1701 controls
Laparoscopic operation done in 49% CME cases and 69% conventional cases
Results
CME has higher incidence of intra-operative injury (spleen , SMV, colon) 9.1% vs 3.6%, p<0.001
CME has higher risk of post-operative sepsis requiring vasopressors 6.6% vs 3.2%, P=0.001
30-day and 90-day mortality is similar: 6.2% vs 4.9% (p=0.2)

14. CME vs conventional resection: on long-term outcome
Bertelson, et al. Lancet Oncology 2014:
4 large centers in Denmark,
364 CME and 1031 controls
R1 resections and stage IV diseases excluded
Results:
Improved overall 4 year disease-free survival 86% vs 76%, p=0.001
Lower recurrence 11% vs 16%, p=0.028
Multivariate analysis showed CME as a predictor of survival for all patients (stage I-III) (HR 0.59, P=0.0025)
More stage II patients received adjuvant chemotherapy in the CME group (24.9% vs 15%, p=0.0053)

15. CME vs. conventional resections
Comments:
Better quality of surgical specimen resected
Higher operative morbidity
Better local control & improved survival

16. Question 2: Should we perform CME+CVL on right colonic cancers?

17. CME+CVL for right colon cancer:
Lateral to medial approach
Kocherization of duodenum
Exposure of the IVC & SMA/SMV
High tie at the root of ileocolic, right colic and right br. of middle colic vessels
Hohenberger W. et al. Colorectal Dis. 2009

18. CME+CVL in right colonic cancer
Galizia et al (Italy), 2014
45 consecutive cases with open CME compared with 58 historical controls using conventional operative techniques, mean FU 60 months
Results
Better lymph node harvest: 20 vs 15 (P<0.01)
No loco-regional recurrences: 0 vs 12 (P=0.03)
Higher disease specific survival: 93% vs 75%
Longer operative time: 178 min vs 130min (P<0.01)
More blood loss: 280ml vs 200ml (P<0.01)
Multivariate analysis: conventional operation associated with poor outcome, HR 1.34 (P<0.01)

19. CME+CVL in right colonic cancer
Comments:
Despite the technical difficulty and potentially higher risk of vascular injury, good oncological results can be obtained in expert hands

20. Question 3: Can CME+CVL be done equally well laparoscopically?

21. Laparoscopic vs. open CME+CVL
Systematic review by Miskovic D. et al (2016)
1 randomized and 7 case control trials from Korea, Japan and Norway.
Total 1377 lap vs 1265 open CME colectomies
Median FU range months
Results
No statistically significant differences in terms of
30 day mortality, anastomotic leakage, postoperative ileus, wound infection, LOS, LN yield, local recurrence & survival
Laparoscopic CME only significant in longer operative time and less blood loss

22. Laparoscopic vs. open CME+CVL
Comments:
Clinical safety and non-inferiority of laparoscopic CME+CVL can be demonstrated in experienced centres

23. Literature critique Most studies are small size retrospective series
Most studies have no control or utilize historical control only
Most studies employ stringent inclusion and exclusion criteria
Most studies are done in specialized centres - external validity & reproducibility questionable
None of them are RCT

24. The debate is going on… For CME – “The theory is sound”
Removing more LN  reduces risk of micrometastasis
Removing colonic mesentery intact  prevent tumour seeding
Allows standardization of operative techniques and improves quality of surgical specimen  leads to better surgical outcome
Against CME – “The risk is high, and evidence is limited”
Higher operative risk (e.g. vascular injury, functional disturbance)
Rare involvement of central nodes, could be over-treating
Latest literature unable to demonstrate significant and reproducible survival benefit

25. Conclusions Q1. Is CME+CVL better than conventional resection?
oncologically YES; clinically PROBABLY YES
Q2: Should we perform CME+CVL on right colonic cancers?
in expert hands, YES
Q3: Can CME+CVL be done equally well laparoscopically?
again in expert hands, YES
The experts’ consensus says:
“…the CME Principle should guide (curative) resection for all colon cancers ... This will theoretically improve the oncological outcome to the patients…”
Hohenberger W, Sugihara K, West NP, Heald RJ, et al
Proceedings of a consensus conference, Int J Colorectal Dis 2014

26. The Way Forward
To conduct high-quality RCT or prospective cohort studies
To define the high risk group who benefit most from CME+CVL
To address the functional outcomes of CME+CVL
To standardize surgical techniques, improve quality of surgical specimen and reduce surgical morbidity

27. Thank you Should we get more? They will say YES
Photo credit: Professors Hohenberger & Bill Heald
Thank you