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

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

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

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

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

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

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

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

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 1978-2002 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

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

CME vs conventional resection Sigmoid colectomy Right hemicolectomy Extended right hemicolectomy

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)

CME vs conventional resection: on short-term outcome Bertelson, et al. BJS 2016: 4 large centers in Denmark, 2008-2013 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)

CME vs conventional resection: on long-term outcome Bertelson, et al. Lancet Oncology 2014: 4 large centers in Denmark, 2008-2011 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)

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

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

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

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)

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

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

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 48-60 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

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

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

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

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

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

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