Colon cancer : aspects on surgical treatment and complete mesocolic excision

In rectal cancer, total mesorectal excision (TME), including surgery with dissection outside the mesorectal fascia, together with pre-operative radiotherapy improves survival. An educational effort on TME improved results in rectal cancer in Stockholm in the 1990’s. The Stockholm Colon Cancer Project (SCCP) was an educational project on the management on colon cancer, launched in 2004, introducing Complete Mesocolic Excision (CME). CME is described as an en-bloc resection of a large part of the mesocolon with preservation of the mesocolic fascia and a proximal vascular ligature. The term ‘CME’ is relatively novel although the concept has been relevant since long ago. A partly synonymous term is D3-surgery, referring to the resection of centrally disposed lymph nodes. The overall aim of this thesis was to evaluate the effect of the introduction of CME on short- and long term outcome for patients with colon cancer.

In Paper I all patients operated for right-sided colon cancer in the Stockholm area, between 1996 and 2009 were divided into three time periods. The number of analyzed lymph nodes increased significantly over the study period. The proportion of patients having less than 12 lymph nodes analyzed in the specimen decreased from 77.1% to 18.3% (p<0.001). Metastatic index (MI) (in lymph node positive patients) was 0.40 in period 1 and 2, compared to 0.25 in period 3 (p<0.001).

In Paper II survival for patients diagnosed with right sided colon cancer before (2001-2003, n=819) and after (2006-2008, n=897) SCCP was studied. The proportion of patients having a tumor resection was larger in the earlier group, 96.6% compared to 91.2% the latter group (p<0.001). There were a larger proportion of patients having emergency tumor resection in the earlier time period and there was a significantly higher proportion of R0 resection in the latter group. The crude three year disease free survival among patients in TNM stage I-III who had their tumor resected was also significantly higher in the latter time period, 71.5% compared to 64.6% (p=0.006).

In Paper III patients operated for right sided colon cancer between 2004 and 2012 was studied in a case-control study. Cases were patients that died within 90 days of surgery or had an emergency re-operation. Two controls per case were matched for sex, age-interval, TNM-stage and emergency surgery. Exposure was CME determined from surgical reports. The reports were classified as “CME” or “no CME” according to pre-defined criteria. The Odds Ratio (OR) for postoperative death or re-operation was 0.75 (95% CI: 0.50-1.13)(p=0.17) for CME surgery compared to no CME surgery, suggesting CME is not associated with short term morbidity or mortality.

In Paper IV, all patients, electively operated for right sided colon cancer (stage I-III) in Stockholm between 2008 and 2012 were studied in a cohort study (n=1171). CME-exposure was determined in a similar way as in paper III. Five year relapse-free survival (RFS) was 73.6% in the “CME” group vs 63.5% in patients classified as “no CME”. The multivariable adjusted model showed a significantly improved RFS for the “CME” group, Hazard Ratio (HR)=0.74 (95% CI: 0.58-0.94, p=0.014).

List of scientific papers

I. Increased lymph node harvest in patients operated on for right-sided colon cancer: a population-based study. R. Bernhoff, T. Holm, A. Sjövall, F. Granath, A. Ekbom, A. Martling. Colorectal Dis. 2012 Jun;14(6):691-6.
https://doi.org/10.1111/j.1463-1318.2012.03020.x

II. Improved survival after an educational project on colon cancer management in the county of Stockholm – A population based cohort study. R. Bernhoff, A. Martling, A. Sjövall, F. Granath, W. Hohenberger, T. Holm. Eur J Surg Oncol. 2015 Nov;41(11):1479-84.
https://doi.org/10.1016/j.ejso.2015.07.019

III. Complete Mesocolic Excision (CME) in right sided colon cancer does not increase severe short term postoperative adverse events. R. Bernhoff, A. Sjövall, C. Buchli, F. Granath, T. Holm, A. Martling. Colorectal Dis. 2017 Nov 1.
https://doi.org/10.1111/codi.13950

IV. Oncological outcomes after Complete Mesocolic Excision (CME) in right sided colon cancer - A population based study. R. Bernhoff, A. Sjövall, T. Holm, A. Martling, C. Buchli. [Manuscript]