The surgical management of Lynch Syndrome remains controversial. There is a lack of robust evidence supporting the hypothesis that there is a greater risk of MCC after a segmental colectomy versus extensive colectomy. Our study shows that there is a five times greater risk of MCC after a segmental colectomy when compared to an extensive colectomy. Although a trend towards decreased mortality in the extensive colectomy cohort is suggested by this meta-analysis, this is not statistically significant. Despite these findings an individualised approach for each patient should be utilised.

It must be recognised that patient centred care is paramount and patients should not only be counselled on the significantly greater risk of MCC after a segmental compared to an extensive colectomy, but also on the impact that more extensive surgery may have on morbidity. Steel et al. demonstrated in patients who were at high risk of MCC that they were well informed about the surgical procedure, however they feared recurrence and information relating to surgical outcome, recovery and lifestyle adjustments were inadequate [21].

Extensive surgery includes a pan-proctocolectomy or a subtotal colectomy. Patients undergoing a pan-proctocolectomy should be counselled that this will necessitate a permanent end ileostomy or ileal anal pouch anastomosis (IPAA) which will require lifestyle and dietary adaptation and has been reported to negatively impact up to 50% of patient’s sex lives [22]. Alternative extensive surgery includes a total colectomy whereby an ileorectal anastomosis is formed or a proctectomy can be performed at later date and an IPAA created. A pan-proctocolectomy will eliminate the risk of MCC however with a total colectomy the risk of a rectal cancer remains. Although proximal cancers are a hallmark of LS, it has been found that up to 15% of tumours can occur within the rectum [23]. In addition it must be acknowledged that there is greater morbidity following an extended colectomy with an increase in bowel motions, poorer functional outcome and reported lower quality of life [24].

A pan-proctocolectomy would be the optimal choice to eliminate a patient’s risk of MCC, especially if the primary tumour has occurred within the rectum. If a patient opts against this and prefers a total colectomy and ileorectal anastomosis or IPAA, then regular endoscopic surveillance of the remaining rectum would be required due to the risk of a rectal cancer. Where a segmental colectomy is the surgical management of choice regular endoscopic surveillance would be sensible due to the five times greater risk of MCC in such patients.

Despite there being a significantly increased risk of MCC, the choice of surgical management has no significant effect on mortality. However, it can logically be assumed that a cancer recurrence, need for repeat surgery and anaesthesia would all increase one’s risk of mortality. Despite our findings contradicting this, the limitations of the mortality meta-analysis must be recognised. There were only 3 studies (548 patients) that included mortality data. Before definitive conclusions are made, the meta-analysis should be repeated when more studies with mortality data becomes available. We therefore suggest that further studies investigating the effect of the choice of surgery on mortality should be conducted and authors should make this data available to allow for a conclusive meta-analysis to be conducted.

It appears that patients with higher penetrance forms of LS may be at the greatest risk of MCC. Germline specific data reveal that most of the cases in the meta-analysis were patients with MLH1 and MSH2 mutations, with only two of the studies reporting mutations for MSH6 and PMS2 mutations as well. Thus the high risk of MCC in the segmental colectomy cohort is largely due to patients with MLH1 and MSH2 mutations, and therefore germline specific information must be taken in to account when counselling patients about the risks of surgery [13, 25].

The choice of surgical management should also take into account the patient’s age and co-morbidities. Parry et al. showed that there was a cumulative increase in the risk of MCC as time following segmental colectomy increases [13]. The risk was demonstrated as 16, 41 and 62% at 10, 20 and 30 years respectively. This cumulative increase in risk should be considered along with the impact upon ones quality of life, particularly in a younger patient compared to a more elderly patient. Elderly patients may also have more co-morbidities further increasing their risk of mortality and morbidity following more extensive surgical intervention. Lynch syndrome is also associatd with extra colonic malignancies such as endometrial and ovarian malignancy. The presence of a concomitant extra colonic malignancy should be taken into consideration when selecting a segmental or extended colectomy.

A systematic review and meta-analysis to ascertain the risk of MCC following a segmental colectomy compared to extensive colectomy has been performed by Heneghan et al. [26] and Anele et al. [27]. There are key differences in the statistical analysis and methodology which makes the current study more advantageous.

Firstly, it is not possible to reproduce the odds ratios calculated for 5 out of 6 of the individual studies within the Heneghan study. 3 out of the 6 studies included in the meta-analysis by Heneghan et al. have also been included by Anele et al. and again the odds ratios calculated for these studies do not correlate. This suggests that they’re may have been an error in statistical analysis of the data by Heneghan at al, thus producing an unreliable overall odds ratio for the risk of MCC. Furthermore Anele and colleagues have made an error when extracting data from the study by Stupart et al. [28]. Mortality following metastatic colorectal cancer following an extensive colectomy has been extracted as opposed to the number of patients with MCC after an extensive colectomy.

Anele and colleagues argue that as the Heneghan study includes patients which meet the Amsterdam criteria but do not necessarily have a confirmed germline mutation, this patient demographic could include patients with familial colorectal cancer type X, which has a lower rate of MCC, thus producing bias [27]. Anele et al. try and overcome this bias by only including patients with a confirmed LS germline mutation. Contrary to this, they included patients which demonstrated microsatellite instability and/or mismatch repair deficiency from a study by Aronson et al., however only 85.4% of these patients have a confirmed germline mutation [29].

To investigate if there is a significant difference in risk between patients which meet the Amsterdam criteria (but have not undergone genetic testing) and those with a confirmed germline mutation we performed a subgroup analysis. The relative risk of MCC in these groups was 3.04 (95% CI 1.46–6.34) and 8.56 (95% CI 3.37–21.73) respectively. Despite the risk being lower within those who meet the Amsterdam criteria, there is no significant difference between the two groups.

The CAPP2 study demonstrated that regular high dose aspirin could lower the risk of developing colorectal cancer in those with LS [30]. One may argue that chemoprevention using aspirin may remove the need for a prophylactic extensive colectomy to prevent MCC. However, despite further studies required to ascertain the optimal dose of aspirin for chemoprevention, the CAPP2 study and other data (Rothwell et al.) demonstrated that the effect of aspirin is delayed and it isn’t until after a latent period of approximately a decade that the risk is significantly lowered when compared to placebo [31]. This delayed effect after 120 months occurs after the mean follow up, 100.73 months, of the patients within this study. By the point of significant effect of aspirin, the risk of MCC after a segmental colectomy compared to extensive colectomy is already increased fivefold, therefore necessitating the need for a prophylactic colectomy to lower one’s risk of MCC.

In addition to chemoprevention, the role of endoscopy in risk modification is not well established. Current international guidance recommends 1–2 yearly colonoscopic surveillance of LS carriers in order to ensure colorectal cancers are identified and managed promptly [2, 3]. Several studies have now demonstrated no significant reduction in risk of MCC in segmental and extensive colectomy patients undergoing regular biennial colonoscopic surveillance [13, 25, 32]. Perhaps more regular or higher quality colonoscopic surveillance may be more beneficial, however the efficacy and cost effectiveness of this would need to be evaluated.