Abstract
Around 5% of colorectal cancers are due to mutations within DNA mismatch repair genes, resulting in Lynch syndrome (LS). These mutations have a high penetrance with early onset of colorectal cancer at a mean age of 45 years. The mainstay of surgical management is either a segmental or extensive colectomy. Currently there is no unified agreement as to which management strategy is superior due to limited conclusive empirical evidence available. A systematic review and meta- analysis to evaluate the risk of metachronous colorectal cancer (MCC) and mortality in LS following segmental and extensive colectomy. A systematic review of the PubMed database was conducted. Studies were included/ excluded based on pre-specified criteria. To assess the risk of MCC and mortality attributed to segmental or extensive colectomies, relative risks (RR) were calculated and corresponding 95% confidence intervals (CI). Publication bias was investigated using funnel plots. Data about mortality, as well as patient ascertainment [Amsterdam criteria (AC), germline mutation (GM)] were also extracted. Statistical analysis was conducted using the R program (version 3.2.3). The literature search identified 85 studies. After further analysis ten studies were eligible for inclusion in data synthesis. Pooled data identified 1389 patients followed up for a mean of 100.7 months with a mean age of onset of 45.5 years of age. A total 1119 patients underwent segmental colectomies with an absolute risk of MCC in this group of 22.4% at the end of follow-up. The 270 patients who had extensive colectomies had a MCC absolute risk of 4.7% (0% in those with a panproctocolecomy). Segmental colectomy was significantly associated with an increased relative risk of MCC (RR = 5.12; 95% CI 2.88–9.11; Fig. 1), although no significant association with mortality was identified (RR = 1.65; 95% CI 0.90–3.02). There was no statistically significant difference in the risk of MCC between AC and GM cohorts (p = 0.5, Chi-squared test). In LS, segmental colectomy results in a significant increased risk of developing MCC. Despite the choice of segmental or extensive colectomies having no statistically significant impact on mortality, the choice of initial surgical management can impact a patient’s requirement for further surgery. An extensive colectomy can result in decreased need for further surgery; reduced hospital stays and associated costs. The significant difference in the risk of MCC, following segmental or extensive colectomies should be discussed with patients when deciding appropriate management. An individualised approach should be utilised, taking into account the patient’s age, co-morbidities and genotype. In order to determine likely germline-specific effects, or a difference in survival, larger and more comprehensive studies are required.
Highlights
In 2012, 694,000 deaths worldwide were attributed to colorectal cancer (CRC) alone [1]
A segmental colectomy was significantly associated with an increased risk of metachronous colorectal cancer (MCC) (RR = 5.12; 95% confidence intervals (CI) 2.88–9.11; Fig. 2)
The relative risk of MCC after a segmental colectomy versus an extended colectomy was 8.56 and 3.04 in patients with a confirmed Lynch syndrome (LS) germline mutation and patients with LS diagnosis using the Amsterdam criteria respectively (Fig. 2)
Summary
In 2012, 694,000 deaths worldwide were attributed to colorectal cancer (CRC) alone [1]. Lynch syndrome (LS), the most common form of hereditary CRC, causes 3.1% of all CRC, and is associated with a high rate of either metachronous (MCC) or synchronous CRC [2]. LS is an autosomal dominantly inherited condition which occurs due to a germline mutation in one or more DNA mismatch repair genes (MMR) Due to highly penetrant germline mutations in MMR genes, the age of onset and risk of developing CRC differs significantly between sporadic CRC and LS patients. The risk of CRC in LS may be as high as 33–46% by the age of 70, compared to ~ 5.5% in the general population. If CRC is identified the mainstay of management is by surgical resection, either a segmental or extensive colectomy
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