ReviewIs right-sided colon cancer different to left-sided colorectal cancer? – A systematic review
Introduction
In the current era of personalized medicine, colorectal cancer (CRC) is no longer regarded as a single entity. Colorectal cancer research has concentrated on providing more effective treatment, resulting in advancement in the knowledge of the genetic and molecular mechanism of carcinogenesis.
Bufill et al. started describing CRC depending on the anatomical site.1 This was an attempt to sub-classify CRC as clinical data showed disparities in incidence and outcome between right-sided and left-sided colon cancer. Subsequent research has described the distinct differences in epidemiology, pathogenesis, genetic and epigenetic alterations, molecular pathways and outcome depending on the anatomical site of tumor. Currently, there is a general consensus that anatomical site is an important factor in management of CRC.
In this review, we aim to present the recent findings and discuss the implications for future research in CRC. For the purposes of this review, proximal or right-sided colon cancer (RCC) will consist of cancers of the caecum, ascending and transverse colon up to the splenic flexure, and distal or left-sided colorectal cancer (LCRC) will consist of cancers of the descending and sigmoid colon and rectum, unless specified.
We performed a systematic review with reference to preferred reporting items for systematic reviews and meta-analysis (PRISMA).2 We identified relevant articles by searching EMBASE, MEDLINE, and Pubmed using a search strategy to identify reports with a combination of controlled vocabulary and text words related to ‘colon’ and ‘colorectum’ (neoplasia, carcinoma, tumor, metastasis, malignancy), and to ‘site’ or ‘subsite’. Searches and cross-references were carried out using a ‘similar articles’ function and hand searches of articles identified. We included all adult human studies in English, published between September 1947 and January 2014. We identified all journal articles that assessed colorectal cancer classification by site in relation to prevalence, presentation, genetic, molecular aspects, immunology, environmental factors, and outcomes (long-term survival and oncological outcome). We did not include conference abstracts due to the insufficient data provided. We also manually explored the reference lists of the included studies for additional supporting articles.
Data were extracted by three independent reviewers (GHL, GM, AA). When recent meta-analyses or systematic reviews were identified, the included studies were not reported individually. Meta-analyses were prioritized, when available. To limit the number of references, the most relevant observational studies were selected. Studies discussing pathophysiological mechanisms were assessed in a narrative way, aiming to balance the arguments for and against different genetic, molecular and immunological hypotheses.
Section snippets
Results
From 394 initial citations, we included 6 meta-analyses, 12 reviews, 62 observational studies and 7 additional supporting articles (see Fig. 1).
Conclusion
As is evident from recent epidemiological studies, the prevalence of RCC is on the rise compared to LCRC, and we have explored various factors leading to differences in presentation and clinical outcome in CRC depending on its subsite (see Fig. 3). This could be attributed to the differences in anatomical, acquired and inherited factors leading to different molecular pathways in the pathogenesis of CRC.
We have also mentioned the complexities and potential challenges in management of CRC. It is
Author's contribution
GHL – conception, literature search and drafted article.
GM/AA – literature search and drafted article on epidemiology section.
HOA/DBO – literature search and drafted article on immunology.
SKC – critically reviewed manuscript and final approval of the version to be published.
Conflict of interest
Authors declare no conflict of interest.
Acknowledgment
HOA was supported by a grant from the Association for International Cancer Research (AICR), (12-0234) Scotland.
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