Right and Left sided colon (Large Gut) cancers – Are they different?
Colon (large gut) is the last six feet of intestine, wider than small intestine and relatively fixed in position
as compared to small gut. It is responsible for bile salt reabsorption, water re-absorption and solidifying the food residue that needs to go as a waste.
Colon cancer is the third highest cause of cancer worldwide. Colon cancer has a high mortality rate especially when detected in advanced stages. The pathogenesis of colon cancers is unique; the anatomical location of the tumor plays an important role in the management
Colorectal cancer originates from the inner lining of the colon, and it may develop either on the right side or the left side of the colon.
Right sided colon cancer has been defined by the American Society of Cancer as cancer of the cecum (where appendix is attached) and the ascending colon up to the bend below the liver. In contrast, left-sided colon cancer comprises cancer of the bend below spleen and cancer in regions distal to the bend including the rectum.
The transverse (horizontal) colon connects the left and right sides and on average is shorter than the right and left sides of the colon. Cancer of the transverse colon is extremely rare.
The right and left sided large gut cancers, differ from each other since inception (from the embryonic stage).
The right side of the colon arises from the middle part of gut, and the left side arises from the last part of gut called hindgut.
The transverse colon, on the other hand, is composed of parts of both structures, although it is believed that the midgut portion may be higher than from the hindgut, although this can differ among individuals.
Depending on the position, colon cancers behave differently in terms of disease progression and overall survival. The difference between these tumours can be attributed to anatomical and developmental origin, or distinct carcinogenic factors such as difference in gut microbiome on the two sides of the colon, or exposure to distinct nutrients and bile acids, or a combination of both.
Observations made over the past 5 to 10 years have concluded that flat polyps are more likely to occur on the right side than on the left side. Further, right-sided tumours are more likely to develop in patients who have a genetic predisposition to colorectal cancer, including those with Lynch syndrome (familial cancer group) or microsatellite instability.
Right-sided colon cancers tend to be diagnosed much later than left-sided colon cancers. This is because right-sided colon cancers will give rise to symptoms only when they are relatively advanced. The stool is still liquid on the right side of the colon, and the typical bowel symptoms of pain, cramps, or blockage rarely occur in the early stages. Sometimes many years go by for these to be discovered.
Early studies noted differences in outcomes in survival and prognosis of the two sides of colon cancers. It was found that survival was slightly better in patients with left sided tumours when compared to patients with right sided tumours. Therapy responses are also totally different between these tumours.
Left-sided colorectal cancer patients benefit more from adjuvant chemotherapies such as 5-fluorouracil – based regimes and targeted therapies such as anti- epidermal growth factor receptor therapy,
and have a better prognosis.
In contrast, right-sided colorectal cancer patients do not respond well to conventional chemotherapies, but demonstrate more promising results with immunotherapy. Therefore, it is essential to assess right-sided and left-sided tumours as separate entities, and design the therapy regime keeping in mind the differences between these tumours.