Lymph nodes, ageing and colorectal cancer

Abstract

Worldwide, each year, more than 1.3 million people are diagnosed with colorectal cancer. The incidence of the disease in New Zealand is among the highest in the world, where it is also the second leading cause of cancer death. The incidence of colorectal cancer also increases with advancing age. Lymph nodes play a critical role in the staging, treatment, and prognosis of colorectal cancer. Recently, the number of lymph nodes in a surgical specimen (lymph node yield [LNY]) has been shown to be an independent prognostic factor in colorectal cancer, with a higher LNY associated with a better prognosis. Given the importance of lymph nodes and the patient’s age in colorectal cancer, the aims of this thesis were to investigate human mesocolic lymph node numbers and morphology in individuals with no known colorectal disease, explore age-related changes in lymph node histoarchitecture, and examine more closely the effects of age and site on LNY in patients with colorectal cancer. A systematic review was initially undertaken to determine what is currently known about the effect of advancing age on normal lymph node number and morphology. Available evidence suggests a decrease in lymph node number and morphologic degeneration in older age groups. A detailed systematic anatomical study evaluated the number and size of lymph nodes in the ascending and sigmoid mesocolons from 10 elderly cadavers with no evidence of colorectal disease. There was considerable individual variability in the total number of mesocolic lymph nodes. More than 90% of lymph nodes were less than 5mm in length and sigmoid mesocolic nodes were smaller than ascending mesocolic nodes. Fatty replacement was seen in almost one-third of nodes. The relationship between age and lymph node histoarchitecture was investigated in a semi-quantitative histological study of mesocolic and paratracheal nodes harvested from 20 deceased adults with no colorectal disease. Comparison of individuals younger and older than 70 years showed no apparent differences in the proportional area of the lymph node occupied by T and B cells. However, there was a decline in lymph node sinus macrophages with advancing age. Finally, the relationship between LNY and other clinico-pathological variables (including age) in colorectal cancer was explored in two patient cohorts: a local group (n=824) and a national database (n=14,646). Patient’s age at the time of operation had the strongest impact on LNY amongst the clinico-pathological variables examined, with a decline of one lymph node for every six-year increment in patient’s age after adjusting for other clinico-pathological variables. Furthermore, overall survival in stage I-III colorectal cancer increased with higher LNY. In this thesis, evidence was gathered at histological, anatomical, and population level to support the concept of lymph node senescence. This may be an important but hitherto neglected factor in colorectal cancer. Further research is required to confirm or refute these findings, determine whether this relationship exists with other cancers, and to explore the functional correlates of lymph node senescence.