Page 162 - Read Online

Singh-Ranger. Mini-invasive Surg 2018;2:39 I http://dx.doi.org/10.20517/2574-1225.2018.23 Page 3 of 5

Table 2. Long term follow-up data from randomised controlled trials
Study Design Duration Number of patients Colon cancer P value GI bleed/
(years) hazard ratio peptic ulcer
Cook NR [13] Post RCT observational 10 33,682 0.80 overall 0.021
follow-up (84.5% of original (0.73 proximal (0.022)
participants) tumors)
Rothwell PM [14] Post RCT data follow up 20 17,164 0.58 rectal < 0.01 Not reported
(5 trials) (0.35 proximal
tumors)

of effect to prevent cancer - the phosphatidylinositol 3-kinase-related pathway , “induced-senescence” by
[20]
interference of the sirtuin1 metabolic pathway , and clotting factor acetylation .
[22]
[21]
The aforementioned provides strong support for the case for using aspirin to prevent rectal cancer, but there
are serious potential problems that need consideration.

Firstly, there is the small but dose-dependent risk of haemorrhagic stroke and gastrointestinal bleeding .
[23]
This might be deemed relatively acceptable in patients already on aspirin for ischaemic heart disease, but
could be a serious issue in younger and otherwise healthy patients being asked to take the medication for
chemoprevention long term - and has been noted as a risk in randomised controlled trials [Table 2].

Secondly, there are known to be cases where aspirin does not “work”, even when taken regularly. This
phenomenon of persistent platelet activation has long been recognised as a cause of persistent strokes/angina
or myocardial infarction in around one quarter of compliant patients taking therapeutic dose aspirin [24,25] .

The reasons for “aspirin resistance” are variable, probably involving supranormal rates of platelet turnover
in some patients, suboptimal levels of actual agent entering the circulation, and possibly different pathways
for thromboxane A2 synthesis and abnormal variants of COX . Aspirin bioavailability can vary from 20%-
[26]
40% and differs markedly depending on route of administration, and formulation - for example, soluble
aspirin has better bioavailability than tablet form [27,28] , and some co-administered agents and lifestyle factors
can have profound effects on bioavailability [29,30] .

Tolerance occurs over time, and is not completely responsive to increased dosing . Studies of aspirin use
[31]
in cardiovascular disease indicate compliance and non-adherence are significant problems - associated
with age, co-morbidity and polypharmacy - essentially in groups who would probably benefit from aspirin
most . Our own preliminary work suggests that although side effect reporting is low (< 6%), only a quarter
[32]
of patients are fully compliant with treatment , and underuse may be associated with female gender, the
[33]
presence of comorbidities and polypharmacy.

CONCLUSION
In summary, regular low dose aspirin would seem to be an ideal candidate for low risk prevention of
rectal cancer based on the most recent research, however, concerns about side effects, underutilisation and
compliance may indicate a selective role only. In the prevention of ischaemic heart disease, aspirin use is
restricted to specific subgroups, and not recommended for general use in primary prevention due to the
incidence of the aforementioned side effects in otherwise healthy patients. One potential target group could
be those at higher risk of a heart attack or stroke, and who do not have risk factors for stomach bleeding,
with the aim of preventing both cardiovascular disease and colorectal cancer. Concerns regarding adverse
effects might also limit use of aspirin in those groups at particular risk of colorectal cancer, such as patients
with hereditary polyposis or Lynch syndrome, and more work is required to clarify the risk - benefit ratio
in these high risk groups.