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r John Burke, Specialist Registrar in Colorectal
Surgery, St Vincent's University Hospital,
Dublin, who has carried out groundbreaking
research on the pathophysiology of stricturing
Crohn's disease, delivered the 36th Millin
Lecture, entitled "From cell signalling to
individualised patient care: lessons learned in the study of Crohn's
disease", which detailed advances in the study and treatment of the
disease. This article provides an overview of some of the key areas
addressed in Dr Burke's lecture.
Crohn's disease (CD), a disease predominantly of the terminal ileum,
affecting mainly young adults, is characterised by a chronic cicatrising
The evolution of medical therapy for the disease can be tracked
through a number of landmark phases beginning with the use of
Cortisone in 1951 followed by Azothioprine in 1971 and, then, in the
1980s the anti-inflammatory drug, 5-aminosalicylic acid (5-ASA).
Since the mid-90s, the management of CD has been revolutionised
by the introduction of biologic medications. The first biologic
medication licensed for use in the Republic of Ireland in 1999 was
infliximab, a mouse-human chimeric antibody to tumour necrosis
factor-alpha (TNFa), which is acknowledged as a very efficacious
therapy for refractory luminal and fistulising CD.
A study of national trends in intestinal resection for CD, following
the introduction of biologic medications, showed that, during the
period 2000-2010, there were 11,796 patient admissions with a
principal diagnosis of CD. Disappointingly in the decade following
the introduction of biologic medications in the Republic of Ireland,
the rate of intestinal resection for CD has not significantly reduced.
This is primarily due to stricture development.
There has been a significant deepening of knowledge of the
pathobiology of stricture formation, including the detailed mapping
of stricture anatomy, an enhanced understanding of the role of
cytokines and abnormal fibroblasts, and the influence of impaired
epithelial barriers. There have also been new findings on medications
impact structure development, such as corticosteroids and
Simvastatin by modulating TGF-a1 and Neutrophil migration.
Alongside these developments, there has been an increase in
multidisciplinary team (MDT) discussion of colorectal patients and
knowledge sharing (a study shows that 82.5 per cent of curative
protectomies were discussed at MDT in 2007, rising to 100 per cent
in 2010) and innovative advances in adjuvant therapy for CD.
The rapid evolution of individualised patient care is driving a number
of treatment approaches in relation to nutrition, tailoring treatment to
the patient, recurrence prevention and outcome predictions based on
genomic studies. For instance, the importance of nutrition has been
underlined by a multicentre study of 524 patients which has shown
that pre-operative hypoalbuminaemia increases surgical site infection
risk 5.7-fold.
With regard to managing recurrence, specific patient-related
behaviour such as smoking, as well as factors such as gender and
whether or not the patient has had an appendectomy, all influence the
probability of recurrence-free survival. In addition, adjuvant therapy
after resection using 5-ASA analogues, Azothioprine or Infliximab,
tailored to the patients' individual risk factors has been shown to
reduce recurrence.
A growing range of methodologies have the potential to significantly
increase accuracy in the prediction of patient outcomes. Radiological
assessment of stenosis (fibrotic and inflammatory) for CD are among
the increasing array of predictive technologies available, but must
be weighed against the risks of radiation exposure. A promising
focus of study is the single nucleotide polymorphism (SNP) single
base changes in a DNA sequence that may cause related alteration
in protein manufacture. The identification of links with CTGF gene
mutation and behaviour could open up genomic approaches that will
greatly assist in the prediction of patient outcomes in the future.
For further background see also:
Burke John P et al. International Journal of Colorectal Disease 2013,
28 (10): 1401-1406
The 37th Millin Lecture will be delivered during the Millin
Symposium in November 2014. Fellows of the College are
invited to nominate candidates.
Completed application forms together with relevant
documentation must be received before Friday, May 2,
2014. Criteria and application form can be downloaded at:
Dr John Burke.
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