64
There are several patient-related factors that have had discordant associations
resulting in inconclusive interpretation. Patient age at onset of disease has been eval-
uated in several studies with conflicting results. It is possible that positive associa-
tion with disease recurrence could be related to increased duration of follow-up and
thus likelihood of recurrence over time rather than a true causative relationship [ 24 ].
Similar to patient age at disease onset, shorter duration of disease prior to surgi-
cal resection may be a factor influencing POR, though this is still in question due to
conflicting results. Varying definitions of “short duration” in individual studies have
hampered pooling and comparative studies. One could imagine that a shorter dura-
tion of disease prior to requiring surgical resection may reflect a more aggressive
disease phenotype, thus placing the patient at higher risk of POR.
A family history of inflammatory bowel disease was demonstrated by Unkart
et al. to convey a 2.2-fold increased risk of repeat surgery in 176 postoperative CD
patients though this finding has not been replicated [ 25 ].
There have also been studies evaluating genetic risk factors for POR. Fowler
et al. examined 194 CD patients who underwent bowel resection with 69 patients
requiring repeat resection. Patients who were homozygous for SMAD3 risk allele
were independently associated with increased risk of repeat surgery (hazard ratio
[HR] 4.04, p = 0.001) [ 26 ]. Similarly, Germain et al. in a study of 200 genetic vari-
ants demonstrated that patients with CARD8 risk allele homozygosity carried a
sevenfold increased risk of surgical recurrence compared to non-risk allele carriers
(OR 7.56, 95% CI 1.13–50.37) [ 27 ]. Several studies have examined the role of
NOD2 (also known as CARD15), which has been previously associated with ileal
and stricturing disease. These studies revealed conflicting results. A meta-analysis
of six cohort studies comprising 1003 CD patients examining the risk of NOD2
polymorphisms suggested an increased risk of further surgical resection but failed
Table 5.3 Factors associated
with development of
postoperative Crohn’s disease
recurrence
Strength of risk
Patient
Smoking ++
Age at onset ~
Disease duration prior to surgery ~
Family history +/~
Disease
Penetrating/perforating ++
Prior CD surgery +++
Anti-TNF prior to surgery +
Surgery/pathology
Anastomosis type ~
Myenteric plexitis +
Active inflammation +
Granulomas present ~
+ Weak
++ Moderate
+++ Strong
~ Equivocal or unknownB.H. Click and M. Regueiro