Recently, there has been a trend to avoid relying on clinical indices for determining CD treatment due to the lack of their correlation with endoscopic and histologic measures of disease activity [15, 16]. According to the latest guidelines, the goal of CD treatment is histological evidence of mucosal healing, which is an objective indicator of the efficacy of CD drugs and is related to the clinical recurrence rate and the reduction of surgical rate [17]. However, there are no accepted endoscopic criteria for mucosal healing at present. It is now essential to define the best way to monitor disease activity. Attempts to correlate outcomes with radiological signs of CD have produced variable findings.
In this retrospective study, it was found that the radiologic findings of CTE correlated closely with CD activity. This is consistent with previous studies [18, 19]. However, the importance of two CTE signs, namely, bowel wall thickening, and mural hyperenhancement, is still controversial, because the normal collapsed intestinal wall itself is thicker than the dilated intestinal wall and has a higher mucosal enhancement value, leading to uncertainty in the results. Interestingly, a prior study quantifying bowel wall thickening and mural hyperenhancement by semi-automated computer software found that the two parameters were significantly correlated with CD activity [20], providing a reference for future research.
Our study found that, compared with mural hyperenhancement, mural stratification is likely to be a more valuable measure reflecting the activity of CD, especially when it is caused by edema [12]. It is worth noting that the specificity of mural stratification is very poor which can be seen in other types of intestinal inflammation such as ischemic bowel disease. However, as the patients in this study were clinically or pathologically confirmed CD patients, the poor specificity did not affect the results. In addition, the comb sign is another commonly recognized CTE sign reflecting CD activity. In a quantitative study of the comb sign [21], it was found that the comb sign score increased significantly in the CD group and predicted CD activity with an accuracy of up to 80% when the appropriate cut-off point was found. Besides, some studies suggest that patients with a typical comb sign may require more hospitalization and invasive treatment, and are more likely to have longitudinal ulcers and extensive organ damage [22], which further demonstrates the importance of the comb sign in evaluating CD condition and provides a reference for more active treatment. In addition, Colombel et al [23] considered that the increase of peri-intestinal fat density was a specific imaging sign of active-stage Crohn's disease, reflecting the inflammatory infiltration of peri-mesenteric fat mediated by mesenteric adipocytes. However, one of the CT signs included in the present study is peri-intestinal adipose fibrosis, although its specificity is very poor in relation to the present results. Nevertheless,the ROC curve analysis shows that it has a low diagnostic significance and, therefore, deserves proper attention.
To date, numerous biomarkers related to inflammatory activity have been described but these depended heavily on clinical or endoscopic assessment as references. There are few studies on the relationship between CT imaging findings and biochemical indicators. Our study found that CTE signs, such as mural stratification and the comb sign, are significantly correlated with inflammatory biochemical indicators. However, this view is controversial at present. Minordi et al showed that the comb sign and intestinal wall thickening were positively correlated with CRP [24] while in another quantitative study of the comb sign, it was considered that the comb sign is not related to CRP [21]. In addition, ESR is also considered to be a useful indicator for monitoring CD activity, but its role has not been fully defined. Some studies have suggested that the comb sign has a good correlation with ESR [24], but other studies have not confirmed these findings. Previous studies have suggested that both the comb sign and lymphadenopathy are correlated with the platelet count rather than fibrinogen. In addition, the platelet count has been reported to be related to CRP [25, 26]. As mentioned above, one-third of IBD patients have iron deficiency anemia which has been reported to be related to the platelet count. Controlling inflammation and improving anemia may reverse the trend of platelet increase, suggesting that the degree of anemia may be related to CD activity. Fecal calcium protein (FC) has been widely studied in IBD [27–29] and has proved to be a valuable predictor of disease relapse and recurrence. Susana and his team recently found that FC performed better than CRP in predicting endoscopic activity and was significantly correlated with the CTE findings [30].
Although previous studies have shown that the severity of endoscopic mucosal lesions is not significantly correlated with the CDAI and blood biochemical parameters, the importance of endoscopic mucosal healing is increasingly recognized [18] as this results in a better prognosis. The CD activity index under capsule endoscopy has been shown in numerous studies to be correlated with intestinal wall thickening, mucosal enhancement, and parenteral manifestations [31]. Interestingly, the current study suggests that only intestinal wall thickening is associated with endoscopic results. All 123 patients successfully completed CT enterography, indicating that this examination can make up for the limitations of enteroscopy and allows improved completion and tolerance. However, the results of this study suggest that CTE is less sensitive in the diagnosis of intestinal stenosis. This may be related to the characteristics of the CT tomographic scan. The thinnest slice of the 64-slice spiral CT scan used in our hospital is 5 mm, while the distribution of intestinal stenosis is limited, and the sensitivity of CTE to intestinal peristalsis is poor, which may result in a missed diagnosis of the narrow segment during the scanning process.
However, one complication of the use of CTE to monitor CD is that it may lead to radiation damage. Fortunately, there are several strategies available to reduce radiation exposure without affecting diagnostic accuracy. In this study, the sample size was relatively small and further studies with a larger sample size should be conducted to confirm the findings. Another limitation is that we have only utilized CTE to evaluate CD activity. Magnetic resonance enterography (MRE) has emerged as a nonionizing alternative to CTE and we intend to compare the differences between CTE and MRE in assessing CD activity.
In conclusion, we have found that, while CTE, endoscopy, and biochemical markers have limitations, all are nevertheless good markers for the evaluation of CD activity. Only when these tools are used comprehensively and in combination, can we judge CD activity more accurately to guide future treatment.