Dra. Ana Echarri Piudo
Complejo Hospitalario Universitario de Ferrol
FACTORS TO CONSIDER WHEN SELECTING AN IMAGING TEST
In the era of biological treatments, the diagnosis and follow-up of inflammatory bowel disease continues to be a challenge. It is important to combine the most suitable technique, within the current arsenal of endoscopic and radiologic tests available, with clinical symptoms and analytical abnormalities at the time and within the most suitable phenotype-progression context.
It is important to determine the role that biological markers for inflammation (C-reactive protein [CRP], calprotectin) can play within this context, and to decide when its use is adequate, thus avoiding more aggressive tests with difficult accessibility or higher costs, while keeping in mind when these tests cannot be replaced by any other marker.
When approaching the disease, special attention must be paid to the onset of the disease and it is important, at the time of diagnosis, to have an in-depth assessment of the disease by analysing the location, extension, and severity of the lesions, factors that contribute to the initial prognostic assessment and that are determinants when it comes to proposing the most adequate therapeutic approach.
During disease follow-up, it is important to keep in mind that the inflammatory abnormality of the mucosa can persist with higher or lower symptomatic expression, and it can progress towards irreversible forms with associated bowel disease. In this regard, asymptomatic phenotypes may exist until the development of progressed forms (stenosing pattern) (Fig. 1) or phenotypes associated with a more rapid progression (stenosing/penetrating) (Fig. 2 and Table I).
Therefore, it seems to be a logical option to apply the most adequate treatment for each situation and conduct follow-up or closer monitoring of the forms associated with a higher progressive aggressiveness, especially in the initial or inflammatory stages of the disease, in order to delay or stop this progression1-6 (Fig. 3, Fig. 4, Video 1).
Within this context, the concept of (total or partial) mucosal healing must also be included, both in Crohn’s disease (CD) as well as in ulcerative colitis (UC), as a factor for a good short- and long-term progression prognosis. Mucosal healing is associated with a lower rate of surgeries and hospitalisations, a longer clinical remission time and a lower possibility of developing neoplasia in UC7-12. Although in current clinical practice it is not strictly defined as a therapeutic objective, certain situations must be recognised in which the evaluation of the mucosa is established as highly advisable.
ADVANTAGES AND DISADVANTAGES OF ENDOSCOPIC TESTS IN ASSESSING THE SMALL INTESTINE
Capsule endoscopy (CE) is the most sensitive test for detecting mucosal lesions in the small intestine (SI) in a non-stenosing CD patient, although its specificity is low. The greatest limitation of the test is the inability to biopsy and the inability to properly evaluate transmural lesions. Due to these limitations and characteristics, it cannot generally be considered as a first-line technique in the diagnosis and follow-up of CD13-15.
In patients with suspected CD diagnosis with no obstructive symptoms and with a negative ileocolonoscopy analysis, given the high sensitivity of the test, CE could be considered an initial diagnostic test. In patients with inflammatory mucosal impairment that predominantly affects the proximal intestine and who experience the aforementioned clinical characteristics, CE can be more yielding than cross-sectional radiologic techniques, although a prior radiological test is generally recommended, with MR enterography being the technique of choice, especially in young patients, since it is radiation-free.
Therefore, with suspected CD, the CE test would be indicated in patients with negative endoscopic tests and sectional imaging techniques, considering that a normal CE presents a high negative predictive value for CD of the SI12,16.
For patients with established CD, as previously mentioned, CE analysis is the most sensitive test for identifying mucosal lesions, although the clinical relevance of this finding is not well-determined. One of the primary disadvantages of CE is its low specificity, which entails a risk of over-diagnosis of active disease that oftentimes entails an unnecessary therapeutic escalation. Therefore, the role of CE in patients diagnosed with CD should be focused on patients with unexplained symptoms, unjustified ferropenia or gastrointestinal bleeding of a dark origin, when the rest of the tests performed are inconclusive. A sectional radiologic technique must always precede the CE test in order to identify stenosis and extraluminal disease and to analyse the anatomic distribution of the lesions12-16 (Fig. 5).
In relation to other indications in which a CE test could be proposed, the following must be considered:
• As a postoperative recurrence evaluation analysis, it should only be considered in cases in which colonoscopy cannot be performed or does not allow access to the neoileum.
• Its potential role in evaluating mucosal healing after therapeutic treatment remains to be defined. Presently, it cannot be considered an indication.
• The use of EC in undetermined inflammatory bowel disease, namely, in situations in which we have not been able to appropriately classify the disease using conventional techniques, can be useful in identifying mucosal lesions in the SI, which would make the diagnosis compatible with CD. However, we must consider that a negative CE does not exclude a future diagnosis of CD.
Enteroscopy in IBD has limited uses, related to the very technical process, since it is a tedious, invasive procedure. Generally, indications for enteroscopy as a diagnostic technique could superpose the indications for CE, with the advantage that enteroscopy enables the biopsy of suspected lesions or the treatment of lesions12,16.
In fact, CE tests and enteroscopy show a similar accuracy for diagnosing CD (60% vs 57%), as shown in a recent meta-analysis17. Therefore, diagnostic testing by endoscopy should only be indicated when biopsy is necessary for suspected lesions, and it is always advisable to perform a cross-sectional radiologic test beforehand (Video 2, Fig. 6).
The double-balloon enteroscopy technique and MR enterography can be considered supplemental techniques, since they assess various aspects of the disease and provide additional information18. Thus, enteroscopy would provide the possibility of analysing superficial lesions that require confirmation via directed biopsies, and MR enterography would assess extraluminal impairment (Table II).
In patients with suspected disease of the SI and in the study of initial radiologic and endoscopic tests (gastroscopy with duodenal biopsies and ileocolonoscopy with negative biopsies and negative sectional radiologic tests) a noninvasive CE test is preferred. CD will locate lesions and determine, based on the findings, the need for enteroscopy and the entry point.
However, if stenosis is present in the imaging tests, enteroscopy is the most suitable technique12,16 (Fig. 7).
If CD diagnosis has been established, the study of the extension of the disease can be done by sectional radiologic imaging tests, preferably MR enterography in young patients, which limit the use of enteroscopy to its therapeutic aspect: stenosis dilatation and removal of retained CE, taking into consideration that the frequency of complications is 10 times higher than in conventional endoscopy18,19.
ENDOSCOPIC MONITORING AND FOLLOW-UP
Although the association between mucosal healing and better control of the disease progression is clear7-12, there are factors in regards to this topic that remain unclear, such as the present lack of a validated definition for mucosal healing or the cut-off point for endoscopic improvement, which can be associated with a better progressive course without the need for complete mucosal healing. Nor do we currently have knowledge about the progressive behaviour of various mucosal lesions visualised via endoscopy12,16,21.
Therefore, in general, endoscopic control is not routinely indicated for patients in remission, given the invasiveness of the test and the lack of scientific evidence that justifies this approach12.
There is a good correlation between the faecal activity markers of the disease, especially calprotectin, and the presence of endoscopic inflammatory activity, especially in cases of colic or ileocolic impairment. Monitoring the disease by measuring calprotectin would allow the degree of mucosal healing to be evaluated in a noninvasive manner and would help in the early detection of relapses or recurrences of the disease22-24.
In selecting patient groups, calprotectin monitoring allows patients with probable inflammatory mucosal abnormalities to be distinguished and allows the need for the performance of confirmatory endoscopic or radiologic tests to be assessed25. Depending on each case and on an individual basis, the early detection of inflammatory activity could bring about a more adjusted follow-up approach or a change in the therapeutic approach.
Endoscopic re-evaluation must be considered in cases of recurrent disease, refractoriness, the appearance of new symptoms or when considering a change in the treatment approach (introducing biological treatment, discontinuing treatment) or a surgical option12. Generally, endoscopic re-evaluation is advised when there are doubts about the control of the disease or suspicions about the progression of the disease25.
Other circumstances in which endoscopic monitoring is necessary in IBD:
• Postoperative recurrence assessment: ileocolonoscopy is the benchmark test for postoperative recurrence assessment (in case of resection of the SI, CE can be assessed as an alternative). Generally, endoscopic evaluation is recommended at 6–12 months post-surgery. The frequency at which subsequent endoscopic explorations are performed will depend on the findings from the first evaluation and the progressive course of the evaluation. In the case of patients with a special risk for postoperative recurrence, the calprotectin test can be useful at 3 months after surgery12,24,26,27.
• Endoscopic management of a stenosis associated with [IBD]: when taking a therapeutic approach to a stenosis associated with IBD, it is important to know various aspects such as location, number, diameter or activity (Fig. 8). Generally, a stenosis must be evaluated with supplemental techniques (for example, endoscopy and MR enterography) (Video 3 and Video 4) in order to analyse, in addition to the previous data, its extension in the case of a non-passable stenosis, the presence of prestenotic dilatation and inflammatory stenosis activity, which are evaluated by measuring variables observed in the various radiological techniques (wall thickness, contrast intensification, oedema, etc.) or the presence of penetrating complications associated with it (fistula, abscess). Thus, in the case of active inflammatory stenosis (clinical, radiological and biological signs), optimised medical treatment will constitute the first-line therapeutic option, while in symptomatic fibrotic stenosis surgical treatment or endoscopic dilatation should be chosen (Video 5 and Video 6).
• Endoscopic monitoring of dysplasia.
ADVANTAGES AND DISADVANTAGES OF RADIOLOGIC TESTS
For the proper evaluation of inflammatory bowel disease, especially in the case of CD with SI impairment, the use of sectional slicing radiological techniques is essential, since they allow for assessment of the extension of the disease and the detection of complications such as the development of stenosis or the appearance of penetrating lesions such as fistulae or abscesses25,28.
In general, the use of sectional slicing radiologic techniques would be indicated for:
• Assessment of the disease during diagnosis. In general, an SI assessment test must be performed in all CD patients12,28.
– Especially in cases of SI impairment assessed via ileoscopy in order to detect, analyse the inflammatory activity and classify the disease.
– In cases of suspected SI impairment with no evidence of lesions in the ileocolonscopy (18%).
– In the case of incomplete endoscopies due to the presence of stenosis, adherences or technical difficulties.
– In the assessment of postoperative recurrence in the event colonoscopy is not valid for diagnosis29,30.
• The analysis and differentiation between inflammatory and fibrotic stenosis, as we have mentioned previously, is a key point in the therapeutic decision. Sectional slicing imaging techniques can be extremely helpful, since various measuring indices of inflammatory activity have been designed that help calibrate the inflammatory activity in a given stenosis by opting for the most therapeutic option31-34. Thus, patients with significant inflammatory activity can benefit from medical treatment, while, for those with a predominance of fibrosis and little inflammatory activity, a surgical approach or endoscopic dilatation would be the most appropriate.
• Follow-up of disease of the SI (can be asymptomatic)28:
– Evaluate responses to or changes of treatment following suspicion of poorly controlled disease.
– Assess the intestinal damage (prognostic implications) and monitor the disease progression (Fig. 9).
• Diagnosis of penetrating disease, abscesses-fistulae.
• In case of UC with atypical impairment or undetermined colitis, sectional slicing radiologic tests can evaluate SI impairment and help clarify the diagnosis.
FACTORS TO CONSIDER IN SELECTING A RADIOLOGIC TECHNIQUE
• Technique of choice: the most important factors when deciding between the various existing sectional slicing radiologic tests (ultrasound, CT or MR enterography) are the experience and accessibility of each hospital centre or each unit. It is best that they be performed by radiologists specialised in IBD.
• Supplemental nature of radiologic and endoscopic techniques: radiologic techniques used in assessing IBD are supplemental to endoscopic assessment and essential in the initial diagnosis of the disease and in follow-up. By combining endoscopic and radiologic findings, we can obtain detailed information on the presence and progression of the intestinal involvement, as well as extramural manifestations of the disease28.
• Ultrasound. Advantages and disadvantages: ultrasound is a well-tolerated, ionising radiation-free technique. It is especially indicated for the analysis of the terminal ileum and the colon. The limitations for its use are obesity or a significant amount of intestinal gas. The jejunum, proximal ileum, transverse colon and rectum are more difficult to evaluate. It is considered a useful technique for the radiologic drainage of abscesses28,35-37 (Table III).
• Localisation of the disease and technique: when analysing the terminal ileum, any of the three options (ultrasound, computed tomography and magnetic resonance) constitutes a valid option of similar diagnostic specificity, while, in the rest of the SI, ultrasound has a more limited role28.
• Computed tomography enterography. Advantages and disadvantages: exploration via computed tomography to assess the SI and colon requires luminal distension (enteric contrasts) and I.V. contrast injection. It is considered a useful technique for the radiologic drainage of abscesses. Its greatest limitation is in relation to radiation exposure and its highest advantage is its accessibility and low time-consumption during performance, as well as the patient’s better tolerability to the tests (they require less time and less pauses in breath) and the ease of its interpretation28,38-40 (Table IV).
• Magnetic resonance enterography. Advantages and disadvantages: the exploration of the SI and colon via magnetic resonance requires luminal distension and the injection of antiperistaltic medication and I.V. contrast. Its best advantage is that it is ionising radiation-free, which makes it the technique of choice in children and youth28,40.
• Pelvic resonance is the technique of choice for analysing perianal disease41,42.
• Stenosis and penetrating complications. Technique of choice: ultrasound and CT or magnetic resonance enterography have high sensitivity and specificity for diagnosing stenoses that affect the SI, and they can help to determine and differentiate the degree of inflammation or fibrosis, as well as evaluate the presence of penetrating complications (abscesses and fistulae), although ultrasound is the least sensitive method for detecting intra-abdominal fistulae28,40,42.
• Other significant details:
– In cases of a severe outbreak of UC, plain abdominal x-ray continues to be a suitable first test for detecting toxic megacolon defined as a dilated transverse colon >5.5 cm (Fig. 10).
– In select cases with suspected complications (perforation, abscess, thrombosis, ischemia) that may require emergency surgery, the test of choice is computed tomography42 (Fig. 11) (Case 6).
– Virtual colonoscopy or CT colonoscopy can be useful for detecting complications or proposing a therapeutic approach in patients in which colonoscopy cannot be performed.
– Sectional imaging techniques, particularly magnetic resonance enterography, can be used in monitoring the therapeutic response. It should be noted that there is a time delay when comparing it to endoscopic or clinical changes25,28,43.
– Tagged white blood cell scan can be considered as an alternative for specific situations (they involve less radiation exposure than other traditional tests, and it can be suitable for children if other more suitable sectional techniques, such as MRI, are not available).
– Intestinal transit or analysis via enteroclysis are generally easy to access, with their primary disadvantage being radiological exposure and the inability to perform extramural evaluation, but they can be useful if access to other tests is limited (Fig. 12).
– Various intestinal damage assessment instruments are being developed and are currently in the validation process, such as the Lémman Index, which measures inflammatory, stenosing and penetrating changes as a whole, as well as permanent damage or intestinal loss after surgery. This index would allow to measure cumulative intestinal damage at a specific developmental time, measure its progression, and provide a classification of patients based on the risk of progression by comparing various treatment strategies28,44.
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