Dr. Vicente Pons Beltrán
Hospital Universitari i Politècnic La Fe. Valencia
TÉCNICA DE DILATACIÓN POR ENTEROSCOPIA: MATERIAL Y MÉTODOS
Enteroscopy plays an important and preferred therapeutic role in inflammatory bowel disease (IBD) and particularly in Crohn’s disease (CD). As a diagnostic tool, it has been shown to be effective where conventional endoscopy (ileocolonoscopy) has failed, and when it is necessary to establish the extent of the disease or the presence of recurrence in cases where capsule endoscopy is contraindicated due to risk of impaction. It is also useful in order to extract foreign bodies, like the endoscopic capsule when it remains trapped due to stenosis of the lumen.
Stenosis may occur in the course of both CD and ulcerative colitis (UC), as a result of either inflammation or fibrosis; however, it is more common in CD due to the associated transmural involvement. Fibrosis appears to be the result of a chronic inflammatory reaction and, although its pathogenesis is unknown, it is known that neutrophils, lymphocytes, macrophages and fibroblasts play a significant role in its genesis. Thickening of the intestinal wall and narrowing of the lumen are a consequence of these alterations, which can lead to dysmotility and varying degrees of obstruction. This results in a clinical picture characterised by abdominal pain, early satiety, anorexia, diarrhoea or constipation, bacterial overgrowth and in some cases, bowel obstruction requiring a likely urgent mechanical solution (surgical or endoscopic).
Although little epidemiological data is available to provide a reliable estimate of the prevalence of this complication in CD, it is known that up to 30% of patients will develop stenosis in the first 10 years of disease1.
Stenoses in IBD can be either fibrotic or inflammatory, although they most likely have a mixed component. It is therefore essential to exhaust all medical treatment options in order to minimise the inflammatory component as much as possible before considering an endoscopic procedure, an approach that can sometimes suffice to improve the stenosis and thus resolve the clinical picture.
CD exhibits different behaviours based on three well-established patterns. In 80% of patients, the disease begins with an inflammatory pattern, but this behaviour changes over time, so that 20 years after diagnosis, 88% of patients show a pervasive or stenotic pattern, and only a minority continues to exhibit inflammatory disease. Until recently, most of these required surgical treatment with bowel resection, but this approach is changing with new biological treatments and other therapeutic options that can delay surgery or even render it unnecessary.
In IBD, stenosis can occur in any part of the digestive tract, but fortunately, it is more common in the terminal ileum, at an ileocolonic anastomosis or even in the colon (Fig. 1, Fig. 2, Fig. 3). This facilitates their endoscopic management, as these stenoses are accessible by conventional endoscopy (ileocolonoscopy). In UC, the appearance of stenosis is far less common and, when encountered, it is mandatory to rule out a neoplastic aetiology, as the likelihood of it being a malignant lesion is 25%, versus only 7% in CD.
Although stenoses are often silent, when there are associated symptoms that fail to respond to medical treatment, one should consider a mechanical solution, whether surgical (strictureplasty or narrowed segment resection) or endoscopic. While surgical treatment has proven effective in resolving stenosis, it is not a definitive solution: the rate of recurrence of stenosis is high (40–50% at 10 years), and repeated recourse to surgery may result in short bowel syndrome2. Endoscopic dilation is an effective procedure that is less invasive than surgery, although in available studies, long-term follow-up is limited and success rates are variable depending on the series (44–76%)3-5.
Since Yamamoto et al. presented their first experiences with double balloon enteroscopy (DBE), in 20036, there have been substantial changes in terms of access to the small intestine, which have allowed endoscopists to have relatively easy access to the entire intestine for both diagnostic and therapeutic purposes, enabling the dilation of stenoses located anywhere in the gastrointestinal tract. In these patients, stenoses must first be located and characterised by imaging tests (intestinal transit, computerised tomography [CT] enterography, magnetic resonance [MR] enterography). Depending on their location, the decision is then made to perform either antegrade or retrograde enteroscopy to proceed to treatment. Double- and then single-balloon enteroscopy have made it possible to dilate stenoses at any level of the small intestine, remove foreign bodies (retained endoscopic capsule), administer topical treatments, and even insert prostheses. New techniques have since been developed such as spiral enteroscopy, whose effectiveness appears similar to that of balloon endoscopy; however, its use is less widespread7. Although we will not go into this approach, because it can be adapted to conventional enteroscopes, all arguments applicable to balloon enteroscopy may also be applied to spiral enteroscopy.
Only a few case series have been published on the dilation of stenosis in IBD using enteroscopy:
• Pohl et al.8 showed the results of a series of patients with CD and stenosis of the small intestine who underwent double balloon enteroscopy. These authors later published the results of follow-up studies in these patients9. In seven of the 24 patients studied, inflammatory stenosis hindered endoscopic dilation, so that medical treatment was either initiated or stepped up; two patients with multiple, long and complex stenoses were referred directly to surgery. The remaining 14 patients had an average of two stenoses (range 1–6) with no inflammatory activity. Dilation was successful in 11 patients (79%), and after nine months of follow-up (range 1–17 months), none required surgery. Three patients required a second dilation procedure at 4.5 and 13 months after the first.
• Despott et al. studied 11 patients with CD4, 10 of whom had previously undergone surgical resection. In two patients, dilation could not be performed due to difficulties secondary to the presence of adhesions. One patient had a perforation. Dilation was performed in the other eight, who remained asymptomatic at 20 months of follow up. In two patients, the dilation procedure had to be repeated at respectively 6.5 and 13 months.
• Hassan et al.3 published a meta-analysis in 2007 that included 13 studies and 347 patients with CD who underwent endoscopic dilation. Over a 33-month follow-up period, (range 2–168 months) 58% of patients remained free of surgery. The remaining 42% required two or more dilation procedures and eventually underwent surgery. In the multivariate analysis, the only predictor of remaining free of surgery during follow-up was the presence of a short stenosis (equal to or less than 4 cm). These results were confirmed in other publications and thus, in their study that included 55 patients who underwent dilation of de novo stenoses, Mueller et al. concluded that in most cases, long-term success depends mainly on the nature of the stenoses, their locations and their lengths10.
While not all patients in whom dilation fails require surgery, they are eligible for further dilation procedures. The need for repeat dilation does not reduce the effectiveness of the procedure; it may therefore be carried out at regular intervals depending on the clinical symptoms of the patients. Thus, and in accordance with the information published in most studies, one third of patients require only one dilation procedure, while the remaining two thirds will require repeated sessions. Surgery is necessary in only 30% of patients11.
When planning a procedure involving balloon enteroscopy, the first thing one needs to know is the particularities of the enteroscope that is going to be used. The table in Section I.1.4 shows the basic characteristics of the different enteroscopes currently available. Primarily, consideration should be given to the fact that these endoscopes are longer than their conventional counterparts, usually measuring over 2 m in length, with the limitation of a working channel measuring a maximum of 2.8 mm (2.2 in the case of a diagnostic double-balloon enteroscope). This is why the accessories used in the performance of any given therapeutic procedure should have a diameter of less than 2.8 mm and a minimum length of 230 cm.
Another important limitation is the consistency of the accessories, since the different curves formed by longer endoscopes with thinner working channels may hinder their passage when inserted deep enough into the small intestine. In such cases, the enteroscope has to be straightened, even at the risk of losing its initial location, in order to facilitate insertion of the accessory up to the tip of the enteroscope before pushing it forward again until reaching the stenosis.
Before performing endoscopic treatment of stenosis in the context of CD, it is necessary to evaluate some of its characteristics:
• The number of stenoses to be treated and their locations.
• The diameter and length of the stenosis.
• Whether the stenosis is inflammatory or fibrotic.
• Whether the stenosis is post-surgical and located on the anastomosis, or is a new stenosis.
It can sometimes be difficult to know all this information in advance, and either MR- or CT-enterography are the most helpful imaging methods in this regard12,13. Since MR enterography does not use ionising radiation and has comparable efficacy to CT enterography, where possible, it should be favoured over its CT counterpart.
Although transabdominal ultrasound has also proven effective in helping discern inflammatory vs fibrotic changes in the wall of the small intestine14, the advantage of MR enterography is that it provides similar information, but for the entire gastrointestinal tract. Together with the use of intravenous contrast agents and a measurement of the increase in wall thickness, an analysis of vascularisation can help characterise the stenosis15,16, although as already mentioned, a mixed inflammatory and fibrotic component tends to be standard.
The location of the stenosis is not thought to constitute a limitation, since antegrade or retrograde balloon enteroscopy can reach any stenosis eligible for treatment.
It is preferable to treat no more than 2–3 stenoses in the same procedure, each no longer than 4–5 cm. It is also essential to rule out any fistulae or abscesses associated with the stenosis before performing a dilation procedure.
MATERIAL REQUIRED FOR DILATION OF STENOSIS VIA ENTEROSCOPY
• Dilation balloons of variable calibre
• Metal guide-wire measuring 0.035″ x 450 cm in length.
• The choice of balloons depends on the length and diameter of the stenosis, always bearing in mind that the length of the introducer should be greater than 230 cm and its inner diameter should allow for its introduction via the 2.8 mm working channel. Table I shows the different models of dilation balloons available on the market.
• If the stenosis is accessible via the oral route, preparation of the patient requires an overnight fast and a liquid, residue-free diet the day prior to the examination. In cases where access requires the retrograde approach, preparation involves the use of purgatives, as for a conventional colonoscopy.
• Exploration should be performed under deep sedation, although due to the length of the procedure and the abundance of oropharyngeal secretions, which could result in aspiration, some authors recommend general anaesthesia when using the antegrade approach.
• Access to a CO2 pump is highly advisable in order to avoid air insufflation. Carbon dioxide is absorbed about 150 times faster than room air, guaranteeing greater comfort and reducing the need for sedation during this type of long examination, while possibly allowing for a greater depth of insertion17.
• The procedure should be performed in a room with access to radiological control. After reaching the stenosis, if it is passable, if there are doubts regarding the presence or absence of fistulae, their absence can be verified using the technique described by Kato et al.18, namely, instilling a contrast medium between the overtube and the enteroscope while keeping two balloons inflated proximally and distally to the area under study. This facilitates the passage of the contrast medium through the fistulous tract (sandwich technique).
• Radiological “mapping” of the area is recommended in order to determine the path and length of the stenosis, and thus ensure that multiple stenoses do not go unnoticed. To this end, a water-soluble contrast medium is injected through the scope channel or via a sufficiently long accessory. It may be helpful to inflate the distal balloon (enteroscope) during instillation of the contrast medium to make sure that it travels distally, thus properly mapping the stenosis.
• After ascertaining the specific characteristics of the stenosis with regard to its length, size and path, a guide-wire is threaded through to help position the balloon. Although dilation balloons typically come readily mounted with a guide measuring about 300 cm in length, it is best to remove said guide and move the balloon through the one initially inserted, thus achieving safer placement of the guide and safer insertion of the balloon along the entire path of the stenosis, avoiding false turns and reducing the rate of complications.
• The dilation technique is similar to that established for any other stenosis located elsewhere in the digestive tract. When using a variable calibre balloon, the procedure starts with a balloon whose diameter at its smallest is 3–4 mm larger than that of the stenosis. The balloon is placed in a manner such that, to the extent possible, its midpoint coincides with the midpoint of the stenosis, to which end radiological control is very helpful (Fig. 4). The balloon is then gradually inflated to its maximum diameter (20 mm). In a stenosis with a reduced diameter, it is best not to attempt to achieve maximum dilation in just one session. Although some authors use the larger balloon from the outset, there seem to be fewer complications when dilation is gradual. While there are no guidelines regarding how long the balloon should remain inflated at its various calibres, it usually maintains each diameter for between 1–4 minutes. Our groups holds each inflated balloon size for one minute (Fig. 5).
As previously mentioned, balloon enteroscopy allows access to stenoses located anywhere in the small intestine; as a result, in the event that several stenoses are present, these can all be dilated simultaneously. Special care should be taken when performing the simultaneous dilation of several stenoses, taking into account that the passage of the enteroscope and overtube through each newly dilated stenosis and bowel refolding manoeuvres may increase the risk of complications (Video 1).
OTHER THERAPEUTIC USES OF ENTEROSCOPY IN INFLAMMATORY BOWEL DISEASE
In an attempt to improve the long-term results of endoscopic dilation in IBD, and following the example of procedures performed on oesophageal stenoses of peptic origin, local injection of corticosteroids in the stenotic area has been proposed after dilation. This process could help prevent restenosis due to scar tissue formation after dilation, thus reducing the number of repeat procedures. Short series have been published on dilation in combination with corticosteroids (triamcinolone 40 mg/ml, 1 ml diluted to 5 ml in saline) with success rates exceeding 77% at more than one year of follow-up19-23. A recent study comparing steroid injections in stenoses in the paediatric population to placebo demonstrated the short- and medium-term effectiveness of this procedure in reducing the need for surgery or re-dilation24. However, other authors failed to demonstrate the same effectiveness and call for caution in its recommendation25.
Infliximab and adalimumab, which are both human IgG1 monoclonal antibodies against human TNF-α, have proven effective in inducing remission and as maintenance treatment of refractory CD26,27, modifying the natural history of the disease. Although the mechanism of action of these anti-TNF agents is not fully understood, it seems clear that they induce apoptosis of activated lymphocytes, resulting in the healing of intestinal mucosal lesions. Several studies have shown that levels of infliximab in tissue can be predictive of mucosal healing in some patients. This suggests that direct intralesional injection could be even more effective than systemic infusion. Two studies have shown the benefit of the direct injection of infliximab in perirectal fistulae1,28, on the basis that direct injection can lead to higher levels of infliximab at the tissue level, thus reducing inflammation and local oedema, and hence dilating the lumen.
Only one pilot study has evaluated the intralesional injection of infliximab in patients with CD1. It was conducted in three patients with colonic stensosis refractory to systemic medical treatment who, without undergoing previous endoscopic dilation, were injected with 100 mg of infliximab distributed circumferentially around the stenosis, in a manner similar to sclerotherapy for oesophageal varices. Two weeks after administration, resolution of stenosis, mucosal healing and clinical improvement were confirmed in all three patients. Two of these patients responded to local injection despite showing no prior response to the systemic infusion of infliximab, which supports the hypothesis that greater local drug concentrations achieved via intralesional administration play a beneficial role. These patients were monitored for 10 months and none of them experienced adverse effects, although two of them required further injections of the drug 4–7 months after the first. Although promising, this approach is as yet little developed and requires the conduct of extensive studies to confirm its actual effectiveness (Video 2).
Another therapeutic indication for enteroscopy in CD is the removal of foreign bodies from the intestinal lumen, typically a retained endoscopic capsule. This can occur in up to 13% of patients with confirmed CD29 and in 1.6% of patients with suspected CD30, even though the use of the Patency capsule has substantially reduced the incidence of this complication. The technique is simple and involves advancing the enteroscope to the location of the capsule. Once reached, the capsule can be removed using a Dormia basket, or preferably a Roth Net. The only difficulty in the procedure is that once the endoscopy capsule has been captured using the Roth Net (Fig. 6), its position tends to be transverse to the axis of the enteroscope, which may hinder its passage through Killian’s triangle. In such cases, it is advisable to open the net slightly, so that the reduced tension enables the positioning of the capsule along the axis of the enteroscope.
The possibility of performing percutaneous endoscopic jejunostomy using enteroscopy has also been described31, which could be of particular interest in relation to the nutrition process in some CD patients, mainly in cases where gastric surgery has been performed, rendering conventional percutaneous endoscopic gastrostomy impossible. The two procedures are technically similar and use the same catheter accessories and models. The only difference is the choice of insertion point, which in the case of jejunostomy must be located in a jejunal loop, hence requiring adequate transillumination in order to avoid complications resulting from the interposition of other bowel loops.
The main complications associated with the dilation of stenosis in IBD are perforation and bleeding. Although the procedure is relatively safe, the risk of perforation in certain situations can reach up to 11%, mainly in long (>5 cm), ulcerated stenoses with a significant associated inflammatory component. The use of larger diameter balloons and performing a greater number of dilations in the same session both appear to be associated with a higher rate of complications32. Moreover, gradual dilation until reaching a diameter considered optimal by the endoscopist can reduce the rate of complications5.
It has already been mentioned how the presence of a certain inflammatory activity in a stenosis classified as fibrotic is not uncommon. In only a few cases do fibrosis and inflammation not coexist. Nonetheless, one should proceed to dilation provided no obvious inflammatory process is present and all available medical alternatives indicated to minimise the inflammatory component have been exhausted, as the risk of complications in these cases may be increased.
In the event of perforation after endoscopic dilation in IBD, one must decide whether to opt for watchful waiting with medical treatment or closure with endoscopic resolution clips, or whether to refer the patient for surgery. The decision must be multidisciplinary and depends on the size of the perforation, the clinical context of the patient and the experience of each centre. If endoscopic treatment is performed, successful closure without leakage should be confirmed by the instillation of hydrosoluble contrast with the enteroscope. In any case, the safety provided by surgical treatment should not be overlooked, given that in addition to repairing the perforation, it enables the resolution of stenosis via the resection of the affected bowel segment.
With regard to special situations such as pregnancy, common sense should obviously prevail and treatment should be as conservative as possible. However, in the event of a highly symptomatic stenosis, endoscopic dilation may be performed, and radiological support should be forgone. Although the process can be somewhat more complex when dispensing with radiology, the latter is not essential since the dilation procedure is purely endoscopic, and radiology is used only as a complementary technique intended to characterise the stenosis and ensure proper positioning of the balloon during dilation.
Since these are long and invasive procedures, they must involve either deep sedation or general anaesthesia with the possible complications that sedation itself can entail.
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