We'll talk about capsule chronicles, when to use it, and when to lose it. I have no disclosures. What we'll be learning about are top reasons to choose capsule endoscopy for your patients, red flags and how to manage patients who aren't the best fit for the procedure, and closely related to that, how capsule endoscopy complements small bowel radiologic techniques. These are the indications for capsule endoscopy. The top two, looking for overt bleeding or a source of iron deficiency anemia, are the most common for most of us. Capsule also has a role in Crohn's, both in establishing a diagnosis and monitoring established Crohn's, in polyposis syndromes, and in celiac. As we know, around 5% of GI bleeding arises from the small bowel in areas not accessible to upper endoscopy and colonoscopy. In a presentation with GI bleeding, except of course hematemesis, capsule endoscopy is a good next step after no etiology is identified on bidirectional endoscopy. The diagnostic yield of capsule endoscopy is higher with more clinically significant bleeding, bleeding that is overt, causes lower hemoglobins, and bigger hemoglobin drops. Timing, the earlier the better, is essential to identifying a source of small bowel bleeding. We know this from a very nice retrospective review of more than 250 capsule endoscopies performed for overt bleeding after negative bidirectional endoscopy. On the left, we see that there is a significant difference in capsule endoscopic detection of active bleeding when performed within the first three days of admission, compared to greater than three days, or outpatient, for both active bleeding and active bleeding plus an intervenable target, defined in this study as an AVM. On the right, we can see that the diagnostic yield for bleeding and intervenable target declines in an almost linear fashion with days after admission. Here is one example of active bleeding on a capsule endoscopy performed in a timely manner of course, with bleeding visualized that then led to identification and therapy of a distal jejunal dulafoil on subsequent double balloon enteroscopy. What about cases of iron deficiency without overt bleeding? A 2020 AGA clinical practice guideline on the GI evaluation of iron deficiency anemia recommended a trial of oral iron supplementation over capsule as an initial step. This was based on a pooled analysis of 16 studies assessing the diagnostic yield of capsule endoscopy, which found that only 1.3% of these identified a small bowel cancer in patients without overt bleeding. The guideline authors moreover noted that this is probably an overestimate because the studies were high risk for referral bias, but also acknowledge that more evidence is needed. We can see the quality of evidence is low. The guideline is careful to clarify this does not apply to patients who have symptoms suggestive of small bowel pathology, patients with increased propensity for small bowel angioictasias, patients on blood thinners, hospitalized patients with acute anemia, or patients with iron deficiency refractory to oral iron supplementation. In those patients, you might opt for a capsule over a trial of oral iron supplementation first. So who is most likely to benefit from capsule endoscopy and the setting of iron deficiency without overt bleeding? Patients who have required blood, have lower hemoglobin in spite of iron replacement, less than 10, and longer standing symptoms. On the right, we see a common finding and capsule in this scenario, several small bowel angioictasias. We can utilize capsule endoscopy and Crohn's both to make an initial diagnosis and for monitoring of disease activity. Clinical practice guidelines from the Canadian Association of Gastroenterology based on a systemic review of the literature actually recommend against capsule endoscopy to assess for Crohn's in patients without any elevation and inflammatory markers because of the low diagnostic yield. In a retrospective analysis of 70 patients with symptoms suggestive of Crohn's, but a negative endoscopic evaluation, 0% of patients with a fecal calprotectin less than 100 had findings on capsule endoscopy, whereas 43% with a fecal cal greater than 100 and 65% with a fecal calprotectin greater than 200 had informative findings on capsule endoscopy. So a really nice way to delineate who we're going to find something in. Capsule has a useful role for initial diagnosis in patients with both symptoms compatible with Crohn's and also some evidence of inflammation objectively. Capsule endoscopy is useful too in patients with Crohn's with symptoms not explained by endoscopic evaluation or cross-sectional imaging. It is generally superior in detecting more proximal small bowel disease or earlier or subtler inflammation than CT enterography or MR enterography. It is a useful non-invasive way to check for mucosal healing in small bowel Crohn's beyond the reach of conventional endoscopy. It can also provide additional information after a negative ileocolonoscopy in patients after surgery who are not having obstructive symptoms. In a meta-analysis of 12 prospective trials with more than 400 patients comparing capsule endoscopy to other diagnostic modalities, the comparator trials looking at diagnostic yield for capsule endoscopy versus CT enterography did show that capsule endoscopy has a higher diagnostic yield. Why might this be? You can see on the left an example of a capsule endoscopy where there is clear erythema, superficial but really distinct ulceration and villus change, but this patient had negative CTE and MRE before ultimately being diagnosed with Crohn's. Capsule endoscopy can detect earlier and milder inflammation that can be overlooked in CT enterography. CTE is of course a very valuable tool in our Crohn's patients, particularly as the inflammation progresses along that pathway. On the top left, we see characteristic findings, Crohn's disease with wall thickening of the cecum, terminal ileum, and distal ileum, and the bottom scan shows Crohn's with an interloop abscess indicated by the helpful arrow sign, something the purely luminal views of capsule endoscopy would not detect, and we also see wall thickening of the distal ileum. On to polyposis syndromes. What do the guidelines suggest? For FAP, role of VCE uncertain. We'll talk about that a bit more. For PJS, there is a well-established role for capsule endoscopy, recommended every one to three years based on findings, beginning at age eight, and the ESGE guidelines clarify the polypectomy by device-assisted enteroscopy is warranted for polyps one and a half centimeters in size or greater. When do we consider capsule endoscopy in FAP? There is data from a small study of 40 patients that patients with significant duodenal polyposis can have additional adenomas downstream of this. About three quarters of patients had adenomas in the proximal jejunum by push enteroscopy or capsule endoscopy, and a quarter had more distal polyps that were only identifiable with capsule endoscopy. Decision-making about capsule endoscopy in this setting should be individualized to the patient and considered most strongly in those with a high burden of duodenal polyps or a strong family history of small bowel cancer. Capsule endoscopy has a very well-established role in PJS and has been an exciting part of really changing the natural history of the disease, sparing these patients many episodes of intussusception and small bowel resections by identifying polyps earlier and facilitating targeted deep enteroscopy with removal of larger polyps. In the images, we see capsule endoscopic appearance of a typical PJS hammertoma and the MRE appearance of two large lesions in the distal jejunum. Because decision-making around PJS polyps is based on size, just a reminder that one centimeter looks different on different capsule endoscopy platforms. For instance, occupying about two-thirds of the image on PillCam versus the whole image on other platforms like EndoCapsule. Capsule endoscopy has a role in celiac for patients with seronegative villus atrophy and to assess for complications in refractory celiac. It is not recommended for initial diagnosis. And in patients with positive serology but negative duodenal biopsies, the diagnostic yield is very low and it is not recommended because it adds cost but not really any additional information. Here are some visual examples of these indications. On the right is the capsule endoscopy of a patient with seronegative villus atrophy due to collagenous sprue. And on the left are endoscopic views of one of the most dreadful complications of celiac enteropathy-associated T-cell lymphoma. In a single center retrospective study of capsule endoscopy in non-responsive celiac, the diagnostic yield was actually pretty high, ranging from 15% to 30%. In this setting, we were predominantly looking for ulcerative jejunitis, lymphoma, and small bowel adenocarcinoma. Here are additional still frames of capsule endoscopic views of different findings in refractory celiac. At the top, refractory celiac type 1. And at the bottom, both refractory celiac type 2. Here we can see mucosal ulceration with severe villus atrophy and circumferential ulceration. Capsule endoscopy is incredibly useful in many settings, as we've covered. When shouldn't we use it? And when should we think twice? The only absolute contraindication is a bowel obstruction. A capsule will simply get stuck. Dysphagia, if the patient cannot swallow other pills, swallowing the large capsule endoscope won't go over well. And gastroparesis and possibly GLP-1 agonists, since the capsule will run through all or most of its recording time in the stomach, are reasons for caution, but also readily surmountable with endoscopic deployment into the duodenum. And pictured here is a very useful device that facilitates this on an upper endoscopy. Other causes for caution are pregnancy, if it's not approved in pregnancy, and also a hostile abdomen where the rare but real risk of retention would be an untenable disaster to manage. For instance, with a frozen abdomen after numerous surgeries or peritoneal carcinomatosis. In Crohn's, which as we've reviewed is an indication for capsule, the risk of retention is higher, in general 5% to 13% versus 1.5% with all comers. And you would want to think about CT enterography, patency capsule, which Dr. Cave did a wonderful job describing, or avoidance in a significant stricturing phenotype with a softer indication. What about pacemakers and ICDs? The labeling that suggests against the use of capsule endoscopy with implantable cardiac devices exists because of early concerns about potential interaction between the capsule and the implanted cardiac device from overlapping bandwidth because during cardiac ablations, radiofrequency ablation has interfered with the function of pacemakers. This purely theoretical concern, extrapolated from a totally different clinical scenario, led the FDA and the capsule manufacturer to adopt guidance that made cardiac devices a relative contraindication to the performance of capsule. Subsequent studies, though, have refuted this concern. Since a substantial portion of the population of patients who most need capsule endoscopy are elderly with implanted cardiac devices, this is very important to know. For instance, in one review of more than 100 patients with implanted cardiac devices, there was no interference with any cardiac device function. And only one patient had a gap in recording, which in post hoc analysis was found to be a problem with the recorder and unrelated to any interference between devices. Therefore, guidelines recommend it is safe to proceed with capsule endoscopy in this setting. What if your patient does have a contraindication to capsule? For patients with small bowel bleeding, usually the first step is CT enterography. If the bleeding is brisk and hemodynamically unstable, we'd consider a CTA to direct angiography. For the right patient, generally a young patient with hematokesia, you could consider a Meckel scan if the CTE is negative. And then if this evaluation is not directive and the patient is still bleeding, deep enteroscopy is a next step. For Crohn's and Celiac, radiographic tests are typically the alternative. If the contraindication is a relative one, like for instance, the history of stricturing disease without clear obstruction, you could consider a patency capsule. For polyposis syndromes, small bowel radiography is the main initial alternative. Though particularly for patients with a high prior polyp burden, we will also sometimes surveil by deep enteroscopy. We can see in the ACG guidelines for diagnosis and management of small bowel bleeding, if there is a possible obstruction, we start with CTE, which will either direct us to a target, or if negative, we would consider options like repeat procedures, Meckel's, if appropriate, deep enteroscopy. Here we see common sources of small bowel bleeding by age, the very familiar appearance of angioictasias, a bleeding polyploid lesion, the classic inset enteritis with that diaphragm-like stricture in Crohn's. And while capsule is excellent, happily there is data that MR enterography is also an excellent tool for Crohn's, as we all know from our practice. In that meta-analysis we alluded to earlier of 12 prospective trials with over 400 patients comparing capsule endoscopy to other diagnostic modalities, the comparator trials looking at diagnostic yield for capsule endoscopy versus MR enterography, specifically, showed very comparable diagnostic yield. So, when capsule endoscopy is contraindicated, our radiology colleagues have a lot to offer with small bowel imaging. Thank you.

capsule endoscopy

Crohn's disease

iron deficiency anemia

small bowel

diagnostic tool