Panenteric capsule endoscopy: a new soldier at the forefront of lower gastrointestinal bleeding workup and…beyond! (2021)

To begin with, it is surprising that there are currently no international guidelines on the management of lower gastrointestinal bleeding (LGIB), a rather frequent and life-threatening gastrointestinal condition. The most recent national guidelines are from the British Society of Gastroenterology in 2019 [1] and have already evolved a lot since the previous ones of the American College of Gastroenterology in 2016 [2], and those of the American Society for Gastrointestinal Endoscopy in 2014 [3], concerning the respective positions of upper gastrointestinal (UGI) endoscopy, colonoscopy and computed tomography (CT)-angiography. In fact, the key points to consider for building a clinical algorithm for the management of patients presenting with LGIB are as follows: (a) the individual level of risk in relation to the severity of bleeding and associated comorbidities is highly variable, calling for improved patient risk stratification to guide the timing of diagnostic/therapeutic procedures; (b) the resuscitation and management of antiplatelet/anticoagulant therapy; (c) CT-angiography (possibly followed by embolization) combines the advantages of ease of access and assessment of the entire gastrointestinal tract with a prep-less approach but it requires significant relevant resources and infrastructure to support the service and (d) colonoscopy can localize and diagnose the source of bleeding allowing also therapeutic intervention(s), but it requires bowel preparation and emergency slots (although there is no clear evidence that an early procedure is needed). It is indeed a pleasure to know that European Society of Gastrointestinal Endoscopy guidelines are underway and should be released in 2021. In the absence of high-quality, randomized controlled trials, the task of the relevant working group will not be an easy one. However, another modality worth acknowledging early on in this setting is the capsule endoscopy. The procedure combines several advantages: it is noninvasive, radiation-free and easy to administer. Up to now, small-bowel capsule endoscopy (SBCE) has been considered in the aforementioned recommendations as a second-line investigation. When performed within 48 h of the presentation of bleeding, the diagnostic yield is maximized to 50% but drops to <30% for any time outside the ‘golden’ 48-h period [4]. The therapeutic impact of the approach for inpatients with LGIB similarly decreases from 18.9% when SBCE is performed within 72 h to only 7.4% when ‘capsuling’ anytime later [4]. Consequently, clinical investigators proposed a paradigm shift aiming to assess the small bowel and the colon seamlessly during the same session. In 2015, Schlag et al. [5] showed that by delivering a small-bowel capsule endoscopically, at the end of a negative UGI endoscopy and after instilling polyethylene glycol (PEG) in the duodenum, they were able to correctly guide further diagnostic and therapeutic procedures in 17 of 20 of their patients and obtain a capsule diagnostic yield of 75%. From a semantic perspective, therefore, this can be seen as a truly panenteric assessment. In issue 5 of this Journal, Mussetto et al. [6] proposed a slightly different strategy [6]; 12 hemodynamically stable selected patients – presenting with an LGIB and a negative UGI endoscopy – received first, a split high-volume PEG-based preparation; second, a second-generation colon capsule (CC2) with the sleeping mode disabled to explore the full length of the small bowel and third, two sodium-phosphate (Na-P) boosters to help with the anal excretion of the capsule. Their evaluation demonstrated a high completion rate (small bowel 100%; colon 91.7%), a high cleanliness rate (small bowel 100%; colon 83.3%), no adverse events, and a high diagnostic yield (83.3%, with findings in the small bowel, in the colon, or both). Therapeutic deep enteroscopy was performed in six (50%) patients, with low rebleeding rates. This study suggests that timely panenteric capsule endoscopy (PCE) for LGIB is feasible, well-tolerated and resource-sparing (by avoiding unnecessary colonoscopy). Indeed, in a setting where timeliness and consistency are essential, all CC2 in this small pilot study were given within 72 h of emergency admission (i.e. within 48 h of negative UGI endoscopy). Moreover, the authors eloquently exploited the advantage of a double-headed capsule endoscopy provided by assessing both the small bowel and the colon in the same setting. Some may argue that a CC2 is not fit for purpose in exploring the small bowel. We believe that this approach is imperceptive in several layers. Technically, the complementary metal–oxide–semiconductor of CC2 is less advanced than a third-generation small bowel capsule (SB3). However, the visual field of a CC2 (2 × 172°) is much wider (1 × 156° for SB3), actually consistent for all double-headed devices. This crucial difference seems to make a significant clinical impact: recent series showed that the use of double-headed capsules can increase the diagnostic yield by 14% in the assessment of the small bowel [7]. Conversely, according to most guidelines listed above, capsule endoscopy is indicated when both UGI endoscopy and colonoscopy are negative. This also means that a positive colonoscopy (with diverticulosis, polyps or cecal angiectasia for instance) may preclude further investigations although the relevance of some of these findings is debatable or at least inconclusive. Indeed, in the series by Mussetto et al., [6] one patient had relevant findings in both the small bowel and the colon. Although conceptually forward-thinking and prospective, the main limitation of this pilot study is its small sample size. A couple of other points should be discussed. The authors report that cleanliness was adequate in the majority of CC2. The overall assessment scale [8] used to assess the small bowel cleanliness has not been validated because of moderate intra- and interobserver reproducibility [9], and it may not be appropriate for colonic assessment. Moreover, although the colon completion rate was high, it should be noted that NaP-based solutions are contraindicated in case of a renal failure. Such patients, of course, were excluded from the present pilot, but there may be concerns about the generalization of the approach to a population of critically ill or elderly patients, often seen in the LGIB clinical setting. Hypertonic agents (mannitol and sorbitol) and several other agents (alone or in combination) have been used as boosters and may be considered as an alternative in future studies and for implementation of PCE in clinical practice (systematic review – unpublished author work). Although definitive conclusions cannot be drawn from this proof-of-concept study, it certainly adds to the body of evidence that regards PCE as a forefront modality in the diagnostic workup of LGIB and possibly beyond that. PCE is a diverse and unifying tool that comes to offer what endoscopy conventional gastrointestinal endoscopy was able to offer till now, that is, inspecting the entirety of the gastrointestinal tract remaining loyal into the idea of the inventors of the capsule device. The approach certainly calls for further evaluation and protocol refinement, regarding the position and the timing of PCE in a (not-so-well-defined) standard of care for LGIB. PCE should be seen as a triage tool with potential advantages not limited to improving diagnostic yield or guiding therapeutic interventions but also reducing the length of inpatient stay and associated costs [10,11]. PCE fits well in the emergency setting as is noninvasive and easy to administer. As a matter of fact, PCE is useful even after a negative CT-scan angiogram; furthermore, if PCE does not yield a diagnosis, it is may be beneficial to give laxatives to lower bleeders because it tells whether the bleeding is active, and it gets the patient prepared for a (therapeutic) colonoscopy when appropriate. Such strategies may indeed add to the workload of time-consuming capsule endoscopy interpretations [12], but just round the corner is the artificial intelligence that will most likely balance this problem in the coming years [13]. Acknowledgements X.D. is a co-founder and shareholder of Augmented Endoscopy; he has received lecture fees from Bouchara Recordati, Fujifilm, Medtronic, MSD, and Pfizer, and has acted as a consultant for Alfasigma, Boston Scientific, Norgine, and Pentax. A.K. is co-founder of AJM Med-i-caps Ltd and codirector of iCERV Ltd he has received research support from SynMed/IntroMedic, travel support from Aquilant/Jinshan, has been in AB meeting (UK) for Ankon and has received honoraria from Jinshan. Conflicts of interest There are no conflicts of interest.