Will the steerable capsule replace upper endoscopy in the future?

Disruptive wireless capsule endoscopy technology has evolved to become a first-line diagnostic tool for the small bowel and is also available for the colon. A major obstacle to conquering the last realm of the gastrointestinal (GI) tract is the spacious anatomy of the stomach, with its unpredictable motility.

Technical developments that enable capsules to be maneuvered around the stomach use external magnets in the form of handheld devices (MiroCam Navi and Medtronic prototype), or within large machines with a joystick-driven robotic arm (Ankon Technologies), or via modified magnetic resonance imaging machines (Olympus/Siemens prototype). Prototypes with active locomotion by remotely controlled rotors or paddles have also been developed [1].

“Magnetic steering with a simple device as described by the authors is an important improvement in gastric capsule endoscopy.”

In the current issue of Endoscopy, a study by Ching et al. evaluated magnetically assisted capsule endoscopy (MACE) of the upper GI tract combined with small-bowel visualization in 49 patients with iron deficiency anemia (IDA) using a single device [2]. Once the magnetic MiroCam Navi capsule (Intromedic Ltd., Seoul, Korea) has been swallowed, it is magnetically captured with an external magnetic handheld device under real-time monitoring of transmitted images. Following a sophisticated protocol including fluid intake, repositioning of the patient, and specific movements of the external magnet, the capsule is maneuvered around the stomach and in some cases into the duodenum. The second part of the examination is essentially a standard small-bowel capsule endoscopy (SBCE), with passive capsule locomotion by natural peristalsis.

In the Ching et al. study, gastric landmarks were visualized in 98 %, but the esophagogastric junction (EGJ) was only seen in 53 % (P < 0.001). Compared with esophagogastroduodenoscopy (EGD), combined gastric endoscopy and SBCE had a higher diagnostic yield in patients with IDA, including the detection of small-bowel lesions in 35 %. MACE alone found 15 major upper GI lesions, whereas EGD alone detected only 5 (P  = 0.04). MACE was also better tolerated by patients irrespectively of whether sedation was used for EGD.

With these findings in mind, can we replace EGD with MACE? The study population of this single-center pilot trial included a specific subgroup of patients with IDA and previous inconclusive upper and lower GI endoscopy, who were scheduled for repeat EGD and SBCE. In this setting, in the search for bleeding sources, MACE might replace repeat EGD. However, the European Society of Gastrointestinal Endoscopy guideline does not recommend routinely repeating EGD before SBCE, but to adopt a case by case approach [3]; the quality of previous EGD examinations might trigger this decision. Interestingly, in the Ching et al. study, more upper GI findings were documented by capsule than by flexible endoscopy. In one patient, MACE detected multiple definite bleeding sources, whereas EGD only described hiatal hernia. As several “benign gastric polyps” were detected with MACE alone, the relevance and specificity of these findings remain uncertain. Some patients underwent EGD before MACE, which might also have caused some artificial lesions. These issues should be addressed by large systematic multicenter trials.

In a more general futuristic vision of the gastric capsule, several advantages are evident. There is no need for sedation, and no potential trauma by the endoscope. The procedure is also better tolerated than EGD. Furthermore, it can be performed by a nurse, leaving only the reading to the physician – or perhaps even only the final diagnosis after pre-reading by the nurse. Single-use capsule devices avoid potential transmission of infection, which has been reported not only for duodenoscopes but also for gastroscopes [4].

At the current time, the video capsule cannot provide high definition endoscopy with image enhancement. Nevertheless, the authors demonstrated sufficient image quality, even in the upper GI tract. Post-processing software with spectral color selection is available, and wireless prototypes with narrow-band imaging or autofluorescence have already been reported for the upper GI tract [1].

As demonstrated, MACE can easily be combined with SBCE. Combined SBCE and colon capsule endoscopy in Crohn’s disease has also been described. If future development could incorporate magnetic technology into double-headed capsules, then real panenteric endoscopy is possible through the combination of MACE with bowel and colon capsule endoscopy.

Nevertheless, there remain relevant shortcomings to tackle. In the Ching et al. study, the EGJ was visible in only half of the patients despite a swallowing protocol being followed, as for the dedicated esophageal capsule. The authors suggest incorporating technical features of this device with double cameras and high image acquisition in order to improve visualization of the EGJ. However, a meta-analysis of the first-generation esophageal capsule demonstrated only a moderate accuracy for the diagnosis of Barrett’s esophagus [5].

The ability to diagnose Barrett’s esophagus and gastritis – diagnoses that are still based on histology – should be confirmed for any new device. It is likely that image analysis augmented by artificial intelligence using large databases might help to selectively refer patients to EGD and biopsy in the future. Furthermore, a pH sensor, as used already in the wireless motility capsule, could be integrated into the optical capsule. This might help to identify patients with gastric hypochloremia, which is associated with a higher risk of atrophic gastritis and intestinal metaplasia [6]. Helicobacter pylori testing would also benefit from additional noninvasive methods.

Good sensitivity for focal gastric lesions has been reported with the Ankon system. In a recent series of 10 patients, all neoplastic gastric lesions scheduled for endoscopic submucosal dissection could be detected by MACE, with a per lesion sensitivity of 91.7 % [7]. A large uncontrolled multicenter screening study detected seven patients with early gastric cancer, consecutively confirmed by biopsy. This resulted in a number needed to diagnose of 135 in those older than 50 years [8].

The risk of capsule retention is low after a normal EGD and colonoscopy in the absence of risks factors. However, data on retention rates with widespread use of a capsule as the first endoscopic test in symptomatic patients are yet needed. Capsule aspiration is even less frequent but should be considered predominately in elderly, multimorbid patients [9] who are deemed unfit for conventional EGD, especially when in the right lateral position after ingesting 1 L of water.

Magnetic steering with a simple device as described by the authors is an important improvement in gastric capsule endoscopy. Larger multicenter studies must confirm the diagnostic accuracy, including the diagnosis of Barrett’s esophagus and gastritis, and the safety profile, and should finally provide robust analysis of cost-effectiveness.

• References

• 1 Ciuti G, Calio R, Camboni D. et al. Frontiers of robotic endoscopic capsules: a review. J Microbio Robot 2016; 11: 1-18
• 2 Ching HL, Hale MF, Kurien M. et al. Diagnostic yield of magnetically assisted capsule endoscopy versus gastroscopy in recurrent and refractory iron deficiency anemia. Endoscopy 2019; 51: 409-418
• 3 Pennazio M, Spada C, Eliakim R. et al. Small-bowel capsule endoscopy and device-assisted enteroscopy for diagnosis and treatment of small-bowel disorders: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline. Endoscopy 2015; 47: 352-376
• 4 Bajolet O, Ciocan D, Vallet C. et al. Gastroscopy-associated transmission of extended-spectrum beta-lactamase-producing Pseudomonas aeruginosa . J Hosp Infect 2013; 83: 341-343
• 5 Bhardwaj A, Hollenbeak CS, Pooran N. et al. A meta-analysis of the diagnostic accuracy of esophageal capsule endoscopy for Barrett’s esophagus in patients with gastroesophageal reflux disease. Am J Gastroenterol 2009; 104: 1533-1539
• 6 Pezzicoli G, Tucci FA, Ummarino A. et al. Perendoscopic real-time assessment of pH improves detection of gastric preneoplastic conditions. Minerva Gastroenterol Dietol 2013; 59: 97-105
• 7 Qian YY, Zhu SG, Hou X. et al. Preliminary study of magnetically controlled capsule gastroscopy for diagnosing superficial gastric neoplasia. Dig Liver Dis 2018; 50: 1041-1046
• 8 Zhao AJ, Qian YY, Sun H. et al. Screening for gastric cancer with magnetically controlled capsule gastroscopy in asymptomatic individuals. Gastrointest Endosc 2018; 88: 466-474
• 9 Yung DE, Plevris JN, Koulaouzidis A. Short article: aspiration of capsule endoscopes: a comprehensive review of the existing literature. Eur J Gastroenterol Hepatol 2017; 29: 428-434