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Capsule Endoscopy (CE), more commonly referenced to as PillCam is an innovative upcoming medical technique that has proven to be extremely useful in a wide range of applications. This approach involves a non surgical or invasive method of visually examining the bowel, providing doctors with a detailed and vast view of the gastrointestinal tract, simply by swallowing a pill. This pill consists of a small wireless camera to take pictures, lights to illuminate your digestive system, and an antenna that sends those images to a recorder you wear on a belt., and all in all is around 26mm x 11mm in size.  This recording device saves the pictures for a specialist to review at a later time. This practice enables the detection and diagnosis of pathologies of the GI tract such as Crohn's disease, small intestinal tumours such as lymphoma and small intestinal cancer.

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Capsule Endoscopy (CE) was introduced in 2000 by Israeli inventor Gaviel Iddan. He initially suggested to using a charged coupled device (CCD) camera connected to an electrical umbilical cord for the first mode before proposing the three parts to CE in 1993. However, this lead to issues such as the CCDs requiring significant amounts of energy from the miniature batteries that were used.

In 2001, the M2A, later established as the PillCam was approved for clinical use in Europe and the United States then subsequently more international companies to provide clinical use of their own capsule models. The new generation of CE involve, improved viewing angle, adaptive frame rates longer battery life in capsules such as PillCam SB3 and EndoCapsule10.

Future development for CE comprise of remotely controlled and self-propelling capsules which have already been tested in 2010, using magnets. CE biopsy is also in development, where projects funded by academic and industry pioneers are designing a capsule with recognition, anchoring and bio-sensing capabilities.
The development of the Endoscopy field is the twentieth century helped detect the highest and lowest digestive tracks. Although, the small intestine was hard to visualize with the technology. CE helped visualize the small intestine easily and accurately.

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The primary reason for use is to evaluate the small intestine which cannot be done using other forms of colonoscopy. This form of endoscopy allows doctors a much more in depth view as it can reach further into the gastrointestinal system due to its small size and pill like qualities that allow it to move freely through the bowel.

CE has had a major impact on detection of small bowel tumours, almost tripling their detection rate.  Interestingly, the patients diagnosed with small bowel tumours had close to five negative examinations before detection of the source of a tumour through capsule endoscopy.

Sidhu R, Sanders DS, Morris AJ, McAlindon ME. Guidelines on small bowel enteroscopy and capsule endoscopy in adults. Gut. 2008;57(1):125–136. [PubMed] [Google Scholar]

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History: Medan, Ghadeer
Application: Eliana, Prahglaad

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The application of capsule endoscopy plays a significant role in the gastroenterology. Capsule endoscopy allows in the diagnosis of gastrointestinal disease without having to operate the patient unnecessarily. The wireless nature of this device allows it to travel into the small intestine which was previous, not possible because of the limited length and the size of the device. Capsule endoscopy has become an essential component in modern medical science because of its diagnostic workup of obscure gastrointestinal bleeding, as modification and evolution of technology take place the role of the capsule will also increase in the field of gastroenterology.

Reference
Gil Y.Melmed,Simon K.Lo

Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California

Lauren B.GersonMD, MScJacquesVan DamMD, PhD

Division of Gastroenterology and Hepatology Stanford University School of Medicine, Stanford, CA.

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A study published by BioMed Central from a group of Doctors at the Gastroenterology Department, Hospital Clinic of Barcelona, was done to assess the validity and compare the number of correct diagnoses of bowel cancer using EC compared to CT colonscopy. The results detecting significant neoplastic lesions (tumorous growth), the sensitivity of CCE and CTC was 96.1% and 79.3%,

GONZÁLEZ-SUÁREZ, B. et al. Colon capsule endoscopy versus CT colonography in FIT-positive colorectal cancer screening subjects: a prospective randomised trial—the VICOCA study. BMC Medicine, [s. l.], v. 18, n. 1, 2020. DOI 10.1186/s12916-020-01717-4.

http://search.ebscohost.com.ezproxy.library.qmul.ac.uk/login.aspx?direct=true&db=edssjs&AN=edssjs.79AA596&site=eds-live. Acesso em: 8 out. 2020.

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1. It can be used to search for intestinal bleeds where normal cameras cannot view
2. Detecting polyps (abnormal tissue growths)
3.inflammatory bowel disease (Crohn’s disease)
3. Ulcers
4.Tumours of the small intestine

5.diagnosing Celiac disease

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Possible refercence for last application

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Possible refercence for last application

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A Fluorescence-Based Wireless Capsule Endoscopy System for Detecting Colorectal Cancer

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Wireless capsule endoscopy (WCE) has been widely used in gastrointestinal (GI) diagnosis that allows the physicians to examine the interior wall of the human GI tract through a pain-free procedure. However, there are still several limitations of the technology, ...

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Few advances in the history of gastroenterology have made as dramatic an impact on the diagnosis of gastrointestinal disease as the development and rapid clinical implementation of wireless capsule endoscopy. Less than 4 years after the landmark publication, capsule endoscopy is widely considered an essential component of the diagnostic workup of obscure gastrointestinal bleeding, and its role is expanding in the diagnosis of small bowel diseases such as Crohn's disease. This review appraises the available literature and highlights practical aspects of capsule endoscopy of interest to the clinician. We discuss safety concerns, optimal preparation for the procedure, diagnostic utility as compared to conventional methods, indications for capsule endoscopy, and outcomes.

Abbreviations used in this paper

View full text

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Few advances in the history of gastroenterology have made as dramatic an impact on the diagnosis of gastrointestinal disease as the development and rapid clinical implementation of wireless capsule endoscopy. Less than 4 years after the landmark publication, capsule endoscopy is widely considered an essential component of the diagnostic workup of obscure gastrointestinal bleeding, and its role is expanding in the diagnosis of small bowel diseases such as Crohn's disease.

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Current statud of CE for gadtrointestinal disorders  

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Current statud of CE for gadtrointestinal disorders  

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Naoki Hosoe

Corresponding Author

E-mail address: nhosoe@z5.keio.jp
https://orcid.org/0000-0002-4516-5648
Center for Diagnostic and Therapeutic Endoscopy, School of Medicine, Keio University, Tokyo, Japan

Corresponding: Naoki Hosoe, Center for Diagnostic and Therapeutic Endoscopy, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku, Tokyo 160‐8582, Japan. Email: nhosoe@z5.keio.jp Search for more papers by this author

First published:

Abstract

Small‐bowel capsule endoscopy (SBCE) is used widely because of its non‐invasive and patient‐friendly nature. SBCE can visualize entire small‐intestinal mucosa and facilitate detection of small‐intestinal abnormalities. In this review article, we focus on the current status of SBCE. Several platforms for SBCE are available worldwide. Third‐generation SBCE (PillCam ® SB3) has a high‐resolution camera equipped with an adaptive frame rate system. Several software modes have been developed to reduce the reading time for capsule endoscopy and to minimize the possibility of missing lesions. The main complication of SBCE is capsule retention. Thus, the main contraindication for SBCE is known or suspected gastrointestinal obstruction unless intestinal patency is proven. Possible indications for SBCE are obscure gastrointestinal bleeding, Crohn's disease, small‐intestinal polyps and tumors, and celiac disease. Colon capsule endoscopy (CCE) can observe inflamed colonic mucosa non‐invasively, and allows for the continuous and non‐invasive observation of the entire intestinal tract (pan‐endoscopy). Recently, application of CCE as pan‐enteric endoscopy for inflammatory bowel diseases (including Crohn's disease) has been reported. In the near future, reading for CE will be assisted by artificial intelligence, and reading CE videos for long periods will not be required.

Introduction

SMALL‐BOWEL CAPSULE ENDOSCOPY (SBCE) was introduced by Iddan et al. 1 in 2000. SBCE is used widely because it is non‐invasive and patient‐friendly. SBCE can visualize the entire small‐intestinal mucosa and facilitate visualization of small‐intestinal abnormalities. Several studies have confirmed the efficacy of SBCE for certain disorders, such as small‐bowel (SB) bleeding, suspected and diagnosed Crohn's disease (CD), SB malignant tumors, and small‐intestinal mucosal injury associated with use of non‐steroidal anti‐inflammatory drugs. 2

Since SBCE's introduction, there has been progress of not only SBCE devices (e.g. wider field of view, analytical software) but also regimens of the SBCE procedure (e.g. use of prokinetics, bowel preparation). Here, we overviewed progress of SBCE and focused on the current status and future perspectives of SBCE.

Current Status of SBCE Devices

SEVERAL PLATFORMS OF SBCE are available worldwide (Table 1). In Japan, two types of platforms, PillCam ® (Given Imaging [eventually purchased by Medtronic], Yokneam, Israel) and EndoCapsule ® (Olympus, Tokyo, Japan), are available. Given Imaging developed the first SBCE device, named the M2A capsule. 3 The M2A capsule was eventually renamed PillCam SB. The size of PillCam SB (first generation) was 11 mm × 26 mm, which was same size as second‐ and third‐generation capsules (Fig. 1). PillCam SB can take 2 pictures/s and has a 140° field of view. A second‐generation SBCE device, PillCam SB2, has a wider angle of view (156°), an automatic light control, higher‐resolution camera and longer battery life (12 h) 4, 5 as compared with the first‐generation SBCE device (M2A).

Capsule endoscopy

PillCam SB3®

EndoCapsule 10®

MiroCam®

OMOM Capsule2®

CapsoCam SV‐1®

Size (mm)

Park et al. 4 evaluated the performance of PillCam SB2 as compared with PillCam SB. They counted the number of photographic images of the ampulla of Vater (AoV) taken by each capsule. They reported that the number of images of AoV was similar between the two capsules ( P = 0.62). Another research team also compared PillCam SB2 with PillCam SB and counted the number of photographic images of the AoV, and reported a similar result. 6

Diagnostic yield of SBCE on the proximal part of an SB tumor is considered to be relatively low. 7, 8 To overcome this issue, a third‐generation SBCE device, PillCam SB3, has a high‐resolution camera equipped with an adaptive frame rate (AFR) system that is able to increase automatically from 2 images/s to 6 images/s if the capsule is accelerated by peristalsis. This third‐generation SBCE device can communicate with an external data recorder (DR3) to recognize the location and speed of the capsule (Fig. 2). The efficacy of the AFR system on SBCE has not been demonstrated.

Xavier et al. 9 compared the findings and completion rate of second‐generation (PillCam SB2) and third‐generation SBCE (PillCam SB3) devices using retrospective analyses. They reported no significant differences between PillCam SB2 and SB3 with regard to completion (93.6% vs 96.2%, P = 0.27), overall endoscopic findings (73.4% vs 78.8%, P = 0.23) or relevant findings (54.3% vs 52.7%, P = 0.76), respectively. They concluded that the third‐generation SBCE device did not improve the diagnostic yield compared with the second‐generation SBCE device. A randomized controlled trial (RCT) is needed to demonstrate the impact of the AFR system on the diagnostic yield of SBCE.

EndoCapsule was first reported in 2008. 10 Olympus has released a second‐generation SBCE 11 device named EndoCapsule 10. This capsule has a new sensor with a wider angle of view (160°), better image quality and longer battery life (12 h) compared with the first‐generation Olympus SBCE (EndoCapsule) device (Table 1). Also, the external portable data recorder is smaller than that of EndoCapsule (Fig. 2). The clinical impact of these improvements of EndoCapsule has not been evaluated, so an RCT is warranted.

IntroMedic (Seoul, Korea) released a unique SBCE device named MiroCam ®, which uses electric‐field propagation instead of radiofrequency transmission of a video signal (Table 1). Thus, the human body acts as an "electricity conductor" to transmit images from the capsule to electrodes on the surface of the body, which are connected to a portable data recorder. This technology uses less energy and saves battery life to obtain a higher AFR and longer recording. However, the efficacy of the electric‐field transmission system has not been tested. 12, 13

Jinshan Science & Technology (Chongqing, China) created the OMOM Capsule ®, which has an outer diameter of 13 mm, length of 27.9 mm and weighs 6 g. Pictures are taken at 2 frames/s, though this frame rate can be changed during the procedure. 14, 15 The second‐generation version (OMOM Capsule 2) has a new sensor with a wider angle of view (165°), better image quality, higher frame rate (2-6 frames/s) and longer battery life as compared with the OMOM Capsule (Table 1). The efficacy of these new functions on SBCE has not been compared.

In 2013, a unique SBCE platform (CapsoCam ® SV; Capso‐Vision, Saratoga, CA, USA) was reported by Friedrich et al. 16 It is equipped with four cameras, installed in the middle of the capsule, at 90° to each other, and provides a lateral 360° panoramic view of the SB mucosa. CapsoCam SV‐1 can take more pictures (12-20 frames/s), with optimized battery‐power consumption. 17 CapsoCam SV‐1 can store the data of images within the capsule itself. Therefore, the excreted capsule must be retrieved.

Tontini et al. 17 conducted a multicenter observational study enrolling 172 consecutive patients. They showed that the performance of CapsoCam SV‐1 was similar to that of a forward‐view SBCE system. Zwinger et al. 18 conducted a head‐to‐head comparison between CapsoCam SV‐1 and PillCam SB3 in a randomized prospective study enrolling patients with obscure gastrointestinal bleeding (OGIB). They reported that CapsoCam SV‐1 detected more bleeding lesions (31/79) and had a higher diagnostic yield (39.7%) as compared with PillCam SB3 (26/75 and 34.6%, respectively). They concluded that CapsoCam SV‐1 could detect more lesions, but relevant bleeding sources were detected by both types of capsule. The true efficacy of a panoramic view for SBCE has not been shown.

Current Status of Reading Software for SBCE

SMALL‐BOWEL CAPSULE ENDOSCOPY is a comfortable modality for patients. However, for the treating physician, reviewing more than 50 000 images is time‐consuming. CE manufacturers have introduced several features in CE software to reduce the time required for analyzing CE results and minimizing the possibility of missing lesions.

The PillCam platform has been equipped with three software modes: automatic, quickview and suspected blood indicator (SBI). In automatic mode, the software reduces the total number of images by pasting similar images. 19, 21- 24, 26 25 In the current version of PillCam software (Rapid version 8.3), manual and automatic modes have been replaced by review mode, and Rapid version 8.3 enables more efficient video reading as compared with a previous version. 23 The SBI mode functions by identifying red pixels on the screen, and then annotating the scroll bar automatically with a red line. 20 In quickview mode, the software reduces the total number of images by identifying the most unusual image and presenting the selected images.

Previously, we reported that the reading time using automatic mode and quickview mode was significantly shorter than that in normal mode. 20 A previous version of SBI had low sensitivity for the detection of active bleeding, 24, 25, 28 reported the performance of the current version of SBI. They stated that eight contiguous SBI markers had a specificity of 100% for identification of active bleeding in the gastrointestinal tract (GIT) regardless of the total number of SBI markers, whereas two or more consecutive SBI markers had a sensitivity of 96.5%. PillCam software also has an image‐enhanced (blue) mode 29 and flexible spectral imaging color enhancement (FICE; Fujifilm, Saitama, Japan). 30- 34 showed that use of these three FICE modes did not improve delineation or detection significantly but, in pigmented lesions, FICE setting‐1 performed better for the delineation and detection of lesions. 33 FICE chromoendoscopy aims to enhance surface and vascular patterns to improve the visualization and detection of mucosal and vascular lesions on SBCE. A recent meta‐analysis 27 and was upgraded using current PillCam software (Rapid version 8.3). Han et al.

The EndoCapsule platform of Olympus has developed CE reading software named auto‐speed‐adjusted, express‐selected playback, 35 overview function and omni modes. 36 The overview function displays a selection of characteristic still images of the CE procedure on a single page. These pictures are selected by comparing pictures with changes from a previous picture; then, pictures with the most changes are selected and displayed. The express‐selected playback mode discards pictures with no significant changes in the CE video. The express‐selected mode discards redundant images and compiles dissimilar images as a running video stream. The auto‐speed‐adjusted mode can speed up the video if the software detects similar images being displayed. 35

Subramanian et al. 35 conducted a retrospective cohort study involving two experienced CE readers who analyzed CE procedures using overview with express‐selected or overview with auto‐speed‐adjusted modes. They showed the reading time for overview with express‐selected mode to be significantly lower than that for overview with auto‐speed‐adjusted mode, with few unrecognized clinically significant lesions. They concluded that these new playback systems could reduce the reading time of CE. The conceptual scheme of omni mode is presented in Figure 3. Omni mode can select and discard redundant images, and display all the areas captured by SBCE. We conducted a multicenter study in Japan and reported the efficacy of omni mode. 36 We did not demonstrate non‐inferiority between using control (normal reading) and omni mode. However, detection of major lesions was not significantly different between control and omni modes. We also demonstrated that the reading time was significantly lower using omni mode than using control.

The MiroCam platform has a software mode named express view which is used to reduce the reading time of SBCE by discarding repetitive and non‐significant SB images. Saurin et al. 37 reported a prospective, multicenter study of express view. They showed the mean reading time of CE video to be 39.7 min (range, 11-180) and 19.7 min (range, 4-40) for standard and express‐view modes, respectively ( P < 0.0001). They also showed that reading using the standard mode and express‐view modes had a sensitivity of 93.3% and 82.2%, respectively. They concluded that the algorithm for express view could significantly shorten the CE reading time with high sensitivity.

Current Status of Preparation for SBCE

QUALITY INDICATORS OF SBCE are the completion rate (CR), small‐bowel visual quality (SBVQ) and diagnostic yield (DY). Various interventions have been reported to attempt to increase these quality indicators. 10, 40, 49 A more recent meta‐analysis 50 and systematic review 51 concluded that preparation with PEG enhanced the SBVQ only, and did not affect the CR or DY. Yung 44- 52 conducted a meta‐analysis regarding bowel preparation in SBCE. They included 40 studies (4380 patients who used laxatives, 2185 who did not use laxatives). They concluded that laxative use in SBCE did not affect DY or the CR significantly, but improved SBVQ. 48 Korean guidelines released in 2013 stated that preparation with PEG solution enhanced the SBVQ and also DY, but it did not affect the CR. 38- 43 Main preparations as interventions are use of laxatives and/or prokinetics. Polyethylene glycol (PEG) solution has been used most often as a preparation during SBCE. et al.

Administration of prokinetics such as erythromycin, 53, 10, 42, 57 concluded that metoclopramide use in SBCE improved the CR, but no prokinetics improved DY. Another systematic review reported that prokinetic use did not affect the CR or DY. 58 In the early phase of SBCE, the battery life of the capsule was relatively short, resulting in 20% of SBCE procedures not being completed. 59 In second and third generations, their longer battery lives allowed a higher CR of SBCE to be obtained. 5 The effect of prokinetics in SBCE with longer recording is considered to be minimal. 56 in SBCE shortens the gastric transit time of the capsule and leads to improved chances of SBCE being completed. A systematic review focusing on prokinetics 55 or mosapride 54 metoclopramide

SBCE Contraindications

THE MAIN COMPLICATION of SBCE is capsule retention. Thus, the main contraindication for SBCE is known or suspected GIT obstruction 60, 61 unless intestinal patency is proven. In general, capsule retention occurs in approximately 1-2% of patients being evaluated for OGIB. Liao 62 conducted a meta‐analysis and reported that the overall prevalence of retention was as low as 1.4% (95% confidence interval [CI], 1.2-1.6). They also reported that, categorized by indication, retention prevalence for OGIB was 1.2% (95% CI, 0.9-1.6), for CD (diagnosed or suspected) was 2.6% (95% CI, 1.6-3.9) and for neoplastic lesions was 2.1% (95% CI, 0.7-4.3). A meta‐analysis published recently showed that the prevalence of capsule retention was 2.1% for patients with OGIB (95% CI, 1.5-2.8). The retention prevalence for patients with suspected inflammatory bowel disease (IBD) was 3.6% (95% CI, 1.7-8.6) but that for patients with established IBD was 8.2% (95% CI, 6.0-11.0). 63 Retention prevalence in patients with established IBD (especially CD) was higher than that of the others. 64, 65 et al.

First, taking an adequate medical history (e.g. previous abdominal surgery, prescribed medications taken, obstructive symptoms) is crucial to avoid capsule retention. 66, 62, 71, 72 to avoid capsule retention. In the next paragraph, we focus on PC. 68- 70 Small‐bowel follow‐through (SBFT) and computed tomography (CT) of the abdomen are considered to be unreliable. Conversely, patency capsule (PC) examination and dedicated SB cross‐sectional imaging methods have been found to be effective 67 A combination of abdominal pain, abdominal distension and nausea/vomiting before CE has been shown to be associated with capsule retention.

PC

A PC IS a dissolvable capsule, which is the same size as the PillCam SB, SB2 and SB3 capsule (11 × 26 mm). A PC also equips a radiofrequency identification (RFID) tag to be identified by a specific scanner. The Japanese version of a PC is RFID tag‐less PC to avoid impaction of the RFID tag in stenosis. 73 The first prospective feasibility study of PC was reported by Spada et al. 71 The efficacy of PC has been reported. 67, 73, 71, 74- 76

Nakamura et al. 73 reported the usefulness of a tag‐less PC. They enrolled 100 patients with symptoms or a high risk of capsule retention. They reported that GI patency was confirmed in 87 patients, and no retention occurred in any patient. They concluded that an RFID tag‐less PC confirmed GI patency in patients at a high risk of capsule retention, which allowed safe SBCE.

Zhang et al. 75 conducted a meta‐analysis to estimate the diagnostic value of PC. They showed that the sensitivity of PC for detection of GIT patency was 97% (95% CI, 93-99) and specificity was 83% (95% CI, 65-94). Nemeth et al. 77 conducted a retrospective study of patients with established CD who underwent SBCE for clinical need. They reported that the risk of capsule retention in the SB was 1.5% without use of a prior PC and was 2.1% after a negative patency test ( P = 0.9). They also reported that the risk of capsule retention was not reduced by the non‐selective use (in asymptomatic patients) of a PC, and that a positive PC test was associated significantly with capsule retention.

Indications for SBCE

POSSIBLE INDICATIONS FOR SBCE are OGIB, CD, small‐intestinal polyps and tumors, and celiac disease. 62, 78, 79 Below, we focus on OGIB and CD.

OGIB

Obscure gastrointestinal bleeding is defined as bleeding from the GIT that persists or recurs without an obvious etiology after esophagogastroduodenoscopy, colonoscopy or radiological evaluation of the SB, such as SBFT or enteroclysis. 80 OGIB can be subdivided into occult (iron‐deficiency anemia and/or positive fecal occult blood test) and overt. 11

The advent of SBCE and balloon‐assisted enteroscopy (BAE) has enabled identification of obscure bleeding sources in the GIT in most cases. Thus, clinical guidelines from the American College of Gastroenterology (ACG) have proposed that the term SB bleeding be replaced for the previous classification of OGIB. ACG guidelines also state that the term OGIB should be reserved for patients in whom a source of bleeding cannot be identified anywhere in the GIT. 81

Obscure gastrointestinal bleeding is the main indication for SBCE. 60, 82- 84, 93 and use of anticoagulant drugs. 87 Several medical societies in Western countries and Korea have released diagnostic algorithms for OGIB. 66, 96 Most medical societies recommend that SBCE be the first‐line method for exploring the source of OGIB without obstructive symptoms. The JGES recommends that CT should be the first‐line modality to examine SB bleeding; if abnormalities are found on CT, direct BAE through the closest route is recommended. 96 Japanese gastroenterologists are accustomed to carrying out BAE, so BAE is emphasized for OGIB in Japan. 80, 81, 94, 95 The Japan Gastroenterological Endoscopy Society (JGES) released diagnostic algorithms for OGIB in 2017. 92 timing of CE 91 The diagnostic yield of CE for significant lesions is dependent upon patient status, 62 The diagnostic yield of SBCE for OGIB is 30-70%.

The role of SBCE on SB bleeding is selection of the closest route in BAE. Kaffes et al. 97 reported favorable results after intervention of BAE in patients with obscure GIT bleeding and positive SBCE, which served as a route selection and a filter test. Gay et al. 98 also reported that SBCE could effectively manage the route selection in BAE. Nakamura et al. 99 conducted retrospective analyses to evaluate the accuracy of the transit time of SBCE to the lesion as a predictive indicator for the route selection of BAE. Their results showed that the cut‐off value for route selection was 50% of the SB transit time. They concluded that the SBCE transit time was useful for selecting the route of BAE.

CD

A clinical guideline published recently in Canada suggests that SBCE should be recommended for patients with pathognomonic symptoms of CD in the presence of a negative ileocolonoscopy and radiological studies. SBCE is recommended in patients with established CD showing clinical features unexplained by ileocolonoscopy or cross‐sectional imaging. SBCE is also recommended in established CD to confirm the small‐intestinal mucosal healing. Canadian guidelines suggest that CE is not recommended in patients with chronic abdominal pain or diarrhea without evidence of increased levels of biomarkers. 100 European Society of Gastrointestinal Endoscopy (ESGE) guidelines recommend that CE is the initial diagnostic device for evaluation of the small intestine in patients presenting with suspected CD and demonstrating negative ileocolonoscopic examination in the absence of obstructive symptoms or radiological stenosis. The ESGE also recommends that careful selection of patients based on meticulous assessment of symptoms and serological/fecal inflammatory biomarkers is important to improve the diagnostic accuracy and yield of CE in patients presenting with suspected CD. 101

Crohn's disease is a heterogeneous disease which can affect the entire GIT. Colon capsule endoscopy (CCE) can observe inflamed colonic mucosa non‐invasively. 102 Also, CCE allows continuous and non‐invasive observation of the entire intestinal tract (pan‐endoscopy). Recently, pan‐enteric surveillance and application of CCE as pan‐enteric endoscopy for CD have been reported. 103, 104 Boal Carvalho 103, 104 undertook pan‐enteric surveillance using CCE in 12 CD patients. They confirmed mucosal healing in the SB and colon in three patients (25%), whereas disease activity was limited to the SB or colon in five patients (42%), and observation of the entire GIT was achieved in 10 of 12 patients (83%). et al.

A small‐bowel colon (SBC) capsule (PillCam Crohn's; Medtronic) has been designed to image the SB and colon. 105 The SBC capsule is similar to a second‐generation colon capsule (PillCam COLON 2; Medtronic) with regard to hardware components, but differs in its operation mode. 105 Leighton et al. 105 compared the diagnostic yield of the SBC capsule with ileocolonoscopy in patients with active CD. The per‐patient diagnostic yield for active CD lesions was 83.3% for SBC and 69.7% for ileocolonoscopy (yield difference, 13.6%; 95% CI, 2.6-24.7); 65% of patients had active‐CD lesions identified by both modalities. Of the 12 people who tested positive for active CD by SBC only. Three individuals were positive for active CD by ileocolonoscopy only. They concluded that the diagnostic yields for SBC may be higher than that for ileocolonoscopy, but further study is needed to confirm their results.

Future Perspectives

SMALL‐BOWEL CAPSULE ENDOSCOPY plays a pivotal part in the diagnosis of SB disorders and will not be replaced by an alternative device. However, SBCE will evolve with new functions. For example, SBCE devices will be advanced further, including high‐frame‐rate imaging, full spherical imaging and high‐resolution imaging. With regard to CE software, artificial intelligence and computer‐assisted diagnosis will be applied to reduce the burden for CE readers. 106 Hence, the need to read CE videos for long periods will be removed.

Acknowledgment

WE THANK ARSHAD Makhdum, Ph.D., from Edanz Group ( www.edanzediting.com/ac) for editing a draft of this manuscript.

Conflicts of Interest

N.H. CONDUCTED INDEPENDENT research supported by a funding contribution from Medtronic. N.H. received a research grant from Olympus. Other authors have no COI to disclose.

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Abstract

Small‐bowel capsule endoscopy (SBCE) is used widely because of its non‐invasive and patient‐friendly nature. SBCE can visualize entire small‐intestinal mucosa and facilitate detection of small‐intestinal abnormalities. In this review article, we focus on the current status of SBCE. Several platforms for SBCE are available worldwide. Third‐generation SBCE (PillCam ® SB3) has a high‐resolution camera equipped with an adaptive frame rate system. Several software modes have been developed to reduce the reading time for capsule endoscopy and to minimize the possibility of missing lesions. The main complication of SBCE is capsule retention. Thus, the main contraindication for SBCE is known or suspected gastrointestinal obstruction unless intestinal patency is proven. Possible indications for SBCE are obscure gastrointestinal bleeding, Crohn's disease, small‐intestinal polyps and tumors, and celiac disease. Colon capsule endoscopy (CCE) can observe inflamed colonic mucosa non‐invasively, and allows for the continuous and non‐invasive observation of the entire intestinal tract (pan‐endoscopy). Recently, application of CCE as pan‐enteric endoscopy for inflammatory bowel diseases (including Crohn's disease) has been reported. In the near future, reading for CE will be assisted by artificial intelligence, and reading CE videos for long periods will not be required.

Introduction

SMALL‐BOWEL CAPSULE ENDOSCOPY (SBCE) was introduced by Iddan et al. 1 in 2000. SBCE is used widely because it is non‐invasive and patient‐friendly. SBCE can visualize the entire small‐intestinal mucosa and facilitate visualization of small‐intestinal abnormalities. Several studies have confirmed the efficacy of SBCE for certain disorders, such as small‐bowel (SB) bleeding, suspected and diagnosed Crohn's disease (CD), SB malignant tumors, and small‐intestinal mucosal injury associated with use of non‐steroidal anti‐inflammatory drugs. 2

Since SBCE's introduction, there has been progress of not only SBCE devices (e.g. wider field of view, analytical software) but also regimens of the SBCE procedure (e.g. use of prokinetics, bowel preparation). Here, we overviewed progress of SBCE and focused on the current status and future perspectives of SBCE.

Current Status of SBCE Devices

SEVERAL PLATFORMS OF SBCE are available worldwide (Table 1). In Japan, two types of platforms, PillCam ® (Given Imaging [eventually purchased by Medtronic], Yokneam, Israel) and EndoCapsule ® (Olympus, Tokyo, Japan), are available. Given Imaging developed the first SBCE device, named the M2A capsule. 3 The M2A capsule was eventually renamed PillCam SB. The size of PillCam SB (first generation) was 11 mm × 26 mm, which was same size as second‐ and third‐generation capsules (Fig. 1). PillCam SB can take 2 pictures/s and has a 140° field of view. A second‐generation SBCE device, PillCam SB2, has a wider angle of view (156°), an automatic light control, higher‐resolution camera and longer battery life (12 h) 4, 5 as compared with the first‐generation SBCE device (M2A).

Capsule endoscopy

PillCam SB3®

EndoCapsule 10®

MiroCam®

OMOM Capsule2®

CapsoCam SV‐1®

Size (mm)

Park et al. 4 evaluated the performance of PillCam SB2 as compared with PillCam SB. They counted the number of photographic images of the ampulla of Vater (AoV) taken by each capsule. They reported that the number of images of AoV was similar between the two capsules ( P = 0.62). Another research team also compared PillCam SB2 with PillCam SB and counted the number of photographic images of the AoV, and reported a similar result. 6

Diagnostic yield of SBCE on the proximal part of an SB tumor is considered to be relatively low. 7, 8 To overcome this issue, a third‐generation SBCE device, PillCam SB3, has a high‐resolution camera equipped with an adaptive frame rate (AFR) system that is able to increase automatically from 2 images/s to 6 images/s if the capsule is accelerated by peristalsis. This third‐generation SBCE device can communicate with an external data recorder (DR3) to recognize the location and speed of the capsule (Fig. 2). The efficacy of the AFR system on SBCE has not been demonstrated.

Xavier et al. 9 compared the findings and completion rate of second‐generation (PillCam SB2) and third‐generation SBCE (PillCam SB3) devices using retrospective analyses. They reported no significant differences between PillCam SB2 and SB3 with regard to completion (93.6% vs 96.2%, P = 0.27), overall endoscopic findings (73.4% vs 78.8%, P = 0.23) or relevant findings (54.3% vs 52.7%, P = 0.76), respectively. They concluded that the third‐generation SBCE device did not improve the diagnostic yield compared with the second‐generation SBCE device. A randomized controlled trial (RCT) is needed to demonstrate the impact of the AFR system on the diagnostic yield of SBCE.

EndoCapsule was first reported in 2008. 10 Olympus has released a second‐generation SBCE 11 device named EndoCapsule 10. This capsule has a new sensor with a wider angle of view (160°), better image quality and longer battery life (12 h) compared with the first‐generation Olympus SBCE (EndoCapsule) device (Table 1). Also, the external portable data recorder is smaller than that of EndoCapsule (Fig. 2). The clinical impact of these improvements of EndoCapsule has not been evaluated, so an RCT is warranted.

IntroMedic (Seoul, Korea) released a unique SBCE device named MiroCam ®, which uses electric‐field propagation instead of radiofrequency transmission of a video signal (Table 1). Thus, the human body acts as an "electricity conductor" to transmit images from the capsule to electrodes on the surface of the body, which are connected to a portable data recorder. This technology uses less energy and saves battery life to obtain a higher AFR and longer recording. However, the efficacy of the electric‐field transmission system has not been tested. 12, 13

Jinshan Science & Technology (Chongqing, China) created the OMOM Capsule ®, which has an outer diameter of 13 mm, length of 27.9 mm and weighs 6 g. Pictures are taken at 2 frames/s, though this frame rate can be changed during the procedure. 14, 15 The second‐generation version (OMOM Capsule 2) has a new sensor with a wider angle of view (165°), better image quality, higher frame rate (2-6 frames/s) and longer battery life as compared with the OMOM Capsule (Table 1). The efficacy of these new functions on SBCE has not been compared.

In 2013, a unique SBCE platform (CapsoCam ® SV; Capso‐Vision, Saratoga, CA, USA) was reported by Friedrich et al. 16 It is equipped with four cameras, installed in the middle of the capsule, at 90° to each other, and provides a lateral 360° panoramic view of the SB mucosa. CapsoCam SV‐1 can take more pictures (12-20 frames/s), with optimized battery‐power consumption. 17 CapsoCam SV‐1 can store the data of images within the capsule itself. Therefore, the excreted capsule must be retrieved.

Tontini et al. 17 conducted a multicenter observational study enrolling 172 consecutive patients. They showed that the performance of CapsoCam SV‐1 was similar to that of a forward‐view SBCE system. Zwinger et al. 18 conducted a head‐to‐head comparison between CapsoCam SV‐1 and PillCam SB3 in a randomized prospective study enrolling patients with obscure gastrointestinal bleeding (OGIB). They reported that CapsoCam SV‐1 detected more bleeding lesions (31/79) and had a higher diagnostic yield (39.7%) as compared with PillCam SB3 (26/75 and 34.6%, respectively). They concluded that CapsoCam SV‐1 could detect more lesions, but relevant bleeding sources were detected by both types of capsule. The true efficacy of a panoramic view for SBCE has not been shown.

Current Status of Reading Software for SBCE

SMALL‐BOWEL CAPSULE ENDOSCOPY is a comfortable modality for patients. However, for the treating physician, reviewing more than 50 000 images is time‐consuming. CE manufacturers have introduced several features in CE software to reduce the time required for analyzing CE results and minimizing the possibility of missing lesions.

The PillCam platform has been equipped with three software modes: automatic, quickview and suspected blood indicator (SBI). In automatic mode, the software reduces the total number of images by pasting similar images. 19, 21- 24, 26 25 In the current version of PillCam software (Rapid version 8.3), manual and automatic modes have been replaced by review mode, and Rapid version 8.3 enables more efficient video reading as compared with a previous version. 23 The SBI mode functions by identifying red pixels on the screen, and then annotating the scroll bar automatically with a red line. 20 In quickview mode, the software reduces the total number of images by identifying the most unusual image and presenting the selected images.

Previously, we reported that the reading time using automatic mode and quickview mode was significantly shorter than that in normal mode. 20 A previous version of SBI had low sensitivity for the detection of active bleeding, 24, 25, 28 reported the performance of the current version of SBI. They stated that eight contiguous SBI markers had a specificity of 100% for identification of active bleeding in the gastrointestinal tract (GIT) regardless of the total number of SBI markers, whereas two or more consecutive SBI markers had a sensitivity of 96.5%. PillCam software also has an image‐enhanced (blue) mode 29 and flexible spectral imaging color enhancement (FICE; Fujifilm, Saitama, Japan). 30- 34 showed that use of these three FICE modes did not improve delineation or detection significantly but, in pigmented lesions, FICE setting‐1 performed better for the delineation and detection of lesions. 33 FICE chromoendoscopy aims to enhance surface and vascular patterns to improve the visualization and detection of mucosal and vascular lesions on SBCE. A recent meta‐analysis 27 and was upgraded using current PillCam software (Rapid version 8.3). Han et al.

The EndoCapsule platform of Olympus has developed CE reading software named auto‐speed‐adjusted, express‐selected playback, 35 overview function and omni modes. 36 The overview function displays a selection of characteristic still images of the CE procedure on a single page. These pictures are selected by comparing pictures with changes from a previous picture; then, pictures with the most changes are selected and displayed. The express‐selected playback mode discards pictures with no significant changes in the CE video. The express‐selected mode discards redundant images and compiles dissimilar images as a running video stream. The auto‐speed‐adjusted mode can speed up the video if the software detects similar images being displayed. 35

Subramanian et al. 35 conducted a retrospective cohort study involving two experienced CE readers who analyzed CE procedures using overview with express‐selected or overview with auto‐speed‐adjusted modes. They showed the reading time for overview with express‐selected mode to be significantly lower than that for overview with auto‐speed‐adjusted mode, with few unrecognized clinically significant lesions. They concluded that these new playback systems could reduce the reading time of CE. The conceptual scheme of omni mode is presented in Figure 3. Omni mode can select and discard redundant images, and display all the areas captured by SBCE. We conducted a multicenter study in Japan and reported the efficacy of omni mode. 36 We did not demonstrate non‐inferiority between using control (normal reading) and omni mode. However, detection of major lesions was not significantly different between control and omni modes. We also demonstrated that the reading time was significantly lower using omni mode than using control.

The MiroCam platform has a software mode named express view which is used to reduce the reading time of SBCE by discarding repetitive and non‐significant SB images. Saurin et al. 37 reported a prospective, multicenter study of express view. They showed the mean reading time of CE video to be 39.7 min (range, 11-180) and 19.7 min (range, 4-40) for standard and express‐view modes, respectively ( P < 0.0001). They also showed that reading using the standard mode and express‐view modes had a sensitivity of 93.3% and 82.2%, respectively. They concluded that the algorithm for express view could significantly shorten the CE reading time with high sensitivity.

Current Status of Preparation for SBCE

QUALITY INDICATORS OF SBCE are the completion rate (CR), small‐bowel visual quality (SBVQ) and diagnostic yield (DY). Various interventions have been reported to attempt to increase these quality indicators. 10, 40, 49 A more recent meta‐analysis 50 and systematic review 51 concluded that preparation with PEG enhanced the SBVQ only, and did not affect the CR or DY. Yung 44- 52 conducted a meta‐analysis regarding bowel preparation in SBCE. They included 40 studies (4380 patients who used laxatives, 2185 who did not use laxatives). They concluded that laxative use in SBCE did not affect DY or the CR significantly, but improved SBVQ. 48 Korean guidelines released in 2013 stated that preparation with PEG solution enhanced the SBVQ and also DY, but it did not affect the CR. 38- 43 Main preparations as interventions are use of laxatives and/or prokinetics. Polyethylene glycol (PEG) solution has been used most often as a preparation during SBCE. et al.

Administration of prokinetics such as erythromycin, 53, 10, 42, 57 concluded that metoclopramide use in SBCE improved the CR, but no prokinetics improved DY. Another systematic review reported that prokinetic use did not affect the CR or DY. 58 In the early phase of SBCE, the battery life of the capsule was relatively short, resulting in 20% of SBCE procedures not being completed. 59 In second and third generations, their longer battery lives allowed a higher CR of SBCE to be obtained. 5 The effect of prokinetics in SBCE with longer recording is considered to be minimal. 56 in SBCE shortens the gastric transit time of the capsule and leads to improved chances of SBCE being completed. A systematic review focusing on prokinetics 55 or mosapride 54 metoclopramide

SBCE Contraindications

THE MAIN COMPLICATION of SBCE is capsule retention. Thus, the main contraindication for SBCE is known or suspected GIT obstruction 60, 61 unless intestinal patency is proven. In general, capsule retention occurs in approximately 1-2% of patients being evaluated for OGIB. Liao 62 conducted a meta‐analysis and reported that the overall prevalence of retention was as low as 1.4% (95% confidence interval [CI], 1.2-1.6). They also reported that, categorized by indication, retention prevalence for OGIB was 1.2% (95% CI, 0.9-1.6), for CD (diagnosed or suspected) was 2.6% (95% CI, 1.6-3.9) and for neoplastic lesions was 2.1% (95% CI, 0.7-4.3). A meta‐analysis published recently showed that the prevalence of capsule retention was 2.1% for patients with OGIB (95% CI, 1.5-2.8). The retention prevalence for patients with suspected inflammatory bowel disease (IBD) was 3.6% (95% CI, 1.7-8.6) but that for patients with established IBD was 8.2% (95% CI, 6.0-11.0). 63 Retention prevalence in patients with established IBD (especially CD) was higher than that of the others. 64, 65 et al.

First, taking an adequate medical history (e.g. previous abdominal surgery, prescribed medications taken, obstructive symptoms) is crucial to avoid capsule retention. 66, 62, 71, 72 to avoid capsule retention. In the next paragraph, we focus on PC. 68- 70 Small‐bowel follow‐through (SBFT) and computed tomography (CT) of the abdomen are considered to be unreliable. Conversely, patency capsule (PC) examination and dedicated SB cross‐sectional imaging methods have been found to be effective 67 A combination of abdominal pain, abdominal distension and nausea/vomiting before CE has been shown to be associated with capsule retention.

PC

A PC IS a dissolvable capsule, which is the same size as the PillCam SB, SB2 and SB3 capsule (11 × 26 mm). A PC also equips a radiofrequency identification (RFID) tag to be identified by a specific scanner. The Japanese version of a PC is RFID tag‐less PC to avoid impaction of the RFID tag in stenosis. 73 The first prospective feasibility study of PC was reported by Spada et al. 71 The efficacy of PC has been reported. 67, 73, 71, 74- 76

Nakamura et al. 73 reported the usefulness of a tag‐less PC. They enrolled 100 patients with symptoms or a high risk of capsule retention. They reported that GI patency was confirmed in 87 patients, and no retention occurred in any patient. They concluded that an RFID tag‐less PC confirmed GI patency in patients at a high risk of capsule retention, which allowed safe SBCE.

Zhang et al. 75 conducted a meta‐analysis to estimate the diagnostic value of PC. They showed that the sensitivity of PC for detection of GIT patency was 97% (95% CI, 93-99) and specificity was 83% (95% CI, 65-94). Nemeth et al. 77 conducted a retrospective study of patients with established CD who underwent SBCE for clinical need. They reported that the risk of capsule retention in the SB was 1.5% without use of a prior PC and was 2.1% after a negative patency test ( P = 0.9). They also reported that the risk of capsule retention was not reduced by the non‐selective use (in asymptomatic patients) of a PC, and that a positive PC test was associated significantly with capsule retention.

Indications for SBCE

POSSIBLE INDICATIONS FOR SBCE are OGIB, CD, small‐intestinal polyps and tumors, and celiac disease. 62, 78, 79 Below, we focus on OGIB and CD.

OGIB

Obscure gastrointestinal bleeding is defined as bleeding from the GIT that persists or recurs without an obvious etiology after esophagogastroduodenoscopy, colonoscopy or radiological evaluation of the SB, such as SBFT or enteroclysis. 80 OGIB can be subdivided into occult (iron‐deficiency anemia and/or positive fecal occult blood test) and overt. 11

The advent of SBCE and balloon‐assisted enteroscopy (BAE) has enabled identification of obscure bleeding sources in the GIT in most cases. Thus, clinical guidelines from the American College of Gastroenterology (ACG) have proposed that the term SB bleeding be replaced for the previous classification of OGIB. ACG guidelines also state that the term OGIB should be reserved for patients in whom a source of bleeding cannot be identified anywhere in the GIT. 81

Obscure gastrointestinal bleeding is the main indication for SBCE. 60, 82- 84, 93 and use of anticoagulant drugs. 87 Several medical societies in Western countries and Korea have released diagnostic algorithms for OGIB. 66, 96 Most medical societies recommend that SBCE be the first‐line method for exploring the source of OGIB without obstructive symptoms. The JGES recommends that CT should be the first‐line modality to examine SB bleeding; if abnormalities are found on CT, direct BAE through the closest route is recommended. 96 Japanese gastroenterologists are accustomed to carrying out BAE, so BAE is emphasized for OGIB in Japan. 80, 81, 94, 95 The Japan Gastroenterological Endoscopy Society (JGES) released diagnostic algorithms for OGIB in 2017. 92 timing of CE 91 The diagnostic yield of CE for significant lesions is dependent upon patient status, 62 The diagnostic yield of SBCE for OGIB is 30-70%.

The role of SBCE on SB bleeding is selection of the closest route in BAE. Kaffes et al. 97 reported favorable results after intervention of BAE in patients with obscure GIT bleeding and positive SBCE, which served as a route selection and a filter test. Gay et al. 98 also reported that SBCE could effectively manage the route selection in BAE. Nakamura et al. 99 conducted retrospective analyses to evaluate the accuracy of the transit time of SBCE to the lesion as a predictive indicator for the route selection of BAE. Their results showed that the cut‐off value for route selection was 50% of the SB transit time. They concluded that the SBCE transit time was useful for selecting the route of BAE.

CD

A clinical guideline published recently in Canada suggests that SBCE should be recommended for patients with pathognomonic symptoms of CD in the presence of a negative ileocolonoscopy and radiological studies. SBCE is recommended in patients with established CD showing clinical features unexplained by ileocolonoscopy or cross‐sectional imaging. SBCE is also recommended in established CD to confirm the small‐intestinal mucosal healing. Canadian guidelines suggest that CE is not recommended in patients with chronic abdominal pain or diarrhea without evidence of increased levels of biomarkers. 100 European Society of Gastrointestinal Endoscopy (ESGE) guidelines recommend that CE is the initial diagnostic device for evaluation of the small intestine in patients presenting with suspected CD and demonstrating negative ileocolonoscopic examination in the absence of obstructive symptoms or radiological stenosis. The ESGE also recommends that careful selection of patients based on meticulous assessment of symptoms and serological/fecal inflammatory biomarkers is important to improve the diagnostic accuracy and yield of CE in patients presenting with suspected CD. 101

Crohn's disease is a heterogeneous disease which can affect the entire GIT. Colon capsule endoscopy (CCE) can observe inflamed colonic mucosa non‐invasively. 102 Also, CCE allows continuous and non‐invasive observation of the entire intestinal tract (pan‐endoscopy). Recently, pan‐enteric surveillance and application of CCE as pan‐enteric endoscopy for CD have been reported. 103, 104 Boal Carvalho 103, 104 undertook pan‐enteric surveillance using CCE in 12 CD patients. They confirmed mucosal healing in the SB and colon in three patients (25%), whereas disease activity was limited to the SB or colon in five patients (42%), and observation of the entire GIT was achieved in 10 of 12 patients (83%). et al.

A small‐bowel colon (SBC) capsule (PillCam Crohn's; Medtronic) has been designed to image the SB and colon. 105 The SBC capsule is similar to a second‐generation colon capsule (PillCam COLON 2; Medtronic) with regard to hardware components, but differs in its operation mode. 105 Leighton et al. 105 compared the diagnostic yield of the SBC capsule with ileocolonoscopy in patients with active CD. The per‐patient diagnostic yield for active CD lesions was 83.3% for SBC and 69.7% for ileocolonoscopy (yield difference, 13.6%; 95% CI, 2.6-24.7); 65% of patients had active‐CD lesions identified by both modalities. Of the 12 people who tested positive for active CD by SBC only. Three individuals were positive for active CD by ileocolonoscopy only. They concluded that the diagnostic yields for SBC may be higher than that for ileocolonoscopy, but further study is needed to confirm their results.

Future Perspectives

SMALL‐BOWEL CAPSULE ENDOSCOPY plays a pivotal part in the diagnosis of SB disorders and will not be replaced by an alternative device. However, SBCE will evolve with new functions. For example, SBCE devices will be advanced further, including high‐frame‐rate imaging, full spherical imaging and high‐resolution imaging. With regard to CE software, artificial intelligence and computer‐assisted diagnosis will be applied to reduce the burden for CE readers. 106 Hence, the need to read CE videos for long periods will be removed.

Acknowledgment

WE THANK ARSHAD Makhdum, Ph.D., from Edanz Group ( www.edanzediting.com/ac) for editing a draft of this manuscript.

Conflicts of Interest

N.H. CONDUCTED INDEPENDENT research supported by a funding contribution from Medtronic. N.H. received a research grant from Olympus. Other authors have no COI to disclose.

Number of times cited according to CrossRef: 5

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Thomas Chateau, Ferdinando Damico, Camille Zallot, Nicolas Mathieu, Laurent Peyrin-Biroulet, Crohn's Disease Only Visible on Small Bowel Capsule Endoscopy: A New Entity, Digestive Diseases and Sciences, 10.1007/s10620-020-06553-3,

Hua‐sheng Lai, Xin‐ke Wang, Jian‐qun Cai, Xin‐mei Zhao, Ze‐long Han, Jie Zhang, Zhen‐yu Chen, Zhi‐zhao Lin, Ping‐hong Zhou, Bing Hu, Ai‐min Li, Si‐de Liu, Standing‐type magnetically guided capsule endoscopy versus gastroscopy for gastric examination: multicenter blinded comparative trial, Digestive Endoscopy, 10.1111/den.13520, 4, (557-564), 32,

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Capsule endoscopy for small‐intestinal disorders: Current status

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Naoki Hosoe Corresponding Author E-mail address: nhosoe@z5.keio.jp https://orcid.org/0000-0002-4516-5648 Center for Diagnostic and Therapeutic Endoscopy, School of Medicine, Keio University, Tokyo, Japan Corresponding: Naoki Hosoe, Center for Diagnostic and Therapeutic Endoscopy, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku, Tokyo 160‐8582, Japan.

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The history of time for capsule endoscopy

Capsule endoscopy entered the domain of clinical gastroenterology in the year 2001 with the clearance by the Food and Drug Administration (FDA) and obtaining CE Mark certification. The journey from conception to implementation started 20 years earlier. In 1981, Gavriel Iddan took a sabbatical from his regular position as a senior engineer at the electro optical design section of Rafael, the research and development (R&D) branch of the Israeli Ministry of Defense. Iddan had taken an interest in medical imaging and spent his leave to study X-ray and ultrasound imaging for Elscint (a company dedicated to medical imaging) in Boston. His neighbor, Eitan Scapa, an Israeli gastroenterologist spent his sabbatical in a medical institution in Boston as well. The two befriended each other and Iddan learned about the use of fiber optics in the gastrointestinal tract. Scapa explained to Iddan that the technology of fiber optics left the small bowel out of reach for medical inspection. That is when Iddan became aware of the medical challenge and started thinking about solutions. In the meanwhile, small charged coupled device (CCD) imaging chips reached the market. Ten years later, on a second sabbatical, Iddan considered using the CCD miniature camera connected to an electrical umbilical cord. The length of the small bowel precluded this option. That is when he suggested cutting the umbilical cord, in its stead attaching a mini transmitter to the CCD camera and letting the device travel on its own. However, the CCD elements consume a lot of energy and miniature batteries would permit at best 10 min transmission time. More problems accumulated. How would the capsule guarantee adequate visibility, debris could obscure the surface of the camera? A capsule study of the small intestine is likely to take many hours and occupy patient and physician at the screen for a large amount of time. How would it be possible to free patient and physician from a lengthy exam and limit the time necessary at the screen? In 1993, Iddan came up with the brilliant idea to split the system into three parts. Part one: the camera and its transmitter. Part two: a recorder attached to a sensor array placed on the surface of the patient's abdomen. Part three: a software package that processes the stored information on the recorder to generate a study that can be reviewed by the physician at his leisure in a reasonable amount of time. The problem of the energy guzzling CCD camera was solved nearly by coincidence. While reading a journal on optical engineering ( 1), Iddan came across an article by Eric Fossum. He described the use of a Silicon chip (CMOS-complementary metal oxide semiconductor) and in near clairvoyance predicted that CMOS would replace CCD. This would happen for multiple reasons not the least that they consume just one percent the amount of energy of CCDs. Fossum would later assist the Given Imaging team of engineers ( 2). Now the pieces were beginning to fall into place. Further miniaturization of the components helped along.

The translation of concept to reality would require an organization with funds but first and foremost the expertise of very innovative engineers to create the elements for a functioning capsule camera. In 1994, Gavriel Iddan met Gavriel Meron who precisely did that, namely raised the necessary funds and recruited the talented physicists and engineers (Here is a list of some of the people involved: Dov Avni, Avner Badichi, A. Reichert, B. Ehrlich, H. Kislev, Y. Avron, D. Adler, M. Frish, A. Glukhovsky, S. Friedman and other talented people. Many of these were students of Prof. Y. Kidron from the Technion in Haifa). The original patent of Gavriel Iddan (awarded in 1997) envisioned a CCD chip, which was too bulky and consumed too much energy. The light generated by a heated filament consumed too much energy, was too weak and did not turn on/off fast enough. The optical design was not suitable. Meron understood that he could not buy the miniature camera elements off the shelf. His team would have to create them. Dov Avni's specialty was analog video. He too had spent many years at Rafael, the same R&D branch of the Israeli Ministry of Defense that Gavriel Iddan was working at. Avni was charged to create de novo an imager, a light source and miniaturize all the components. Once he informed Meron that he had solved the technical challenges of the CMOS chip imager, Meron was ready to move. Meron's team consulted with the Sarnoff Corporation at Princeton, an institute dedicated to the research in vision, video and semiconductor technology. The leading research expert of the Sarnoff Corporation predicted that it would be impossible to generate sharp images with CMOS technology because at body temperature the signal to noise ratio was too low due to the presence of random photons. Avni though, knew that engineers at Tower Semiconductor (Migdal Haemek, Israel) had solved this problem. They confirmed Avni's design. Together they had developed a process to manufacture CMOS imagers that overcame this particular problem. Then Meron founded Given Imaging in 1998. He defined the company's mission "to develop, produce... swallowable disposable electronic capsule". Avni and his team mate Oded Koren were the first to use Nakamura's invention of LED as a light source for an optical device. This allowed for energy saving and management at the microsecond level. The optical dome received an ellipsoid shape to prevent light reflection.

While this activity was in full progress in Israel, Paul Swain, independently in the United Kingdom experimented with wireless transmission from mini cameras and succeeded to send live images from a pig's stomach to a video screen ( 3). Meron met Swain in 1997 at the United European Gastroenterology Week (UEGW) in Birmingham. They decided to join forces. Swain was keenly aware of the colossal achievements made in Israel. He reports "... successfully overcoming the enormous obstacles of size, transmission strength, battery power, image resolution, among many others working prototypes were produced in January 1999 by the Given Imaging R&D group headed by Dr. Arkady Glukhovsky" ( 4). Paul Swain received the honor to be the first human on planet earth to swallow a capsule endoscope. This took place October 1999 in Dr. Scapa's office in Ramat Hasharon near Tel Aviv. Eitan Scapa, Paul Swain and nearly the entire Given Imaging team (8 to 10 people) gathered in his basement, their eyes glued to the screen. A minor drama took place. The capsule did not leave Paul Swain's stomach for over three hours. Scapa passed an endoscope without sedation into Swain and with a snare moved the capsule into the duodenum. Three years later, in April 2002, the first international capsule endoscopy conference took place in Rome, Italy. I was among the over 90 physicians who had convened from 12 different countries to share their first experience on some 850 studies. I remember the excitement that was palpable in the hall during the three-day conference when every presenter produced new images and videos of small intestinal pathology that had remained hidden to the human eye until then. All of us were aware that we had just set foot on terra incognita and that the capsule had moved the border of knowledge in gastroenterology another mile forward. A month later, at Digestive Disease Week (DDW) in San Francisco, physicians presented more than 30 abstracts on capsule endoscopy. Since then the number of peer-reviewed publications on capsule endoscopy has skyrocketed (see ). At DDW I ran into Gavriel Iddan, the dreamer of capsule endoscopy. Beaming with happiness, he said to me, do you know what a physician just told me? Because of your capsule, I was able to save a patient's life! Iddan had realized his dream. He had wanted to help patients.

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The history of time for capsule endoscopy

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Capsule endoscopy was conceived by inventive minds of good people. In the beginning there was a will to do something for medicine. The idea fomented after a discourse between the talented engineer with his physician friend. It took years to develop the ...

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Abstract

Capsule endoscopy (CE) has transformed investigation of the small bowel providing a non-invasive, well tolerated means of accurately visualising the distal duodenum, jejunum and ileum. Since the introduction of small bowel CE thirteen years ago a high volume of literature on indications, diagnostic yields and safety profile has been presented. Inclusion in national and international guidelines has placed small bowel capsule endoscopy at the forefront of investigation into suspected diseases of the small bowel. Most commonly, small bowel CE is used in patients with suspected bleeding or to identify evidence of active Crohn's disease (CD) (in patients with or without a prior history of CD). Typically, CE is undertaken after upper and lower gastrointestinal flexible endoscopy has failed to identify a diagnosis. Small bowel radiology or a patency capsule test should be considered prior to CE in those at high risk of strictures (such as patients known to have CD or presenting with obstructive symptoms) to reduce the risk of capsule retention. CE also has a role in patients with coeliac disease, suspected small bowel tumours and other small bowel disorders. Since the advent of small bowel CE, dedicated oesophageal and colon capsule endoscopes have expanded the fields of application to include the investigation of upper and lower gastrointestinal disorders. Oesophageal CE may be used to diagnose oesophagitis, Barrett's oesophagus and varices but reliability in identifying gastroduodenal pathology is unknown and it does not have biopsy capability. Colon CE provides an alternative to conventional colonoscopy for symptomatic patients, while a possible role in colorectal cancer screening is a fascinating prospect. Current research is already addressing the possibility of controlling capsule movement and developing capsules which allow tissue sampling and the administration of therapy.

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Capsule endoscopy: current practice and future directions.

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Capsule endoscopy: current practice and future directions.

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CONTENTS

1.0 Introduction

2.0 Formulation of guidelines

2.1 Grading of recommendations

2.2 Scheduled review

3.0 Summary of recommendations

4.0 Types of small bowel enteroscopy

4.1 Enteroscopy using a colonoscope

4.2 Sonde enteroscopy

4.3 Push enteroscopy

4.4 Intraoperative enteroscopy

4.5 Double balloon (push and pull) enteroscopy

5.0 Capsule endoscopy

5.1. Technique

5.2 Indications for capsule endoscopy

5.3 Complications of capsule endoscopy

5.4 Patency capsule

6.0 Service provision and training

References

1.0 INTRODUCTION

The small bowel has historically been a difficult area to examine due to its anatomy, location and relative tortuosity. Examination beyond the duodenojejunal flexure is of importance in a number of small bowel disorders. Before the advent of enteroscopy or capsule endoscopy, radiographic studies had been the main investigative modality of the small bowel. Barium follow-through and enteroclysis permits indirect examination of the small bowel but has a low diagnostic yield particularly in the context of obscure gastrointestinal bleeding.1 ⁻ 3

Capsule endoscopy and enteroscopy are now the preferred methods to examine the small bowel in most situations. These guidelines are intended to provide an evidence based document describing endoscopic investigation of small bowel disorders.

2.0 FORMULATION OF GUIDELINES

These guidelines were commissioned by the Clinical Services and Standards Committee of the British Society of Gastroenterology (BSG) and have been produced by the small bowel and endoscopy sections of the BSG. The guidelines have been produced to conform to the North of England evidence based guidelines development project.4 5 They have been drawn up from a Medline, Embase and Ovid literature search using terms "enteroscopy", "push enteroscopy", "intraoperative enteroscopy", "double balloon enteroscopy" and "capsule endoscopy". There have been 180 peer review studies, seven review articles, 58 case reports and letters, and one set of American guidelines on enteroscopy.6 The literature search for capsule endoscopy includes 100 peer review studies, 51 review articles, 74 ...

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Guidelines on small bowel enteroscopy and capsule endoscopy in adults

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1.0 Introduction 2.0 Formulation of guidelines 2.1 Grading of recommendations 2.2 Scheduled review 3.0 Summary of recommendations 4.0 Types of small bowel enteroscopy 4.1 Enteroscopy using a colonoscope 4.2 Sonde enteroscopy 4.3 Push enteroscopy 4.4 Intraoperative enteroscopy 4.5 Double balloon (push and pull) enteroscopy 5.0 Capsule endoscopy 5.1.

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Eliana
Medan
Ghadeer
Prahglaad
Pravin

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Samuel N. Adler, (2017). The history of time for capsule endoscopy. Annals of Translational Medicine, 5(9), p.194.