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May 5, 2017 - Salvatore Olivaa, Salvatore Cucchiaraa and Stanley Allen Cohenb. aPediatric Gastroenterology and Liver Unit, Department of Pediatrics, ...
Expert Review of Gastroenterology & Hepatology

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Recent advances in pediatric gastrointestinal endoscopy: an overview Salvatore Oliva, Salvatore Cucchiara & Stanley Allen Cohen To cite this article: Salvatore Oliva, Salvatore Cucchiara & Stanley Allen Cohen (2017): Recent advances in pediatric gastrointestinal endoscopy: an overview, Expert Review of Gastroenterology & Hepatology, DOI: 10.1080/17474124.2017.1321986 To link to this article: http://dx.doi.org/10.1080/17474124.2017.1321986

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Date: 09 May 2017, At: 19:17

EXPERT REVIEW OF GASTROENTEROLOGY & HEPATOLOGY, 2017 https://doi.org/10.1080/17474124.2017.1321986

REVIEW

Recent advances in pediatric gastrointestinal endoscopy: an overview Salvatore Olivaa, Salvatore Cucchiaraa and Stanley Allen Cohenb Pediatric Gastroenterology and Liver Unit, Department of Pediatrics, Sapienza – University of Rome, Rome, Italy; bChildren’s Center for Digestive Health Care, Atlanta, GA, USA

a

ABSTRACT

ARTICLE HISTORY

Introduction: Pediatric gastrointestinal endoscopy has become a fundamental component of health care for infants and children. New imaging technologies and creative extraluminal applications have brought exciting and clinically important benefits to pediatric gastrointestinal endoscopy. Areas covered: The impact of different new technologies in pediatric endoscopy and focused on improvements in mucosa visualization and the application of new noninvasive tools and procedures to avoid biopsies or surgery are reviewed. Expert commentary: Enhancement in mucosal visualization and reduction of anesthesia and biopsies are the main goals that guide the endoscopy development in pediatrics. The advent of newer imaging modalities has allowed clinicians to characterize and evaluate subtle mucosal lesions better, while advancements in current endoscopes have created the opportunity to monitor chronic conditions noninvasively. Continued expansion of these modalities seems certain, with increased utilization in pediatric gastroenterology.

Received 26 November 2016 Accepted 19 April 2017

1. Introduction

2. Advances in imaging

Since the advent of endoscopy, applications in pediatrics have improved the health care of infants and children, with an increased number of pediatric gastroenterologists now trained in basic and advanced procedures (including enteroscopy, endoscopic retrograde cholangiopancreatography, endoscopic ultrasonography, etc.). The evolution of endoscopic technology and the development of many novel devices, diagnostic techniques, and treatments have furthered that thrust. These new technologies and therapies have usually targeted adult patients with slower adaptation for pediatric patients, due to constraints because of size limitations, economics related to relative indications in the different populations, and perceived difficulties in performing the necessary research to evaluate efficacy and safety. Fortunately, several procedures begun in adults, such as percutaneous endoscopic gastrostomy, variceal band ligation, and endoscopic retrograde cholangiopancreatography, are now established procedures in pediatric gastroenterology. Recently, new imaging and resection technologies, novel ablation, and creative extraluminal applications have taken pediatric gastrointestinal endoscopy to an exciting threshold. The benefits are already being recognized in terms of reduced procedural invasiveness, decreased sedation and cost, improved diagnostic yield, and better monitoring of chronic diseases (Table 1). This review aims to discuss some of the most recent advances in pediatric endoscopy that have broadened the horizons of pediatric endoscopy (Figure 1).

2.1. High-definition endoscopy

KEYWORDS

Pediatric endoscopy; capsule endoscopy; children; high definition endoscopy; narrow band imaging

High-definition (HD) endoscopy results in visualization of the mucosa in more detail and better definition of very small lesions. HD endoscopes have up to 1 million charged-coupled device (CCD) chips, compared with the 100,000–300,000 chips in a conventional endoscope [2]. All the constituents (endoscope, processor, monitor, cables) must be HD qualified in order to acquire HD images during examinations. These HD chips have a lower light sensitivity, caused by pixels of reduced size, and necessitate of a strong light source [3]. In adults, the improved detection of dysplastic changes in IBD and Barrett’s esophagus is remarkable. A retrospective adult study has demonstrated a higher adenoma detection rate of HD colonoscopy (especially with flat- or right-sided lesions) in long-standing colonic IBD [4]. While HD endoscopy aims less to detect dysplastic lesions in children (due to the lower incidence of childhood GI cancers), its use is also becoming more widespread in the last years. Indeed, despite the absence of pediatric data on HD in clinical practice, the majority of the main pediatric endoscopic centers throughout the world use this technology such that HD endoscopy is becoming the standard of care [5]. For this reason, it is of critical importance for centers to consider using HD endoscopy when setting up or renovating a pediatric endoscopy room.

2.2. Wide-view full-spectrum endoscopy The viewing angle of endoscopes is also improving, bringing the standard viewing angle from 170° to 330°. This platform is

CONTACT Salvatore Oliva [email protected] Department of Pediatrics, Pediatric Gastroenterology and Liver Unit, Sapienza - University of Rome, University Hospital Umberto I, Viale Regina Elena 324, 00161 Rome © 2017 Informa UK Limited, trading as Taylor & Francis Group

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HD: High definition; NBI: narrow band imaging; CLE: confocal laser endomicroscopy; CCE: colon capsule endoscopy; SBC: small bowel and colon capsule; POEM: peroral endoscopic myotomy; OCT: optical coherence tomography.

No routine indications. Discriminating between squamous esophagus and Barret’s Esophagus with or without dysplasia

No routine indications, only research setting (personalized medicine and targeted therapies) Monitoring colonic disease in a noninvasive way. Monitoring IBD with small bowel and colonic locations Promising indications in pan-intestinal monitoring of IBD Monitoring chronic esophageal conditions, such as Barrett’s esophagus and eosinophilic esophagitis in the pediatric age Treatment achalasia in children and adolescents

Differentiation of inflammatory, dysplastic, or heterotopic lesions. To guide targeted biopsies in celiac disease as well as in IBD No routine indications, only research setting

Potential role in incomplete cecal intubation and terminal ileum evaluation

Indications Disadvantages Advantages

Visualization of a more detailed mucosa and a better definition of very small Increased costs compared to standard lesions definition Wide-view full Extended view with a 330° angle Increased costs and limited availability spectrum NBI Readily available (push-of-a-button technologies) improved detection of Expert skills required and adequate training lesions CLE Real-time histologic imaging with 1000-fold magnification potentially Time- and cost-intensive procedure, expert improved evaluation of mucosal inflammation skills required Molecular Beyond the detections of lesions, it could enhance drug delivery and monitor Time- and cost-intensive procedure, needing imaging drug response of molecular probes CCE Lack of ionizing radiation, deep sedation, and general anesthesia. Possibility Inability to perform biopsies, not developed to obtain images from small bowel and colon for small bowel evaluation SBC Same advantages of CCE but specifically designed for pan-endoscopy Limited availability, recent development Ultra-slim Reduce and eliminate the need for the anesthesia while improving patient Increased costs and limited availability satisfactions POEM Shorter operative time, reduces intraprocedural blood loss, shorter hospital The data of POEM in the children are very stay limited OCT Noninvasive, not require conscious sedation Low-contrast imaging and decrease the prediction of pathology HD

Technique

Table 1. New endoscopic techniques with advantages and indications.

Assessment of dysplastic lesions, but it is becoming the standard of care

S. OLIVA ET AL.

called ‘wide-view full-spectrum endoscopy’ and was first developed for polyp detection [6]. Its utility was recently evaluated in a small cohort of adult patients in order to obtain a 100% cecal intubation rate with the technology highly appreciated by both patients and endoscopists [7]. According to recent pediatric data with the standard scope, the terminal ileal intubation rate is approximately 70–80% [8,9], with the potential for this new platform to contribute to improved terminal ileum evaluation.

2.3. Narrow band imaging Narrowed-spectrum endoscopy is so called because this group of image-enhancement techniques relies on using only a fraction of the available spectral bandwidth, mainly corresponding to ‘blue light.’ This is accomplished through optical or digital filtering and has also been termed ‘virtual chromoendoscopy.’ Narrow band imaging (NBI) functions by filtering the illumination light. The red component of the standard red, green, and blue filters is discarded and the spectral bandwidth of the blue and green light filters, centered on 415 and 540 nm, respectively, is reduced from 50–70 nm to 20–30 nm. The incoming signals from the CCD are combined by the video processor to produce a false-color image. Hemoglobin presents an absorption peak at 415 nm and therefore, it strongly absorbs the ‘blue’ light; furthermore, these shorter wavelengths penetrate the mucosa less deeply than red light which presents a wavelength of 650 nm [10]. This results in increased contrast for superficial microvessels which appear brown/ black and in greater clarity of mucosal surface structures [11]. All major manufacturers now offer this functionality built into endoscopic systems as a standard feature of HD endoscopes [3]. In adults, NBI has been applied in Barrett’s esophagus, gastric metaplasia, and colonic polyps to enhance the targeting of both intestinal metaplasia and dysplasia [12,13]. There are insufficient data on NBI in inflammatory bowel disease, despite several small studies. However, according to the largest surveillance study in (adult) ulcerative colitis, NBI seems to have a higher diagnostic yield compared to random biopsies (9% vs. 0.04%) [14]. In the pediatric population, NBI might be applied in discriminating heterotopic lesions (i.e. inlet patch) or differentiating between suspected eosinophilia and erosive esophagitis (Figure 2(a,b)), as well as to guide targeted biopsies in celiac disease. However, only low-quality evidence has come out to date and NBI has not yet increased the diagnostic yield of endoscopy [15–18]. On the other hand, the increased knowledge and diffusion of this tool, combined with the absence of additional equipment costs, makes this an appealing technique [21,22]. The development of new NBI techniques which are able to provide a greater illumination and lighter images has overcome the difficulty of older systems to evaluate broad areas of mucosa or lesions in larger lumens. Future data are needed to employ this technique in clinical pediatric GI practice and to increase training in pediatric units.

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Figure 1. Overview of existing and emerging endoscopic technologies to visualize macroscopic or microscopic features of the intestine. Macroscopic technologies include: high-definition endoscopy, wide-view full-spectrum endoscopy, chromoendoscopy, and autofluorescence endoscopy. Microscopic technologies include: endocytoscopy, confocal laser endoscopy, multiphoton endoscopy, and molecular imaging endoscopy. A detailed description for each modality is given in the text. Reproduced from world j gastroenterol 2016; 22: 5642–5654 [1].

Figure 2. Images of narrow band imaging. (a) Endoscopic image in white light showing linear furrows, white plaques, and subtle rings in EOE. (b) The corresponding narrowing band image of the same endoscopic findings of the (a). Reprinted from Clinical Gastroenterology and Hepatology 2011; 9:475–480 Peery, Cao, Dominik, et. al, Variable Reliability of Endoscopic Findings with White-Light and Narrow-Band Imaging for Patients with Suspected Eosinophilic Esophagitis [17] with permission from Elsevier. Images of CONFOCAL LASER ENDOMICROSCOPY

(c) Normal colonic mucosa with regularly distributed round crypts at Confocal Laser Endomicroscopy. The crypt openings are small and dark because no fluorescein is leaking (arrow). (d) The epithelial cells of the colonic crypt are eroding with subsequent fluorescein leakage into the lumen (arrow) at CLE. Reprinted from Gastrointest Endosc. 2016;84:279–286 Karstensen, Săftoiu, Brynskov et. al. Confocal laser endomicroscopy in ulcerative colitis: a longitudinal study of endomicroscopic changes and response to medical therapy [19] with permission from Elsevier. Images of MOLECULAR IMAGING

(e) Representative endoscopic images of the inflamed mucosa of patients with Crohn’s disease (n = 25). While there are similar levels of mucosal inflammation, molecular in vivo imaging revealed high (top) or low (bottom) mucosal mTNF expression. Scale bars, 50 μm. Reprinted by permission from Macmillan Publishers Ltd: Nat Med. 2014; 20: 313–318 Atreya, Neumann, Neufert et al. In vivo imaging using fluorescent antibodies to tumor necrosis factor predicts therapeutic response in Crohn’s disease [20], copyright 2014.

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2.4. Confocal laser endomicroscopy Confocal laser endomicroscopy (CLE) is a new technology that supposedly can provide endoscopic images similar to histology. By applying a blue laser light and specific filters, it is possible to obtain a single gray-scale image of a single plane. There are two different systems of CLE, one using a specific probe (pCLE) (Cellvizio; Mauna Kea Technologies, Paris, France) of up to 2.8 mm in diameter that can be inserted in an endoscope’s working channel and the other incorporated at the tip of the endoscope (eCLE) (Optiscan, Nottinghill, Victoria, Australia and PENTAX Medical, Montvale, NJ), though the latter has not been commercially available since 2014 [23]. The clinical application of CLE has demonstrated encouraging results. In adults, this technology has been widely studied in detection of Barrett’s esophagus or gastric lesions, but there are also reports of it assisting in the diagnosis of celiac disease [24,25]. The most important advantage of CLE seems to be the ability to better identify dysplastic lesions (34% vs. 7% of standard endoscopy) with a significant reduction of the number of biopsies [26]. A recent pediatric study has shown the ability of pCLE in predicting moderate-to-severe IBD relapse in children by evaluating barrier dysfunction in the terminal ileum. The addition of pCLE to routine colonoscopy may significantly aid clinicians to risk stratify and better manage patients [27,28] (Figure 2(c,d)). A future field of application would be in discriminating between IBS and food allergy. Indeed, a recent adult study reported the possibility of verifying hypersensitivity reactions to food antigens using pCLE when conventional testing failed to provide a diagnosis [29]. The major limitation still remains the significantly increased procedural duration incurred by such detailed imaging. Also, there is a steep learning curve to gain the needed skill to interpret the images that are vastly different from traditional endoscopic images. One study estimated that an average of 35 cases is required to interpret post-procedural CLE images with 93% accuracy [30,31]. Case selection and adequate training in specialized units will be key to maximizing outcomes obtained from this modality and in gaining pediatric applicability beyond the few tertiary centers currently using the technique.

2.5. Molecular imaging The constant improvement in medical imaging may allow clinicians to target and highlight desired pathology by using exogenous molecular probes that specifically enhance tissue signals, not only for detection of lesions but also for drug delivery and/or drug response [32,33]. Autofluorescence uses a natural tissue fluorescence of endogenous molecules (fluorophores) to obtain virtual chromoendoscopy [34]. Indeed, by using this tool, it is possible to identify dysplasia or cancer, which usually emanates a different autoflorescene spectrum compared to normal tissue. In a recent pilot study on 25 Crohn’s disease patients, the monitoring of antitumor necrosis factor (TNF) alpha therapy response has been assessed by a molecular-targeted confocal endomicroscopy. By using a topical fluorescent anti-TNF-antibody which is able to visualize and fix selectively membrane-

bound TNF, it was possible to predict higher short-term response of therapy or mucosal healing in patients with a higher numbers of TNF on inflammatory cells [20] (Figure 2(e)). This study actuates the long-held goal of personalized medicine in which endoscopy can guide and monitor-targeted therapies.

3. Advances in endoscopes 3.1. Colon capsule and pan-enteric capsule endoscopy Capsule endoscopy (CE) use is increasing over time, especially in children, because of the opportunity to avoid deep sedation or ionizing radiation. The advent of new technologies has extended its applicability to the evaluation of the esophagus and colon as well as to new indications in the diagnosis or monitoring of GI disease. A new colon CE model (CCE, PillCam COLON 2, Medtronic, formerly known as Given Imaging, Yoqneam, Israel) contains two cameras and a wider angle of view (172°). This CCE has an extended battery and it is able to capture images with an adaptive frame between 4 and 35 fps according to its movement along the GI tract. Although CCE was initially developed as a tool for colon cancer screening, its best results have been obtained in IBD, especially in children. Different studies have described its potential application as a less invasive colonoscopy in assessing Ulcerative Colitis (UC) [35]. In the largest adult study on 100 UC patients, CCE showed a sensitivity of 89% and a specificity of 75% in detecting colonic inflammation. In the pediatric age group, better results were obtained as described recently in 29 pediatric UC patients. The sensitivity and specificity of CCE were 96% [95% CI 79–99] and 100% [95% CI 61–100], respectively. Moreover, the technique appeared highly reproducible, obtaining an excellent interobserver agreement (kappa > 0.81) [36]. Despite these promising results, there are still limitations in the use of CCE to assess UC. The capsule may not reach the rectum because of the 12-h battery life expiring. And while the majority of pediatric UC has an extensive disease location, cases could be missed by CCE. In common with CE of the small bowel, the inability to obtain biopsy specimens is a further limitation [37]. As a result, its role can not include any indication requiring biopsies (i.e. surveillance, Cytomegalovirus infections). Although CCE was developed for the assessment of the colon, images of the entire GI tract can be obtained [38]. This has prompted interest in establishing its potential for pan-intestinal endoscopy. In a small adult cohort, its efficacy has been verified in evaluating small bowel and colon of 12 CD patients [39]. As in UC, CCE has demonstrated its best applicability in pediatric age. In a recent report, this technique has proven to be effective in evaluating both Small Bowel (SB) and colon in pediatric CD in comparison with other imaging modalities and standard colonoscopy. CCE was able to explore the entire GI tract with a high diagnostic accuracy (sensitivity of 89% and specificity of 92%) [40]. According this study, CCE can be considered as a noninvasive tool to evaluate both SB and colon concurrently and as ‘one-step’ device (Figure 3), which can change the monitoring of pediatric IBD, obtaining better results and reducing cost and the need of anesthesia.

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Figure 3. Colon capsule images of the small bowel and colon.

On the basis of the emerging data on the usefulness of panenteric endoscopy for monitoring IBD, a small-bowel colon (SBC) capsule, PillCam Crohn’ s (Medtronic) has been designed to image the small bowel and colon (Figure 4), replacing multiple diagnostic procedures in CD patient management and doing so without sedation. The SBC capsule is a two-headed video capsule, with a field of view of 172° in each head, and a frame rate up to 35 frames per second that adapts to the speed of capsule transit through the bowel. The SBC capsule is thus similar to the CCE in all its hardware components but differs in its operation mode, designed to provide complete coverage of the small bowel in addition to the colon. The video compilation for the SBC system has been optimized for efficient visualization of lesions indicative of inflammatory bowel disease. Preliminary data in 66 adult CD show that the diagnostic yields for SBC might be higher when compared to standard colonoscopy (83.3% and 69.7%, respectively). However, further prospective studies are needed to corroborate these data, especially in pediatrics. The advent of these noninvasive technologies seems to be able to change our way to monitoring IBD and other chronic diseases. Indeed, a recent pediatric study confirmed the ability of CCE in guiding therapy in a treat-to-target strategy of pediatric IBD, demonstrating a significant increase of mucosal healing and deep remission rate [41].

3.2. Ultra-slim endoscopes Endoscope diameter of pediatric instruments has always been smaller than the adult designated endoscopes. The newest

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slimmer generation colonoscope and upper endoscope may reduce or eliminate the need for anesthesia during procedures. Indeed, the ultra-slim gastroscope (GIF-XP190N, Olympus, Japan) can be suitable for trans-nasal Esophagogastroduodenoscopy (EGD). This seems of particular value in monitoring chronic esophageal conditions, such as Barrett’s esophagus and eosinophilic esophagitis. A recent pediatric report has evaluated the performance of unsedated trans-nasal EGD with biopsies in monitoring the esophageal mucosa of pediatric patients with eosinophilic esophagitis. This technique appeared accurate and well tolerated by children, considering that 76.2% of subjects would undergo the procedure again [42]. The use of such new endoscopes has the added value of reducing the use of anesthesia, which may lower the risk of complications, reduce sedation costs, and preserve or improve patient satisfaction.

4. Advances in therapeutic options 4.1. Peroral endoscopic myotomy Peroral endoscopic myotomy (POEM) can be performed by gastroenterologists and surgeons to treat achalasia. This technique uses transluminal endoscopic surgery to obtain results similar to the Heller myotomy. The myotomy is performed by creating a submucosal tunnel in the esophagus and performing minimal dissection of the inner circular muscle of the distal esophageal part as well as the lower sphincter. The advantage of this tool is that the equipment is easily accessible and well suited for standard endoscopes. There are few studies on POEM in the pediatric age group. The first experience in a 3-year-old child showed an excellent symptom response at 1-year follow-up [43]. Same results have been observed in a small series with satisfactory outcome [44]. Various studies have confirmed the safety and efficacy of POEM in pediatrics [45–47]. The strengths of this technique are the shorter operative time and hospital stay, reduced intraprocedural bleeding as well as the ability to elongate the myotomy depending on achalasia type [48–50]. Additionally, the risk of post-procedure gastroesophageal

Figure 4. PillCam Crohn’s capsule. Image of the 2-headed video capsule for evaluation of the small bowel and colon.

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reflux disease seems to be lower compared to Heller myotomy, due to the absence of dissection of the diaphragmatic hiatus and division of the crura [51]. Hopefully, long-term outcome data will assess the technique’s benefits and role in the pediatric age group.

5. Advances beyond the gut 5.1. Optical coherence tomography Optical coherence tomography (OCT) uses a low-coherence laser to help health-care professionals visualize the internal microstructure of tissues by measuring differences in time delay between light that backscatters from below the tissue surface and a reference beam. It was initially developed for ophthalmology, is noninvasive, and analogous to Endoscopic Ultrasonography though it uses a laser instead of sound waves, without air producing artifacts [52]. Imaging depth is limited by optical attenuation from tissue scattering and absorption such that assessment only extends to 3 mm depth in most tissues [53]. Other limitations include low-contrast imaging and high interobserver and intra-observer variation between image interpretation and prediction of pathology [54] A swallowable, tethered capsule endomicroscopy (TCE) device that can acquire microscopic OCT images of GI tract luminal organs has recently been developed to provide a more comfortable procedure that does not require conscious sedation or the assistance of endoscopy [55,56]. The OCT–TCE procedure is also simple, as it does not need to be conducted in a specialized setting and can be performed by a nurse or other nonphysician medical personnel. However, the capsule optics focuses light approximately 500 μm outside the capsule wall and the best quality images are obtained when the tissue is in a full contact with the capsule. Usually, peristalsis ensures that this occurs, but there are cases where the esophagus opens during the transit of the capsule. The current mode of operation for loss of contact is to stop the movement of the device and ask the patient to sip water, at which point the esophagus reengages the capsule. It is therefore crucial for the catheter operator to receive feedback about tissue contact during the imaging procedure to acquire best quality data. TCE provides detailed information about tissue microstructure. By analyzing TCE images, it is possible to characterize the esophageal wall, discriminating between squamous esophagus and Barrett’s esophagus with or without dysplasia (i.e. lack of layered structure) since TCE visualizes the squamous architecture in detail [57]. This fully automated method for the segmentation and characterization of esophageal tissue using OCT–TCE in vivo could be applied in the near future for evaluation and monitoring of eosinophilic inflammation in Eosinophilic Esophagitis (EoE) patients, potentially lessening the need for biopsies and sedation. Only preliminary animal models are available so far, and new studies are critically awaited [58].

6. Expert commentary Over the past years, pediatric gastroenterologists have seen multiple advances and new techniques in diagnostic and

therapeutic endoscopy that are continuously transforming the field. However, only a part of the overall innovations in adult endoscopy is ideally suited for pediatric patients. This is related, in part, to the disease prevalence in each population and the specific requirements entailed for each. The advent of newer imaging modalities has allowed physicians to better characterize and evaluate subtle mucosal lesions, while the upgrading of current endoscopes, as well as the development of novel tools (such as the latest capsule models), has opened the door of noninvasive monitoring of chronic conditions (i.e. IBD, EoE, Barrett’s esophagus). Finally, the use of molecular tools and other techniques able to appreciate the microscopic and intestinal wall changes are offering the opportunity to avoid biopsies and reduce procedure duration. The interventional value of pediatric GI endoscopy is well documented. With the advances obtained in recent years, we are now observing the beginning of a new era in which therapeutic endoscopy will be even closer to minimal invasive surgery. However, optimal diagnostic acumen must be balanced by minimizing intrusion into our children’s lives and maintaining the greatest margin. Reduction of anesthesia and biopsies and the enhancement in mucosal visualization remain the principle goals that guide the endoscopy development in pediatrics.

7. Five-year view Endoscopy will be increasingly utilized in the practice of pediatric gastroenterology in the future, revolutionizing our concept of these evolving modalities. Innovators will attempt to guide us to newer less invasive examination of GI tract and greater applicability. Meanwhile, the challenge will be the addition of HD imaging and further software image enhancement of the current noninvasive modalities to the point of offering accurate and sustainable pan-intestinal examination.

Key issues ● Since the advent of endoscopy, applications in pediatrics have improved the health care of infants and children, with an increased number of pediatric gastroenterologists now trained in basic and advanced procedures. ● Despite the absence of pediatric data on the new HighDefinition (HD) Endoscopy in clinical practice, the majority of the main pediatric endoscopic centers over the world use this technology with HD becoming the standard of care. ● Narrow Band Imaging (NBI) may be able to be applied in pediatric patients to define heterotopic lesions (i.e. inlet patch) and differentiate between suspected eosinophilic and erosive esophagitis, as well as to guide targeted biopsies in celiac disease. However, only low quality evidence has come out to date and NBI has not yet increased the diagnostic yield of endoscopy. ● Capsule endoscopy (CE) application is continuously increasing over the time, especially in children because of the opportunity to avoid deep sedation or ionizing radiation. The advent of new technologies has extended its applicability to the evaluation of the esophagus and

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colon as well as to new indications in the diagnosis or monitoring of GI diseases. ● The Small Bowel and Colon (SBC) capsule is similar to the CCE in all its hardware components, but differs in its operation mode, designed to provide complete coverage of the small bowel in addition to the colon and optimized for efficient visualization of lesions indicative of inflammatory bowel disease. The SBC capsule has the advantage of imaging the entire small bowel and colon in a single endoscopic procedure while avoiding sedation. The advent of these noninvasive technologies seems to be able to change our way to monitoring IBD and other chronic diseases. ● Several studies have demonstrated the safety and efficacy of POEM in pediatric age. The strengths of this technique are: the shorter operative time and hospital stay, reduced intraprocedural bleeding as well as the ability to elongate the myotomy when needed, depending upon achalasia type.

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Funding This paper was not funded.

Declaration of interest Salvatore Oliva received consulting fees and research grants from Medtronic. Stanley Cohen received consulting fees from Medtronic. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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