![Cancer [Version 1; Peer Review: 2 Approved] James Franklin 1, Janusz Jankowski1-3](http://data.docslib.org/img/d79a9b09610cdf1c33820e28e45ec853-1.webp)
F1000Research 2020, 9(F1000 Faculty Rev):276 Last updated: 21 APR 2020
REVIEW Recent advances in understanding and preventing oesophageal cancer [version 1; peer review: 2 approved] James Franklin 1, Janusz Jankowski1-3
1Gastroenterology and Endoscopy Department, Kings Mill Hospital NHS Foundation Trust, Sutton-in-Ashfield, Nottinghamshire, NG17 4JL, UK 2University of Liverpool, Liverpool, UK 3University of Roehampton, London, UK
First published: 21 Apr 2020, 9(F1000 Faculty Rev):276 ( Open Peer Review v1 https://doi.org/10.12688/f1000research.21971.1) Latest published: 21 Apr 2020, 9(F1000 Faculty Rev):276 ( https://doi.org/10.12688/f1000research.21971.1) Reviewer Status
Abstract Invited Reviewers Oesophageal cancer is a common cancer that continues to have a poor 1 2 survival. This is largely in part due to its late diagnosis and early metastatic spread. Currently, screening is limited to patients with multiple risk factors version 1 via a relatively invasive technique. However, there is a large proportion of 21 Apr 2020 patients diagnosed with oesophageal cancer who have not been screened. This has warranted the development of new screening techniques that could be implemented more widely and lead to earlier identification and subsequently improvements in survival rates. This article also explores F1000 Faculty Reviews are written by members of progress in the surveillance of Barrett’s oesophagus, a pre-malignant the prestigious F1000 Faculty. They are condition for the development of oesophageal adenocarcinoma. In recent commissioned and are peer reviewed before years, advances in early endoscopic intervention have meant that more publication to ensure that the final, published version patients are considered at an earlier stage for potentially curative treatment. is comprehensive and accessible. The reviewers Keywords who approved the final version are listed with their oesophageal cancer, Barrett’s oesophagus, screening, surveillance names and affiliations.
1 Richard van Hillegersberg, University Medical Center Utrecht, Utrecht, The Netherlands
2 Wayne L Hofstetter, The University of Texas MD Anderson Cancer Center, Houston, USA
Any comments on the article can be found at the end of the article.
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Corresponding author: Janusz Jankowski ([email protected]) Author roles: Franklin J: Writing – Original Draft Preparation; Jankowski J: Writing – Review & Editing Competing interests: Janusz Jankowski served as Chief Investigator for the AspECT clinical trial. James Franklin declares that he has no competing interests. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2020 Franklin J and Jankowski J. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite this article: Franklin J and Jankowski J. Recent advances in understanding and preventing oesophageal cancer [version 1; peer review: 2 approved] F1000Research 2020, 9(F1000 Faculty Rev):276 (https://doi.org/10.12688/f1000research.21971.1) First published: 21 Apr 2020, 9(F1000 Faculty Rev):276 (https://doi.org/10.12688/f1000research.21971.1)
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Introduction that a reduction in acid suppression, through the use of PPIs, Worldwide, oesophageal cancer is the sixth most common cause can reduce the risk of neoplasia9. More recently, the chemopre- of cancer-associated death, with 508,585 deaths reported in 20181. ventive properties of aspirin in OAC have also been explored. Since the early 1990s, incidence rates have increased; however, AspECT, a randomised prospective study, has evaluated the over the past decade, the incidence rate has stabilised, with efficacy and safety of aspirin (300–325 mg) with a PPI (esome- currently 9,100 new cases reported in the UK every year, equating prazole 40 mg twice daily or 20 mg daily) in BO patients. High- to 25 every day2. The prognosis remains poor, as diagnosis is often dose PPIs in combination with aspirin were found to be most late owing to a lack of early easily identifiable symptoms. The beneficial to patient outcomes, including reducing mortality, OAC, survival rate has tripled over the past 40 years; however, the 10-year and HGD10. Although concerns have been raised regarding the survival still remains poor at only 12%2. safety of prescribing aspirin, which has known serious side effects, including major haemorrhage and death, in light of the aggres- Oesophageal cancer can be subdivided into two main histological sive nature of OAC, coupled with the often-late presentation and types: adenocarcinoma (OAC), normally affecting the lower third poor survival rates, there is an argument for a strong benefit:risk of the oesophagus and often preceded by Barrett’s oesophagus ratio. The current British Society of Gastroenterology (BSG) and (BO), a recognised pre-malignant condition, and squamous cell American College of Gastroenterology (ACG) guidelines do carcinoma (OSCC), affecting the upper two-thirds of the not promote the routine use of aspirin in BO; however, further oesophagus3. The risk factors for OSCC include smoking and population-based studies are warranted to explore the potential alcohol consumption, whereas for OAC, obesity, Caucasian race, long-term chemopreventive implications of aspirin. gastro-oesophageal reflux disease (GORD), smoking, poor high- fat diet, and family history are widely recognised risk factors4. Screening Historically, OSCC has been the most prevalent subtype; however, Currently, all national and worldwide screening guidelines particularly in developed countries such as the UK, the USA, and recommend against general population screening and instead Australia, it has now been superseded by OAC5. This is likely a recommend limiting screening to patients with associated risk result of the increase in GORD caused by obesity and poor diet, factors such as male gender, chronic GORD symptoms, >50 years which directly contributes to the development of BO. The relative of age, Caucasian ethnicity, obesity, smoking, and family history risk of OAC in BO patients was found to be 11.36; this is of BO/OAC. However, the number and severity of these risk comparable to the risk of breast cancer in first-degree relatives with factors differ substantially between organisations; as a result, there a BRCA1/BRCA2 mutation with breast cancer7. are variations in the screening of patients depending on where they live, even within a single country. Often those diagnosed BO is the metaplastic change of the normal squamous oesophageal with OAC do not have a prior diagnosis of BO11, and more than a epithelium to columnar epithelium (see Figure 1). The severity of third deny a history of symptomatic reflux disease12. This suggests BO is graded on the presence and degree of dysplasia assessed via that there is a need for a larger-scale screening program that is not histopathological analysis of biopsy samples. The annual cancer limited to individuals presenting with GORD symptoms. There risk for non-dysplastic BO is estimated at 0.33%, for low-grade is evidence that screening for OAC leads to earlier detection and dysplasia (LGD) 0.54%, and for high-grade dysplasia (HGD) 7%8. better outcomes, with the 5-year survival rate increasing from 17 to 74%13. Chemoprevention Proton pump inhibitors (PPIs) are routinely prescribed in patients The current gold standard for BO screening is oesophago- with BO with a view to reduce acid reflux, a key component in gastro-duodenoscopy (OGD) with associated biopsies following its pathogenesis. A systematic review of observational data showed the Seattle protocol8,14,15. An OGD is a relatively invasive and
Figure 1. Development and progression of Barrett’s oesophagus to oesophageal adenocarcinoma. Re-printed from Evans et al., 201616 licenced under CC BY-NC 4.0.
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expensive procedure that is not well tolerated by some patients of nine studies (n = 618)33. It is safe and well tolerated with a high and is associated with a small risk of complications such as patient preference score, with 80% preferring OCE to OGD34. bleeding and perforation, making it an unideal tool for large-scale However, it has not been found to be more cost effective, and population-based screening17,18. For wider-scale screening to there are concerns over its validity due to lack of biopsy samples be implemented, there is a need for the development of novel with this technique35. strategies capable of early diagnosis of BO and OAC that are minimally invasive and affordable without increasing the burden Liquid biopsy on endoscopic surveillance programs. Several screening strategies Liquid biopsy involves the identification of DNA-encoded markers are currently in development. that are uniquely expressed or dysregulated in BO via a blood sample. A systematic review of 11 studies identified several Unsedated transnasal endoscopy microRNAs as promising biomarkers for diagnosing BO36. A recent Unsedated transnasal endoscopy (uTNE) is an endoscopic tech- study reported a sensitivity of 78% and specificity of 86% when nique that involves inserting an ultrathin endoscope transnasally identifying four circulating microRNAs37. This technique is in its with the use of topical anaesthetic. It is well tolerated in patients relative infancy, and further refinement of relevant biomarkers and has an excellent safety profile19,20. It has been shown to provide is required before there can be a recommendation for its clinical an assessment of the oesophagus of a quality comparable to that use. of OGD, with a sensitivity and specificity for BO of 98% and 100%, respectively21. uTNE can easily be performed in a non- Exhaled volatile organic compounds hospital setting, allowing novel mobile screening at a significantly A new technology that is not commonly used in diagnostic lower cost22. Further benefits of uTNA are a shorter evaluation time medicine is the detection of subtle changes in volatile organic and quicker patient recovery of 15 minutes versus 1 hour23,24. compounds (VOCs) that can occur in altered disease states and can be detected by electronic nose (e-nose) devices from exhaled CytospongeTM breath. Distinctive exhaled VOC profiles have been identified that CytospongeTM is a novel transoral non-endoscopic cell collection are capable of distinguishing BO from controls38. In a recent study device. It comprises a gelatine capsule on a string that is swallowed comparing 66 BO patients to 56 controls, the e-nose was able to into the stomach, where it expands to 3 cm in 5–10 minutes. As detect BO with a sensitivity of 82% and a specificity of 80%39. it is retrieved, it collects cells from the oesophagus lining before This is an attractive method of screening, as it is non-invasive, being cytologically analysed for the biomarker Trefoil Factor potentially cost effective, and easily implemented in a primary 3 (TFF3), a key component of BO identification25. The largest care setting. Further studies are required to validate its use on a study to date to investigate the efficacy of the CytospongeTM is the larger scale as well as its development for possible identification BEST2 study, which found a sensitivity of 80% that increased to of dysplasia grade from VOC levels. 87% in patients with ≥3 cm of BO and a specificity of 92%26. It was rated more favourably than OGD by patients, with a high Surveillance success rate of 91–94% of patients able to swallow the device, BO is classified as the pre-malignant stage of OAC, and the most on the first attempt26,27. Cost effectiveness models have recommended current method of surveillance for patients with estimated a reduction in screening costs of 38–41% compared to diagnosed BO is white light endoscopic surveillance accompanied endoscopic screening in patients with GORD symptoms28. by quadratic biopsies at 2 cm intervals. The interval of surveillance is dependent on the length of metaplasia because of a positive Balloon cytology correlation between length and OAC risk. The arbitrary cut off Balloon cytology is another non-endoscopic technique capable of 3 cm is considered higher risk and therefore a shorter of obtaining a DNA sample from the distal oesophagus using surveillance period is recommended15. a specifically designed textured balloon followed by molecular cytology analysis29. Two molecular diagnostic markers for BO The aim of surveillance is to detect cancer at an early, poten- (cytosine methylation of CCNA1 and VIM DNA) have been tially curable stage, crucially before the invasion of the identified and have been reported to detect BO with a sensitivity submucosa, which increases the risk of lymph node metastasis40. and specificity greater than 90%29,30. The device is well tolerated, There is debate regarding the benefit of surveillance given the with 82% able to swallow the device and little or no reported financial and resource burden it brings to gastroenterology depart- anxiety or pain29. Furthermore, 95% would recommend the ments along with potential complication risks, which many feel procedure to others. do not outweigh its long-term efficacy given the low risk of pro- gression. However, a recent large-scale cohort study (n = 30,000) Oesophageal capsule endoscopy found that patients diagnosed with OAC during surveillance Oesophageal capsule endoscopy (OCE) is a non-invasive micro- were detected at an earlier stage, had improved survival, and had scopic imaging technique requiring the use of a tethered camera a lower cancer-related mortality compared to those diagnosed in encased in a vitamin-sized capsule that is swallowed transorally31. a non-surveillance program41. The eagerly awaited results of the It is already commercially available and is widely used for the BOSS trial, a RCT comparing two-yearly endoscopic surveillance investigation and diagnosis of various lower gastrointestinal versus an ‘at need’ endoscopy, aims to shed light on the efficacy conditions32. It is only recently that its potential use for BO of this surveillance method and also its cost effectiveness42. This screening has been explored. A pooled sensitivity of 77% and surveillance strategy is time consuming and expensive, and the pooled specificity of 86% have been reported by a meta-analysis development of various image enhancement techniques has been
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proposed to improve its accuracy, reliability, and diagnostic and reduces the number of biopsies taken, with one study reporting capability. The implementation of these techniques could be that two-thirds of patients did not require biopsies at all51. Despite potentially revolutionary, with one of the shortcomings of the this, the technique is considered relatively expensive and lacks current strategy being the difficulty in the histopathological analysis standardised criteria for diagnosis52. of dysplasia, which currently requires the input of two GI pathologists. Although these advanced imaging techniques are Volumetric laser endomicroscopy not currently commercially available or recommended in clinical Volumetric laser endomicroscopy (VLE) is an imaging technique guidelines, it has been estimated that they could increase the that scans the oesophageal surface in 360o to a depth of up to diagnostic yield for detection of dysplasia and OAC by 35%43. 3 mm53. It has the capability of visualising mucosal lesions invis- Furthermore, recent promising work in the development of a p53 ible to white light and is expected to facilitate targeted biopsies54. immunostain could further enhance diagnostic reproducibility and It has been found to be safe and accurate, with an adequate play a role in prognosis prediction44. sensitivity (86%) and specificity (88%)55.
Dye-based chromoendoscopy Artificial intelligence In order to overcome the limitations of white light endoscopy, Artificial intelligence (AI) is a brand new and promising research dye-based chromoendoscopy was developed utilising a dye for area across medicine as a whole. The development of AI for BO mucosal and image enhancement during endoscopy. The dyes identification has been largely focussed on the identification of investigated include methylene blue, indigo carmine, and acetic BO and OAC from endoscopic images and videos through auto- acid. The most compelling evidence has been shown with the use analysis56. For example, the analysis of VLE images is complex, of acetic acid, with a recent meta-analysis reporting a sensitivity with approximately 1,200 cross-sectional images produced for of 92% and a specificity of 96% for HGD and OAC45. Although each 6 cm oesophageal segment scanned, so the development this technique is cheap and universally available, a lack of RCT of image analysis software could be considerably beneficial for data has halted its implementation in routine clinical practice. the endoscopist57,58. Further validation is needed to ascertain its accuracy; however, AI has a potential role in aiding the surveillance Optical/digital chromoendoscopy of BO. Optical/digital chromoendoscopy utilises narrow band imaging (NBI), a well-recognised advance in endoscopic imaging. In Early endoscopic intervention contrast to white light imaging, optical filters are used to narrow Historically, regular surveillance and in some cases radical the wavelength to blue and green, enhancing the visualisation of oesophagectomy have been the only options available for the microvasculature46. It has been reported as highly accurate, with treatment of BO. Many patients have been reluctant to undertake a higher sensitivity and equivalent specificity compared to tra- such a major operation for a pre-malignant condition, and BO ditional white light endoscopy47, as well as requiring a reduced patients are often older and overweight with associated cardiac number of biopsies48. This is a simple technique that can be easily and respiratory co-morbidities, making them unfit for such an implemented worldwide in combination with current white light operation. Over the past decade, significant advances in -endo endoscopy surveillance. scopic techniques have been developed that have broadened the options available to patients with both HGD and LGD for early Virtual chromoendoscopy intervention strategies. Virtual chromoendoscopy is based on the principle of digital post-processing such that endoscopic images are reconstructed, in Crucially, these techniques are performed endoscopically rather real time, into virtual images without the need for dyes. Different than surgically, which carries a high mortality rate59. This includes filters and image algorithms can be applied to these images to developments in ablation and resection-based strategies, which further improve the visualisation and enhancement of the super- have been shown to have a high level of efficacy. The less- ficial structures of the mucosa and the mucosal microvasculature. invasive nature of these techniques has meant that more patients The use of virtual chromoendoscopy has been shown to improve can be considered at an earlier stage in diagnosis for potentially dysplasia detection sensitivity from 69 to 78% as well as improve curative treatment. specificity from 70 to 81% compared to white light endoscopy49. This improvement was shown in both a trainee and an expert Ablation techniques group of endoscopists and could result in a reduction in the need Current guidelines from the ACG and BSG agree that ablation and number of biopsies required or greater targeting of biopsies. techniques such as radiofrequency ablation (RFA) and photody- namic therapies (PDTs) are promising emerging techniques in BO Confocal laser endomicroscopy treatment. Both techniques aim to ablate anomalous oesophageal Confocal laser endomicroscopy (CLE) allows in vivo histological mucosa, causing tissue necrosis and regrowth of neo-squamous assessment with 1,000x magnification using a blue laser light mucosa. following intravenous fluorescein administration. The high- resolution images produced are comparable to histological RFA uses controlled pulses of radiofrequency waves to thermally evaluation. There is a great future potential for this technique as ablate the affected area. A RCT comparison of RFA against a a diagnostic tool, allowing interventional steps such as resection control (sham procedure) (n = 127) reported complete eradication or ablation to be performed at the point of care50. CLE has been of dysplasia of 91% in LGD and 81% in HGD compared to shown to have a high sensitivity (90.4%) and specificity (92.7%) 23% and 19%, respectively, in the sham procedure. Furthermore,
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eradication of metaplasia was 81% and 74% in LGD and HGD complete resection rate75,76. The complication rate was also compared to 4% and 0%, respectively, in the sham procedure60. lower, with a stenosis rate of 1.9%77. A systematic review Even more importantly, a RCT comparison of RFA against comparing EMR and RFA reported equal efficacy in the treatment surveillance in LGD patients also found a significant reduction in of BO; however, EMR encountered a higher proportion of dysplasia and metaplasia as well as a reduced risk of progression complications78. to OAC61. The main complication with RFA was found to be strictures in 8–12% of patients, all of which were able to be An alternative to EMR is endoscopic submucosal dissection (ESD), successfully treated with endoscopic dilatation61,62. which is a longer and more-advanced procedure that resects the lesion and deeper tissues, allowing a potentially larger clearance PDT is a technique that involves the use of a photosensitising margin. Owing to the complexity of the procedure, it is currently agent injected intravenously, which increases the sensitivity of only available in specialist centres. the oesophagus lining to light. This agent is activated with a red- light laser, resulting in destruction of the abnormal epithelial cells The added benefit of resection-based strategies is that the tissue through a photochemical as opposed to a thermal reaction as in sample removed can be assessed; this has been found to be the RFA63. The rate of dysplasia eradication with PDT in HGD has most accurate staging technique for neoplasia and is therefore been found to range from 40–77%15. Complications following preferred over surveillance biopsies79. PDT were high, with oesophageal strictures reported in 23–34% of patients64,65, skin reactions in a third66, and oesophageal Endoscopic eradication therapy perforation, pleural effusion, and atrial fibrillation in 3–4%67. More recently, both of the above techniques have been combined to form endoscopic eradication therapy (EET), which has become RFA has been shown to achieve a high rate of eradication of the standard of care for patients with both LGD and HGD as metaplasia and dysplasia as well as a reduction in disease recommended by the BSG and ACG8,15. EET consists of progression68. The safety and efficacy of RFA are well documented, endoscopic resection followed by endoscopic ablation. In patients and it is currently the most commonly used ablation technique69. with HGD, a recent systematic review found that EMR followed Current NICE guidance advocates the use of RFA for LGD and by RFA resulted in a 93% neoplasia eradication rate and a 73% HGD and PDT for HGD70. PDT has a significant photosensitivity dysplasia eradication rate80. EET has been associated with a low and stricture risk; therefore, although good outcomes have been morbidity and mortality81,82. reported, it has largely been already replaced by RFA. Other ablation techniques are in development, such as cryotherapy71; A UK-based cost effectiveness analysis of EET was recently however, there is a lack of evidence for its safe use and efficacy, performed. For patients with LGD and HGD, EET was more cost with a lack of RCTs and long-term follow up data. effective than regular endoscopic surveillance and is estimated to provide a 5-year financial benefit to the NHS of £7.1 million83. Resection-based strategies Endoscopic mucosal resection (EMR) was first developed Conclusions in 1978 for gastric cancers72 but has since been adapted for BO Oesophageal cancer commonly presents late, often after disease treatment. Two common methods of EMR have been developed: has spread and curative treatment is no longer possible. A key the cap and snare technique and band ligation. In the cap and issue is identifying at-risk individuals, particularly those with BO, snare technique, the lesion is marked for resection using elec- and recent advances in screening methods, including non-invasive trocautery and then injected with fluid. A dedicated transparent strategies, could aid the identification and potential detection of cap on the distal end of the endoscope is used. A preloaded cancer at an earlier stage. This could have a significant impact crescent-shaped snare forms a pseudopolyp through suction of on survival rates, as emerging early endoscopic interventions the lesion, which is then removed with a diathermy loop73. have been shown to be successful at eradicating dysplasia and This method has been reported to have a 91% neoplasia and metaplasia. Individuals identified with BO have also been shown metaplasia eradication rate at 18-month follow up but a high to benefit from surveillance strategies, which aim to identify stenosis rate of 40%74. The band ligation method creates a progression from metaplasia to dysplasia. The current universal pseudopolyp using a band to ligate the lesion. It is then removed surveillance strategy with the use of an OGD is time consuming similarly to the cap and snare technique with diathermy73. The and expensive, but the development of various image enhancement band ligation method has been shown to be faster and cheaper techniques has been proposed to improve its accuracy, reliability, than the cap and snare method as well as having a 92.3% and diagnostic capability.
References F1000 recommended
2. Cancer Research UK: Oesophageal cancer statistics. 1. Bray F, Ferlay J, Soerjomataram I, et al.: Global cancer statistics 2018: Reference Source GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68(6): 394–424. 3. Domper Arnal MJ, Ferrández Arenas Á, Lanas Arbeloa ÁE: sophageal cancer: PubMed Abstract | Publisher Full Text | F1000 Recommendation Risk factors, screening and endoscopic treatment in Western and Eastern
Page 6 of 9 F1000Research 2020, 9(F1000 Faculty Rev):276 Last updated: 21 APR 2020
countries. World J Gastroenterol. 2015; 21(26): 7933–43. 24. Sami SS, Dunagan KT, Johnson ML, et al.: A randomized comparative PubMed Abstract Publisher Full Text Free Full Text | | effectiveness trial of novel endoscopic techniques and approaches for 4. Eslick GD: Epidemiology of esophageal cancer. Gastroenterol Clin North Am. Barrett’s esophagus screening in the community. Am J Gastroenterol. 2015; 2009; 38(1): 17–25, vii. 110(1): 148–58. PubMed Abstract | Publisher Full Text PubMed Abstract | Publisher Full Text | Free Full Text | F1000 Recommendation 5. Wong MCS, Hamilton W, Whiteman DC, et al.: Global Incidence and 25. Paterson AL, Gehrung M, Fitzgerald RC, et al.: Role of TFF3 as an adjunct in mortality of oesophageal cancer and their correlation with socioeconomic the diagnosis of Barrett’s esophagus using a minimally invasive esophageal indicators temporal patterns and trends in 41 countries. Sci Rep. 2018; 8(1): sampling device—The CytospongeTM. Diagn Cytopathol. 2020; 48(3): 253–64. 4522. PubMed Abstract | Publisher Full Text | Free Full Text | F1000 Recommendation PubMed Abstract Publisher Full Text Free Full Text F1000 Recommendation | | | 26. Ross-Innes CS, Debiram-Beecham I, O'Donovan M, et al.: Evaluation of a 6. Hvid-Jensen F, Pedersen L, Drewes AM, et al.: Incidence of adenocarcinoma minimally invasive cell sampling device coupled with assessment of trefoil among patients with Barrett’s esophagus. N Engl J Med. 2011; 365(15): factor 3 expression for diagnosing Barrett’s esophagus: a multi-center case- 1375–83. control study. PLoS Med. 2015; 12(1): e1001780. PubMed Abstract | Publisher Full Text | F1000 Recommendation PubMed Abstract | Publisher Full Text | Free Full Text 7. Rebbeck TR, Domchek SM: Variation in breast cancer risk in BRCA1 and 27. Januszewicz W, Tan WK, Lehovsky K, et al.: Safety and Acceptability of BRCA2 mutation carriers. Breast Cancer Res. 2008; 10(4): 108. Esophageal Cytosponge Cell Collection Device in a Pooled Analysis of Data PubMed Abstract | Publisher Full Text | Free Full Text From Individual Patients. Clin Gastroenterol Hepatol. 2019; 17(4): 647–656.e1. 8. Shaheen NJ, Falk GW, Iyer PG, et al.: ACG Clinical Guideline: Diagnosis and PubMed Abstract | Publisher Full Text | Free Full Text | F1000 Recommendation Management of Barrett’s Esophagus. Am J Gastroenterol. 2016; 111(1): 30–50; quiz 51. 28. Heberle CR, Omidvari AH, Ali A, et al.: Cost Effectiveness of Screening PubMed Abstract Publisher Full Text Patients With Gastroesophageal Reflux Disease for Barrett’s Esophagus With | a Minimally Invasive Cell Sampling Device. Clin Gastroenterol Hepatol. 2017; 9. Singh S, Garg SK, Singh PP, et al.: Acid-suppressive medications and risk 15(9): 1397–1404.e7. of oesophageal adenocarcinoma in patients with Barrett’s oesophagus: a PubMed Abstract Publisher Full Text Free Full Text F1000 Recommendation systematic review and meta-analysis. Gut. 2014; 63(8): 1229–37. | | | PubMed Abstract | Publisher Full Text | Free Full Text 29. Moinova HR, LaFramboise T, Lutterbaugh JD, et al.: Identifying DNA methylation biomarkers for non-endoscopic detection of Barrett’s esophagus. 10. Jankowski JAZ, de Caestecker J, Love SB, et al.: Esomeprazole and aspirin Sci Transl Med. 2018; 10(424): pii: eaao5848. in Barrett’s oesophagus (AspECT): a randomised factorial trial. Lancet. 2018; PubMed Abstract Publisher Full Text Free Full Text F1000 Recommendation 392(10145): 400–8. | | | PubMed Abstract Publisher Full Text Free Full Text F1000 Recommendation 30. Moinova H, Leidner RS, Ravi L, et al.: Aberrant vimentin methylation is | | | characteristic of upper gastrointestinal pathologies. Cancer Epidemiol 11. Dulai GS, Guha S, Kahn KL, et al.: Preoperative Prevalence of Barrett’s Biomarkers Prev. 2012; 21(4): 594–600. Esophagus in Esophageal Adenocarcinoma: A Systematic Review. PubMed Abstract Publisher Full Text Free Full Text Gastroenterology. 2002; 122(1): 26–33. | | PubMed Abstract Publisher Full Text 31. Gora MJ, Simmons LH, Quénéhervé L, et al.: Tethered capsule endomicroscopy: | from bench to bedside at a primary care practice. J Biomed Opt. 2016; 21:(10): 12. Lagergren J, Bergström R, Lindgren A, et al.: Symptomatic Gastroesophageal 104001. Reflux as a Risk Factor for Esophageal Adenocarcinoma. N Engl J Med. 1999; PubMed Abstract Publisher Full Text Free Full Text 340(11): 825–31. | | PubMed Abstract | Publisher Full Text 32. Park J, Cho YK, Kim JH: Current and Future Use of Esophageal Capsule 13. Kastelein F, van Olphen SH, Steyerberg EW, et al.: Impact of Surveillance Endoscopy. Clin Endosc. 2018; 51(4): 317–322. for Barrett’s Oesophagus on Tumour Stage and Survival of Patients With PubMed Abstract | Publisher Full Text | Free Full Text | F1000 Recommendation Neoplastic Progression. Gut. 2016; 65(4): 548–54. 33. Bhardwaj A, Hollenbeak CS, Pooran N, et al.: A meta-analysis of the PubMed Abstract | Publisher Full Text diagnostic accuracy of esophageal capsule endoscopy for Barrett’s 14. Levine DS, Haggitt RC, Blount PL, et al.: An Endoscopic Biopsy Protocol Can esophagus in patients with gastroesophageal reflux disease. Am J Differentiate High-Grade Dysplasia From Early Adenocarcinoma in Barrett’s Gastroenterol. 2009; 104(6): 1533–9. Esophagus. Gastroenterology. 1993; 105(1): 40–50. PubMed Abstract | F1000 Recommendation PubMed Abstract | Publisher Full Text 34. Ramirez FC, Akins R, Shaukat M: Screening of Barrett’s esophagus with string- 15. Fitzgerald RC, Di Pietro M, Ragunath K, et al.: British Society of Gastroenterology capsule endoscopy: a prospective blinded study of 100 consecutive patients Guidelines on the Diagnosis and Management of Barrett’s Oesophagus. Gut. using histology as the criterion standard. Gastrointest Endosc. 2008; 68(1): 2014; 63(1): 7–42. 25–31. PubMed Abstract | Publisher Full Text PubMed Abstract | Publisher Full Text 16. Evans RP, Mourad MM, Fisher SG, et al.: Evolving management of metaplasia and 35. Rubenstein JH, Inadomi JM, Brill JV, et al.: Cost utility of screening for dysplasia in Barrett’s epithelium. World J Gastroenterol. 2016; 22(47): 10316–24. Barrett’s esophagus with esophageal capsule endoscopy versus conventional PubMed Abstract | Publisher Full Text | Free Full Text upper endoscopy. Clin Gastroenterol Hepatol. 2007; 5(3): 312–8. 17. Inadomi JM: Cost Considerations in Implementing a Screening and PubMed Abstract | Publisher Full Text | F1000 Recommendation Surveillance Strategy for Barrett’s Oesophagus. Best Pract Res Clin 36. Mallick R, Patnaik SK, Wani S, et al.: A Systematic Review of Esophageal Gastroenterol. 2015; 29(1): 51–63. MicroRNA Markers for Diagnosis and Monitoring of Barrett’s Esophagus. Dig PubMed Abstract | Publisher Full Text Dis Sci. 2016; 61(4): 1039–50. 18. Saxena N, Inadomi JM: Effectiveness and Cost-Effectiveness of PubMed Abstract | Publisher Full Text Endoscopic Screening and Surveillance. Gastrointest Endosc Clin N Am. 2017; 37. Bus P, Kestens C, Ten Kate FJ, et al.: Profiling of circulating microRNAs in 27(3): 397–421. patients with Barrett’s esophagus and esophageal adenocarcinoma. PubMed Abstract | Publisher Full Text | F1000 Recommendation J Gastroenterol. 2016; 51(6): 560–70. 19. Chung JW, Park S, Chung MJ, et al.: A novel disposable, transnasal PubMed Abstract | Publisher Full Text | Free Full Text esophagoscope: a pilot trial of feasibility, safety, and tolerance. Endoscopy. 38. Kumar S, Huang J, Abbassi-Ghadi N, et al.: Mass Spectrometric Analysis 2012; 44(2): 206–9. of Exhaled Breath for the Identification of Volatile Organic Compound PubMed Abstract | Publisher Full Text Biomarkers in Esophageal and Gastric Adenocarcinoma. Ann Surg. 2015; 20. Peery AF, Hoppo T, Garman KS, et al.: Feasibility, safety, acceptability, and 262(6): 981–90. yield of office-based, screening transnasal esophagoscopy (with video). PubMed Abstract | Publisher Full Text Gastrointest Endosc. 2012; 75(5): 945–953.e2. 39. Chan DK, Zakko L, Visrodia KH, et al.: Breath Testing for Barrett’s PubMed Abstract | Publisher Full Text | Free Full Text Esophagus Using Exhaled Volatile Organic Compound Profiling With an 21. Shariff MK, Bird-Lieberman EL, O’Donovan M, et al.: Randomized crossover Electronic Nose Device. Gastroenterology. 2017; 152(1): 24–26. study comparing efficacy of transnasal endoscopy with that of standard PubMed Abstract | Publisher Full Text | F1000 Recommendation endoscopy to detect Barrett’s esophagus. Gastrointest Endosc. 2012; 75(5): 40. Dunbar KB, Spechler SJ: The risk of lymph-node metastases in patients 954–61. with high-grade dysplasia or intramucosal carcinoma in Barrett’s esophagus: PubMed Abstract | Publisher Full Text | F1000 Recommendation a systematic review. Am J Gastroenterol. 2012; 107(6): 850–62; quiz 863. 22. Moriarty JP, Shah ND, Rubenstein JH, et al.: Costs associated with PubMed Abstract | Publisher Full Text | Free Full Text | F1000 Recommendation Barrett’s esophagus screening in the community: an economic analysis of a 41. El-Serag HB, Naik AD, Duan Z, et al.: Surveillance endoscopy is associated with prospective randomized controlled trial of sedated versus hospital unsedated improved outcomes of oesophageal adenocarcinoma detected in patients with versus mobile community unsedated endoscopy. Gastrointest Endosc. 2018; Barrett’s oesophagus. Gut. 2016; 65(8): 1252–60. 87(1): 88–94.e2. PubMed Abstract | Publisher Full Text PubMed Abstract | Publisher Full Text | Free Full Text | F1000 Recommendation 42. Old O, Moayyedi P, Love S, et al.: Barrett’s Oesophagus Surveillance versus 23. Crews NR, Gorospe EC, Johnson ML, et al.: Comparative quality endoscopy at need Study (BOSS): protocol and analysis plan for a multicentre assessment of esophageal examination with transnasal and sedated randomized controlled trial. J Med Screen. 2015; 22(3): 158–64. endoscopy. Endosc Int Open. 2017; 5(5): E340–E344. PubMed Abstract | Publisher Full Text PubMed Abstract | Publisher Full Text | Free Full Text | F1000 Recommendation 43. Qumseya BJ, Wang H, Badie N, et al.: Advanced imaging technologies increase
Page 7 of 9 F1000Research 2020, 9(F1000 Faculty Rev):276 Last updated: 21 APR 2020
detection of dysplasia and neoplasia in patients with Barrett’s esophagus: a 460–8. meta-analysis and systematic review. Clin Gastroenterol Hepatol. 2013; 11(12): PubMed Abstract | Publisher Full Text | Free Full Text | F1000 Recommendation 1562–70.e1-2. 63. Mimura S: New strategies in cancer treatment - Photodynamic therapy. Journal PubMed Abstract | Publisher Full Text | Free Full Text of Tokyo Medical College. 1997; 54(3): 382–424. 44. Kaye PV, Ilyas M, Soomro I, et al.: Dysplasia in Barrett’s oesophagus: p53 64. Overholt BF, Panjehpour M, Haydek JM: Photodynamic therapy for Barrett’s immunostaining is more reproducible than haematoxylin and eosin diagnosis esophagus: follow-up in 100 patients. Gastrointest Endosc. 1999; 49(1): 1–7. and improves overall reliability, while grading is poorly reproducible. PubMed Abstract | Publisher Full Text Histopathology. 2016; 69(3): 431–40. 65. Overholt BF, Panjehpour M, Halberg DL: Photodynamic therapy for Barrett’s PubMed Abstract Publisher Full Text | esophagus with dysplasia and/or early stage carcinoma: Long-term results. 45. Coletta M, Sami SS, Nachiappan A, et al.: Acetic acid chromoendoscopy for the Gastrointest Endosc. 2003; 58(2): 183–188. diagnosis of early neoplasia and specialized intestinal metaplasia in Barrett’s PubMed Abstract | Publisher Full Text esophagus: a meta-analysis. Gastrointest Endosc. 2016; 83(1): 57–67.e1. 66. Wolfsen HC, Ng CS: Cutaneous consequences of photodynamic therapy. Cutis. PubMed Abstract Publisher Full Text | 2002; 69(2): 140–2. 46. Lee MM, Enns R: Narrow band imaging in gastroesophageal reflux disease and PubMed Abstract Barrett’s esophagus. Can J Gastroenterol. 2009; 23(2): 84–7. 67. Wolfsen HC, Woodward TA, Raimondo M: Photodynamic therapy for dysplastic PubMed Abstract Publisher Full Text Free Full Text | | Barrett esophagus and early esophageal adenocarcinoma. Mayo Clin Proc. 47. Jayasekera C, Taylor AC, Desmond PV, et al.: Added value of narrow band 2002; 77(11): 1176–1181. imaging and confocal laser endomicroscopy in detecting Barrett’s esophagus PubMed Abstract | Publisher Full Text neoplasia. Endoscopy. 2012; 44(12): 1089–95. PubMed Abstract | Publisher Full Text 68. Rajaram R, Hofstetter WL: Mucosal Ablation Techniques for Barrett’s Esophagus and Early Esophageal Cancer. Thorac Surg Clin. 2018; 28(4): 473– 48. Sharma P, Hawes RH, Bansal A, et al.: Standard endoscopy with random 480. biopsies versus narrow band imaging targeted biopsies in Barrett’s PubMed Abstract | Publisher Full Text | F1000 Recommendation oesophagus: a prospective, international, randomised controlled trial. Gut. 69. Singh A, Chak A: Advances in the management of Barrett’s esophagus and 2012; 62(1): 15–21. early esophageal adenocarcinoma. Gastroenterol Rep (Oxf). 2015; 3(4): 303–15. PubMed Abstract Publisher Full Text F1000 Recommendation | | PubMed Abstract | Publisher Full Text | Free Full Text 49. Everson MA, Lovat LB, Graham DG, et al.: Virtual chromoendoscopy by 70. NICE: Barrett’s oesophagus: ablative therapy [CG106]. 2010. using optical enhancement improves the detection of Barrett’s esophagus- Reference Source associated neoplasia. Gastrointest Endosc. 2019; 89(2): 247–256.e4. PubMed Abstract | Publisher Full Text | F1000 Recommendation 71. Ghorbani S, Tsai FC, Greenwald BD, et al.: Safety and efficacy of endoscopic spray cryotherapy for Barrett’s dysplasia: results of the National 50. Leggett CL, Gorospe EC: Application of confocal laser endomicroscopy in the Cryospray Registry. Dis Esophagus. 2016; 29(3): 241–247. diagnosis and management of Barrett’s esophagus. Ann Gastroenterol. 2014; PubMed Abstract Publisher Full Text F1000 Recommendation 27(3): 193–9. | | PubMed Abstract Free Full Text 72. Faivre J, Bory R, Moulinier B: Benign Tumors of Oesophagus: Value of | Endoscopy. Endoscopy. 1978; 10(4): 264–8. 51. Dunbar KB, Canto MI: Confocal laser endomicroscopy in Barrett’s esophagus PubMed Abstract Publisher Full Text and endoscopically inapparent Barrett’s neoplasia: a prospective, | randomized, double-blind, controlled, crossover trial. Gastrointest Endosc. 73. Ning B, Abdelfatah MM, Othma MO: Endoscopic submucosal dissection 2010; 72(3): 668. and endoscopic mucosal resection for early stage esophageal cancer. Ann PubMed Abstract | Publisher Full Text Cardiothorac Surg. 2017; 6(2): 88–98. 52. Fugazza A, Gaiani F, Carra MC, et al.: Confocal Laser Endomicroscopy in PubMed Abstract | Publisher Full Text | Free Full Text | F1000 Recommendation Gastrointestinal and Pancreatobiliary Diseases: A Systematic Review and 74. Conio M, Fisher DA, Blanchi S, et al.: One-step circumferential endoscopic Meta-Analysis. Biomed Res Int. 2016; 2016: 4638683. mucosal cap resection of Barrett’s esophagus with early neoplasia. Clin Res PubMed Abstract | Publisher Full Text | Free Full Text Hepatol Gastroenterol. 2014; 38(1): 81–91. PubMed Abstract | Publisher Full Text 53. Kandel P, Wallace MB: The Role of Adjunct Imaging in Endoscopic 75. Zhang YM, Boerwinkel DF, Qin X, et al.: A randomized trial comparing multiband Detection of Dysplasia in Barrett’s Esophagus. Gastrointest Endosc Clin N Am. mucosectomy and cap-assisted endoscopic resection for endoscopic 2017; 27(3): 423–446. piecemeal resection of early squamous neoplasia of the esophagus. PubMed Abstract Publisher Full Text F1000 Recommendation | | Endoscopy. 2016; 48(4): 330–8. 54. Jain D, Fatima S, Jain S, et al.: Volumetric Laser Endomicroscopy for PubMed Abstract | Publisher Full Text | Free Full Text Barrett’s Esophagus - Looking at the Fine Print. J Gastrointestin Liver Dis. 2017; 76. Alvarez Herrero L, Pouw RE, van Vilsteren FGI, et al.: Safety and efficacy 26(3): 291–297. of multiband mucosectomy in 1060 resections in Barrett’s esophagus. PubMed Abstract | Publisher Full Text | F1000 Recommendation Endoscopy. 2011; 43(3): 177–83. 55. Leggett CL, Gorospe EC, Chan DK, et al.: Comparative diagnostic performance PubMed Abstract | Publisher Full Text of volumetric laser endomicroscopy and confocal laser endomicroscopy in 77. Jin XF, Sun QY, Chai TH, et al.: Clinical value of multiband mucosectomy for the detection of dysplasia associated with Barrett’s esophagus. Gastrointest the treatment of squamous intraepithelial neoplasia of the esophagus. Endosc. 2016; 83(5): 880–888.e2. J Gastroenterol Hepatol. 2013; 28(4): 650–5. PubMed Abstract | Publisher Full Text | Free Full Text PubMed Abstract | Publisher Full Text 56. de Souza LA Jr, Palm C, Mendel R, et al.: A survey on Barrett’s esophagus 78. Chadwick G, Groene O, Markar SR, et al.: Systematic review comparing analysis using machine learning. Comput Biol Med. 2018; 96: 203–213. radiofrequency ablation and complete endoscopic resection in treating PubMed Abstract Publisher Full Text F1000 Recommendation dysplastic Barrett’s esophagus: a critical assessment of histologic outcomes | | and adverse events. Gastrointest Endosc. 2014; 79(5): 718–731.e3. 57. Trindade AJ, McKinley MJ, Fan C, et al.: Endoscopic Surveillance of PubMed Abstract | Publisher Full Text Barrett’s Esophagus Using Volumetric Laser Endomicroscopy With Artificial 79. Mino-Kenudson M, Hull MJ, Brown I, et al.: EMR for Barrett’s esophagus-related Intelligence Image Enhancement. Gastroenterology. 2019; 157(2): 303–305. superficial neoplasms offers better diagnostic reproducibility than mucosal PubMed Abstract | Publisher Full Text | F1000 Recommendation biopsy. Gastrointest Endosc. 2007; 66(4): 660–6; quiz 767, 769. PubMed Abstract Publisher Full Text 58. Swager AF, van der Sommen F, Klomp SR, et al.: Computer-aided detection | of early Barrett’s neoplasia using volumetric laser endomicroscopy. 80. Desai M, Saligram S, Gupta N, et al.: Efficacy and safety outcomes of Gastrointest Endosc. 2017; 86(5): 839–846. multimodal endoscopic eradication therapy in Barrett’s esophagus-related PubMed Abstract | Publisher Full Text | F1000 Recommendation neoplasia: a systematic review and pooled analysis. Gastrointest Endosc. 2017; 59. Bollschweiler E, Schröder W, Hölscher AH, et al.: Preoperative risk analysis 85(3): 482–495.e4. in patients with adenocarcinoma or squamous cell carcinoma of the PubMed Abstract | Publisher Full Text | F1000 Recommendation oesophagus. Br J Surg. 2000; 87(8): 1106–10. 81. Menon D, Stafinski T, Wu H,et al.: Endoscopic treatments for Barrett’s PubMed Abstract | Publisher Full Text esophagus: a systematic review of safety and effectiveness compared to esophagectomy. BMC Gastroenterol. 2010; 10: 111. 60. Shaheen NJ, Sharma P, Overholt BF, et al.: Radiofrequency ablation in PubMed Abstract Publisher Full Text Free Full Text Barrett’s esophagus with dysplasia. N Engl J Med. 2009; 360(22): | | 2277–2288. 82. Zehetner J, DeMeester SR, Hagen JA, et al.: Endoscopic resection and PubMed Abstract | Publisher Full Text | F1000 Recommendation ablation versus esophagectomy for high-grade dysplasia and intramucosal adenocarcinoma. J Thorac Cardiovasc Surg. 2011; 141(1): 39–47. 61. Phoa KN, van Vilsteren FGI, Weusten BL, et al.: Radiofrequency ablation vs PubMed Abstract | Publisher Full Text endoscopic surveillance for patients with Barrett esophagus and low-grade dysplasia: a randomized clinical trial. JAMA. 2014; 311: 1209. 83. Pollit V, Graham D, Leonard C, et al.: A cost-effectiveness analysis of PubMed Abstract | Publisher Full Text | F1000 Recommendation endoscopic eradication therapy for management of dysplasia arising in patients with Barrett’s oesophagus in the United Kingdom. Curr Med Res Opin. 62. Shaheen NJ, Overholt BF, Sampliner RE, et al.: Durability of radiofrequency 2019; 35(5): 805–15. ablation in Barrett’s esophagus with dysplasia. Gastroenterology. 2011; 141(2): PubMed Abstract | Publisher Full Text | F1000 Recommendation
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Editorial Note on the Review Process F1000 Faculty Reviews are written by members of the prestigious F1000 Faculty. They are commissioned and are peer reviewed before publication to ensure that the final, published version is comprehensive and accessible. The reviewers who approved the final version are listed with their names and affiliations.
The reviewers who approved this article are: Version 1
1 Wayne L Hofstetter Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Competing Interests: No competing interests were disclosed. 2 Richard van Hillegersberg Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands Competing Interests: No competing interests were disclosed.
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