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doi:10.1111/jgh.12879
O R I G I N A L A RT I C L E
Surveillance of short-segment Barrett’s esophagus using ultrathin transnasal endoscopy Hiroko Sugimoto,* Takashi Kawai,* Sakiko Naito,* Kyosuke Yanagizawa,* Tetsuya Yamagishi,* Masakatsu Fukuzawa,† Kenji Yagi,† Jun Matsubayashi,‡ Toshitaka Nagao,‡ Hirofumi Tomiyama,§ Sumito Hoshino,¶ Akihiko Tsuchida¶ and Fuminori Moriyasu† *Endoscopy Center, †Department of Gastroenterology and Hepatology, ‡Department of Pathology and §Department of Cardiovascular, Tokyo Medical University Hospital, Tokyo, Japan, ¶Department of Gastrointestinal and pediatric Surgery, Tokyo Medical University Hospital
Keywords Barrett’s esophagus, transnasal endoscopy, Narrow band imaging, close examination, mucosal structure. Correspondence Dr Takashi Kawai, Endoscopy Center, Tokyo Medical University Hospital, 6-7-1 Nishi-Shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan. Email: [email protected]
Abstract Background and Aim: Newly developed ultrathin transnasal endoscope, the GIFXP290N, makes possible a resolving power similar to the GIF-H260 at a distance of 3 mm. We conducted surveillance of subjects with Barrett’s esophagus using this ultrathin transnasal endoscopy. In Japan the lower margin of the lower esophageal palisade vessels is defined the gastroesophageal junction in deep inspiration. We diagnose Barrett’s esophagus if columnar epithelium is present on the oral side of the gastroesophageal junction. Methods and Results: Barrett’s esophagus was confirmed in 116 out of 135 subjects (85.9%), with 17 cases of short-segment Barrett’s esophagus (SSBE) and 99 of ultra-shortsegment Barrett’s esophagus. Close observation of the Barrett’s esophagus mucosal structural pattern using narrow band imaging revealed 29 cases with an oval or round pattern, 29 with a long straight pattern, 47 with a villous pattern, 8 with a cerebriform pattern, and 6 with an irregular pattern according to Goda classification. Mucosal biopsies from all subjects with SSBE are examined. Histological examination revealed intestinal metaplasia in only eight subjects. We grouped the oval/round and long straight patterns as closed type, and the villous, cerebriform, and irregular patterns as open type. Analysis of the relationship between these mucosal patterns and background factors revealed a significant correlation between intestinal metaplasia and the open-type pattern. Conclusion: We consider this new ultrathin transnasal endoscopy to be a useful technique for surveillance of Barrett’s esophagus, especially SSBE.
Introduction Barrett’s esophagus is a condition in which chronic inflammation of the lower esophagus associated with gastrointestinal reflux disease causes replacement of squamous epithelium by columnar epithelium. The intestinal metaplasia of Barrett’s esophagus can further lead to Barrett’s esophageal adenocarcinoma. The incidence of Barrett’s esophagus and Barrett’s esophageal adenocarcinoma is increasing, particularly in Western countries.1,2 Although there have been no reports of definitive epidemiological studies of esophageal adenocarcinoma in Japan, studies indicate a gradual increase in the incidence of adenocarcinoma of the esophagogastric junction.3 In comparison with Western countries, in Asian countries including Japan the incidence of long-segment Barrett’s esophagus (LSBE), with a circumferential segment of columnar epithelium greater than 3 cm in length, is lower, and short-segment Barrett’s esophagus (SSBE) is more common.4 However, the malignant potential of this
SSBE is also high, and surveillance is recommended as for LSBE.5 In fact, Koike et al. reported that 24 out of 28 cases of Barrett’s esophageal adenocarcinoma diagnosed between June 2001 and September 2010 arose from SSBE.6 Endoscopic surveillance of patients with Barrett’s esophagus has been reported to contribute to early detection of esophageal adenocarcinoma and improved outcomes.7,8 However, the optimum method and interval for surveillance has yet to be clarified. In recent years, transnasal endoscopy has become widely used for screening of the upper gastrointestinal tract. Until now, transnasal endoscopes have been inferior to transoral endoscopes in terms of optical resolution. However, the recently developed ultrathin transnasal endoscope, the GIF-XP290N, has a brighter light source and uses an objective optical system that prevents any reduction in contrast when the endoscope tip nears the area of interest. This makes possible a resolving power similar to the GIF-H260 at a distance of 3 mm.9 Furthermore, close observation
Journal of Gastroenterology and Hepatology 2015; 30 (Suppl. 1): 41–45 © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd
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Figure 1 Procedure of observation for Barrett’s esophagus. We then confirm the lower margin of the lower esophageal palisade vessels, the gastroesophageal junction as defined in Japan (left). If Barrett’s esophagus is detected (center), we switch over to NBI, making a close observation of the mucosal structure at a distance of 3 mm (right). NBI, narrow band imaging; WLI, white light imaging.
Table 1
Characteristics of subjects
Subjects Atrophic gastritis Gastric polyps Gastric ulcer Duodenal ulcer Gastric cancer (post-ESD) Esophageal cancer (post-ESD) Gastric submucosal tumor
71 cases 24 cases 15 cases 7 cases 14 cases 2 cases 2 cases
ESD, endoscopic submucosal dissection.
using narrow band imaging (NBI) enables us to delineate the mucosal structure, useful in the endoscopic diagnosis (in particular qualitative diagnosis) of lesions. In this paper, we present the results of endoscopic surveillance of Barrett’s esophagus using the GIF-XP290N.
Methods This prospective continuous study was conducted at the Tokyo Medical University Hospital Endoscopy Center between August 2012 and May 2013. The subjects were 135 patients who underwent upper gastrointestinal screening using thin transnasal endoscopy. Their average age was 63.5 ± 9.7 years, with a male : female ratio of 2.5:1. All examinations were conducted using both white light imaging (WLI) and close examination using NBI. Subject diagnoses are given in Table 1. The following subject background factors were collated: age, gender, history of smoking and alcohol intake, Helicobacter pylori (H. pylori) infection (including history of eradication therapy), and medication (suppressors of gastric acid secretion). First, we examine from the upper esophagus to the gastroesophageal junction using WLI. We also check for the presence of a hiatus hernia. We then confirm the lower margin of the lower esophageal palisade vessels, the gastroesophageal junction as defined in Japan (Fig. 1 left),10 with the diaphragm lowered in deep inspiration. We diagnose Barrett’s esophagus if columnar epithelium is present on the oral side of the gastroesophageal junction. If Barrett’s esophagus is detected (Fig. 1 center), we switch over to NBI, making a close observation of the mucosal structure at a 42
distance of 3 mm (Fig. 1 right). Barrett’s esophagus is classified as LSBE (> 30 mm), SSBE (< 30 mm, > 10 mm), or ultra-shortsegment Barrett’s esophagus (USSBE) (< 10 mm). We classify the mucosal pattern as oval or round pattern (Fig. 2a), long straight pattern (Fig. 2b), villous pattern (Fig. 2c), cerebriform pattern (Fig. 2d), or irregular pattern (Fig. 2e) according to Goda classification.11 Mucosal biopsies from all subjects with SSBE are examined histologically for the presence of metaplasia. We measure the length of segments of Barrett’s esophagus using biopsy forceps. We also check reflux esophagitis (grades A, B, C, D) according to Los Angeles Classification.12 We diagnose H. pylori infection using either the rapid urease test, urea breath test, histology, or serum IgG H. pylori antibodies. We excluded subjects aged < 20 years and those with a history of gastrointestinal surgery, including the esophagus or stomach. Subjects taking inhibitors of gastric acid secretion, such as proton pump inhibitors, were also excluded. The study protocol was approved by Tokyo Medical University Hospital Clinical Ethics Committee on Human Experiments, in accordance with the Helsinki Declaration of 1975 as revised in 1983. Endoscopy system. Endoscopic examinations are performed on unsedated subjects. We use the Olympus GIF-XP290N transnasal endoscopy (Olympus Medical System, Tokyo, Japan; outer diameter at the distal end 5.0 mm) and endoscope (Evis Lucera Elite System; Olympus Medical System). Premedication and anesthesia to the nasal cavity are performed as previously described.13 Antispasmodics, such as scopolamine butyl-bromide, are not administered as premedication. Histological examination. Biopsy specimens are fixed in formalin, then embedded in paraffin, and 4-μm slices were made. These specimens were examined for the presence of intestinal metaplasia. Statistical analysis. Statistical analyses were performed using the analysis software SPSS 16.0J for Windows (SPSS: SPSSR22.0J, IBM, New York, USA). For subject background factors, age was analyzed using the unpaired t-test, whereas other
Journal of Gastroenterology and Hepatology 2015; 30 (Suppl. 1): 41–45 © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd
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Table 2 Correlations between the presence of Barrett’s esophagus and subject background factors
Age Male : female Height Weight Tobacco Alcohol Hiatus hernia H. pylori infection
BE present n = 116
%
BE absent n = 19
%
P-value
65.8 ± 10.4 62:54 160.5 58.1 27 48 84 17
— — — — 23.3 41.4 72.4 14.6
66.0 ± 12.5 9:10 160.8 60.4 4 8 3 5
— — — — 21.1 42.1 15.7 26.3
0.987 0.649 0.914 0.457 0.803 0.976 0.000 0.205
BE, Barrett’s esophagus.
Table 3 Correlation between mucosal pattern of Barrett’s esophagus and subject background factors
Age Male : female Height Weight Tobacco Alcohol Hiatus hernia H. pylori infection Intestinal metaplasia
Closed type n = 54
%
Open type n = 62
%
P-value
65.4 ± 10.8 27:27 160.3 57.7 13 24 28 13 0
— — — — 24.1 44.4 51.8 24.1 0
66.3 ± 10.2 35:27 160.9 58.5 14 24 56 4 8
— — — — 22.5 38.7 90.3 6.5 12.5
0.710 0.491 0.710 0.743 0.729 0.547 0.000 0.006 0.006
Closed type: oval/round pattern and long straight pattern. Open type: villous pattern, cerebriform pattern, and irregular pattern.
background factors, as well as the presence of H. pylori infection and hiatus hernia, were analyzed using the χ2 test or Fisher’s exact test. A level of significance < 5% derived using these tests was considered statistically significant.
Results
Figure 2 Picture and schema of Barrett’s esophagus was divided into five patterns using close observation of GIF-XP290N: (a) oval or round pattern, (b) long straight pattern, (c) villous pattern, (d) cerebriform pattern, and (e) irregular pattern.
Barrett’s esophagus was confirmed in 116 subjects (85.9%). All were < 30 mm in length, with 18 cases of SSBE and 98 of USSBE. Only 6 cases of reflux esophagitis (LA-A:3, LA-B:1, LA-C:2) were recognized in BE. The mucosal pattern was oval or round pattern in 29 cases, long straight pattern in 29, villous pattern in 47, cerebriform pattern in 8, and irregular pattern in 6. Histological examination revealed intestinal metaplasia in eight subjects, three of whom showed a villous pattern, two a cerebriform pattern, and three an irregular pattern. There were 22 subjects positive and 28 negative for H. pylori infection, with 85 having successfully undergone eradication therapy. Analysis of the relationship between the presence of Barrett’s esophagus and background factors revealed a significant correlation with the presence of hiatus hernia, but no other significant correlations (Table 2). Using the simplified classification of mucosal patterns proposed by Yuki et al., we grouped the oval/ round and long straight patterns as closed type, and the villous,
Journal of Gastroenterology and Hepatology 2015; 30 (Suppl. 1): 41–45 © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd
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50 45 40 35 30 25 20 15 10 5 0
1
2
3
4
5
6
7
8
9
cerebriform, and irregular patterns as open type.14 Analysis of the relationship between these mucosal patterns and background factors revealed a significant correlation between hiatus hernia, intestinal metaplasia, and H. pylori infection, and the open-type pattern (Table 3). The longest orientation of Barrett’s esophagus was the 7 o’clock position, seen in 49 cases, followed by the 1 o’clock position in 35 cases (Fig. 3). The longest orientation of SSBE was 1 o’clock in eight cases, followed by the 7 o’clock in five cases; on the other hand, the longest orientation of USSBE was 7 o’clock in 44 cases, followed by the 1 o’clock in 27 cases.
Discussion We used ultrathin transnasal endoscopy for surveillance of Barrett’s esophagus for the following four reasons: (i) reduced patient discomfort allows us to observe the gastroesophageal junction thoroughly and without haste; (ii) because the patient is awake, we can identify the lower esophageal palisade vessels in deep inspiration (under sedation, we cannot examine the lower esophagus in deep inspiration, making identification of the lower esophageal palisade vessels difficult); (iii) close examination allows us to delineate the Barrett’s esophagus mucosal pattern; and (iv) we can take biopsy specimens. In this study, the incidence of Barrett’s esophagus was 85.9%, considerably greater than that of 20.9% reported by Kawano et al.15 However, none were LSBE, and 85.3% were USSBE, indicating that thorough examination of the gastroesophageal junction using an ultrathin transnasal endoscope enabled the detection of small segments of Barrett’s esophagus, leading to the high incidence in this study. Ishimura et al. have also identified inconsistencies between endoscopists in the diagnosis of Barrett’s esophagus.16 We use the classification of Goda et al. to classify the mucosal structural pattern of Barrett’s esophagus into five patterns.11 Of these patterns, correlations have been reported between the villous and cerebriform patterns with intestinal metaplasia and Barrett’s esophageal adenocarcinoma. Apart from Goda et al., there have 44
10
11
12
Figure 3 Number of orientation of Barrett’s esophagus.
been a number of reports of mucosal and vascular classifications of Barrett’s esophagus,17–19 although these have all used high-vision or magnifying endoscopes. These endoscopes are larger in caliber, requiring sedation, and are unsuited to screening endoscopy. Accordingly, we used a newly developed ultrathin transnasal endoscope, allowing close observation of the mucosal structure, and investigated the incidence of Barrett’s esophagus, in particular SSBE/USSBE, and the usefulness of classification of mucosal structural patterns. Yuki et al. classified mucosal patterns into an open type and closed type, reporting dysplasia was more common with the open type.14 We similarly grouped patterns into closed type (oval/round and long straight patterns) and open type (villous, cerebriform, and irregular patterns), and found that histological intestinal metaplasia was more common with the open type. The presence of intestinal metaplasia is reported to be associated with malignancy, and careful follow-up using ultrathin transnasal endoscopy is required in patients with open-type Barrett’s esophagus. Our findings of the orientation of segments of Barrett’s esophagus and the multidirectionality were consistent in previous reports that Barrett’s esophagus and adenocarcinoma are most commonly located on the right esophageal wall.20,21 Concerning background factors, Fujiwara et al. and Amano et al. reported advanced age, male gender, smoking, H. pylori infection, presence of hiatus hernia, and elevated body mass index as significant risk factors for gastroesophageal reflux disease (GERD), but only hiatus hernia for SSBE.22,23 Although the risk factors for LSBE are similar to those for GERD, all cases of Barrett’s esophagus in this study were SSBE or USSBE, accounting for our identification of only hiatus hernia as a significant risk factor. In conclusion, we believe that transnasal endoscopy will be a useful method for surveillance of SSBE/USSBE, common conditions in Japanese people.
References 1 Powell J, McConkey CC. The rising trend in oesophageal adenocarcinoma and gastric cardia. Eur. J. Cancer Prev. 1992; 1: 265–9.
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2 Powell J, McConkey CC, Gillison EW, Spychal RT. Continuing rising trend in oesophageal adenocarcinoma. Int. J. Cancer 2002; 102: 422–7. 3 Kusano C, Gotoda T, Khor CJ et al. Changing trends in the proportion of adenocarcinoma of the esophagogastric junction in a large tertiary referral center in Japan. J. Gastroenterol. Hepatol. 2008; 23: 1662–5. 4 Amano Y, Kinoshita Y. Barrett esophagus: perspectives on its diagnosis and management in Asian populations. Gastroenterol. Hepatol. 2008; 4: 45–53. 5 Sharma P, Morales TG, Bhattacharyya A, Garewal HS, Sampliner RE. Dysplasia in short-segment Barrett’s esophagus: a prospective 3-year follow-up. Am. J. Gastroenterol. 1997; 92: 2012–6. 6 Koike T, Abe Y, Iijima K et al. Diagnosis of Barrett’s esophageal cancer by conventional endoscopic examination (in Japanese). Stomach and Intestine 2011; 46: 1800–14. 7 Corley DA, Levin TR, Habel LA, Weiss NS, Buffler PA. Surveillance and survival in Barrett’s adenocarcinomas: a population-based study. Gastroenterology 2002; 122: 633–40. 8 Cooper GS, Kou TD, Chak A. Receipt of previous diagnoses and endoscopy and outcome from esophageal adenocarcinoma: a population-based study with temporal trends. Am. J. Gastroenterol. 2009; 104: 1356–62. DOI: 10.1038/ajg.2009.159. 9 Kawai T, Fukuzawa M, Gotoda T. Evolution of ultra thin endoscope. Dig. Endosc. 2013; 25: 46. 10 The Japan Esophageal Society, ed. Japanese Classification of Esophageal Cancer (The 10th Edition/Revised Version). Tokyo: Kanehara Shuppan, 2008; 40–2. 11 Goda K, Tajiri H, Ikegami M, Urashima M, Nakayoshi T, Kaise M. Usefulness of magnifying endoscopy with narrow band imaging for the detection of specialized intestinal metaplasia in columnar-lined esophagus and Barrett’s adenocarcinoma. Gastrointest. Endosc. 2007; 65: 36–46. 12 Armstrong D, Bennett JR, Blum AL et al. The endoscopic assessment of esophagitis: a progress report on observer agreement. Gastroenterology 1996; 111: 85–92. 13 Kawai T, Miyazaki I, Yagi K et al. Comparison of the effects on cardiopulmonary function of ultrathin transnasal versus normal
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23
diameter transoral esophagogastroduodenoscopy in Japan. Hepatogastroenterology 2007; 54: 770–4. Yuki T, Amano Y, Kushiyama Y et al. Evaluation of modified crystal violet chromoendoscopy procedure using new mucosal pit pattern classification for detection of Barrett’s dysplastic lesions. Dig Liv Dis. 2006; 38: 296–300. GERD Society Study Committee, Kawano T, Kouzu T, Ohara S, Kusano M. The prevalence of Barrett’s mucosa in the Japanese (in Japanese). Gastroenterol Endosc 2005; 47: 951–61. Ishimura N, Amano Y, Kinoshita Y. Endoscopic definition of esophagogastric junction for diagnosis of Barrett’s esophagus: importance of systematic education and training. Dig. Endosc. 2009; 21: 213–18. Sharma P, Bansal A, Mathur S et al. The utility of a novel narrow band imaging endoscopy system in patients with Barrett’s esophagus. Gastrointest. Endosc. 2006; 64: 167–75. Curvers WL, Bohmer CJ, Mallant-Hent RC et al. Mucosal morphology in Barrett’s esophagus: interobserver agreement and role of narrow band imaging. Endoscopy 2008; 40: 799–805. Singh R, Anagnostopoulos GK, Yao K et al. Narrow-band imaging with magnification in Barrett’s esophagus: validation of a simplified grading system of mucosal morphology patterns against histology. Endoscopy 2008; 40: 457–63. Okita K, Amano Y, Takahashi Y et al. Barrett’s esophagus in Japanese patients: its prevalence, form, and elongation. J. Gastroenterol. 2008; 43: 928–34. Moriyama N, Amano Y, Okita K, Mishima Y, Ishihara S, Kinoshita Y. Localization of early-stage dysplastic Barrett’s lesions in patients with short-segment Barrett’s esophagus. Am. J. Gastroenterol. 2006; 101: 2666–7. Fujiwara Y, Higuchi K, Shiba M et al. Differences in clinical characteristics between patients with endoscopy-negative reflux disease and erosive esophagitis in Japan. Am. J. Gastroenterol. 2005; 100: 754–8. Amano K, Adachi K, Katsube T et al. Role of hiatus hernia and gastric mucosal atrophy in the development of reflux esophagitis in the elderly. J. Gastroenterol. Hepatol. 2001; 16: 132–6.
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doi:10.1111/jgh.12879
O R I G I N A L A RT I C L E
Surveillance of short-segment Barrett’s esophagus using ultrathin transnasal endoscopy Hiroko Sugimoto,* Takashi Kawai,* Sakiko Naito,* Kyosuke Yanagizawa,* Tetsuya Yamagishi,* Masakatsu Fukuzawa,† Kenji Yagi,† Jun Matsubayashi,‡ Toshitaka Nagao,‡ Hirofumi Tomiyama,§ Sumito Hoshino,¶ Akihiko Tsuchida¶ and Fuminori Moriyasu† *Endoscopy Center, †Department of Gastroenterology and Hepatology, ‡Department of Pathology and §Department of Cardiovascular, Tokyo Medical University Hospital, Tokyo, Japan, ¶Department of Gastrointestinal and pediatric Surgery, Tokyo Medical University Hospital
Keywords Barrett’s esophagus, transnasal endoscopy, Narrow band imaging, close examination, mucosal structure. Correspondence Dr Takashi Kawai, Endoscopy Center, Tokyo Medical University Hospital, 6-7-1 Nishi-Shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan. Email: [email protected]
Abstract Background and Aim: Newly developed ultrathin transnasal endoscope, the GIFXP290N, makes possible a resolving power similar to the GIF-H260 at a distance of 3 mm. We conducted surveillance of subjects with Barrett’s esophagus using this ultrathin transnasal endoscopy. In Japan the lower margin of the lower esophageal palisade vessels is defined the gastroesophageal junction in deep inspiration. We diagnose Barrett’s esophagus if columnar epithelium is present on the oral side of the gastroesophageal junction. Methods and Results: Barrett’s esophagus was confirmed in 116 out of 135 subjects (85.9%), with 17 cases of short-segment Barrett’s esophagus (SSBE) and 99 of ultra-shortsegment Barrett’s esophagus. Close observation of the Barrett’s esophagus mucosal structural pattern using narrow band imaging revealed 29 cases with an oval or round pattern, 29 with a long straight pattern, 47 with a villous pattern, 8 with a cerebriform pattern, and 6 with an irregular pattern according to Goda classification. Mucosal biopsies from all subjects with SSBE are examined. Histological examination revealed intestinal metaplasia in only eight subjects. We grouped the oval/round and long straight patterns as closed type, and the villous, cerebriform, and irregular patterns as open type. Analysis of the relationship between these mucosal patterns and background factors revealed a significant correlation between intestinal metaplasia and the open-type pattern. Conclusion: We consider this new ultrathin transnasal endoscopy to be a useful technique for surveillance of Barrett’s esophagus, especially SSBE.
Introduction Barrett’s esophagus is a condition in which chronic inflammation of the lower esophagus associated with gastrointestinal reflux disease causes replacement of squamous epithelium by columnar epithelium. The intestinal metaplasia of Barrett’s esophagus can further lead to Barrett’s esophageal adenocarcinoma. The incidence of Barrett’s esophagus and Barrett’s esophageal adenocarcinoma is increasing, particularly in Western countries.1,2 Although there have been no reports of definitive epidemiological studies of esophageal adenocarcinoma in Japan, studies indicate a gradual increase in the incidence of adenocarcinoma of the esophagogastric junction.3 In comparison with Western countries, in Asian countries including Japan the incidence of long-segment Barrett’s esophagus (LSBE), with a circumferential segment of columnar epithelium greater than 3 cm in length, is lower, and short-segment Barrett’s esophagus (SSBE) is more common.4 However, the malignant potential of this
SSBE is also high, and surveillance is recommended as for LSBE.5 In fact, Koike et al. reported that 24 out of 28 cases of Barrett’s esophageal adenocarcinoma diagnosed between June 2001 and September 2010 arose from SSBE.6 Endoscopic surveillance of patients with Barrett’s esophagus has been reported to contribute to early detection of esophageal adenocarcinoma and improved outcomes.7,8 However, the optimum method and interval for surveillance has yet to be clarified. In recent years, transnasal endoscopy has become widely used for screening of the upper gastrointestinal tract. Until now, transnasal endoscopes have been inferior to transoral endoscopes in terms of optical resolution. However, the recently developed ultrathin transnasal endoscope, the GIF-XP290N, has a brighter light source and uses an objective optical system that prevents any reduction in contrast when the endoscope tip nears the area of interest. This makes possible a resolving power similar to the GIF-H260 at a distance of 3 mm.9 Furthermore, close observation
Journal of Gastroenterology and Hepatology 2015; 30 (Suppl. 1): 41–45 © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd
41
Barrett’s esophagus and transnasal endoscopy
H Sugimoto et al.
Figure 1 Procedure of observation for Barrett’s esophagus. We then confirm the lower margin of the lower esophageal palisade vessels, the gastroesophageal junction as defined in Japan (left). If Barrett’s esophagus is detected (center), we switch over to NBI, making a close observation of the mucosal structure at a distance of 3 mm (right). NBI, narrow band imaging; WLI, white light imaging.
Table 1
Characteristics of subjects
Subjects Atrophic gastritis Gastric polyps Gastric ulcer Duodenal ulcer Gastric cancer (post-ESD) Esophageal cancer (post-ESD) Gastric submucosal tumor
71 cases 24 cases 15 cases 7 cases 14 cases 2 cases 2 cases
ESD, endoscopic submucosal dissection.
using narrow band imaging (NBI) enables us to delineate the mucosal structure, useful in the endoscopic diagnosis (in particular qualitative diagnosis) of lesions. In this paper, we present the results of endoscopic surveillance of Barrett’s esophagus using the GIF-XP290N.
Methods This prospective continuous study was conducted at the Tokyo Medical University Hospital Endoscopy Center between August 2012 and May 2013. The subjects were 135 patients who underwent upper gastrointestinal screening using thin transnasal endoscopy. Their average age was 63.5 ± 9.7 years, with a male : female ratio of 2.5:1. All examinations were conducted using both white light imaging (WLI) and close examination using NBI. Subject diagnoses are given in Table 1. The following subject background factors were collated: age, gender, history of smoking and alcohol intake, Helicobacter pylori (H. pylori) infection (including history of eradication therapy), and medication (suppressors of gastric acid secretion). First, we examine from the upper esophagus to the gastroesophageal junction using WLI. We also check for the presence of a hiatus hernia. We then confirm the lower margin of the lower esophageal palisade vessels, the gastroesophageal junction as defined in Japan (Fig. 1 left),10 with the diaphragm lowered in deep inspiration. We diagnose Barrett’s esophagus if columnar epithelium is present on the oral side of the gastroesophageal junction. If Barrett’s esophagus is detected (Fig. 1 center), we switch over to NBI, making a close observation of the mucosal structure at a 42
distance of 3 mm (Fig. 1 right). Barrett’s esophagus is classified as LSBE (> 30 mm), SSBE (< 30 mm, > 10 mm), or ultra-shortsegment Barrett’s esophagus (USSBE) (< 10 mm). We classify the mucosal pattern as oval or round pattern (Fig. 2a), long straight pattern (Fig. 2b), villous pattern (Fig. 2c), cerebriform pattern (Fig. 2d), or irregular pattern (Fig. 2e) according to Goda classification.11 Mucosal biopsies from all subjects with SSBE are examined histologically for the presence of metaplasia. We measure the length of segments of Barrett’s esophagus using biopsy forceps. We also check reflux esophagitis (grades A, B, C, D) according to Los Angeles Classification.12 We diagnose H. pylori infection using either the rapid urease test, urea breath test, histology, or serum IgG H. pylori antibodies. We excluded subjects aged < 20 years and those with a history of gastrointestinal surgery, including the esophagus or stomach. Subjects taking inhibitors of gastric acid secretion, such as proton pump inhibitors, were also excluded. The study protocol was approved by Tokyo Medical University Hospital Clinical Ethics Committee on Human Experiments, in accordance with the Helsinki Declaration of 1975 as revised in 1983. Endoscopy system. Endoscopic examinations are performed on unsedated subjects. We use the Olympus GIF-XP290N transnasal endoscopy (Olympus Medical System, Tokyo, Japan; outer diameter at the distal end 5.0 mm) and endoscope (Evis Lucera Elite System; Olympus Medical System). Premedication and anesthesia to the nasal cavity are performed as previously described.13 Antispasmodics, such as scopolamine butyl-bromide, are not administered as premedication. Histological examination. Biopsy specimens are fixed in formalin, then embedded in paraffin, and 4-μm slices were made. These specimens were examined for the presence of intestinal metaplasia. Statistical analysis. Statistical analyses were performed using the analysis software SPSS 16.0J for Windows (SPSS: SPSSR22.0J, IBM, New York, USA). For subject background factors, age was analyzed using the unpaired t-test, whereas other
Journal of Gastroenterology and Hepatology 2015; 30 (Suppl. 1): 41–45 © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd
H Sugimoto et al.
Barrett’s esophagus and transnasal endoscopy
Table 2 Correlations between the presence of Barrett’s esophagus and subject background factors
Age Male : female Height Weight Tobacco Alcohol Hiatus hernia H. pylori infection
BE present n = 116
%
BE absent n = 19
%
P-value
65.8 ± 10.4 62:54 160.5 58.1 27 48 84 17
— — — — 23.3 41.4 72.4 14.6
66.0 ± 12.5 9:10 160.8 60.4 4 8 3 5
— — — — 21.1 42.1 15.7 26.3
0.987 0.649 0.914 0.457 0.803 0.976 0.000 0.205
BE, Barrett’s esophagus.
Table 3 Correlation between mucosal pattern of Barrett’s esophagus and subject background factors
Age Male : female Height Weight Tobacco Alcohol Hiatus hernia H. pylori infection Intestinal metaplasia
Closed type n = 54
%
Open type n = 62
%
P-value
65.4 ± 10.8 27:27 160.3 57.7 13 24 28 13 0
— — — — 24.1 44.4 51.8 24.1 0
66.3 ± 10.2 35:27 160.9 58.5 14 24 56 4 8
— — — — 22.5 38.7 90.3 6.5 12.5
0.710 0.491 0.710 0.743 0.729 0.547 0.000 0.006 0.006
Closed type: oval/round pattern and long straight pattern. Open type: villous pattern, cerebriform pattern, and irregular pattern.
background factors, as well as the presence of H. pylori infection and hiatus hernia, were analyzed using the χ2 test or Fisher’s exact test. A level of significance < 5% derived using these tests was considered statistically significant.
Results
Figure 2 Picture and schema of Barrett’s esophagus was divided into five patterns using close observation of GIF-XP290N: (a) oval or round pattern, (b) long straight pattern, (c) villous pattern, (d) cerebriform pattern, and (e) irregular pattern.
Barrett’s esophagus was confirmed in 116 subjects (85.9%). All were < 30 mm in length, with 18 cases of SSBE and 98 of USSBE. Only 6 cases of reflux esophagitis (LA-A:3, LA-B:1, LA-C:2) were recognized in BE. The mucosal pattern was oval or round pattern in 29 cases, long straight pattern in 29, villous pattern in 47, cerebriform pattern in 8, and irregular pattern in 6. Histological examination revealed intestinal metaplasia in eight subjects, three of whom showed a villous pattern, two a cerebriform pattern, and three an irregular pattern. There were 22 subjects positive and 28 negative for H. pylori infection, with 85 having successfully undergone eradication therapy. Analysis of the relationship between the presence of Barrett’s esophagus and background factors revealed a significant correlation with the presence of hiatus hernia, but no other significant correlations (Table 2). Using the simplified classification of mucosal patterns proposed by Yuki et al., we grouped the oval/ round and long straight patterns as closed type, and the villous,
Journal of Gastroenterology and Hepatology 2015; 30 (Suppl. 1): 41–45 © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd
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cerebriform, and irregular patterns as open type.14 Analysis of the relationship between these mucosal patterns and background factors revealed a significant correlation between hiatus hernia, intestinal metaplasia, and H. pylori infection, and the open-type pattern (Table 3). The longest orientation of Barrett’s esophagus was the 7 o’clock position, seen in 49 cases, followed by the 1 o’clock position in 35 cases (Fig. 3). The longest orientation of SSBE was 1 o’clock in eight cases, followed by the 7 o’clock in five cases; on the other hand, the longest orientation of USSBE was 7 o’clock in 44 cases, followed by the 1 o’clock in 27 cases.
Discussion We used ultrathin transnasal endoscopy for surveillance of Barrett’s esophagus for the following four reasons: (i) reduced patient discomfort allows us to observe the gastroesophageal junction thoroughly and without haste; (ii) because the patient is awake, we can identify the lower esophageal palisade vessels in deep inspiration (under sedation, we cannot examine the lower esophagus in deep inspiration, making identification of the lower esophageal palisade vessels difficult); (iii) close examination allows us to delineate the Barrett’s esophagus mucosal pattern; and (iv) we can take biopsy specimens. In this study, the incidence of Barrett’s esophagus was 85.9%, considerably greater than that of 20.9% reported by Kawano et al.15 However, none were LSBE, and 85.3% were USSBE, indicating that thorough examination of the gastroesophageal junction using an ultrathin transnasal endoscope enabled the detection of small segments of Barrett’s esophagus, leading to the high incidence in this study. Ishimura et al. have also identified inconsistencies between endoscopists in the diagnosis of Barrett’s esophagus.16 We use the classification of Goda et al. to classify the mucosal structural pattern of Barrett’s esophagus into five patterns.11 Of these patterns, correlations have been reported between the villous and cerebriform patterns with intestinal metaplasia and Barrett’s esophageal adenocarcinoma. Apart from Goda et al., there have 44
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Figure 3 Number of orientation of Barrett’s esophagus.
been a number of reports of mucosal and vascular classifications of Barrett’s esophagus,17–19 although these have all used high-vision or magnifying endoscopes. These endoscopes are larger in caliber, requiring sedation, and are unsuited to screening endoscopy. Accordingly, we used a newly developed ultrathin transnasal endoscope, allowing close observation of the mucosal structure, and investigated the incidence of Barrett’s esophagus, in particular SSBE/USSBE, and the usefulness of classification of mucosal structural patterns. Yuki et al. classified mucosal patterns into an open type and closed type, reporting dysplasia was more common with the open type.14 We similarly grouped patterns into closed type (oval/round and long straight patterns) and open type (villous, cerebriform, and irregular patterns), and found that histological intestinal metaplasia was more common with the open type. The presence of intestinal metaplasia is reported to be associated with malignancy, and careful follow-up using ultrathin transnasal endoscopy is required in patients with open-type Barrett’s esophagus. Our findings of the orientation of segments of Barrett’s esophagus and the multidirectionality were consistent in previous reports that Barrett’s esophagus and adenocarcinoma are most commonly located on the right esophageal wall.20,21 Concerning background factors, Fujiwara et al. and Amano et al. reported advanced age, male gender, smoking, H. pylori infection, presence of hiatus hernia, and elevated body mass index as significant risk factors for gastroesophageal reflux disease (GERD), but only hiatus hernia for SSBE.22,23 Although the risk factors for LSBE are similar to those for GERD, all cases of Barrett’s esophagus in this study were SSBE or USSBE, accounting for our identification of only hiatus hernia as a significant risk factor. In conclusion, we believe that transnasal endoscopy will be a useful method for surveillance of SSBE/USSBE, common conditions in Japanese people.
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