今日の臨床サポート

バレット食道(バレット食道癌含む)

著者: 藤崎順子 がん研有明病院 消化器センター

監修: 木下芳一 兵庫県立姫路循環器病センター/製鉄記念広畑病院

著者校正/監修レビュー済:2021/07/07
参考ガイドライン:
  1. 臨床・病理食道癌取扱い規約 第11版 日本食道学会編 金原出版株式会社(J)
  1. 食道癌診療ガイドライン 2017年版 特定非営利活動法人 日本食道学会編 金原出版株式会社(J)
  1. AGA clinical practice update on Endoscopic Treatment of Barrett's Esophagus with Dysplasia and/or Early cancer: Expert review. Gastroenterology 2020;158:760-69
  1. ASGE guideline on screening and surveillance of Barrett’s esophagus Prepared by: ASGE STANDARDS OF PRACTICE COMMITTEE. GIE 2019;90:335-59
患者向け説明資料

概要・推奨   

  1. ガイドラインではバレット食道のサーベイランスが弱く推奨されている欧米ではLSBEは発リスク因子の1つと考えられている。
  1. GERDがバレット食道の発生と関連することがいわれている。
  1. GERD患者の25%にバレット食道が確認できた。
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧には
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
藤崎順子 : 特に申告事項無し[2021年]
監修:木下芳一 : 講演料(アストラゼネカ,武田,大塚,第一三共)[2021年]

改訂のポイント:
食道学会より規約、ガイドラインが改訂されたことにより修正を行った。
  1. バレット食道をサーベイランスすることを弱く推奨する。(J)
  1. バレット食道腺癌のガイドライン上の内視鏡切除術の適応は現時点で壁深達度が粘膜固有層にとどまるもの(EP【上皮内にとどまる(非浸潤性病変)】、SMM【浅層粘膜筋板にとどまる】、およびLPM【深層粘膜筋板に達しない】)とされるが、症例の積み重ねが必要である。近年わが国多施設のretrospective studyの結果からリスク因子(脈管侵襲陰性、深部未分化成分なし、3cm以下)なし、SM500μmまでのpT1b癌の内視鏡治療的論文がでた。今後前向き試験の結果が待たれる。(J)
  1. AGAの最新版ではサーベイランス間隔は生検結果により異なる。またバレット食道腺癌T1aは内視鏡治療を推奨している。(Gastroenterology 2020:158)

病態・疫学・診察

疾患情報(疫学・病態)  
バレット食道:
  1. バレット食道とは、食道下端の扁平上皮が胃から連続する円柱上皮で置換された状態である。
  1. 食道胃接合部とSCJ(squam-columnar junction)に挟まれた部分がバレット粘膜である。
  1. わが国における診断は、食道癌取扱い規約第11版に従っている[1]
  1. 食道癌取扱い規約:(J)
  1. 欧米(英国を除く)ではバレット食道の診断に腸上皮化成の存在が必須であり、わが国と異なる。
  1. バレット食道の発生には食道内酸逆流が大きく関与する[2]。食生活の変化、肥満の増加、H. pylori感染率の低下などに よ り、逆 流 性 食 道 炎 をはじめ胃食道逆流症(gastro-esophageal reflux disease;GERD)の患者が急増しており、その結果、Barrett食道さらにはBarrett食道癌の患者が増えることが危惧されている。
  1. GERD患者の25%にバレット食道が確認できた[2]
  1. GERD患者の中でも加齢、男性、喫煙、肥満がバレット食道の独立した危険因子であることがいわれている[3]
  1. 日本における有病率は、Long Segment Barrett’s Esophagus(LSBE)0.2%、Short Segment Barrett’s Esophagus(SSBE)20.8%が報告されている[3]
  1. 欧米における診断基準はわが国と異なり、特殊腸上皮化成(specialized intestinal metaplasia、SIM)の存在が重要となる。
  1. バレット食道からの食道腺癌の発生率は年率0.1~0.6%と報告されている[4][5][6]。LSBEで発癌ポテンシャルが高いことが報告されている[7][8]。最近のわが国からの多施設によるLSBEの向こう5年にわたる追跡調査では、年率1.2%の腺癌の発生があり、既報とほぼ同等であった[9]
 
  1. GERDがバレット食道の発生と関連することがいわれている(Rs)
  1. バレット食道からhigh grade dysplasiaへ進展し、その後、浸潤癌に発展する頻度は5年以内に30~35%と高く、バレット食道癌の予後は5年生存率が15~20%と悪い[10]
  1. わが国ではhigh grade dysplasiaは粘膜内癌にあたる[11]。(J)
 
  1. LSBE患者には年1回の上部消化管内視鏡検査(EGD)が勧められる。
  1. LSBE経過観察中、5年後にバレット食道癌が発見された。
  1. 病歴:胸やけ症状があった。
  1. 診察:2006年のEGDでLSBEが確認された。
  1. 治療:PPIは近医で投与され、定期的な内服は行っていなかった。
  1. 転帰:ESDが行われ、病理診断では深達度SM2、追加手術が施行された。
  1. 追記:胸やけ症状があり、年に1回EGDが近医で行われていた。バレット食道内の隆起性病変が発見され、生検で腺癌の診断がついた。
 
バレット食道腺癌

a:2006年LSBE
b:2012年隆起の部分より腺癌

出典

img1:  著者提供
 
 
 
バレット食道癌:
  1. 欧米ではバレット腺癌が増加しており、全食道癌の70%を超えている。
  1. わが国の食道腺癌の割合は2001年2%、2006年4%と報告されている[12]
問診・診察のポイント  
  1. GERD症状があるかについて問診を行う(推奨度1)。バレット食道癌があれば、食道のつかえ感などの症状を訴えることがある。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

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文献 

著者: Brenda Westhoff, Scott Brotze, Allan Weston, Christian McElhinney, Rachel Cherian, Matthew S Mayo, Holly J Smith, Prateek Sharma
雑誌名: Gastrointest Endosc. 2005 Feb;61(2):226-31.
Abstract/Text BACKGROUND: The reported frequency of Barrett's esophagus (BE) in patients with reflux symptoms varies from 5% to 15%. The exact frequency of long-segment BE (LSBE) (>3 cm) and short-segment BE (SSBE) (<3 cm) in patients with chronic symptoms of GERD is uncertain. The aim of this study was to determine the frequency of LSBE and SSBE in consecutive patients presenting for a first endoscopic evaluation with GERD as the indication.
METHODS: Consecutive patients presenting to the endoscopy unit of a Veterans Affairs Medical Center for a first upper endoscopy with the indication of GERD were prospectively evaluated. Demographic information (gender, race, age), data on tobacco use and family history of esophageal disease, and body mass index (BMI) were recorded for all patients. Before endoscopy, all patients completed a validated GERD questionnaire. The diagnosis of BE was based on the presence of columnar-appearing mucosa in the distal esophagus, with confirmation by demonstration of intestinal metaplasia in biopsy specimens. All patients with erosive esophagitis on the initial endoscopy underwent a second endoscopy to document healing and to rule-out underlying BE. Patients with a history of BE, alarm symptoms (dysphagia, weight loss, anemia, evidence of GI bleeding), or prior endoscopy were excluded.
RESULTS: A total of 378 consecutive patients with GERD (94% men, 86% white; median age 56 years, range 27-93 years) were evaluated. A diagnosis of BE was made in 50 patients (13.2%). The median length of Barrett's esophagus (BE) was 1.0 cm (range 0.5-15.0 cm). Of the patients with BE, 64% had short-segment BE (SSBE) (overall SSBE frequency 8.5%). The overall frequency of long-segment BE (LSBE) was 4.8%. A hiatal hernia was detected in 62% of the patients with BE. Of the 50 patients with BE (median age 62 years, range 29-81 years), 47 (94%) were men and 98% were white. Eighteen patients (36%) were using tobacco at the time of endoscopy; 23 (46%) were former users. The median body mass index (BMI) of patients with BE was 27.3 (overweight). There were no significant differences between patients with LSBE and SSBE with respect to age, gender, ethnicity, BMI, and GERD symptom duration.
CONCLUSIONS: The frequency of BE in a high-risk patient group (chronic GERD, majority white men, age > 50 years) who sought medical attention is 13.2%, with the majority (64%) having SSBE. These data suggest that the frequency of BE in patients with GERD has not changed. The true prevalence of BE in the general population, including those who do not seek care, is undoubtedly lower, currently and historically. The majority of patients with BE are overweight and have a hiatal hernia. Demographic data for patients with LSBE and SSBE are similar, indicating that these are a continuum of the same process.

PMID 15729230  Gastrointest Endosc. 2005 Feb;61(2):226-31.
著者: Frederik Hvid-Jensen, Lars Pedersen, Asbjørn Mohr Drewes, Henrik Toft Sørensen, Peter Funch-Jensen
雑誌名: N Engl J Med. 2011 Oct 13;365(15):1375-83. doi: 10.1056/NEJMoa1103042.
Abstract/Text BACKGROUND: Accurate population-based data are needed on the incidence of esophageal adenocarcinoma and high-grade dysplasia among patients with Barrett's esophagus.
METHODS: We conducted a nationwide, population-based, cohort study involving all patients with Barrett's esophagus in Denmark during the period from 1992 through 2009, using data from the Danish Pathology Registry and the Danish Cancer Registry. We determined the incidence rates (numbers of cases per 1000 person-years) of adenocarcinoma and high-grade dysplasia. As a measure of relative risk, standardized incidence ratios were calculated with the use of national cancer rates in Denmark during the study period.
RESULTS: We identified 11,028 patients with Barrett's esophagus and analyzed their data for a median of 5.2 years. Within the first year after the index endoscopy, 131 new cases of adenocarcinoma were diagnosed. During subsequent years, 66 new adenocarcinomas were detected, yielding an incidence rate for adenocarcinoma of 1.2 cases per 1000 person-years (95% confidence interval [CI], 0.9 to 1.5). As compared with the risk in the general population, the relative risk of adenocarcinoma among patients with Barrett's esophagus was 11.3 (95% CI, 8.8 to 14.4). The annual risk of esophageal adenocarcinoma was 0.12% (95% CI, 0.09 to 0.15). Detection of low-grade dysplasia on the index endoscopy was associated with an incidence rate for adenocarcinoma of 5.1 cases per 1000 person-years. In contrast, the incidence rate among patients without dysplasia was 1.0 case per 1000 person-years. Risk estimates for patients with high-grade dysplasia were slightly higher.
CONCLUSIONS: Barrett's esophagus is a strong risk factor for esophageal adenocarcinoma, but the absolute annual risk, 0.12%, is much lower than the assumed risk of 0.5%, which is the basis for current surveillance guidelines. Data from the current study call into question the rationale for ongoing surveillance in patients who have Barrett's esophagus without dysplasia. (Funded by the Clinical Institute, University of Aarhus, Aarhus, Denmark.).

PMID 21995385  N Engl J Med. 2011 Oct 13;365(15):1375-83. doi: 10.1056・・・
著者: Pieter J F de Jonge, Mark van Blankenstein, Caspar W N Looman, Mariël K Casparie, Gerrit A Meijer, Ernst J Kuipers
雑誌名: Gut. 2010 Aug;59(8):1030-6. doi: 10.1136/gut.2009.176701.
Abstract/Text BACKGROUND: Reported incidence rates of oesophageal adenocarcinoma (OAC) in Barrett's oesophagus (BO) vary widely. As the effectiveness of BO surveillance is crucially dependent on this rate, its clarification is essential.
METHODS: To estimate the rate of malignant progression in patients with BO, all patients with a first diagnosis of BO with no dysplasia (ND) or low-grade dysplasia (LGD) between 1991 and 2006 were identified in the Dutch nationwide registry of histopathology (PALGA). Follow-up data were evaluated up to November 2007.
RESULTS: 42 207 patients with BO were included; 4132 (8%) of them had LGD. Re-evaluation endoscopies at least 6 months after initial diagnosis were performed in 16 365 patients (39%), who were significantly younger than those not re-examined (58+/-13 vs 63+/-16 years, p<0.001). These patients were followed-up for a total of 78 131 person-years, during which 666 (4%) high-grade dysplasia (HGD)/OACs occurred, affecting 4% of the surveillance patient population (mean age: 69+/-12 years, 76% male). After excluding HGD/OAC cases detected within 1 year after BO diagnosis (n=212, 32%), incidence rates per 1000 person-years were 4.3 (95% CI 3.4 to 5.5) for OAC and 5.8 (95% CI 4.6 to 7.0) for HGD/OAC combined. Risk factors for HGD/OAC were increased age (eg, >75 years HR 12; 95% CI 8.0 to 18), male sex (2.01; 1.68 to 2.60) and presence of LGD at baseline (1.91; 1.53 to 2.40).
CONCLUSION: In this largest reported cohort of unselected patients with BO, the annual risk of OAC was 0.4%. Male sex, older age and LGD at diagnosis are independent predictors of malignant progression, and should enable an improved risk assessment in BO.

PMID 20639249  Gut. 2010 Aug;59(8):1030-6. doi: 10.1136/gut.2009.17670・・・
著者: Shivaram Bhat, Helen G Coleman, Fouad Yousef, Brian T Johnston, Damian T McManus, Anna T Gavin, Liam J Murray
雑誌名: J Natl Cancer Inst. 2011 Jul 6;103(13):1049-57. doi: 10.1093/jnci/djr203. Epub 2011 Jun 16.
Abstract/Text BACKGROUND: Barrett's esophagus (BE) is a premalignant lesion that predisposes to esophageal adenocarcinoma. However, the reported incidence of esophageal adenocarcinoma in patients with BE varies widely. We examined the risk of malignant progression in patients with BE using data from the Northern Ireland Barrett's esophagus Register (NIBR), one of the largest population-based registries of BE worldwide, which includes every adult diagnosed with BE in Northern Ireland between 1993 and 2005.
SUBJECTS AND METHODS: We followed 8522 patients with BE, defined as columnar lined epithelium of the esophagus with or without specialized intestinal metaplasia (SIM), until the end of 2008. Patients with incident adenocarcinomas of the esophagus or gastric cardia or with high-grade dysplasia of the esophagus were identified by matching the NIBR with the Northern Ireland Cancer Registry, and deaths were identified by matching with records from the Registrar General's Office. Incidence of cancer outcomes or high-grade dysplasia was calculated as events per 100 person-years (% per year) of follow-up, and Cox proportional hazard models were used to determine incidence by age, sex, length of BE segment, presence of SIM, macroscopic BE, or low-grade dysplasia. All P values were from two-sided tests.
RESULTS: After a mean of 7.0 years of follow-up, 79 patients were diagnosed with esophageal cancer, 16 with cancer of the gastric cardia, and 36 with high-grade dysplasia. In the entire cohort, incidence of esophageal or gastric cardia cancer or high-grade dysplasia combined was 0.22% per year (95% confidence interval [CI] = 0.19% to 0.26%). SIM was found in 46.0% of patients. In patients with SIM, the combined incidence was 0.38% per year (95% CI = 0.31 to 0.46%). The risk of cancer was statistically significantly elevated in patients with vs without SIM at index biopsy (0.38% per year vs 0.07% per year; hazard ratio [HR] = 3.54, 95% CI = 2.09 to 6.00, P < .001), in men compared with women (0.28% per year vs 0.13% per year; HR = 2.11, 95% CI = 1.41 to 3.16, P < .001), and in patients with low-grade dysplasia compared with no dysplasia (1.40% per year vs 0.17% per year; HR = 5.67, 95% CI = 3.77 to 8.53, P < .001).
CONCLUSION: We found the risk of malignant progression among patients with BE to be lower than previously reported, suggesting that currently recommended surveillance strategies may not be cost-effective.

PMID 21680910  J Natl Cancer Inst. 2011 Jul 6;103(13):1049-57. doi: 10・・・
著者: Heiko Pohl, Oliver Pech, Haris Arash, Manfred Stolte, Hendrik Manner, Andrea May, Klaus Kraywinkel, Amnon Sonnenberg, Christian Ell
雑誌名: Gut. 2016 Feb;65(2):196-201. doi: 10.1136/gutjnl-2015-309220. Epub 2015 Jun 25.
Abstract/Text OBJECTIVE: Although it is well understood that the risk of oesophageal adenocarcinoma increases with Barrett length, transition risks for cancer associated with different Barrett lengths are unknown. We aimed to estimate annual cancer transition rates for patients with long-segment (≥3 cm), short-segment (≥1 to <3 cm) and ultra-short-segment (<1 cm) Barrett's oesophagus.
DESIGN: We used three data sources to estimate the annual cancer transition rates for each Barrett length category: (1) the distribution of long, short and ultra-short Barrett's oesophagus among a large German cohort with newly diagnosed T1 oesophageal adenocarcinoma; (2) population-based German incidence of oesophageal adenocarcinoma; and (3) published estimates of the population prevalence of Barrett's oesophagus for each Barrett length category.
RESULTS: Among 1017 patients with newly diagnosed T1 oesophageal adenocarcinoma, 573 (56%) had long-segment, 240 (24%) short-segment and 204 (20%) ultra-short-segment Barrett's oesophagus. The base-case estimates for the prevalence of Barrett's oesophagus among the general population were 1.5%, 5% and 14%, respectively. The annual cancer transition rates for patients with long, short and ultra-short Barrett's oesophagus were 0.22%, 0.03% and 0.01%, respectively. To detect one cancer, 450 patients with long-segment Barrett's oesophagus would need to undergo annual surveillance endoscopy; in short segment and ultra-short segment, the corresponding numbers of patients would be 3440 and 12,364. Similar results were obtained when applying US incidence data.
CONCLUSIONS: The large number of patients, who need to undergo endoscopic surveillance to detect one cancer, raises questions about the value of surveillance endoscopy in patients with short segment or ultra-short segment of Barrett's oesophagus.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
PMID 26113177  Gut. 2016 Feb;65(2):196-201. doi: 10.1136/gutjnl-2015-3・・・
著者: Sharmila Anandasabapathy, Jagriti Jhamb, Marta Davila, Caimiao Wei, Jeffrey Morris, Robert Bresalier
雑誌名: Cancer. 2007 Feb 15;109(4):668-74. doi: 10.1002/cncr.22451.
Abstract/Text BACKGROUND: Barrett esophagus is highly prevalent in the Western world; however, only a minority of affected individuals progress to esophageal adenocarcinoma. Whereas many studies have examined risk factors for development of Barrett metaplasia, few data are available on risk factors for progression to neoplasia. Identifying simple, reliable, clinical, and endoscopic predictors of high-grade dysplasia and adenocarcinoma would be helpful for risk stratification in screening and surveillance programs.
METHODS: Clinical, endoscopic, and histologic data were reviewed for patients with a new Barrett diagnosis between 2002 and 2005. Patients were classified, by an expert gastrointestinal pathologist, as having intestinal metaplasia, indefinite-for-dysplasia, low-grade dysplasia, high-grade dysplasia, and esophageal adenocarcinoma. Gender, age, race, ethnicity, hiatal hernia presence and size, Barrett segment length, H. pylori status, alcohol, smoking, proton pump inhibitor (PPI) use and duration, and reflux symptom duration were evaluated by logistic regression analysis for their association with dysplasia severity.
RESULTS: In all, 109 patients (26 women, 83 men, mean age: 58.8) were newly diagnosed with Barrett metaplasia (n = 39), indefinite/low-grade dysplasia (n = 35), and high-grade dysplasia/esophageal adenocarcinoma (n = 35) over a 3-year period. On logistic regression analysis, duration of reflux symptoms for >or=20 years (odds ratio [OR]: 5.66, P = .012), longer Barrett segment length (OR for 3-6 cm vs. <3 cm: 9.05, P < .0001; OR for >or=6 cm: 8.374, P < .0001), hernia size >or=4 cm (OR: 10.63, P = .014), and male gender (OR: 4.03, P = .0019) were associated with higher pathologic grade. Duration of reflux symptoms and Barrett length were significant as both discrete and continuous variables. Absence of H. pylori (OR: 2.731, P = .060) approached significance in predicting dysplasia severity. In bivariate models, gender and Barrett length (continuous form) were significantly associated with grade when considered together (OR: 2.52, P = .0490 and OR: 1.30, P < .0001), as were gender and hernia size >4 cm (OR: 4.64, P = .0049 and OR: 12.18, P = .0197).
CONCLUSIONS: Male gender, longstanding gastroesophageal reflux disease, hiatal hernia size, and segment length are strongly associated with higher grades of dysplasia at index diagnosis. These factors along with H. pylori status warrant further prospective evaluation as predictors of risk for development of high-grade dysplasia and esophageal adenocarcinoma.

PMID 17211862  Cancer. 2007 Feb 15;109(4):668-74. doi: 10.1002/cncr.22・・・
著者: Nobuyuki Matsuhashi, Eiji Sakai, Ken Ohata, Norihisa Ishimura, Fujisaki Junko, Tomoki Shimizu, Katsunori Iijima, Tomoyuki Koike, Takao Endo, Takefumi Kikuchi, Tatsuya Inayoshi, Yuji Amano, Takahisa Furuta, Ken Haruma, Yoshikazu Kinoshita
雑誌名: J Gastroenterol Hepatol. 2016 Jul 15;. doi: 10.1111/jgh.13491. Epub 2016 Jul 15.
Abstract/Text BACKGROUND AND AIM: The incidence of esophageal adenocarcinoma (EAC) in cases with long-segment Barrett esophagus (BE) has not been investigated in Japan. The aim of this study is to investigate the incidence of EAC in Japanese cases with long-segment BE prospectively.
METHODS: This is a multicenter prospective cohort study investigating the incidence rate of EAC in patients with BE with a length of at least 3 cm. Study subjects received index esophagogastroduodenoscopy at the time of enrollment, and they were instructed to undergo yearly follow-up esophagogastroduodenoscopy. Patients in whom EAC was diagnosed in the endoscopic examinations underwent subsequent treatment and their prognosis was observed.
RESULTS: Of 215 enrolled patients, six (2.8%) were initially diagnosed with EAC at the enrollment. Among the remaining 209 patients, 132 received at least one follow-up esophagogastroduodenoscopy. In this follow-up, three EACs developed in observed 251 patient-year (incidence rate; 1.2% per year). Most of the EACs detected at the initial endoscopic examination (5/6, 83%) were already at advanced stages. Meanwhile, all the three lesions detected in the follow-up esophagogastroduodenoscopies were identified as early cancers and underwent curative resection.
CONCLUSIONS: The incidence rate of EAC in Japanese cases with long-segment BE was calculated to be 1.2% in a year.

This article is protected by copyright. All rights reserved.
PMID 27416773  J Gastroenterol Hepatol. 2016 Jul 15;. doi: 10.1111/jgh・・・
著者: Marjolein Sikkema, Pieter J F de Jonge, Ewout W Steyerberg, Ernst J Kuipers
雑誌名: Clin Gastroenterol Hepatol. 2010 Mar;8(3):235-44; quiz e32. doi: 10.1016/j.cgh.2009.10.010. Epub 2009 Oct 20.
Abstract/Text BACKGROUND & AIMS: As the risk of esophageal adenocarcinoma (EAC) and mortality in patients with Barrett's esophagus (BE) are important determinants of the potential yield and cost-effectiveness of BE surveillance, clarification of these factors is essential. We therefore performed a systematic review and meta-analysis to determine the incidence of EAC and mortality due to EAC in BE under surveillance.
METHODS: Databases were searched for relevant cohort studies in English language that reported EAC risk and mortality due to EAC in BE. Studies had to include patients with histologically proven BE, documented follow-up, and histologically proven EAC on surveillance. A random effects model was used with assessment of heterogeneity by the I(2)-statistic and of publication bias by Begg's and Egger's tests.
RESULTS: Fifty-one studies were included in the main analysis. The overall mean age of BE patients was 61 years; the mean overall proportion of males was 64%. The pooled estimate for EAC incidence was 6.3/1000 person-years of follow-up (95% confidence interval, 4.7-8.4) with considerable heterogeneity (P < .001; I(2) = 79%). Nineteen studies reported data on mortality due to EAC. The pooled incidence of fatal EAC was 3.0/1000 person-years of follow-up (95% confidence interval, 2.2-3.9) with no evidence for heterogeneity (P = .4; I(2) = 7%). No evidence of publication bias was found.
CONCLUSIONS: Patients with BE are at low risk of malignant progression and predominantly die due to causes other than EAC. This undermines the cost-effectiveness of BE surveillance and supports the search for valid risk stratification tools to identify the minority of patients that are likely to benefit from surveillance.

Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
PMID 19850156  Clin Gastroenterol Hepatol. 2010 Mar;8(3):235-44; quiz ・・・
著者: H J Stein, J R Siewert
雑誌名: Dysphagia. 1993;8(3):276-88.
Abstract/Text Barrett's esophagus (i.e. columnar epithelial metaplasia in the distal esophagus) is an acquired condition that in most patients results from chronic gastroesophageal reflux. It is a disorder of the white male in the Western world with a prevalence of about 1/400 population. Due to the decreased sensitivity of the columnar epithelium to symptoms, Barrett's esophagus remains undiagnosed in the majority of patients. Gastroesophageal reflux disease in patients with Barrett's esophagus has a more severe character and is more frequently associated with complications as compared with reflux patients without columnar mucosa. This appears to be due to a combination of a mechanically defective lower esophageal sphincter, inefficient esophageal clearance function, and gastric acid hypersecretion. Excessive reflux of alkaline duodenal contents may be responsible for the development of complications (i.e., stricture, ulcer, and dysplasia). Therapy of benign Barrett's esophagus is directed towards treatment of the underlying reflux disease. Barrett's esophagus is associated with a 30- to 125-fold increased risk for adenocarcinoma of the esophagus. The reasons for the dramatic rise in the incidence of esophageal adenocarcinoma, which occurred during the past years, are unknown. High grade dysplasia in a patient with columnar mucosa is an ominous sign for malignant degeneration. Whether an esophagectomy should be performed in patients with high grade dysplasia remains controversial. Complete resection of the tumor and its lymphatic drainage is the procedure of choice in all patients with a resectable carcinoma who are fit for surgery. In patients with tumors located in the distal esophagus, this can be achieved by a transhiatal en-bloc esophagectomy and proximal gastrectomy. Early adenocarcinoma can be cured by this approach. The value of multimodality therapy in patients with advanced tumors needs to be shown in randomized prospective trials.

PMID 8359051  Dysphagia. 1993;8(3):276-88.
著者: Prateek Sharma, John Dent, David Armstrong, Jacques J G H M Bergman, Liebwin Gossner, Yoshio Hoshihara, Janusz A Jankowski, Ola Junghard, Lars Lundell, Guido N J Tytgat, Michael Vieth
雑誌名: Gastroenterology. 2006 Nov;131(5):1392-9. doi: 10.1053/j.gastro.2006.08.032. Epub 2006 Aug 16.
Abstract/Text BACKGROUND & AIMS: Barrett's esophagus (BE) is a premalignant condition for esophageal adenocarcinoma, its diagnosis relying initially on recognition of a columnar-lined distal esophagus. We aimed to develop and validate explicit, consensus-driven criteria for the endoscopic diagnosis and grading of BE.
METHODS: An international working group agreed on criteria and developed materials for their formal evaluation using video-endoscopic recordings gathered in a standardized manner in 29 patients. The criteria included assessment of the circumferential (C) and maximum (M) extent of the endoscopically visualized BE segment as well as endoscopic landmarks. The recordings were scored according to these criteria by a separate international panel of 29 endoscopists.
RESULTS: The Prague C & M Criteria give explicit guidance on the endoscopic recognition of BE and grading of its extent. The overall reliability coefficients (RC) for the assessment of the C & M extent of the endoscopic BE segment above the gastroesophageal junction were 0.95 and 0.94, respectively. The rates of exact agreement (for C & M values) for pairwise comparisons of individual patient values were 53% and 38%, respectively, whereas the values for agreement within a 2-cm interval were 97% and 95%, respectively. The overall RC for endoscopic recognition of BE >/=1 cm was 0.72, whereas for BE <1 cm, it was 0.22. The RCs for recognizing the location of the gastroesophageal junction and the diaphragmatic hiatus were 0.88 and 0.85, respectively.
CONCLUSIONS: The Prague C & M Criteria have high overall validity for the endoscopic assessment of visualized BE lengths.

PMID 17101315  Gastroenterology. 2006 Nov;131(5):1392-9. doi: 10.1053/・・・
著者: Richard E Sampliner, Practice Parameters Committee of the American College of Gastroenterology
雑誌名: Am J Gastroenterol. 2002 Aug;97(8):1888-95. doi: 10.1111/j.1572-0241.2002.05910.x.
Abstract/Text
PMID 12190150  Am J Gastroenterol. 2002 Aug;97(8):1888-95. doi: 10.111・・・
著者: ASGE STANDARDS OF PRACTICE COMMITTEE, Bashar Qumseya, Shahnaz Sultan, Paul Bain, Laith Jamil, Brian Jacobson, Sharmila Anandasabapathy, Deepak Agrawal, James L Buxbaum, Douglas S Fishman, Suryakanth R Gurudu, Terry L Jue, Sapna Kripalani, Jeffrey K Lee, Mouen A Khashab, Mariam Naveed, Nirav C Thosani, Julie Yang, John DeWitt, Sachin Wani, ASGE Standards of Practice Committee Chair
雑誌名: Gastrointest Endosc. 2019 Sep;90(3):335-359.e2. doi: 10.1016/j.gie.2019.05.012.
Abstract/Text
PMID 31439127  Gastrointest Endosc. 2019 Sep;90(3):335-359.e2. doi: 10・・・
著者: Sravanthi Parasa, Madhav Desai, Anusha Vittal, Viveksandeep T Chandrasekar, Asad Pervez, Kevin F Kennedy, Neil Gupta, Nicholas J Shaheen, Prateek Sharma
雑誌名: Gut. 2019 Dec;68(12):2122-2128. doi: 10.1136/gutjnl-2018-317800. Epub 2019 Mar 14.
Abstract/Text BACKGROUND: Biopsies are obtained to confirm intestinal metaplasia and rule out prevalent dysplasia and cancer when Barrett's oesophagus (BE) is detected at index upper endoscopy (oesophagogastroduodenoscopy [EGD]).
AIM: The purpose of this systematic review was to obtain summary estimates of the prevalence of high-grade dysplasia (HGD) and oesophageal adenocarcinoma (EAC) associated with BE during index EGD for chronic GERD symptoms, defined as neoplasia detection rate (NDR) which could be used as a quality measure.
METHODS: An extensive search was performed within PUBMED, EMBASE and the Cochrane Library databases to identify studies in which patients underwent index endoscopy for the evaluation of the presence of BE. Two reviewers independently evaluated both the study eligibility and methodological quality and data extraction. A random-effects model (REM) based on the binomial distribution was used to calculate the pooled effects of the prevalence of BE-associated dysplasia and EAC.
RESULTS: For the calculation of dysplasia and EAC prevalence rates, a total of 11 studies with 10 632 patients met the inclusion criteria including 80.4% men with a mean age of 58.7 years and average BE length of 3.5 cm. The pooled prevalence of EAC, HGD and LGD was 3%(95% CI 2 to 5, 9 studies: 396/10 539 patients), 3%(95% CI 2 to 5 [REM], 9 studies: 388/10 539 patients) and 10%(95% CI 7 to 15 [REM], 10 studies: 907/8945 patients), respectively. For NDR, that is, the pooled prevalence of HGD/EAC was 7%(95% CI 4 to 10 [REM], 10 studies: 795/10 632 patients).
CONCLUSION: NDR is approximately 4% and could be used as a quality measure.

© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.
PMID 30872393  Gut. 2019 Dec;68(12):2122-2128. doi: 10.1136/gutjnl-201・・・
著者: Tomoki Shimizu, Junko Fujisaki, Masami Omae, Akira Yamasaki, Yusuke Horiuchi, Akiyoshi Ishiyama, Toshiyuki Yoshio, Toshiaki Hirasawa, Yorimasa Yamamoto, Tomohiro Tsuchida
雑誌名: Digestion. 2018;97(4):316-323. doi: 10.1159/000486197. Epub 2018 Mar 14.
Abstract/Text BACKGROUND: In recent years, effective outcomes of endoscopic submucosal dissection (ESD) for esophagogastric junction cancer including short-segment Barrett's esophagus (SSBE) cancer have been reported. However, the efficacy of ESD for long-segment Barrett's esophagus (LSBE) cancer is unknown.
AIM: To clarify the treatment outcomes of ESD for LSBE cancer versus SSBE cancer.
METHODS: A total of 86 patients with 91 superficial Barrett's esophageal adenocarcinomas who underwent ESD were enrolled; of these, 68 had underlying SSBE and 18 had LSBE. Procedure outcomes and prognosis were compared.
RESULTS: There was no significant difference in age and tumor diameter among patients. The only complication observed was stricture, but it was not significant (2 vs. 9%). No significant difference was observed in the negative horizontal margin rates (94.1 vs. 95.7%), R0 resection rates (83.8 vs. 82.6%), curative resection rates (72.1 vs. 73.9%), and noncurative factors. Both LSBE and SSBE cancer showed favorable 3-year overall survival rates (95.0 vs. 94.4%) in the median observation period of 28.5 months.
CONCLUSIONS: ESD for LSBE cancer achieved procedure outcomes and short-term prognosis comparable to SSBE. ESD has the potential to be an effective therapeutic option for esophageal neoplasms in patients with LSBE.

© 2018 S. Karger AG, Basel.
PMID 29539629  Digestion. 2018;97(4):316-323. doi: 10.1159/000486197. ・・・
著者: Prateek Sharma, Nicholas J Shaheen, David Katzka, Jacques J G H M Bergman
雑誌名: Gastroenterology. 2020 Feb;158(3):760-769. doi: 10.1053/j.gastro.2019.09.051. Epub 2019 Nov 12.
Abstract/Text DESCRIPTION: The purpose of this best practice advice article is to describe the role of Barrett's endoscopic therapy (BET) in patients with Barrett's esophagus (BE) with dysplasia and/or early cancer and appropriate follow-up of these patients.
METHODS: The best practice advice provided in this document is based on evidence and relevant publications reviewed by the committee. BEST PRACTICE ADVICE 1: In BE patients with confirmed low-grade dysplasia, a repeat examination with high-definition white-light endoscopy should be performed within 3-6 months to rule out the presence of a visible lesion, which should prompt endoscopic resection. BEST PRACTICE ADVICE 2: Both BET and continued surveillance are reasonable options for the management of BE patients with confirmed and persistent low-grade dysplasia. BEST PRACTICE ADVICE 3: BET is the preferred treatment for BE patients with high-grade dysplasia (HGD). BEST PRACTICE ADVICE 4: BET should be preferred over esophagectomy for BE patients with intramucosal esophageal adenocarcinoma (T1a). BEST PRACTICE ADVICE 5: BET is a reasonable alternative to esophagectomy in patients with submucosal esophageal adenocarcinoma (T1b) with low-risk features (<500-μm invasion in the submucosa [sm1], good to moderate differentiation, and no lymphatic invasion) especially in those who are poor surgical candidates. BEST PRACTICE ADVICE 6: In all patients undergoing BET, mucosal ablation should be applied to 1) all visible esophageal columnar mucosa; 2) 5-10 mm proximal to the squamocolumnar junction and 3) 5-10 mm distal to the gastroesophageal junction, as demarcated by the top of the gastric folds (ie, gastric cardia) using focal ablation in a circumferential fashion. BEST PRACTICE ADVICE 7: Mucosal ablation therapy should only be performed in the presence of flat BE without signs of inflammation and in the absence of visible abnormalities. BEST PRACTICE ADVICE 8: BET should be performed by experts in high-volume centers that perform a minimum of 10 new cases annually. BEST PRACTICE ADVICE 9: BET should be continued until there is an absence of columnar epithelium in the tubular esophagus on high-definition white-light endoscopy and preferably optical chromoendoscopy. In case of complete endoscopic eradication, the neosquamous mucosa and the gastric cardia are sampled by 4-quadrant biopsies. BEST PRACTICE ADVICE 10: If random biopsies obtained from the neosquamous epithelium demonstrate intestinal metaplasia/dysplasia or subsquamous intestinal metaplasia, a repeat endoscopy should be performed and visible islands or tongues should undergo targeted focal ablation. BEST PRACTICE ADVICE 11: Intestinal metaplasia of the gastric cardia (without residual columnar epithelium in the tubular esophagus) should not warrant additional ablation therapy. BEST PRACTICE ADVICE 12: When consenting patients for BET, the most common complication of therapy to be quoted is post-procedural stricture formation, occurring in about 6% of cases. Bleeding and perforation occur at rates <1%. BEST PRACTICE ADVICE 13: After complete eradication (endoscopic and histologic) of intestinal metaplasia has been achieved with BET, surveillance endoscopy with biopsies should be performed at the following intervals: for baseline diagnosis of HGD/esophageal adenocarcinoma: at 3, 6, and 12 months and annually thereafter; and baseline diagnosis of low-grade dysplasia: at 1 and 3 years. BEST PRACTICE ADVICE 14: Endoscopic surveillance post therapy should be performed with high-definition white-light endoscopy, including careful inspection of the neosquamous mucosal and retroflexed inspection of the gastric cardia. BEST PRACTICE ADVICE 15: The approach to recurrent disease is similar to that of the initial therapy; visible recurrent nodular lesions require endoscopic resection, whereas flat areas of columnar mucosa in the tubular esophagus can be treated with mucosal ablation. BEST PRACTICE ADVICE 16: Patients should be counseled on cancer risk in the absence of BET, as well as after BET, to allow for informed decision-making between the patient and the physician.

Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.
PMID 31730766  Gastroenterology. 2020 Feb;158(3):760-769. doi: 10.1053・・・
著者: Ryu Ishihara, Tsuneo Oyama, Seiichiro Abe, Hiroaki Takahashi, Hiroyuki Ono, Junko Fujisaki, Mitsuru Kaise, Kenichi Goda, Kenro Kawada, Tomoyuki Koike, Manabu Takeuchi, Rie Matsuda, Dai Hirasawa, Masayoshi Yamada, Junichi Kodaira, Masaki Tanaka, Masami Omae, Akira Matsui, Takashi Kanesaka, Akiko Takahashi, Shinichi Hirooka, Masahiro Saito, Yosuke Tsuji, Yuki Maeda, Hiroharu Yamashita, Ichiro Oda, Yasuhiko Tomita, Takashi Matsunaga, Shuji Terai, Soji Ozawa, Tatsuyuki Kawano, Yasuyuki Seto
雑誌名: J Gastroenterol. 2016 Oct 18;. doi: 10.1007/s00535-016-1275-0. Epub 2016 Oct 18.
Abstract/Text BACKGROUND: Little is known about the specific risks of metastasis in esophageal adenocarcinoma in relation to invasion depth or other pathologic factors.
METHODS: We conducted a multicenter retrospective study in 13 high-volume centers in Japan from January 2000 to October 2014 to elucidate the risk of metastasis of esophageal adenocarcinoma. A total of 458 patients (217 surgically resected and 241 endoscopically resected) with esophageal adenocarcinoma or esophagogastric adenocarcinoma involving the esophagus were included. Metastasis was considered positive if there was histologically confirmed metastasis in the surgical specimen or clinically confirmed metastasis during follow-up. Metastasis was considered negative if no metastasis was identified in resected specimens and during follow-up in patients treated surgically or no metastasis during follow-up for >5 years in patients treated by endoscopic resection.
RESULTS: Metastasis was identified in 72 patients. Multivariate analysis confirmed lymphovascular involvement [odds ratio (OR) 6.20; 95 % confidence interval (CI) 3.12-12.32; p < 0.001], a poorly differentiated component (OR 3.69; 95 % CI 1.92-7.10; p < 0.001), and lesion size >30 mm (OR 3.12; 95 % CI 1.63-5.97; p = 0.001) as independent risk factors for metastasis. No metastasis was detected in patients with mucosal cancer without lymphovascular involvement and a poorly differentiated component (0/186 lesions) or in patients with cancer invading the submucosa (1-500 µm) without lymphovascular involvement, a poorly differentiated component, and ≤30 mm (0/32 lesions).
CONCLUSIONS: Mucosal and submucosal cancers (1-500 µm invasion) without risk factors have a low incidence of metastasis and may thus be good candidates for endoscopic resection.

PMID 27757547  J Gastroenterol. 2016 Oct 18;. doi: 10.1007/s00535-016-・・・

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