胃と腸46巻12号

2011年11月発行

今月の主題 Barrett食道癌の診断 主題研究

Barrett食道癌の組織発生―人体病理と実験病理から

著者： 向所賢一¹ 九嶋亮治² 竹村しづき¹³ 荒木克夫¹ 杉原洋行¹ 服部隆則¹

所属機関： ¹滋賀医科大学病理学講座分子診断病理学部門 ²国立がん研究センター中央病院病理科 ³栗東指月病理診断科 ⁴Institut für Pathologie, Klinikum Bayreuth GmbH

ページ範囲：P.1861 - P.1874

要旨　ドイツ人の表在型下部食道腺癌およびその周囲粘膜の解析結果とラット胃・十二指腸液逆流モデルを用いた実験結果に文献的考察を加え，Barrett食道癌の組織発生について考察した．SSBE（short segment Barrett esophagus）にみられるcardiac-type mucosaは，胃側もしくは胃食道接合部に存在する噴門腺が食道側に伸びた胃型粘膜が多い．一方，LSBE（long segment Barrett esophagus）にみられる杯細胞のあるspecialized intestinal metaplasiaは，高濃度の胆汁酸を含む胃液の逆流により発生した化生性の腸型粘膜であり，SSBEより発癌率は高いことが示唆された．

参考文献

1）Pera M, Cameron AJ, Trastek VF, et al. Increasing incidence of adenocarcinoma of the esophagus and esophagogastric junction. Gastroenterology 104 : 510-513, 1993

2）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 and Hepatol 23 : 1662-1665, 2008

3）日本食道学会（編）．臨床・病理─食道癌取扱い規約，10版補訂版．金原出版，2008

4）Rosai J. Rosai and Ackerman's Surgical Pathology, 9th ed. Mosby, New York, 2004

5）Schlemper RJ, Riddell RH, Kato Y, et al. The Vienna classification of gastrointestinal epithelial neoplasia. Gut 47 : 251-255, 2000

6）Tsukashita S, Kushima R, Bamba M, et al. MUC gene expression and histogenesis of adenocarcinoma of the stomach. Int J Cancer 94 : 166-170, 2001

7）Chen KH, Mukaisho K, Sugihara H, et al. High animal-fat intake changes the bile-acid composition of bile juice and enhances the development of Barrett's esophagus and esophageal adenocarcinoma in a rat duodenal-contents reflux model. Cancer Sci 98 : 1683-1688, 2007

8）Miwa K, Sahara H, Segawa M, et al. Reflux of duodenal or gastro-duodenal contents induces esophageal carcinoma in rats. Int J Cancer 67 : 269-274, 1996

9）Kumagai H, Mukaisho K, Sugihara H, et al. Cell kinetic study on histogenesis of Barrett's esophagus using rat reflux model. Scand J Gastroenterol 38 : 687-692, 2003

10）向所賢一，服部隆則．Barrett食道の発生起源は何か─実験病理からみて．分子消化器病 7 : 7-14, 2010

11）Skinner DB, Walther BC, Riddell RH, et al. Barrett's esophagus. Comparison of benign and malignant cases. Ann Surg 198 : 554-565, 1983

12）Hamilton SR, Smith RR. The relationship between columnar epithelial dysplasia and invasive adenocarcinoma arising in Barrett's esophagus. Am J Clin Pathol 87 : 301-312, 1987

13）Gatenby PA, Ramus JR, Caygill CP, et al. Relevance of the detection of intestinal metaplasia in non-dysplastic columnar-lined oesophagus. Scand J Gastroenterol 43 : 524-530, 2008

14）Takubo K, Aida J, Naomoto Y, et al. Cardiac rather than intestinal-type background in endoscopic resection specimens of minute Barrett adenocarcinoma. Hum Pathol 40 : 65-74, 2009

15）Nakanishi Y, Saka M, Eguchi T, et al. Distribution and significance of the oesophageal and gastric cardiac mucosae : a study of 131 operation specimens. Histopathology 51 : 515-519, 2007

16）Riddell RH, Odze RD. Definition of Barrett's esophagus : time for a rethink―is intestinal metaplasia dead ? Am J Gastroenterol 104 : 2588-2594, 2009

17）Oberg S, DeMeester TR, Peters JH, et al. The extent of Barrett's esophagus depends on the status of the lower esophageal sphincter and the degree of esophageal acid exposure. J Thorac Cardiovasc Surg 117 : 572-580, 1999

18）Srinivas G, Patrick EY, Benjamin RA, et al. Relationship between Barrett's esophagus（BE）length and the risk of high grade dysplasia（HGD）and esophageal adenocarcinoma（EAC）in patients with non dysplastic Barrett's esophagus results from a large multicenter cohort. AGA in Chicago, 2011

19）木下芳一，数森秀章，石村典久．前癌病変としてのBarrett食道．G.I. Res 18 : 45-52, 2010

20）服部隆則，向所賢一，三輪晃一．バレット食道基礎研究と臨床研究の進歩─基礎研究の進歩 : バレット食道の発生機序─ラット十二指腸液逆流モデルからの知見．日臨 63 : 1341-1349, 2005

21）下田忠和．胃食道接合部領域の特性とBarrett食道における最近の病理学的知見．分子消化器病 7 : 15-24, 2010

22）Taupin D, Podolsky DK. Trefoil factors : initiators of mucosal healing. Nat Rev Mol Cell Biol 4 : 721-732, 2003

23）Dixon MF, Neville PM, Mapstone NP, et al. Bile reflux gastritis and Barrett's oesophagus : further evidence of a role for duodenogastro-oesophageal reflux? Gut 49 : 359-363, 2001

24）Wong NA, Wilding J, Bartlett S, et al. CDX1 is an important molecular mediator of Barrett's metaplasia. Proc Natl Acad Sci USA 102 : 7565-7570, 2005

25）Kazumori H, Ishihara S, Rumi MA, et al. Bile acids directly augment caudal related homeobox gene Cdx2 expression in oesophageal keratinocytes in Barrett's epithelium. Gut 55 : 16-25, 2006

26）Mizoshita T, Tsukamoto T, Takenaka Y, et al. Gastric and intestinal phenotypes and histogenesis of advanced glandular stomach cancers in carcinogen-treated, Helicobacter pylori-infected Mongolian gerbils. Cancer Sci 97 : 38-44, 2006

27）Tatsuta T, Mukaisho K, Sugihara H, et al. Expression of Cdx2 in early GRCL of Barrett's esophagus induced in rats by duodenal reflux. Dig Dis Sci 50 : 425-431, 2005

28）Mukaisho K, Miwa K, Kumagai H, et al. Gastric carcinogenesis by duodenal reflux through gut regenerative cell lineage. Dig Dis Sci 48 : 2153-2158, 2003

29）Suo M, Mukaisho K, Shimomura A, et al. Thioproline prevents carcinogenesis in the remnant stomach induced by duodenal reflux. Cancer Lett 237 : 256-262, 2006

30）Kumagai H, Mukaisho K, Sugihara H, et al. Thioproline inhibits development of esophageal adenocarcinoma induced by gastroduodenal reflux in rats. Carcinogenesis 25 : 723-727, 2004

31）Terasaki M, Totsuka Y, Nishimura K, et al. Detection of endogenous DNA adducts, O-carboxymethyl-2'-deoxyguanosine and 3-ethanesulfonic acid-2'-deoxycytidine, in the rat stomach after duodenal reflux. Cancer Sci 99 : 1741-1746, 2008

32）Araki Y, Mukaisho K, Sugihara H, et al. Detection of N-nitroso-bile acids at 285 nm in reverse-phase HPLC. J Sep Sci 31 : 2827-2830, 2008

33）Kuipers EJ. Barrett's oesophagus, proton pump inhibitors and gastrin : the fog is clearing. Gut 59 : 148-149, 2010