Development of Pancreatic Acinar Cell Metaplasia During Gastric Repair in a Rat Duodenal Contents Reflux Model.

1. Doglioni C, Laurino L, Dei Tos AP, et al. Pancreatic (acinar)

metaplasia of the gastric mucosa. Histology, ultrastructure, immunocytochemistry, and clinicopathologic correlations of 101 cases.

Am J Surg Pathol. 1993;17:1134–1143.

2. Krishnamurthy S, Dayal Y. Pancreatic metaplasia in Barrett’s

esophagus. An immunohistochemical study. Am J Surg Pathol.

1995;19:1172–1180.

3. Stachura J, Konturek JW, Urbanczyk K, et al. Endoscopic and

histological appearance of pancreatic metaplasia in the human

gastric mucosa: a preliminary report on a recently recognized new

type of gastric mucosal metaplasia. Eur J Gastroenterol Hepatol.

1996;8:239–243.

4. Integlia MJ, Krishnamurthy S, Berhane R, et al. Pancreatic metaplasia of the gastric mucosa in pediatric patients. Am J Gastroenterol. 1997;92:1553–1556.

5. Wang HH, Zeroogian JM, Spechler SJ, et al. Prevalence and significance of pancreatic acinar metaplasia at the gastroesophageal

junction. Am J Surg Pathol. 1996;20:1507–1510.

6. Ambrosini-Spaltro A, Potì O, De Palma M, et al. Pancreatic-type

acinar cell carcinoma of the stomach beneath a focus of pancreatic

metaplasia of the gastric mucosa. Hum Pathol. 2009;40:746–749.

7. Håkansson HO, Mellblom L, Johansson J, et al. Synthesis and

localization of pancreatic secretory proteins in pancreatic acinarlike metaplasia in the distal part of the oesophagus. Pancreatic

acinar metaplasia: another source of pancreatic enzymes! Scand

J Gastroenterol. 2003;38:10–13.

8. Stachura J, Konturek J, Urbańczyk K, et al. Pancreatic metaplasia

of the human gastric mucosa is associated with high expression

of transforming growth factor alpha but not of epidermal growth

factor. Histopathology. 1995;27:509–515.

9. Jhala NC, Montemor M, Jhala D, et al. Pancreatic acinar cell

metaplasia in autoimmune gastritis. Arch Pathol Lab Med.

2003;127:854–857.

10. Johansson J, Håkansson HO, Mellblom L, et al. Pancreatic acinar metaplasia in the distal oesophagus and the gastric cardia:

prevalence, predictors and relation to GORD. J Gastroenterol.

2010;45:291–299.

11. Chlumská A, Boudová L, Benes Z, et al. Autoimmune gastritis. A

clinicopathologic study of 25 cases. Cesk Patol. 2005;41:137–142.

12. Schneider NI, Plieschnegger W, Geppert M, et al. Pancreatic acinar cells—a normal finding at the gastroesophageal junction? Data

from a prospective Central European multicenter study. Virchows

Arch. 2013;463:643–650.

13. Thowfeequ S, Myatt EJ, Tosh D. Transdifferentiation in

developmental biology, disease, and in therapy. Dev Dyn.

2007;236:3208–3217.

14. IARC. Infection with Helicobacter pylori. Monogr Eval Carcinog

Risks Hum. 1994;61:177–240.

15. Xia HH-X, Yang Y, Lam SK, et al. Aberrant epithelial expression of trefoil family factor 2 and mucin 6 in Helicobacter pylori

infected gastric antrum, incisura, and body and its association with

antralisation. J Clin Pathol. 2004;57:861–866.

16. Graham DY. History of Helicobacter pylori, duodenal ulcer,

gastric ulcer, and gastric cancer. World J Gastroenterol.

2014;20:5191–5204.

17. Fox JG, Rogers AB, Whary MT. Accelerated progression of

gastritis to dysplasia in the pyloric antrum of TFF2 –/– C57BL6

x Sv 129 Helicobacter pylori-infected mice. Am J Pathol.

2007;171:1520–1528.

18. Fiocca R, Villani L, Tenti P, et al. Characterization of four main

cell types in gastric cancer: foveolar, mucopeptic, intestinal

columnar and goblet cells. An histopathologic, histochemical and

ultrastructural study of early and advanced tumors. Pathol Res

Pract. 1987;182:308–325.

19. Ho SB, Roberton AM, Shekels LL, et al. Expression cloning of

gastric mucin complementary DNA and localization of mucin

gene expression. Gastroenterology. 1995;109:735–747.

20. De Bolos C, Garrido M, Real FX. MUC6 apomucin shows a

distinct normal tissue distribution that correlates with Lewis

antigen expression in the human stomach. Gastroenterology.

1995;190:723–734.

21. Ishihara K, Kurihara M, Goso Y, et al. Peripheral alpha-linked

N-acetylglucosamine on the carbohydrate moiety of mucin

derived from mammalian gastric gland mucous cells: epitope recognized by a newly characterized monoclonal antibody. Biochem

J. 1996;318:409–416.

22. Mukaisho K, Miwa K, Kumagai H, et al. Gastric carcinogenesis

by duodenal reflux through gut regenerative cell lineage. Dig Dis

Sci. 2003;48:2153–2158. https​://doi.org/10.1023/B:DDAS.00000​

04519​.26201​.a4.

23. Kumagai H, Mukaisho K, Sugihara H, et al. Thioproline inhibits

development of esophageal adenocarcinoma induced by gastroduodenal reflux in rats. Carcinogenesis. 2004;25:723–727.

24. Mukaisho K, Kanai S, Kushima R, et al. Barretts’s carcinogenesis. Pathol Int. 2019;69:319–330.

25. Kushima R, Mukaisho K, Takemura S, et al. Barrett’s esophagus: analyses from human and experimental animal studies.

Pathologe. 2013;34:138–147. (in German).

26. Mukaisho K. Relationship between development of pancreatic

acinar cell metaplasia and duodenal contents reflux: analyses

from experimental animal studies. Ther Res. 2014;35:387–392.

27. Tran CP, Cook GA, Yeomans ND, et al. Trefoil peptide

TFF2 (spasmolytic polypeptide) potently accelerates healing and reduces inflammation in a rat model of colitis. Gut.

1999;44:636–642.

28. Cook GA, Familari M, Thim L, et al. The trefoil peptides TFF2

and TFF3 are expressed in rat lymphoid tissues and participate in

the immune response. FEBS Lett. 1999;456:155–159.

29. Nomura S, Yamaguchi H, Ogawa M, et al. Alterations in gastric

mucosal lineages induced by acute oxyntic atrophy in wild-type

and gastrin-deficient mice. Am J Physiol Gastrointest Liver Physiol. 2005;288:G362–G375.

30. Goldenring JR. Pyloric metaplasia, pseudopyloric metaplasia,

ulcer-associated cell lineage and spasmolytic polypeptide-expressing metaplasia: reparative lineages in the gastrointestinal mucosa.

J Pathol. 2018;245:132–137.

31. Kaise M, Miwa J, Fujimoto A, et al. Influence of Helicobacter

pylori status and eradication on the serum levels of trefoil factors

and pepsinogen test: serum trefoil factor 3 is a stable biomarker.

Gastric Cancer. 2013;16:329–337.

32. Hattori T, Fujita S. Tritiated thymidine autoradiographic study on

cellular migration in the gastric gland of the golden hamster. Cell

Tissue Res. 1976;172:171–184.

33. Barker N, Huch M, Kujala P, et al. Lgr5(+ve) stem cells drive selfrenewal in the stomach and build long-lived gastric units in vitro.

Cell Stem Cell. 2010;6:25–36.

34. Krishnamurthy S, Integlia MJ, Grand RJ, et al. Pancreatic acinar cell clusters in pediatric gastric mucosa. Am J Surg Pathol.

1998;22:100–105.

35. Schmidt PH, Lee JR, Joshi V, et al. Identification of a metaplastic

cell lineage associated with human gastric adenocarcinoma. Lab

Invest. 1999;79:639–646.

36. Lennerz JK, Kim SH, Oates EL, et al. The transcription factor

MIST1 is a novel human gastric chief cell marker whose expression is lost in metaplasia, dysplasia and carcinoma. Am J Pathol.

2010;177:1514–1533.

37. Bertaux-Skeirik N, Wunderlich M, Teal E, et al. CD44

variant isoform 9 emerges in response to injury and

13

contributes to the regeneration of the gastric epithelium. J Pathol.

2017;242:463–475.

38. Goldenring JR, Gregory S, Ray Robert J, et al. Reversible drug-induced oxyntic atrophy in rats. Gastroenterology.

2000;118:1080–1093.

39. Nam KT, Lee HJ, Sousa JF, et al. Mature chief cells are cryptic progenitors for metaplasia in the stomach. Gastroenterology.

2010;139:2028–2037.

40. Huh WJ, Khurana SS, Geahlen JH, et al. Tamoxifen induces rapid,

reversible atrophy, and metaplasia in mouse stomach. Gastroenterology. 2012;142:21–24.

41. Hagiwara T, Mukaisho K, Ling ZQ, et al. Development of pancreatic acinar cell metaplasia after successful administration of

omeprazole for 6 months in rats. Dig Dis Sci. 2007;52:1219–1224.

https​://doi.org/10.1007/s1062​0-006-9253-7.

42. Dall’Olmo L, Fassan M, Dassie E, et al. Role of proton pump

inhibitor on esophageal carcinogenesis and pancreatic acinar cell

metaplasia development: an experimental in vivo study. PLoS

ONE. 2014;9:e112862.

43. Mukaisho K, Hagiwara T, Nakayama T, et al. Potential mechanism

of corpus-predominant gastritis after PPI therapy in Helicobacter pylori-positive patients with GERD. World J Gastroenterol.

2014;20:11962–11965.

13

Digestive Diseases and Sciences

44. Stamp DH. Three hypotheses linking bile to carcinogenesis in

the gastrointestinal tract: certain bile salts have properties that

may be used to complement chemotherapy. Med Hypotheses.

2002;59:398–405.

45. Foltz E, Azad S, Everett ML, et al. An assessment of human gastric fluid composition as a function of PPI usage. Physiol Rep.

2015;3:e12269.

46. Nehra D, Howell P, Williams CP, et al. Toxic bile acids in gastro-oesophageal reflux disease: influence of gastric acidity. Gut.

1999;44:598–602.

47. Sun D, Wang X, Gai Z, et al. Bile acids but not acidic acids induce

Barrett’s esophagus. Int J Clin Exp Pathol.. 2015;8:1384–1392.

48. Stein HJ, Barlow AP, DeMeester TR, et al. Complications of

gastroesophageal reflux disease. Role of the lower esophageal

sphincter, esophageal acid and acid/alkaline exposure, and duodenogastric reflux. Ann Surg. 1992;216:35–43.

Publisher’s Note Springer Nature remains neutral with regard to

jurisdictional claims in published maps and institutional affiliations.

...