Gastric juice protects against the development of esophageal adenocarcinoma in the rat

Adrian P. Ireland, Jeffrey H. Peters, Thomas Christopher Smyrk, Tom R. DeMeester, Geoffrey W B Clark, Sidney S. Mirvish, Thomas E. Adrian

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

Objective: The authors investigate the effects of gastric juice on tumorigenesis in a rat model of esophageal adenocarcinoma. Summary Background Data: In rats treated with the carcinogen methyl-n-amyl nitrosamine, squamous cancer of the esophagus develops in a time and dose dependent manner. When methyl-n-amyl nitrosamine treatment is preceded by an operation to induce reflux of duodenal and gastric juice into the esophagus, there is an increased yield of esophageal tumors, many of which are adenocarcinomas. When only gastric juice refluxes into the esophagus, the tumor yield is less and adenocarcinomas are not found. Methods: Two hundred seventy 8-week old Sprague-Dawley rats were studied. Twenty unoperated rats served as controls The remaining rats underwent the following operations: esophagoduodenostomy with gastric and vagal preservation to induce duodenogastroesophageal reflux (n = 48); esophagoduodenostomy with antrectomy and Billroth 1 reconstruction to produce reflux of duodenogastric juice with the exclusion of the antrum (n = 53); esophagoduodenostomy with proximal gastrectomy to induce hypergastrinemia and reflux of duodenogastric juice with exclusion of the body and forestomach (n = 51); esophagoduodenostomy plus total gastrectomy to produce reflux of duodenal juice alone (n = 50); and esophagoduodenostomy with vagal and gastric preservation but with division of the duodenum just beyond the pylorus and reimplantation into the jejunum, 13 cm distal to the esophagoduodenostomy. This produced reflux of duodenal juice with gastric juice diverted downstream, (n = 48). At 10 weeks of age, all rats were given 4 weekly doses of carcinogen (methyl-n-amyl nitrosamine, 25 mg/kg intraperitoneally), and survivors were killed at 36 weeks of age. Results: The prevalence rate of esophageal adenocarcinoma was 30% in rats with duodenogastroesophageal reflux and 87% in rats with reflux of duodenal juice alone. Fifty-six percent of rats with reflux of duodenogastric juice with exclusion of the antrum and 72% of rats with reflux of duodenogastric juice with the exclusion of the body and forestomach developed adenocarcinoma, showing a progressive increase in the prevalence of adenocarcinoma as less gastric juice was permitted to reflux with duodenal juice into the esophagus. Conclusion: In this rat model, the presence of gastric juice in refluxed duodenal juice protects against the development of esophageal adenocarcinoma. The protective effect appears to be due to acid secretion from the stomach. Continuous profound acid suppression therapy may be detrimental by encouraging esophageal metaplasia and tumorigenesis in patients with duodenogastroesophageal reflux.

Original languageEnglish (US)
Pages (from-to)358-371
Number of pages14
JournalAnnals of Surgery
Volume224
Issue number3
DOIs
StatePublished - 1996
Externally publishedYes

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Duodenogastric Reflux
Gastric Juice
Adenocarcinoma
Nitrosamines
Esophagus
Stomach
Gastrectomy
Carcinogens
Carcinogenesis
Acids
Replantation
Pylorus
Metaplasia
Jejunum
Esophageal Neoplasms
Duodenum
Sprague Dawley Rats
Survivors
Neoplasms

ASJC Scopus subject areas

  • Surgery

Cite this

Ireland, A. P., Peters, J. H., Smyrk, T. C., DeMeester, T. R., Clark, G. W. B., Mirvish, S. S., & Adrian, T. E. (1996). Gastric juice protects against the development of esophageal adenocarcinoma in the rat. Annals of Surgery, 224(3), 358-371. https://doi.org/10.1097/00000658-199609000-00012

Gastric juice protects against the development of esophageal adenocarcinoma in the rat. / Ireland, Adrian P.; Peters, Jeffrey H.; Smyrk, Thomas Christopher; DeMeester, Tom R.; Clark, Geoffrey W B; Mirvish, Sidney S.; Adrian, Thomas E.

In: Annals of Surgery, Vol. 224, No. 3, 1996, p. 358-371.

Research output: Contribution to journalArticle

Ireland, AP, Peters, JH, Smyrk, TC, DeMeester, TR, Clark, GWB, Mirvish, SS & Adrian, TE 1996, 'Gastric juice protects against the development of esophageal adenocarcinoma in the rat', Annals of Surgery, vol. 224, no. 3, pp. 358-371. https://doi.org/10.1097/00000658-199609000-00012
Ireland AP, Peters JH, Smyrk TC, DeMeester TR, Clark GWB, Mirvish SS et al. Gastric juice protects against the development of esophageal adenocarcinoma in the rat. Annals of Surgery. 1996;224(3):358-371. https://doi.org/10.1097/00000658-199609000-00012
Ireland, Adrian P. ; Peters, Jeffrey H. ; Smyrk, Thomas Christopher ; DeMeester, Tom R. ; Clark, Geoffrey W B ; Mirvish, Sidney S. ; Adrian, Thomas E. / Gastric juice protects against the development of esophageal adenocarcinoma in the rat. In: Annals of Surgery. 1996 ; Vol. 224, No. 3. pp. 358-371.
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abstract = "Objective: The authors investigate the effects of gastric juice on tumorigenesis in a rat model of esophageal adenocarcinoma. Summary Background Data: In rats treated with the carcinogen methyl-n-amyl nitrosamine, squamous cancer of the esophagus develops in a time and dose dependent manner. When methyl-n-amyl nitrosamine treatment is preceded by an operation to induce reflux of duodenal and gastric juice into the esophagus, there is an increased yield of esophageal tumors, many of which are adenocarcinomas. When only gastric juice refluxes into the esophagus, the tumor yield is less and adenocarcinomas are not found. Methods: Two hundred seventy 8-week old Sprague-Dawley rats were studied. Twenty unoperated rats served as controls The remaining rats underwent the following operations: esophagoduodenostomy with gastric and vagal preservation to induce duodenogastroesophageal reflux (n = 48); esophagoduodenostomy with antrectomy and Billroth 1 reconstruction to produce reflux of duodenogastric juice with the exclusion of the antrum (n = 53); esophagoduodenostomy with proximal gastrectomy to induce hypergastrinemia and reflux of duodenogastric juice with exclusion of the body and forestomach (n = 51); esophagoduodenostomy plus total gastrectomy to produce reflux of duodenal juice alone (n = 50); and esophagoduodenostomy with vagal and gastric preservation but with division of the duodenum just beyond the pylorus and reimplantation into the jejunum, 13 cm distal to the esophagoduodenostomy. This produced reflux of duodenal juice with gastric juice diverted downstream, (n = 48). At 10 weeks of age, all rats were given 4 weekly doses of carcinogen (methyl-n-amyl nitrosamine, 25 mg/kg intraperitoneally), and survivors were killed at 36 weeks of age. Results: The prevalence rate of esophageal adenocarcinoma was 30{\%} in rats with duodenogastroesophageal reflux and 87{\%} in rats with reflux of duodenal juice alone. Fifty-six percent of rats with reflux of duodenogastric juice with exclusion of the antrum and 72{\%} of rats with reflux of duodenogastric juice with the exclusion of the body and forestomach developed adenocarcinoma, showing a progressive increase in the prevalence of adenocarcinoma as less gastric juice was permitted to reflux with duodenal juice into the esophagus. Conclusion: In this rat model, the presence of gastric juice in refluxed duodenal juice protects against the development of esophageal adenocarcinoma. The protective effect appears to be due to acid secretion from the stomach. Continuous profound acid suppression therapy may be detrimental by encouraging esophageal metaplasia and tumorigenesis in patients with duodenogastroesophageal reflux.",
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AU - Peters, Jeffrey H.

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AU - Mirvish, Sidney S.

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N2 - Objective: The authors investigate the effects of gastric juice on tumorigenesis in a rat model of esophageal adenocarcinoma. Summary Background Data: In rats treated with the carcinogen methyl-n-amyl nitrosamine, squamous cancer of the esophagus develops in a time and dose dependent manner. When methyl-n-amyl nitrosamine treatment is preceded by an operation to induce reflux of duodenal and gastric juice into the esophagus, there is an increased yield of esophageal tumors, many of which are adenocarcinomas. When only gastric juice refluxes into the esophagus, the tumor yield is less and adenocarcinomas are not found. Methods: Two hundred seventy 8-week old Sprague-Dawley rats were studied. Twenty unoperated rats served as controls The remaining rats underwent the following operations: esophagoduodenostomy with gastric and vagal preservation to induce duodenogastroesophageal reflux (n = 48); esophagoduodenostomy with antrectomy and Billroth 1 reconstruction to produce reflux of duodenogastric juice with the exclusion of the antrum (n = 53); esophagoduodenostomy with proximal gastrectomy to induce hypergastrinemia and reflux of duodenogastric juice with exclusion of the body and forestomach (n = 51); esophagoduodenostomy plus total gastrectomy to produce reflux of duodenal juice alone (n = 50); and esophagoduodenostomy with vagal and gastric preservation but with division of the duodenum just beyond the pylorus and reimplantation into the jejunum, 13 cm distal to the esophagoduodenostomy. This produced reflux of duodenal juice with gastric juice diverted downstream, (n = 48). At 10 weeks of age, all rats were given 4 weekly doses of carcinogen (methyl-n-amyl nitrosamine, 25 mg/kg intraperitoneally), and survivors were killed at 36 weeks of age. Results: The prevalence rate of esophageal adenocarcinoma was 30% in rats with duodenogastroesophageal reflux and 87% in rats with reflux of duodenal juice alone. Fifty-six percent of rats with reflux of duodenogastric juice with exclusion of the antrum and 72% of rats with reflux of duodenogastric juice with the exclusion of the body and forestomach developed adenocarcinoma, showing a progressive increase in the prevalence of adenocarcinoma as less gastric juice was permitted to reflux with duodenal juice into the esophagus. Conclusion: In this rat model, the presence of gastric juice in refluxed duodenal juice protects against the development of esophageal adenocarcinoma. The protective effect appears to be due to acid secretion from the stomach. Continuous profound acid suppression therapy may be detrimental by encouraging esophageal metaplasia and tumorigenesis in patients with duodenogastroesophageal reflux.

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