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Background: The initial response of esophageal mucosa to gastroduodenal reflux is inflammation and hyperplasia. Secretory phospholipase A(2) (sPLA(2)) is a known mediator of gut inflammation, and its levels are increased in Barrett's esophagus. We hypothesized that the sPLA(2) gene is required to produce esophageal mucosal hyperplasia in response to gastroduodenal reflux., Methods: C57BL/6 (n = 5) sPLA(2) (-/-) mice and C57BL/6( Cg-Tg(PLA2G2A)703N16 ) mice (n = 4) sPLA(2) (-/+) underwent a side-to-side surgical anastomosis between the duodenum and gastroesophageal junction (DGEA). Control animals [sPLA(2) (-/-) (n = 5), sPLA(2) (-/+) (n = 4)] underwent laparotomy with incision and repair of the esophagus. Tissue was harvested after 4 weeks, and H&E staining was performed to quantify esophageal mucosal thickness. Ki67 and sPLA(2) immunostaining were performed to quantitate differences in cell division and sPLA(2) expression., Results: Mice expressing human sPLA(2) had a 2.5-fold increase in thickness of the esophageal mucosa as compared to controls (p = 0.01). A 6.5-fold increase in proliferation (p = 0.02) and a twofold increase in sPLA(2) expression (p = 0.04) were demonstrated in animals exposed to gastroduodenal reflux., Conclusions: The presence of sPLA(2) is necessary for early mucosal hyperplasia produced by exposure of the esophagus to gastroduodenal contents. sPLA(2) expression is upregulated by gastroduodenal reflux, strengthening its role as a critical mediator of early mucosal hyperplasia.

Experimental gastroduodenal ulcer was simulated after pre-injection of serotonin; gastroesophageal reflux disease and duodenogastral reflux were induced. Activation of the serotoninergic system promoted the development of alteration processes in gastroduodenal ulcer.

Background: Subtotal esophagectomy and gastric pull-up with cervical anastomosis is the main treatment for advanced achalasia. This surgical technique has been associated to esophagitis and also Barrett's epithelium following esophagectomy., Aim: To analyze late clinical, endoscopic, and pathologic findings in the esophageal stump (ES) mucosa after subtotal esophagectomy in patients treated for advanced chagasic achalasia., Methods: 101 patients submitted to esophagectomy and cervical gastroplasty were followed-up prospectively for a mean of 10.5 +/- 8.8 years. All patients underwent clinical, endoscopic and histopathological evaluation every 2 years. Gastric acid secretion was also assessed., Results: The incidence of esophagitis in the esophageal stump (45.9% at 1 year; 71.9% at 5 years, and 70.0% at 10 years follow-up); gastritis in the transposed stomach (20.4% at 1 year, 31.0% at 5 years, and 40.0% at 10 or more years follow-up), and the occurrence of ectopic columnar metaplasia and Barrett's Esophagus in the ES (none until 1 year; 10.9% between 1 and 5 years; 29.5% between 5 and 10 years; and 57.5% at 10 or more years follow-up), all rose over time. Gastric acid secretion returns to its preoperative values 4 years postoperatively. Esophageal stump cancer was detected in the setting of chronic esophagitis in five patients: three squamous cell carcinomas and two adenocarcinomas., Conclusion: (1) Esophagitis and Barrett's esophagus in the esophageal stump rose over time. (2) These mucosal alterations and the development of squamous cell carcinoma and adenocarcinoma are probably due to exposure to duodenogastric reflux, and progressively higher acid output in the transposed stomach.

Background: Reflux of duodenal content into the lower esophagus of rats enhances the formation of nitrosamine-induced esophageal cancer and results in the induction of adenocarcinoma. We investigated the extent of the mucosal injury that was produced when the lower esophagus of rats was exposed to the reflux of gastroduodenal juice in the presence or absence of a carcinogen and tested the hypothesis that induction of esophageal cancer in this model would be influenced by the intake of dietary fat., Methods: Esophagoduodenostomy with gastric preservation was performed in 165 Sprague-Dawley rats in order to expose the lower esophagus to the reflux of gastroduodenal juice. Postoperatively selected groups of rats were treated with the carcinogen methyl-n-amylnitrosamine (MNAN). Subsequently, rats were fed diets of differing fat and calorie content for 20 weeks until they were put to death., Results: Refluxed gastroduodenal juice, in the absence of MNAN, induced esophageal inflammatory changes (diffuse papillomatosis and hyperkeratosis) in 38 of 39 rats (97%), specialized columnar metaplasia (Barrett's esophagus) in four of 39 (10%), dysplasia in three of 39 (8%), and squamous cell carcinoma in one of 39 (3%). Diet did not influence the incidence of neoplasia in the absence of MNAN treatment. In rats treated with MNAN, refluxed gastroduodenal juice induced inflammation in 110 of 111 rats (99%), columnar metaplasia in 14 of 111 (13%), and cancer in 63 of 111 (57%). Fifty-eight percent of esophageal tumors were squamous cell carcinoma and 42% were adenocarcinoma. The highest incidence of tumors was observed in rats fed the semipurified high-fat diet (24 of 29; 83%) compared with rats fed the semipurified control diet (13 of 29; 45%), semipurified, calorie-restricted diet (15 of 27; 55%), and chow diet (11 of 26; 42%), p < 0.05., Conclusions: Reflux of gastroduodenal content into the lower esophagus of rats can induce both Barrett's metaplasia and neoplasia. Addition of a carcinogen increases the tumor yield and results in a proportion of the lesions being adenocarcinoma. This carcinogenic process is promoted by a diet with a high fat content.

In an experimental study on 74 rats the ulcer risk was analyzed after Billroth-I-resection changed into secondary Roux-Y-gastro-jejunostomy resp. jejunal interposition. The following results were obtained: 1) 10 months postoperatively stomal ulcers were found in up to 75%. 2) The gastric pH was comparable with the control and significantly lower than after Billroth-I-resection. 3) An additional vagotomy caused a reduction but not an elimination of the ulcer risk. We conclude from our results that there is a protective role of the postresectional intestino-gastric reflux on the gastrojejunal anastomosis. A reflux-preventive procedure is therefore heavily ulcer-prone.