Acta Medica Mediterranea, 2019, 35: 1481 EVALUATION OF GASTRIC INFLAMMATORY PARAMETERS CAUSED BY PYLORIC RING FAILURE MuhaMMed Zübeyr üçüncü1, bünyaMin Gürbulak2, Şükrü Çolak2 1TC Gelişim University, Healt Sciences Institute, Istanbul Turkey - 2Istanbul Training and Research Hospital, Department of General Surgery, Fatih 34098, Istanbul, Turkey ABSTRACT Introduction: We aimed to compare the inflammatory parameters of patients with have failure of pyloric ring with those of that have intact pyloric ring. Material and methods: Patients who underwent upper gastrointestinal endoscopy between May and September 2017 in- cluded in this study. The data of the study were collected prospectively and analysed retrospectively. Results: A total of 205 patients were included in this study. 69 (33.7 %) male and 136 (66.3%) female patients, the mean age was 40.1 ± 11.38 years. Endoscopically, failure of pyloric ring was detected in 86 patients and intact pyloric ring in 119 patients. The histopathological examination of antrum; chronic gastritis in 91 patients (44.4 %), active chronic gastritis in 89 patients (44.3%) and normal findings were found in 23 patients (11.2%). The histopathological examination of corpus; chronic gastritis in 105 patients (51.2%), active chronic gastritis in 25 patients (12.2%) and normal findings were found in 73 patients (35.6%). Comparing the patients that have intact and pyloric ring failure, the inflammation and activation scores and Helicobac- ter Pylori (H. Pylori ) density were higher in pyloric ring failure group (p:0.001, p: 0,018, p: 0,006). It was seen that in patients with pyloric ring failure had a significant decrease in inflammatory activation and H. Pylori density toward from antrum to the corpus, and this was statistically significant (p: 0.001, p: 0.001, p: 0.001). Conclusion: Because of the high inflammatory histopathologic parameters caused by pyloric ring failure, these patients should be followed closely. Keywords: Intestinal metaplasia, Bile reflux, Failures of pyloric ring, Gastric imflammation, Helicobacter Pylori, Gastric cancer. DOI: 10.19193/0393-6384_2019_3_229 Received November 30, 2018; Accepted March 20, 2019 Introduction Therefore, the demonstration of the pathological effects of chronic bile reflux due to pyloric ring failure Duodeno gastric reflux (DGR) is defined as du- in patients without gastric resection combined by or odenal content’s reflux from the duodenum to stom- absence of H. Pylori is clinically important and there ach(1). The effects of chronic biliary reflux have been are few studies in the literature with this regard. In studied either by experimental models or by evalu- this study, we aimed to compare the histopathological ating mucosal injury after surgical procedures such inflammation parameters which means that lympho- as gastric resection, pyloroplasty or gastroenteric cytes and neutrophils infiltrate the mucosa in a char- anastomosis. In mucosal damage caused by DGR, acteristically manner in patients that intact and failure the number of inflammatory cells increases in the of pyloric ring in upper gastrointestinal endoscopy. gastric mucosa, parietal cells decrease, and glandular morphology changes due to hyperplasia in mucous Material and methods cells(2). These events have been associated with gas- tric intestinal metaplasia, reflux esophagitis, barrett Patients who underwent upper gastrointestinal esophagus and even adenocancer development(3-7). endoscopy between May and September 2017 in- Even the bile acids are shown to have an antibacterial cluded in this study. We retrospectively reviewed a effect against H. Pylori, there are conflicting results in prospective database of a tertiary referral center. The the literature(8). demographic, endoscopic, and histopathological find- 1482 Muhammed Zübeyr Üçüncü, Bünyamin Gürbulak et Al ings of the patients were compared. Endoscopically, analysis of quantitative data, chi - square test was status of pyloric ring (failure or intact) ,erythema, used in the analysis of qualitative data. P <0.05 was erosion, ulcer, metaplastic areas, presence of bile at considered statistically significant. antrum, corpus and cardiac regions of stomach were evaluated. Antrum and corpus biopsy specimens were Results buffered in 10% formalin solution and paraffin blocks were prepared and stained with Giemsa and Hema- Upper gastrointestinal endoscopy was per- toxylin-Eosin(9). H. Pylori density and gastric histo- formed in 205 patients with dyspeptic complaints. 69 pathological findings were evaluated by the patholo- (33.7%) of the patients were male and 136 (66.3%) gist who did not know the clinical background and were female. The mean age of the patients was 40.1 endoscopic findings of the patient. ± 11.38. In the upper gastrointestinal endoscopy, py- Patients whom previously underwent upper gas- loric ring failure in 86 patients and intact pyloric ring trointestinal or gastric surgery, patients with gastric were detected in 119 patients. In the histopathologi- cancer, patients who use non-steroid anti-inflamma- cal examination of antral biopsy, the chronic gastritis tory drug (NSAID), neuropathic diseases such as di- was found in 91 (44.4%), active chronic gastritis in 89 abetes, inflammatory bowel disease (IBD), patients (44.3%) and normal findings in 23 (11.2%) patients. with collagen vascular disease and those who had H. The chronic gastritis in 105 (51.2%), active chron- Pylori eradication in the last year were excluded from ic gastritis in 25 (12.2%) and normal findings in 73 this study. (35.6%) were detected in the corpus biopsy. In this study, we did not use quantitative param- There was no statistically significant differ- eters such as gastric pH monitoring, 24 hour gastric ence between the groups in terms of age and gender bile monitoring with devices such as bilitec 2000, (p:0.084, p:0.249). There was no statistically signifi- hepatobiliary scintigraphy, amylase and bilirubin lev- cant difference between the groups in terms of indi- els in gastric fluid. We planned to monitor and eval- gestion, belching, nausea-vomiting, gas or bloating uate the patients according to the histopathological feeling (p> 0,05). findings of intact and pyloric sphicter failure in the When the histopathological parameters of the upper gastrointestinal endoscopy performed by the antrum were compared in patients that have intact and experienced endoscopist. pyloric ring failure, there was a statistically significant We describe the pyloric ring failure that the di- difference between the H. Pylori density, inflamma- ameter of pyloric ring allows at least two endoscopes tion and activation scores of the patients. But no sig- could pass comfortably, which does not contraction nificant difference was found in the atrophy and meta- during the procedure and or causing DGR. The intact plasia scores (p: 0.006, p: 0.001, p:0.018) (Table 1). pyloric ring was described as which can be opened by direct contact with the tip of the endoscope and Histopathological parameters Failures in pylorus Intact pylorus p contracted during the procedure. Again, there is no H. Pylori density 2,17±0,88 1,83±0,78 0,006 exact description pyloric insufficiency or failure in Inflammation 2,79±0,68 2,35±0,83 0,001 literature. All procedures were performed under propofol Activation 1,79±0,84 1,50±0,65 0,018 and midazolom sedation anesthesia, to exclude to the Atrophy 1±0 1,09±0,92 0,391 provocative bile reflux caused by vomiting. Written informed consent was obtained from all patients in- Metaplasia 1,16±0,5 1,09±0,32 0,439 cluded in this study. The information was collected in accordance with the Declaration of Helsinki. The eth- Table 1: Histopathological findings of antrum in intact and failure pyloric ring. ical committee approval was obtained for this study. When the histopathological parameters of cor- Statistical Analysis pus were examined, only the inflammation scores Descriptive statistical methods such as mean, were significantly different (p:0.002) (Table 2). When standard deviation, frequency, and percentage were the data of 86 patients were examined who have py- used in the evaluation of the study data. The distri- loric ring failure, it was seen that the decrease in in- bution of variables was checked by the Kolmogor- flammation, activation and H. Pylori density scores ov-Simirnov test. Independent sampling t - test, Mann were statistically significant toward from antrum to - Whitney U test and Wilcoxon test were used in the the corpus. (p: 0.001, p: 0.001, p:0.001) (Table 3). Evaluation of gastric inflammatory parameters caused by pyloric ring failure 1483 Failures in Gastric mucosal damage is caused by the release Histopathological parameters pylorus Intact pylorus p of vasoactive materials such as histamine due to mast cell degranulation, resulting in vascular congestion in H. Pylori density 1,33±0,56 1,23±0,46 0,181 lamina propria(15). These findings can also be seen in Inflammation 1,97±0,77 1,72±0,69 0,002 other conditions such as H. pylori infection. Patients which used proton pump inhibitors(P- Activation 1,16±0,43 1,14±0,39 0,637 PI) have been shown to have higher gastric pH, which in turn increases mucosal damage and suggesting that Atrophy 1±0 1±0 1 DGR-induced inflammatory scores may be higher Metaplasia 1±0 1±0 1 in patients that pyloric ring failure. In other words, gastric acid has a protective effect against DGR and Table 2: Histopathological findings of corpus in intact and failure pyloric ring. GER. In particular, patients which used PPI, and who have pyloric ring failure should be followed closely and carefully for gastric cancer(16). Histopathological parameters Antrum Corpus p It has been shown that enzymes such as trypsin and PLA2 in biliary and pancreatic juice in DGR cause H. Pylori density 2,17±0,88 1,33±0,56 <0,001 damage to gastric mucosa(17). Bile reflux causes antral Inflammation 2,79±0,68 1,97±0,77 <0,001 G-cell hyperplasia and hypergastrinemia and reduces (18,19) Activation 1,79±0,84 1,16±0,43 <0,001 somatostatin release . Decreased somatostatin lev- els increases the hypergastrinemia and hypergatrinemia Table 3: Comparison of histopathological findings of an- further increases the bile reflux(20). Cholecystokinin-2 trum and corpus in pyloric ring failure. (CCK-2) is a gastrin-specific receptor and is expressed in gastric pariatel cells and ECL cells(21). CCK-2 re- Discussion ceptors are exposed in normal esophagus, reflux es- ophagitis, barrette esophagus and adenocarcinoma(22). DGR is a risk factor for atrophy and intestinal It is known that H. Pylori is caused by precancerous metaplasia (IM) development(10). Duodenal fluid in- lesions. Therefore, it was seen that the intensity of H. creases inflammatory cells in the gastric mucosa and Pylori was increased in patients with have pyloric ring changes the glandular morphology by reducing pari- failure and it was accompanied synergistically with etal cells and mucous cell hyperplasia. These changes precancerous lesions such as atrophic gastritis and in- leading to esophagitis, gastritis, gastric and duodenal testinal metaplasia. Therefore, hypergastrinemia due ulcers(2). When gastric microenvironment resembles to chronic biliary reflux, gastric epithelial hyperplasia to duodenum, intestinal metaplasia develops in the and gastric gland expansions are caused by the same gastric mucosa to reduce the mucosal damage caused mechanism. Previously, only endoscopic examination by alkaline fluid. of DGR was reported to be intuitive and subjective, In our study, the IM scores of patients with py- and endoscopic findings would not be sufficient(23). In loric ring failure were high, but not statistically sig- our study, we found that histopathological scores were nificant. We think that this is due to DGR caused by higher in patients which have pyloric ring failure by pyloric ring failure. DGR is physiological in the early endoscopically. morning and postprandial period(11). However, exces- We consider that, the status of the pyloric ring sive DGR causes gastritis, esophagitis, ulcers, gastric (failures or intact ) can be evaluated during the proce- polyps, metaplasia, esophageal and gastric cancers(12). dure due to the simplicity of the method and that the In 30 to 40% of patients, DGR may be associated endoscopic findings alone are adequate for predicting with reflux esophagitis or gastroesophageal reflux risky patients. (GER). DGR is widespread in asymptomatic cases, Biliary reflux can not be diagnosed in the up- as well as in patients with gastric and duodenal ulcer, per gastrointestinal endoscopy with the presence of pulmonary disease and whom underwent cholecys- bile in the stomach. Fuchs et al. described DGR in tectomy(13). Endoscopically, pyloric ring failure and gastric fluid with high pH, demonstrating bilirubin duodenal gastric reflux, erythema and erosion, gastric and pancreatic enzymes(24). 99mTc-EHIDA (99m Tc- atrophy, petechiae, gastric plea thickening, metapla- ethyl hepatic iminodiacetic acid) scintigraphy showed sia, and history of gastric surgery may be associated 78.7% of cases diagnosed with DGR23 Bile acids have with DGR diagnosis(14). a surfactant effect and this effect is necessary for lipid 1484 Muhammed Zübeyr Üçüncü, Bünyamin Gürbulak et Al absorption. This effect is due to hydrophilic-hydro- cascade. We recommend the addition of pyloric ring phobic balance. If the surfactant effect is too strong, failure to DGR-associated risk factors which has de- the effect is cytotoxic. The hydrophilic and hydropho- scribed in the literature. bic balance shifts hydrophobic to increase the toxic effect on the epithelium(25,26). The diagnosis of bile Conclusion reflux should be made carefully, excluding H. Pylori infection, NSAID with alcohol use, and other factors DGR is a risk factor for atrophy and IM develop- that cause mucosal inflammation. ment. Because of higher histopathological inflamma- After distal gastrectomy, it is thought that bilroth tion scores caused by DGR which patients that have 2 increases the risk of remnant gastric cancer, accord- pyloric ring failure, it is important that patients have ing to bilroth 1, and it is thought to be the effect of bile close follow-up with multiple biopsies by yearly. acids in duodenal fluid(27). It was showed in an exper- imental study, that rats infected H. Pylori and under- went pyloroplasty, have positive correlation between metaplasia, dysplasia and cancer development. Ne- References oplasia was observed in 40% of rats that underwent pylorplasty(28). 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