Histological Changes In The Oesophageal Squamous Mucosa And The Association With The Symptoms Of Gastroesophageal Relfux Disease

Background Not only acid,but also visceral hypersensitivity contributed tosymptoms of gastroesophageal reflux disease. The pathophysiology of oesophagealhypersensitivity is complex and far from being elucidated. It involves peripheral andcentral sensitisation as well as psychoneuroimmune interactions. The histologicalchanges in the oesophageal squamous mucosa,including histological morphology(such as dilated interstitial space) and receptors (such as transient receptor potentialvanilloid type l),may be involved in peripheral sensitisation, and their correlationswith symptoms of the patients remain to be studied.Objective1. To study the histological morphological changes in the oesophageal squamousmucosa of patients with gastroesophageal reflux disease（GERD）,quantitativemeasurement of intracellular space diameter using computer-assisted morphometryand an immersion objective, and to estimate the diagnostic value of histologicalmorphological changes in GERD and their associations with the symptoms of thepatients.2. To study the expression of the TRPV1in the esophageal mucosa of patients withGERD and to analyse the relationship between TRPV1and the symptoms of thepatients.Methods54GERD patients (28RE patients,26NERD patients) and25healthycontrols under endoscopic examination between Oct2010and Nov2011at the department of gastroenterology,the first affiliated hospital of Anhui MedicalUniversity were recruited into the study. Symptoms of patients were evaluatedthrough the reflux disease diagnostic questionnaire(RDQ).During the endoscopicexamination, two biopsies were taken from esophagus at a fixed position3cm abovethe gastroesophageal junction in all subjects. Biopsies were used forHematoxylin-eosin histological staining. We compared the histological parametersof RE, NERD and controls.The overall severity of all the lesions was described bymeans of global score (GS).Quantitative measurement of intracellular spacediameter(ISD) using computer-assisted morphometry(Image-Pro Plus6.0) and animmersion objective(1000×magnification).These biopsies were studied byimmunohistochemistry using antibodies to TRPV1and protein gene product9.5.Results①All these features(hyperplasia of the esophageal basal cell layer，elongation of the papillae，intraepithelial eosinophils，dilated interstitial space) weremore prevalent in GERD patients than controls(P<0.05),but there were nostatistically significant difference between patients with RE and NERD (P>0.05).②The global score (GS) was significantly higher in patients with RE than NERDpatients and in controls(P<0.05),and NERD patients were also significantly higherthan controls(P<0.05).③Intracellular space diameter was significantly greater in REpatients and NERD patients than controls(P=0.000),but there was no statisticallydifference in RE patients and NERD patients (p=0.702).④For global score,the0.415cut-off permitted the distinction of GERD patients from controls with83.3%sensitivity and84%specificity. The cut-off value we calculated from mean DIS was0.86um. When we used GERD symptoms, endoscopy, and PPI test as the goldstandard for GERD diagnosis, sensitivity was80%and specificity was100%.⑤Theglobal scores (GS) was correlated positively with the reflux disease diagnosticquestionnaire(RDQ) scores （Spearman correlation r=0.341， p=0.012）,whileseparately,the GS in RE group correlated with RDQ scores (r=0.458，p=0.014),andthe GS in NERD group correlated with RDQ scores（r=0.44，p=0.024）. And theintracellular space diameter of the GERD group was also correlated positively with the RDQ scores（r=0.482，p=0.000）,while the intracellular space diameter in REgroup correlated with RDQ scores （r=0.598，p=0.002）,and the intracellular spacediameter in NERD group correlated with RDQ scores（r=0.529，p=0.007）separately.⑥The expression levels of TRPV1were significantly different(P <0.01) betweenGERD group and controls, but were no difference between NERD and RE（p=0.63）.⑦The expression levels of TRPV1of GERD patients were positively correlated withthe RDQ scores（r=0.527，p <0.001）,and correlation coefficient in RE groupr=0.614(p=0.001）,and that in NERD group r=0.678(p <0.001）.⑧The expressionlevels of TRPV1of GERD patients were positively correlated with the GS（r=0.562，p <0.001）,and correlation coefficient in RE group r=0.535(p=0.003),and that inNERD group r=0.509(p=0.008）.Conclusion1. With the symptoms of heartburn, regurgitation and so on, GS or DIS maycontribute to the diagnosis of GERD,especially for NERD.2. The symptoms of GERD patients may associate with the histologicalmorphological changes in the oesophageal squamous mucosa,especially with DIS.3. Increased expression of TRPV1in the esophageal mucosa may contribute tosymptoms in GERD patients.