M. Cicala

Intra‐oesophageal distribution and perception of acid reflux in patients with non‐erosive gastro‐oesophageal reflux disease

Background: The majority of patients with gastro‐oesophageal reflux disease do not present with erosive oesophagitis and make up a heterogeneous group. Patients with non‐erosive gastro‐oesophageal reflux disease are less responsive than patients with oesophagitis to acid‐suppressive therapy.

Dilated intercellular spaces and acid reflux at the distal and proximal oesophagus in patients with non-erosive gastro-oesophageal reflux disease

Backgroundu2002 Acid exposure of proximal oesophagus and dilated intercellular space diameters of oesophageal epithelium are relevant in the perception of gastro‐oesophageal reflux.

Regional oesophageal sensitivity to acid and weakly acidic reflux in patients with non‐erosive reflux disease

Abstractu2002 The mechanisms underlying symptoms in non‐erosive reflux disease (NERD) remain to be elucidated. Non‐erosive reflux disease patients appear to be more sensitive to intraluminal stimula than erosive patients, the proximal oesophagus being the most sensitive. In order to assess regional oesophageal changes in reflux acidity and sensitivity to reflux, according either to the acidity or the composition of the refluxate, combined multiple pH and multiple pH‐impedance (pH‐MII) was performed in 16 NERD patients. According to multiple pH‐metry, 29% and 12% of reflux events reached the middle and proximal oesophagus respectively, and 35% and 19% according to conventional pH‐MII (Pu2003<u20030.05). The per‐individual analysis confirmed the difference between the two techniques. According to combined distal and proximal pH‐MII, approximately 30% of distal acid reflux became weakly acidic at the proximal oesophagus. In all patients, the frequency of symptomatic refluxes, both acid and weakly acidic, was significantly higher at the proximal, compared with distal oesophagus (25u2003±u20038%vs 11u2003±u20032% for acid reflux and 27u2003±u20038%vs 8u2003±u20032% for weakly acidic reflux; Pu2003<u20030.05). Compared with multiple pH‐metry, pH‐MII shows a higher sensitivity in the detection of proximal reflux. As approximately 30% of acid reflux becomes weakly acidic along the oesophageal body, to better characterize proximal reflux, in clinical practice, combined proximal pH‐impedance monitoring should be used. In NERD patients, the proximal oesophagus seems to be more sensitive to both acid and weakly acidic reflux.

Effect of hiatal hernia on proximal oesophageal acid clearance in gastro-oesophageal reflux disease patients

Proximal acid reflux is common in gastro‐oesophageal reflux disease and is a determinant of symptoms. Patients with hiatal hernia complain of more symptoms than those without and are less responsive to proton‐pump inhibitors.

Immunohistochemical evaluation of pRb2/p130, VEGF, EZH2, p53, p16, p21waf-1, p27, and PCNA in Barrett's esophagus.

Control of the G1/S‐phase transition as well as angiogenic switch are two of the most studied mechanisms in cancer. The current study examined the correlation between the immunohistochemical expression of pRb2/p130, VEGF, EZH2, p53, p16, p21waf‐1, p27, and PCNA in Barretts esophagus (BE). Overall, p53 showed a much higher expression in BE patients (up to 50%) than in controls (1–10%) (Pu2009<u20090.005). Also p21 showed a downregulation in BE when compared to normal esophagus (70% of cells vs. 65%), but the difference did not show any statistical significance (Pu2009=u20090.45). pRb2/p130 was detected in 80% of cells in normal controls, but showed positive in only 20% of cells in BE biopsies. Additionally, Rb2/p130 expression was inversely correlated to that of VEGF, EZH2, and PCNA (Pu2009<u20090.0001, Pu2009=u20090.0032, Pu2009<u20090.001, respectively). p27 stained more intensely and in a widespread manner (70%) cells in normal esophageal tissues but about only 30% in BE samples (Pu2009<u20090.001). Lastly, in accordance with other reports, we also found p16 expressed by immunohistochemistry at high levels in normal controls and at low levels in BE (Pu2009<u20090.001). In conclusion, p16, p21, p27, and p53 staining confirmed previously published data. Interestingly, pRb2/p130 expression was found significantly decreased in metaplastic epithelium compared to normal controls and showed significant inverse correlation with the expression of other markers, such as VEGF, EZH2, and PCNA. These data, taken together, indicate that these molecular events occurring in Barretts metaplasia (BM) may represent one of the many steps taking place during esophageal malignant progression such as impairment of cell‐cycle control, altered differentiation, and unbalanced angiogenesis. J. Cell. Physiol. 207: 512–519, 2006.

Intercellular space diameters of the oesophageal epithelium in NERD patients: Head to head comparison between light and electron microscopy analysis

BACKGROUNDnDilation of intercellular space diameters of oesophageal epithelium detected at transmission electron microscopy morphometry is a marker of tissue injury in non-erosive reflux disease patients. Semi-quantitative evaluation of intercellular space diameters using light microscopy seems to provide promising results.nnnAIM/METHODSnTo comparatively evaluate intercellular space diameters in the same patients, by means of morphometry and semi-quantitative analysis, both on light microscopy and transmission electron microscopy microphotographs, biopsies were taken in 29 non-erosive reflux disease patients at distal and proximal oesophagus. Twelve asymptomatic controls underwent the same protocol.nnnRESULTSnMorphometric analysis on transmission electron microscopy microphotographs showed mean intercellular space diameter values of patients, at distal and proximal oesophagus, 3- and 2-fold, respectively, higher than those in controls (p<0.001). On light microscopy microphotographs, mean intercellular space diameter values of patients at distal oesophagus were higher than those in controls, an overlap between patients and controls being observed. The semi-quantitative score was positive in 79% of patients and in 25% of controls at distal esophagus.nnnCONCLUSIONSnIntercellular space diameter morphometric analysis at light microscopy is widely available, allows intercellular space diameter to be quantitatively measured with good sensitivity and specificity and could represent a useful tool in non-erosive reflux disease diagnosis. Despite satisfactory sensitivity, the semi-quantitative score at light microscopy is hampered by much lower specificity than transmission electron microscopy- and light microscopy-morphometry.

Gut Microbiota Dysbiosis as Risk and Premorbid Factors of IBD and IBS Along the Childhood-Adulthood Transition.

Abstract:Gastrointestinal disorders, although clinically heterogeneous, share pathogenic mechanisms, including genetic susceptibility, impaired gut barrier function, altered microbiota, and environmental triggers (infections, social and behavioral factors, epigenetic control, and diet). Gut microbiota has been studied for inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) in either children or adults, while modifiable gut microbiota features, acting as risk and premorbid factors along the childhood-adulthood transition, have not been thoroughly investigated so far. Indeed, the relationship between variations of the entire host/microbiota/environmental scenario and clinical phenotypes is still not fully understood. In this respect, tracking gut dysbiosis grading may help deciphering host phenotype–genotype associations and microbiota shifts in an integrated top–down omics-based approach within large-scale pediatric and adult case-control cohorts. Large-scale gut microbiota signatures and host inflammation patterns may be integrated with dietary habits, under genetic and epigenetic constraints, providing gut dysbiosis profiles acting as risk predictors of IBD or IBS in preclinical cases. Tracking dysbiosis supports new personalized/stratified IBD and IBS prevention programmes, generating Decision Support System tools. They include (1) high risk or flare-up recurrence -omics-based dysbiosis profiles; (2) microbial and molecular biomarkers of health and disease; (3) -omics-based pipelines for laboratory medicine diagnostics; (4) health apps for self-management of score-based dietary profiles, which can be shared with clinicians for nutritional habit and lifestyle amendment; (5) -omics profiling data warehousing and public repositories for IBD and IBS profile consultation. Dysbiosis-related indexes can represent novel laboratory and clinical medicine tools preventing or postponing the disease, finally interfering with its natural history.

Effect of ursodeoxycholic acid on inflammatory infiltrate in gallbladder muscle of cholesterol gallstone patients

Backgroundu2002 Reduced gallbladder (GB) contractility and chronic inflammatory changes in the mucosa have been reported in patients with cholesterol gallstones (GS). Ursodeoxycholic acid (UDCA) restores GB contractility and antagonises liver macrophage activation. In the colon, hydrophobic bile acid, not hydrophilic UDCA, induces mast cell degranulation. We studied the presence of monocyte/macrophage infiltrate, cyclooxygenase (COX)‐2, inducible nitric oxide synthase (iNOS) expression, the number of total and degranulated mast cells in the GB muscle layer of cholesterol GS patients, and the effect of UDCA administration.

Proximal oesophagus: the added value in understanding GORD symptoms.

Abstractu2002 Over the past decade, the approach to the understanding of the mechanisms involved in the aetiology of gastro‐oesophageal reflux disease (GORD) symptoms has changed, and growing evidence now supports the concept that visceral hyper‐sensitivity to intra‐oesophageal stimuli plays a major role. Among the recent advances, one of the more consistent findings is that the contact of the refluxate, either acidic or weakly acidic, with the proximal oesophageal mucosa, is a main determinant of GORD symptoms, particularly in the large majority of patients affected by non‐erosive reflux disease. The data reported in the current issue of Neurogastroenterology and Motility by Bredenoord et al., showing only a small proportion of proximal reflux in patients with Barrett’s oesophagus, who are less sensitive to gastro‐oesophageal reflux, further support the consistency of this finding in the pathogenesis of symptoms. In the light of these results, we shall look forward, in the management of patients, to approaches aimed at restoring the antireflux barrier, hopefully decreasing the amount of reflux and, in turn, its proximal extent.

Bloating is associated with worse quality of life, treatment satisfaction, and treatment responsiveness among patients with constipation-predominant irritable bowel syndrome and functional constipation

The management of bloating is unclear and its relationship with patients well‐being and treatment satisfaction independent of other abdominal symptoms is uncharacterized. We evaluated the association of bloating with patient‐reported outcomes.