L. Ceccarelli

Role of faecal calprotectin as non-invasive marker of intestinal inflammation.

BACKGROUND/AIM Faecal calprotectin, a neutrophil granulocyte cytosol protein, is considered a promising marker of intestinal inflammation. We assessed and compared the faecal calprotectin concentration in patients with organic and functional chronic intestinal disorders. PATIENTS AND METHODS The study was carried out, using a commercially available ELISA test, measuring calprotectin in stool samples collected from 131 patients with inflammatory bowel diseases, 26 with intestinal neoplasms, 48 with irritable bowel syndrome and 34 healthy subjects. RESULTS Median faecal calprotectin was significantly increased in Crohns disease (231 microg/g, 95% confidence interval (CI) 110-353 microg/g), ulcerative colitis (167 microg/g, 95% CI 59-276 microg/g), and neoplasms (105 microg/g, 95% CI 0-272 microg/g), whereas normal values were found in patients with irritable bowel syndrome (22 microg/g, 95% CI 9-35 microg/g) and in healthy subjects (11 microg/g, 95% CI 3-18 microg/g). A positive correlation was observed with clinical activity scores in Crohns disease and ulcerative colitis. In both groups, patients with clinically active disease showed higher calprotectin levels than those observed in patients with quiescent disease (405 microg/g, 95% CI 200-610 microg/g vs. 213 microg/g, 95% CI 85-341 microg/g in CD patients, p<0.05, and 327 microg/g, 95% CI 104-550 microg/g vs. 123 microg/g, 95% CI 40-206 microg/g in UC patients, p<0.001). CONCLUSIONS Faecal calprotectin appears to be a promising and non-invasive biomarker of intestinal inflammation. If these findings are confirmed, it may provide a useful test for the diagnosis and follow up of inflammatory bowel diseases.

How many cases of laryngopharyngeal reflux suspected by laryngoscopy are gastroesophageal reflux disease-related?

AIM To investigate the prevalence of gastroesophageal reflux disease (GERD) in patients with a laryngoscopic diagnosis of laryngopharyngeal reflux (LPR). METHODS Between May 2011 and October 2011, 41 consecutive patients with laryngopharyngeal symptoms (LPS) and laryngoscopic diagnosis of LPR were empirically treated with proton pump inhibitors (PPIs) for at least 8 wk, and the therapeutic outcome was assessed through validated questionnaires (GERD impact scale, GIS; visual analogue scale, VAS). LPR diagnosis was performed by ear, nose and throat specialists using the reflux finding score (RFS) and reflux symptom index (RSI). After a 16-d wash-out from PPIs, all patients underwent an upper endoscopy, stationary esophageal manometry, 24-h multichannel intraluminal impedance and pH (MII-pH) esophageal monitoring. A positive correlation between LPR diagnosis and GERD was supposed based on the presence of esophagitis (ERD), pathological acid exposure time (AET) in the absence of esophageal erosions (NERD), and a positive correlation between symptoms and refluxes (hypersensitive esophagus, HE). RESULTS The male/female ratio was 0.52 (14/27), the mean age ± SD was 51.5 ± 12.7 years, and the mean body mass index was 25.7 ± 3.4 kg/m(2). All subjects reported one or more LPS. Twenty-five out of 41 patients also had typical GERD symptoms (heartburn and/or regurgitation). The most frequent laryngoscopic findings were posterior laryngeal hyperemia (38/41), linear indentation in the medial edge of the vocal fold (31/41), vocal fold nodules (6/41) and diffuse infraglottic oedema (25/41). The GIS analysis showed that 10/41 patients reported symptom relief with PPI therapy (P < 0.05); conversely, 23/41 did not report any clinical improvement. At the same time, the VAS analysis showed a significant reduction in typical GERD symptoms after PPI therapy (P < 0.001). A significant reduction in LPS symptoms. On the other hand, such result was not recorded for LPS. Esophagitis was detected in 2/41 patients, and ineffective esophageal motility was found in 3/41 patients. The MII-pH analysis showed an abnormal AET in 5/41 patients (2 ERD and 3 NERD); 11/41 patients had a normal AET and a positive association between symptoms and refluxes (HE), and 25/41 patients had a normal AET and a negative association between symptoms and refluxes (no GERD patients). It is noteworthy that HE patients had a positive association with typical GERD-related symptoms. Gas refluxes were found more frequently in patients with globus (29.7 ± 3.6) and hoarseness (21.5 ± 7.4) than in patients with heartburn or regurgitation (7.8 ± 6.2). Gas refluxes were positively associated with extra-esophageal symptoms (P < 0.05). Overall, no differences were found among the three groups of patients in terms of the frequency of laryngeal signs. The proximal reflux was abnormal in patients with ERD/NERD only. The differences observed by means of MII-pH analysis among the three subgroups of patients (ERD/NERD, HE, no GERD) were not demonstrated with the RSI and RFS. Moreover, only the number of gas refluxes was found to have a significant association with the RFS (P = 0.028 and P = 0.026, nominal and numerical correlation, respectively). CONCLUSION MII-pH analysis confirmed GERD diagnosis in less than 40% of patients with previous diagnosis of LPR, most likely because of the low specificity of the laryngoscopic findings.

Lower pH values of weakly acidic refluxes as determinants of heartburn perception in gastroesophageal reflux disease patients with normal esophageal acid exposure

Multichannel impedance pH monitoring has shown that weakly acidic refluxes are able to generate heartburn. However, data on the role of different pH values, ranging between 4 and 7, in the generation of them are lacking. The aim of this study was to evaluate whether different pH values of weakly acidic refluxes play a differential role in provoking reflux symptoms in endoscopy-negative patients with physiological esophageal acid exposure time and positive symptom index and symptom association probability for weakly acidic refluxes. One hundred and forty-three consecutive patients with gastroesophageal reflux disease, nonresponders to proton pump inhibitors (PPIs), were allowed a washout from PPIs before undergoing: upper endoscopy, esophageal manometry, and multichannel impedance pH monitoring. In patients with both symptom index and symptom association probability positive for weakly acidic reflux, each weakly acidic reflux was evaluated considering exact pH value, extension, physical characteristics, and correlation with heartburn. Forty-five patients with normal acid exposure time and positive symptom association probability for weakly acidic reflux were identified. The number of refluxes not heartburn related was higher than those heartburn related. In all distal and proximal liquid refluxes, as well as in distal mixed refluxes, the mean pH value of reflux events associated with heartburn was significantly lower than that not associated. This condition was not confirmed for proximal mixed refluxes. Overall, a low pH of weakly acidic reflux represents a determinant factor in provoking heartburn. This observation contributes to better understand the pathophysiology of symptoms generated by weakly acidic refluxes, paving the way toward the search for different therapeutic approaches to this peculiar condition of esophageal hypersensitivity.

Obesity is a Risk Factor for Erosive Gastroesophageal Reflux Disease: Prospective Case-Control Study

Background and aim: An association between high body mass index (BMI) and gastroesophageal reflux disease (GERD) has been proposed but the relationship between the severity of obesity, the prevalence of symptoms and gravity of esophagitis is still unclear. Aim of this study was to evaluate the prevalence of symptomatic GERD and esophagitis in female obese subjects compared to a group of female with typical GERD symptoms. Material and methods: 193 obese women (Group A) scheduled for bariatric surgery and 193 normal weight female with typical GERD symptoms (Group B) were submitted to complete history (recording voluptuary habits) and validated questionnaire for symptomatic diagnosis of GERD (GIS: GERD Impact Scale). Each patient underwent upper GI endoscopy to evaluate the prevalence of erosive esophagitis. Erosive esophagitis was diagnosed according to Los Angeles Classification of esophagitis. Results: We enrolled 193 female patients in Group A and 193 patients in Group B. Mean age (± sd) was 48.6 ± 13.6 years in Group A and 51.4 ± 15.3 years in group B. Mean BMI was 43.6 ± 9.2 in group A and 23.6 ± 3.7 in Group B (P<0.001). The perception of GERD symptoms was higher in group B: the mean value of GIS was 1.72 when compared with 0.34 obtained in Group A (P<0.001). The mean value of score for typical GERD symptoms was 2.65 in group B and 0.85 in group A (P<0.001). All patients in Group B recorded at least one typical GERD symptom (heartburn and regurgitate) but only 26.9% of patients in Group A recorded these symptoms (P<0.001). Esophageal erosion were present in 97/193 (50.3%) in Group A and in 45/193 (23.3%) in Group B (P<0.001). Conclusions: We can conclude that the impact of erosive esophagitis in obese patients could be considered more severe than gravity and frequency of symptoms.

From bench to bedside: Fecal calprotectin in inflammatory bowel diseases clinical setting

Fecal calprotectin (FC) has emerged as one of the most useful tools for clinical management of inflammatory bowel diseases (IBD). Many different methods of assessment have been developed and different cut-offs have been suggested for different clinical settings. We carried out a comprehensive literature review of the most relevant FC-related topics: the role of FC in discriminating between IBD and irritable bowel syndrome (IBS) and its use in managing IBD patients In patients with intestinal symptoms, due to the high negative predictive value a normal FC level reliably rules out active IBD. In IBD patients a correlation with both mucosal healing and histology was found, and there is increasing evidence that FC assessment can be helpful in monitoring disease activity and response to therapy as well as in predicting relapse, post-operative recurrence or pouchitis. Recently, its use in the context of a treat-to-target approach led to a better outcome than clinically-based therapy adjustment in patients with early Crohn’s disease. In conclusion, FC measurement represents a cheap, safe and reliable test, easy to perform and with a good reproducibility. The main concerns are still related to the choice of the optimal cut-off, both for differentiating IBD from IBS, and for the management of IBD patients.

Vegetal and Animal Food Proteins Have a Different Impact in the First Postprandial Hour of Impedance-pH Analysis in Patients with Heartburn

Background and Aims By means of 24 h impedance-pH monitoring, we aimed to evaluate the effect of two different meals with a bromatological balanced composition: one with a prevailing component of animal proteins and the other with vegetable proteins. Patients and Methods We enrolled 165 patients with heartburn and negative endoscopy, who underwent impedance-pH monitoring off therapy. Patients were allocated to receive a Mediterranean diet with a total caloric intake of about 1694 kcal, divided into two meals: one with a prevailing component of animal proteins and the other with vegetable proteins. We evaluated the total reflux number, acid exposure time (AET), and symptom-reflux association with impedance-pH analysis. Moreover, during the first postprandial hour (at lunch and dinner), we evaluated the total reflux number, number of acid and weakly acidic refluxes, AET, and presence of symptoms. Results The male/female ratio was 80/85. Mean age was 51.9 ± 12.1 years. Impedance-pH analysis showed that 55/165 patients had pathological AET or a number of refluxes (nonerosive reflux disease (NERD)), 49/165 had normal AET and a number of refluxes but positive symptom-reflux association (hypersensitive esophagus (HE)), and 61/165 had normal AET and a number of refluxes with negative symptom-reflux association (functional heartburn (FH)). The overall first postprandial hour analysis showed a higher total reflux number, acid reflux number, and AET after the animal protein meal than after the vegetable protein meal. Moreover, more symptoms were reported after the animal protein meal. Similar results have been observed in the three different subcategories of patients (NERD, HE, and FH). Conclusions Vegetable proteins are associated with a lower number of refluxes, particularly acid refluxes, and with a reduced number of symptoms during the first postprandial hour. This is a pilot study and future investigations are warranted to confirm these results.

Sa1351 Voluntary and Controlled Weight Loss Can Reduce Symptoms and Allow a Lowering of Proton Pump Inhibitor Dosage in Patients With Gastroesophageal Reflux Disease. A Case-Control Study

Voluntary and Controlled Weight Loss Can Reduce Symptoms and Allow a Lowering of Proton Pump Inhibitor Dosage in Patients With Gastroesophageal Reflux Disease. A Case-Control Study Nicola de Bortoli, Giada Guidi, Edoardo Savarino, Lorenzo Bertani, Riccardo Franchi, Irene Martinucci, Lorenzo Macchia, Linda Ceccarelli, Salvatore Russo, Manuele Furnari, Massimo Bellini, Vincenzo Savarino, Santino Marchi

Su1190 Role of Contrast-Enhanced Ultrasonography (CEUS) in Assessment of Inflammatory Activity in Patients With Small Bowel Crohn's Disease

INTRODUCTION Although in CD mucosal healing is regarded as a major therapeutic end-point, the mere mucosal examination can underestimate disease activity in a tipically transmural disease. A reliable assessment of parietal inflammation should be part of the diagnostic work up and, if regularly performed during treatment, it could contribute to evaluate the therapeutic response and to decide if and when to stop therapy Contrast Enhaced Ultrasound (CEUS) is a promising, non invasive tool which is able to quantify the gut wall inflammation allowing a more accurate assessment of disease activity in CD patients AIMS The aim of the study was to evaluate if CEUS is a useful tool to quantify the variation of parietal inflammation in patients with small bowel CD before and after therapy PATIENTS AND METHODS Fifteen CD patients (6 males, 9 females; mean age 38 yrs) with luminal disease confined to terminal ileum (L1B1 sec. Montreal classification) on maintenance therapy with biologics underwent clinical (CDAI), biological (serology and faecal markers) and CEUS assessment before and 12 months after starting therapy. Bowel wall thickness (BWT) was measured in all patients and quantification of wall gut inflammation was obtained by applying a digital image processing software based on Sun-Java and released in public domain (Image J). The analysis of intensity light was performed within particular Region of Interest (ROI) drawn by the operator within the ileum avoiding perivisceral structures. Time-signal intensity curves were processed and maximum enhancement (ME) was analyzed. Statistical analysis was performed by using Wilcoxons signed rank test and Spearmans rank correlation coefficient. RESULTS All patients were in clinical remission after 12 months of therapy. Overall results (mean+/-SD) are shown in table 1 A significant correlation was found between ME and CDAI (r=0.73 p=0.004), PCR (r=0.69 p=0.007), Faecal calprotectin (r= 0.54 p=0.044). CONCLUSION In small bowel CD, CEUS may be a helpful non-invasive procedure to quantify the transmural inflammation and to follow the inflammatory process during therapy Table 1