Paola Balestrieri

Weak peristalsis with large breaks is associated with higher acid exposure and delayed reflux clearance in the supine position in GERD patients.

OBJECTIVES:Ineffective esophageal motility is frequently observed in gastroesophageal reflux disease (GERD) patients but its clinical relevance remains controversial. In healthy subjects and in patients with nonobstructive dysphagia, it has been demonstrated, by means of high-resolution manometry (HRM), that long breaks of esophageal peristalsis predict delayed bolus clearance.METHODS:HRM and 24-h multichannel impedance-pH (MI-pH) monitoring were performed in 40 GERD patients with no evidence of hiatal hernia. Total bolus clearing time (BCT) in upright and supine position and acid exposure time (AET) were calculated.RESULTS:Of the 40 patients, 23 showed a pathological AET and 15 erosive reflux disease (ERD). Patients with a pathological number of large breaks were characterized by a significantly lower BCT value in the supine position and higher AET. In all, 10/15 ERD patients (67%) and 5/25 nonerosive reflux disease patients (20%) were characterized by an abnormal number of small or large breaks (P<0.05). ERD patients were characterized by significantly higher AET and BCT in the supine position.CONCLUSIONS:GERD patients with a pathological number of large breaks, assessed by HRM, are characterized by a significantly prolonged reflux clearance in the supine position and higher AET. ERD patients display a higher number of esophageal breaks that might explain the development of erosions.

Reflux pattern and role of impedance-pH variables in predicting PPI response in patients with suspected GERD-related chronic cough.

Gastro‐oesophageal reflux disease (GERD) may contribute to the onset of chronic cough (CC); however, the multichannel intraluminal impedance‐pH (MII‐pH) monitoring is often within the normal range and the response to proton pump inhibitors (PPIs) unsatisfactory. The measure of impedance baseline (IB) increases the sensitivity of MII‐pH in patients with typical symptoms.

Impedance baseline and reflux perception in responder and non-responder non-erosive reflux disease patients

Abstract Background. It was recently shown that GERD patients have lower impedance baseline (IB) values than healthy controls and, that the esophageal acid exposure time (AET) correlates with IB levels. Goals. To explore the sensitivity of IB measurements in NERD patients, responders and non-responders to PPIs, when compared with pH-impedance (MII-pH) variables, and to evaluate whether this variable could represent a marker of GERD symptoms. Reproducibility and inter-observer agreement of IB measurement were also assessed. Study. MII-pH tracings from 44 NERD responders and 22 non-responders were analysed. Ten healthy volunteers underwent the same protocol. IB values were measured at the distal and proximal esophagus. IB was also analysed in a subgroup of patients and in controls with two methods and by two blinded operators. Results. Mean IB values at the distal esophagus were significantly lower in NERD patients than in controls. IB values did not differ between responders and non-responders. Of the 8 responders with negative AET and symptom association probability (SAP), 3 (37.5%) showed IB values lower than controls. IB values in responders with positive and negative SAP were similar (1832 (1596–2068) Ω vs 1667 (1361–1973) Ω, p: n.s.). No differences were found between the IB values measured with the two methods and the inter-observer agreement was good. Conclusions. IB is a promising and easy to calculate MII-pH variable and appears to increase the sensitivity of MII-pH monitoring. IB values cannot predict PPI response and are not associated with reflux perception in NERD patients.

Increased frequency and enhanced perception of reflux in non-erosive reflux disease patients non-responders to proton pump inhibitors.

BACKGROUND The unsatisfactory response to medical treatment in non-erosive patients is becoming a real challenge for gastroenterologists. Non-responder patients, evaluated under treatment, present symptoms which are related to non-acidic, mixed and proximal reflux episodes. METHODS To elucidate the reflux pattern and mechanisms related to persistence of symptoms despite treatment, oesophageal pH-impedance was performed in 55 non-erosive responder and 24 non-responder patients, studied off therapy. Ten responder and 10 non-responder patients underwent a repeated study during proton pump inhibitor treatment. RESULTS Non-responders were characterised by a higher overall number and larger proportion of symptomatic reflux episodes. Non-responders were also characterised by an enhanced sensitivity to acidic, mixed and proximal refluxes. Weakly acidic reflux accounted for 29% of symptomatic refluxes in non-responders and 34% in responders. Proportions of acidic and weakly acidic reflux episodes were comparable both in responders and non-responders when analysed off and on treatment. CONCLUSIONS An increased overall number of reflux episodes and enhanced sensitivity to reflux are strongly associated with treatment failure. Treatment strategies aimed at decreasing transient lower oesophageal sphincter relaxations, pain modulators or anti-reflux surgery should be considered in non-responders in whom a significant relationship between symptoms and reflux has been confirmed.

Impedance-High Resolution Manometry Analysis of Patients With Nonerosive Reflux Disease

BACKGROUND & AIMS Transient lower esophageal sphincter relaxations (TLESRs) contribute to episodes of reflux. Few studies have assessed the frequencies or compositions of TLESRs and reflux episodes in patients with reflux disease. We used combined high-resolution manometry and impedance monitoring to analyze reflux episodes and esophageal motility in these patients, compared with those of healthy individuals. METHODS We evaluated the frequency of TLESRs and the relationship between the reflux pattern and esophageal pressures during TLESRs in 14 patients with nonerosive reflux disease (NERD) and 11 controls. Study participants underwent combined high-resolution manometry and impedance monitoring before and 60 minutes after a solid and liquid meal. The diagnosis of NERD was confirmed by a 24-hour pH impedance test. RESULTS The frequency of TLESRs did not differ between patients with NERD and controls. In patients with NERD, TLESRs were associated more often with reflux episodes than in controls (93% ± 6% vs 66% ± 19%; P < .05). Patients with NERD had a higher percentage of pure liquid reflux episodes (33% ± 15% vs 10% ± 2%; P < .05), whereas controls had a higher percentage of mixed reflux episodes (45% ± 16% vs 67% ± 17% in patients with NERD; P < .05). Patients with NERD also had a higher percentage of reflux (liquid and mixed) associated with common cavities (74% ± 18% vs 50% ± 20% in controls; P < .05). CONCLUSIONS In contrast to previous studies, we found that TLESRs are associated more often with reflux in patients with NERD than control subjects; this association increases when only liquid and mixed refluxes are considered. These findings indicate that factors involved in the occurrence of reflux in patients with NERD during TLESRs are different from those in healthy subjects.

Role of Mixed Reflux and Hypomotility with Delayed Reflux Clearance in Patients with Non-cardiac Chest Pain

Background/Aims Gastroesophageal reflux disease (GERD) is the most common cause of non-cardiac chest pain (NCCP). Currently available data reveal a weak relationship between NCCP and dysmotility. Moreover, it is unclear why some refluxes are perceived as heartburn and others as NCCP. We aimed to evaluate the role of the reflux pattern and the esophageal motility in patients with NCCP. Methods Forty-eight patients with NCCP (Group 1) and 50 only typical GERD symptoms (Group 2) were included and underwent high-resolution manometry (HRM) and multichannel intraluminal impedance-pH monitoring. Results Impaired peristalsis was found in 60% of patients with NCCP and in 24% of patients with typical symptoms (P < 0.05). In patients belonging to Group 1, the majority of reflux episodes associated with chest pain were acid and mixed. The proportion of mixed refluxes was higher than that in Group 2. In Group 1, the reflux clearing time at 5, 9, and 15 cm, measured in reflux episodes associated to NCCP was longer than in reflux episodes associated to typical symptoms (mean ± 95% CI: 27.2 ± 5.6, 23.3 ± 4.4, and 14.6 ± 2.3 seconds vs 18.3 ± 3.5, 13.3 ± 2.2, and 11.1 ± 1.8 seconds; P < 0.01). Conclusions The presence of gas in the refluxate seems to be associated with NCCP. The impaired motility observed in NCCP patients may play a relevant role in delaying reflux clearing, hence increasing the time of contact between refluxate and esophageal mucosa.

Nutritional status and bioelectrical phase angle assessment in adult Crohn disease patients receiving anti-TNFα therapy

BACKGROUND Altered body composition is frequently observed in Crohns disease (CD) patients. AIMS To investigate the nutritional status, and the effect of different therapeutic regimes in adult CD patients. METHODS Fat free mass (FFM) and BIA-derived phase angle (PhA) were assessed in 45 CD patients, 22 on conventional therapy (CT) and 23 on maintenance therapy with infliximab (MT). Nutritional status was also assessed in 12 CD patients before and following the induction protocol with infliximab. BIA data of CD patients were compared with those of 20 healthy asymptomatic volunteers. In CD patients C Reactive Protein (CRP) and albuminaemia dosage were obtained. RESULTS The mean values of PhA and of FFM were significantly lower in CT patients when compared with control group and MT patients. Following infliximab treatment FFM increased, although not significantly, while mean phase angle value significantly increased from 4.6±0.3 to 6.2±0.4 (p<0.05). CRP was significantly lower in MT patients compared to that in CT patients. CONCLUSION CD patients on conventional therapy showed a lower FFM and a lower mean phase angle score compared to those on infliximab therapy. Following infliximab treatment the mean phase angle score normalized. PhA is a reliable nutritional indicator in IBD patients and could be considered as an additional tool for assessing response to treatment.

Therapeutic Drug Monitoring is More Cost-Effective than a Clinically Based Approach in the Management of Loss of Response to Infliximab in Inflammatory Bowel Disease: An Observational Multicentre Study

Background Empirical dose intensification and therapeutic drug monitoring (TDM) of infliximab (IFX) trough levels (ITL) and antibody (ATI) assays are recognised approaches for managing the loss of response (LoR) in inflammatory bowel disease (IBD) patients. Aim To compare these two interventions in a clinical setting, in terms of effectiveness and cost savings. Methods Consecutive IBD patients, experiencing LoR, were clinically managed according to a TDM algorithm. A historical group of empirically treated patients, for whom sera for ITL and ATI assays were collected, served as the control group. Clinical outcomes 12 weeks after the therapeutic interventions were compared between the two groups. A cost-minimization analysis was performed to compare the economic impact of these two approaches. Results Ninety-six patients were enrolled prospectively and compared with 52 controls. The two cohorts were similar in characteristics and the distribution of TDM results. In the prospective cohort, however, we observed less IFX dose escalations compared with controls (45% versus 71%, p=0.003). Also, more patients were switched to a different anti-TNF in the prospective cohort than in the control one (25% versus 4%, p=0.001). The percentages of patients achieving a clinical response at 12 weeks were 52% and 54% for the prospective and control groups, respectively. By cost analysis, we estimated a savings of 15% if the TDM algorithm was applied. Conclusions In our population, applying a TDM algorithm for LoR to IFX resulted in less dose escalations, without loss of efficacy, compared with empirical adjustment. In addition, the TDM approach was cost-effective.

Tu1134 Layered Pattern of Enhancement and Retrodilation At Magnetic Resonance Enterography Predict the Outcome of Anti-TNF Alpha Therapy in Patients With Moderate-to-Severe Ileal Crohn's Disease

of 1-31. New/worse inflammation was found in 43.8% of CTs while any new/worse finding was found in 57.4%. PA+ occurred in 16.8% of CTs. Univariate analysis shows that younger and female patients were less likely to have I but not PA+. Steroid use did predict a higher probability of PA+ (OR 1.58, 95%CI 1.01-2.47) but not I (OR 1.01, 95%CI 0.70-1.44). Biologic agents and other immunosuppression did not predict either outcome. Among the labs, CRP was a good predictor of I and PA+ while ESR only predicted PA+. Higher absolute neutrophil count and lymphocyte count predicted both outcomes. The multivariable model for I had a c statistic of 0.68; a cutoff of 16% has a sensitivity of 99.6% and negative predictive value of 92.3%. The model for PA+ had better performance characteristics with a c statistic of 0.80; a cutoff of 5% has a sensitivity of 94.9% and a negative predictive value of 97.7%. Conclusions: Patients with CD are exposed to radiation frequently but have significant new/worse findings less than 60% of the time. Models with good negative predictive values predicting I and PA+ were identified. Automated use of these models could aid ER physicians in the decision to avoid CT scans in patients with low likelihood of a positive scan. Prospective studies are needed to validate these models and their utility in clinical practice.

Tu1782 Weak Peristalsis With Large Breaks Is Associated With Higher Acid Exposure and Delayed Reflux Clearance in the Supine Position in GERD Patients

INTRODUCTION It has been demonstrated that among esophageal motor abnormalities, impaired peristalsis of the esophageal body may account for delayed bolus transit and impaired esophageal refl ux clearance in patients with complicated gastroesophageal refl ux disease (GERD) ( 1,2 ). In particular, several studies have shown that ineffective esophageal motility (IEM), defi ned as the presence of peristaltic waves at the distal esophagus with amplitude < 30 mm Hg and / or nontransmitted proximal contractions, is frequently observed in GERD patients; however, the functional relevance remains controversial ( 3 ). In GERD patients, increasing degrees of esophageal mucosal damage have been reported either to cause, or be the result of, severe worsening of esophageal function ( 4,5 ). Nevertheless, even if IEM has been associated with prolonged acid exposure time (AET) ( 6 ), it has been demonstrated that in GERD patients, only severe, but not mild IEM, is associated with prolonged clearance and AET, particularly when in the supine position ( 7 ). Th e recent development of high-resolution manometry (HRM) has led to an improvement of our knowledge regarding esophageal motility and is considered the gold standard in the study of esophageal motor disorders ( 8 ). Indeed, HRM combined with multichannel impedance (HRM-MI) monitoring allows simultaneous recording and analysis of the esophageal motility and of the bolus transit. Fox et al. ( 9 )demonstrated, using HRM coupled with videofl uoroscopy, that HRM pressure topography plots predict bolus transit more accurately than conventional manometry. Moreover, these authors reported that, as a consequence of the increased spatial resolution, HRM is also able to detect segmental breaks of the esophageal peristalsis that would otherwise have been missed with conventional manometry. More recently, Bulsiewicz et al. ( 10 ) showed in healthy subjects and in patients with nonobstructive dysphagia that peristaltic breaks of < 2 cm in the 20 mm Hg or < 3 cm in the 30 mm Hg isobaric contour are associated with complete bolus clearance, whereas larger breaks predict delayed bolus clearance. Moreover, it has been proposed that weak peristalsis could be defi ned Weak Peristalsis With Large Breaks Is Associated With Higher Acid Exposure and Delayed Refl ux Clearance in the Supine Position in GERD Patients