Anatomy and mechanical properties of the anal sphincter muscles in healthy senior volunteers.

BACKGROUND: A large proportion of age-related fecal incontinence is attributed to weakness or degeneration of the muscles composing the anal continence organ. However, the individual role of these muscles and their functional interplay remain poorly understood. METHODS: This study employs a novel technique based on the combination of MR imaging and FLIP measurements (MR-FLIP) to obtain anatomical and mechanical information simultaneously. Unlike previous methods used to assess the mechanics of the continence organ, MR-FLIP allows inter-individual comparisons and statistical analysis of the sphincter morpho-mechanical parameters. The anatomy as well as voluntary and involuntary mechanical properties of the anal continence organ were characterized in 20 healthy senior volunteers. RESULTS: Results showed that the external anal sphincter (EAS) forms a funnel-like shape with wall thickness increasing by a factor of 2.5 from distal (6 ± 0 mm) to proximal (15 ± 3 mm). Both voluntary and involuntary mechanical properties in this region correlate strongly with the thickness of the muscle. The positions of least compliance and maximal orifice closing were both located toward the proximal EAS end. In addition, maximal contraction during squeeze maneuvers was reached after 2 s, but high muscle fatigue was measured during a 7 s holding phase, corresponding to about 60% loss of the energy produced by the muscles during the contraction phase. CONCLUSIONS: This work reports baseline parameters describing the morpho-mechanical condition of the sphincter muscle of healthy elderly volunteers. New parameters were also proposed to quantify the active properties of the muscles based on the mechanical energy associated with muscle contraction and fatigue. This information could be used to assess patients suffering from AI or for the design of novel implants.

Ambulatory reflux monitoring for diagnosis of gastro-esophageal reflux disease: Update of the Porto consensus and recommendations from an international consensus group.

BACKGROUND: An international group of experts evaluated and revised recommendations for ambulatory reflux monitoring for the diagnosis of gastro-esophageal reflux disease (GERD). METHODS: Literature search was focused on indications and technical recommendations for GERD testing and phenotypes definitions. Statements were proposed and discussed during several structured meetings. KEY RESULTS: Reflux testing should be performed after cessation of acid suppressive medication in patients with a low likelihood of GERD. In this setting, testing can be either catheter-based or wireless pH-monitoring or pH-impedance monitoring. In patients with a high probability of GERD (esophagitis grade C and D, histology proven Barrett's mucosa >1 cm, peptic stricture, previous positive pH monitoring) and persistent symptoms, pH-impedance monitoring should be performed on treatment. Recommendations are provided for data acquisition and analysis. Esophageal acid exposure is considered as pathological if acid exposure time (AET) is greater than 6% on pH testing. Number of reflux episodes and baseline impedance are exploratory metrics that may complement AET. Positive symptom reflux association is defined as symptom index (SI) >50% or symptom association probability (SAP) >95%. A positive symptom-reflux association in the absence of pathological AET defines hypersensitivity to reflux. CONCLUSIONS AND INFERENCES: The consensus group determined that grade C or D esophagitis, peptic stricture, histology proven Barrett's mucosa >1 cm, and esophageal acid exposure greater >6% are sufficient to define pathological GERD. Further testing should be considered when none of these criteria are fulfilled.

The selective metabotropic glutamate receptor 5 antagonist mavoglurant (AFQ056) reduces the incidence of reflux episodes in dogs and patients with moderate to severe gastroesophageal reflux disease.

BACKGROUND: Transient lower esophageal sphincter relaxations (TLESRs) induced by gastric distension are modulated by the metabotropic glutamate receptor 5 (mGluR5) that influences the vagal reflex loop. We therefore aimed to examine the effects of the selective mGluR5 antagonist mavoglurant (AFQ056) on the number of TLESRs in dogs and reflux episodes in patients with gastroesophageal reflux disease (GERD). METHODS: In a dog model, the number of meal-induced TLESRs was determined after intravenous (0.03, 0.1, 0.3, and 1 mg kg-1 ) and oral (1, 3, and 10 mg kg-1 ) doses of mavoglurant with reference to vehicle. In a multicenter, randomized, double-blind, placebo-controlled, three-period crossover study, the incidence of meal-induced reflux episodes was assessed by esophageal impedance monitoring after single, oral doses of mavoglurant (50 and 400 mg) or baclofen (40 mg) in 30 patients with moderate to severe GERD. KEY RESULTS: In dogs, mavoglurant reduced the number of TLESRs after intravenous and oral administration. In patients with GERD, the incidence of postprandial reflux episodes was significantly lower at a dose of 400 mg mavoglurant (-37.5% ; 90% confidence interval [CI]: -57.8, -17.2), whereas there was no significant difference at 50 mg of mavoglurant compared to placebo. A significantly lower incidence of reflux episodes was also noted with the active comparator baclofen (-50.3%; 90% CI: -66.2, -34.3), thereby validating this study. CONCLUSIONS AND INFERENCES: These data suggest a potential clinical benefit of mGluR5 antagonists such as mavoglurant in patients with GERD, particularly in those with persisting symptoms despite treatment with proton pump inhibitors.

MR-FLIP: a new method that combines a functional lumen imaging probe with anatomical information for spatial compliance assessment of the anal sphincter muscles.

AIM: Continence results from a complex interplay between anal canal (AC) muscles and sensorimotor feedback mechanisms. The passive ability of the AC to withstand opening pressure - its compliance - has recently been shown to correlate with continence. A functional lumen imaging probe (FLIP) is used to assess AC compliance, although it provides no anatomical information. Therefore, assessment of the compliance specific anatomical structures has not been possible, and the anatomical position of critical functional zones remains unknown. In addition, the FLIP technique assumes a circular orifice cross-section, which has not been shown for the AC. To address these shortcomings, a technique combining FLIP with a medical imaging modality is needed. METHOD: We implemented a new research method (MR-FLIP) that combines FLIP with MR imaging. Twenty healthy volunteers underwent MR-FLIP and conventional FLIP assessment. MR-FLIP was validated by comparison with FLIP results. Anatomical markers were identified, and the cross-sectional shape of the orifice was investigated. RESULTS: MR-FLIP provides compliance measurements identical to those obtained by conventional FLIP. Anatomical analysis revealed that the least compliant AC zone was located at the proximal end of the external anal sphincter (EAS). The cross-sectional shape of the AC was found to deviate only slightly from circularity in healthy volunteers. CONCLUSION: The proposed method is equivalent to classical FLIP. It establishes for the first time direct mapping between local tissue compliance and anatomical structure, which is key to gaining novel insights into (in)continence. In addition, MR-FLIP provides a tool for better understanding conventional FLIP measurements in the AC by quantifying its limitations and assumptions.

Vigor of peristalsis during multiple rapid swallows is inversely correlated with acid exposure time in patients with NERD.

BACKGROUND: Multiple rapid swallowing (MRS) during high-resolution manometry (HRM) is increasingly utilized as provocative test to assess esophageal peristaltic reserve. The aim of this study was to evaluate the correlation between MRS response and impedance and pH (MII-pH) parameters in endoscopy negative heartburn (ENH) patients. METHODS: We enrolled consecutive ENH patients, who underwent HRM and MII-pH study, with a selected MII-pH profile: abnormal MII-pH (pH+/MII+); normal MII-pH (pH-/MII-). HRM was performed with 10 wet swallows (WS) and one MRS. Mean distal contractile integral (DCI) during WS and MRS were calculated. MII-pH parameters including acid exposure time (AET), reflux events, baseline impedance levels (BI) and the efficacy of chemical clearance evaluated with the postreflux swallow-induced peristaltic wave (PSPW) index were measured. KEY RESULTS: We analyzed 103 patients: 49 MII+/pH+ (27 male), and 54 MII-/pH- (19 male). Mean age was similar between the two groups. As expected, mean AET and number of refluxes were higher in pH+/MII+ (p < 0.05). HRM was normal in all selected patients. Mean DCI-WS was similar between two groups (p = n.s.). Mean DCI-MRS- was higher in MII-/pH- vs MII+/pH+ (p < 0.05). The increase in DCI-MRS was inversely correlated with AET (-0.699; p < 0.001) and directly correlated with BI values (0.631; p < 0.001) and PSPW index (0.626; p < 0.001). CONCLUSIONS & INFERENCES: Following MRS, patients with abnormal impedance-pH test showed suboptimal contraction response as compared with those with normal impedance-pH test. Moreover, MRS response was inversely correlated with AET and directly correlated with BI values and PSPW index.

Inter-observer agreement for diagnostic classification of esophageal motility disorders defined in high-resolution manometry.

High-resolution esophageal manometry (HRM) is a recent development used in the evaluation of esophageal function. Our aim was to assess the inter-observer agreement for diagnosis of esophageal motility disorders using this technology. Practitioners registered on the HRM Working Group website were invited to review and classify (i) 147 individual water swallows and (ii) 40 diagnostic studies comprising 10 swallows using a drop-down menu that followed the Chicago Classification system. Data were presented using a standardized format with pressure contours without a summary of HRM metrics. The sequence of swallows was fixed for each user but randomized between users to avoid sequence bias. Participants were blinded to other entries. (i) Individual swallows were assessed by 18 practitioners (13 institutions). Consensus agreement (≤ 2/18 dissenters) was present for most cases of normal peristalsis and achalasia but not for cases of peristaltic dysmotility. (ii) Diagnostic studies were assessed by 36 practitioners (28 institutions). Overall inter-observer agreement was 'moderate' (kappa 0.51) being 'substantial' (kappa > 0.7) for achalasia type I/II and no lower than 'fair-moderate' (kappa >0.34) for any diagnosis. Overall agreement was somewhat higher among those that had performed >400 studies (n = 9; kappa 0.55) and 'substantial' among experts involved in development of the Chicago Classification system (n = 4; kappa 0.66). This prospective, randomized, and blinded study reports an acceptable level of inter-observer agreement for HRM diagnoses across the full spectrum of esophageal motility disorders for a large group of clinicians working in a range of medical institutions. Suboptimal agreement for diagnosis of peristaltic motility disorders highlights contribution of objective HRM metrics.

Differentiation between active and chronic Crohn's disease using MRI small-bowel motility examinations - initial experience.

AIM: To evaluate the influence of locally active Crohn's disease on systemic small-bowel motility in patients with chronic Crohn's disease compared to healthy individuals. MATERIAL AND METHODS: Fifteen healthy individuals (11 men, four women; mean age 37 years) and 20 patients with histopathologically proven active (n = 15; 10 women, 5 men; mean age 45 years) or chronic (n = 5; four women, one man; mean age 48 years) Crohn's disease were included in this institutional review board-approved, retrospective study. Magnetic resonance imaging (MRI; 1.5 T) was performed after standardized preparation. Two-dimensional (2D) cine sequences for motility acquisition were performed in apnoea (27 s). Motility assessment was performed using dedicated software in three randomly chosen areas of the small-bowel outside known Crohn's disease-affected hotspots. The main quantitative characteristics (frequency, amplitude, occlusion rate) were compared using Student's t-test and one-way analysis of variance (ANOVA). RESULTS: Three randomly chosen segments were analysed in each participant. Patients with active Crohn's disease had significantly (p < 0.05) reduced contraction frequencies (active Crohn's disease: 2.86/min; chronic: 4.14/min; healthy: 4.53/min) and luminal occlusion rates (active: 0.43; chronic: 0.70; healthy: 0.73) compared to healthy individuals and patients with chronic Crohn's disease. Contraction amplitudes were significantly reduced during active Crohn's disease (6.71 mm) compared to healthy participants (10.14 mm), but this only reached borderline significance in comparison to chronic Crohn's disease (8.87 mm). Mean bowel lumen diameter was significantly (p = 0.04) higher in patients with active Crohn's disease (16.91 mm) compared to healthy participants (14.79 mm) but not in comparison to patients with chronic Crohn's disease (13.68). CONCLUSION: The findings of the present study suggest that local inflammatory activity of small-bowel segments in patients with active Crohn's disease alters small-bowel motility in distant, non-affected segments. The motility patterns revealed reduced contraction-wave frequencies, amplitudes, and decreased luminal occlusion rates. Thus evaluation of these characteristics potentially helps to differentiate between chronic and active Crohn's disease.

MR imaging in Crohn's disease: correlation of MR motility measurement with histopathology in the terminal ileum.

BACKGROUND: The objective of the study was to correlate MR-detectable motility alterations of the terminal ileum with biopsy-documented active and chronic changes in Crohn's disease. METHODS: This IRB approved retrospective analysis of 43 patients included magnetic resonance enterography (MRE) and terminal ileum biopsies (<2 weeks apart). Motility was measured at the terminal ileum using coronal 2D trueFISP pulse sequences (1.5T MRI,TR 83.8,TE1.89) and dedicated motility assessment software. Motility grading (hypermotility, normal, hypomotility, complete arrest) was agreed by two experienced readers. Motility was compared and correlated with histopathology using two-tailed Kruskal-Wallis test and paired Spearman Rank-Order Correlation tests. KEY RESULTS: Motility abnormalities were present in 27/43 patients: nine hypomotility and 18 complete arrest. Active disease was diagnosed on 15 biopsies: eight moderate and seven severe inflammatory activity. Chronic changes were diagnosed on 17 biopsies: 13 moderate and four severe cases. In four patients with normal motility alterations on histopathology were diagnosed. Histopathology correlated with presence (P = 0.0056 for hypomotility and P = 0.0119 for complete arrest) and grade (P < 0.0001; P = 0.0004) of motility alterations. A significant difference in the motility was observed in patients with active or chronic CD compared with patients without disease (P < 0.001; P = 0.0024). CONCLUSIONS & INFERENCES: MR-detectable motility changes of the terminal ileum correlate with histopathological findings both in active and chronic CD. Motility changes may indicate the presence pathology, but do not allow differentiation of active and chronic disease.

Swallowing activity assessed by ambulatory impedance-pH monitoring predicts awake and asleep periods at night.

INTRODUCTION: Voluntary muscle activity, including swallowing, decreases during the night. The association between nocturnal awakenings and swallowing activity is under-researched with limited information on the frequency of swallows during awake and asleep periods. AIM: The aim of this study was to assess nocturnal swallowing activity and identify a cut-off predicting awake and asleep periods. METHODS: Patients undergoing impedance-pH monitoring as part of GERD work-up were asked to wear a wrist activity detecting device (Actigraph(®)) at night. Swallowing activity was quantified by analysing impedance changes in the proximal esophagus. Awake and asleep periods were determined using a validated scoring system (Sadeh algorithm). Receiver operating characteristics (ROC) analyses were performed to determine sensitivity, specificity and accuracy of swallowing frequency to identify awake and asleep periods. RESULTS: Data from 76 patients (28 male, 48 female; mean age 56 ± 15 years) were included in the analysis. The ROC analysis found that 0.33 sw/min (i.e. one swallow every 3 min) had the optimal sensitivity (78 %) and specificity (76 %) to differentiate awake from asleep periods. A swallowing frequency of 0.25 sw/min (i.e. one swallow every 4 min) was 93 % sensitive and 57 % specific to identify awake periods. A swallowing frequency of 1 sw/min was 20 % sensitive but 96 % specific in identifying awake periods. Impedance-pH monitoring detects differences in swallowing activity during awake and asleep periods. Swallowing frequency noticed during ambulatory impedance-pH monitoring can predict the state of consciousness during nocturnal periods.

Esophageal hypertensive peristaltic disorders.

BACKGROUND: Esophageal motility abnormalities include a series of manometric findings that differ to a significant degree from findings in normal, asymptomatic volunteers. METHODS: Current review summarizes conventional and high-resolution esophageal manometry criteria used to define and characterize esophageal hypertensive motility abnormalities. KEY RESULTS: In the conventional esophageal manometry classification scheme hypertensive esophageal motility abnormalities include nutcracker esophagus (average distal contraction amplitude >180 mmHg), hypertensive lower esophageal sphincter (average resting LES pressure >45 mmHg) and poorly relaxing lower esophageal sphincter (average LES residual pressure >8 mmHg). The new, high resolution esophageal manometry scheme includes in the group of hypertensive peristaltic disorders hypertensive peristalsis ("nutcracker esophagus": mean DCI >5000 mmHg*sec*cm) and hypercontractile esophagus ("jackhammer esophagus": at least one contraction with DCI > 8,000 mmHg*sec*cm) and defines a separate group for disorders with impaired esophageal-gastric junction relaxation (mean integrated residual (LES) pressure >15 mmHg). CONCLUSIONS & INFERENCES: Hypertensive motility disorders represent a heterogeneous condition subdivided into hypercontractile esophagus and hypertensive peristalsis. Further studies are required to determine the clinical relevance of this new classification.

Oesophageal motility and bolus transit abnormalities increase in parallel with the severity of gastro-oesophageal reflux disease.

BACKGROUND: Limited data are available regarding the frequency of oesophageal motility and bolus transit abnormalities in subgroups of patients with gastro-oesophageal reflux disease (GERD). AIM: To assess oesophageal motility and bolus transit in endoscopically defined GERD subgroups. METHODS: Patients (N=755) with typical reflux symptoms underwent upper endoscopy, conventional or impedance oesophageal manometry and/or impedance-pH testing. They were divided into: erosive oesophagitis (EO; N=340), Barrett Oesophagus (BO; N=106), non-erosive reflux disease (NERD; endoscopy-, abnormal pH and/or SAP/SI+; N=239) and functional heartburn (FH; endoscopy-, normal pH and SAP/SI-; N=70). Manometric patterns and bolus transit were defined according to previously published criteria. RESULTS: Increasing GERD severity was associated with decreased lower oesophageal sphincter resting pressure (P< 0.05) and distal oesophageal amplitude (P<0.01), higher prevalence of hiatal hernia (P<0.01) and increased prevalence of ineffective oesophageal motility (P<0.01). Patients with EO and BO had a significantly lower percentage of complete bolus transit compared with NERD and FH (P<0.01). Overall, abnormal bolus transit (ABT) for liquid swallows was found in 12% of FH, 20% of NERD, 54% of EO and 56% of BO (P<0.01). Combined impedance-manometry showed abnormal oesophageal function in 4% of FH, 4% of NERD, 22% of EO and 21% of BO patients with normal oesophageal manometry. CONCLUSIONS: Oesophageal motility abnormalities increase in parallel with the severity of GERD from NERD to EO and BO. Bolus transit abnormalities in severe reflux disease underscore the importance of impaired oesophageal function in the development of mucosal injury.

Randomised clinical trial: effects of monotherapy with ADX10059, a mGluR5 inhibitor, on symptoms and reflux events in patients with gastro-oesophageal reflux disease.

BACKGROUND: ADX10059, a metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulator, has been shown to reduce gastro-oesophageal reflux events and oesophageal acid exposure in patients with gastro-oesophageal reflux disease (GERD) and healthy subjects. AIM: To evaluate the effects of ADX10059 monotherapy for 2 weeks on symptom control in patients with GERD. METHODS: This was a double-blind, placebo-controlled, multi-centre trial in GERD patients who were responders to proton pump inhibitors (PPIs). Following PPIs withdrawal, a 2-week baseline washout period was followed by 2-week treatment with either ADX10059 120 mg or placebo b.d. The primary clinical efficacy endpoint was the number of GERD symptom-free days in treatment week 2 compared with the last 7 days of baseline. The effect on reflux events using 24-h impedance-pH monitoring was also determined in a subset of 24 patients. RESULTS: The full analysis set comprised 103 patients ADX10059 (N= 50), Placebo (N=53). In treatment week 2, ADX10059 significantly increased GERD symptom-free days (P=0.045) and heartburn-free days (P=0.037), reduced antacid use (P=0.017), improved total symptom score (P=0.048) including subscale heartburn/regurgitation (P=0.007) and sleep disturbance because of GERD (P= 0.022). ADX10059 significantly reduced total (P=0.034) and acidic reflux events (P=0.003). ADX10059 was well tolerated. Most common adverse events for ADX10059 were mild to moderate dizziness 16% and vertigo 12% (placebo 4% and 2%). CONCLUSIONS: Inhibition of mGluR5 with ADX10059 monotherapy reduces reflux events and improves symptoms in GERD patients. This mechanism has promise for the management of GERD.

Diagnosing lactase deficiency in three breaths.

BACKGROUND: Lactose hydrogen breath tests (H(2)-BTs) are widely used to diagnose lactase deficiency, the most common cause of lactose intolerance. The main time-consuming part of the test relates to the sampling frequency and number of breath samples. AIM: Evaluate sensitivities and specificities of two- and three-sample breath tests compared with standard breath sampling every 15 min. METHODS: Lactose H(2)-BT with probes samples every 15 min served as gold standard. Sensitivity, specificity, positive and negative predictive value of two-sample tests (0-60 min, 0-90 min or 0-120 min) and three-sample tests (0-60-90 min, 0-60-120 min or 0-90-120 min) were calculated. RESULTS: Among 1049 lactose H(2)-BT performed between July 1999 and December 2005, 337 (32%) had a positive result. Two-sample tests had sensitivity and specificity of 52.5 and 100.0% (0-60 min), 81.9 and 99.7% (0-90 min), and 92.6 and 99.2% (0-120 min), respectively. Three-sample tests had sensitivity and specificity of 83.4 and 99.7% (0-60-90 min), 95.0 and 99.2% (0-60-120 min), and 95.0 and 98.9% (0-90-120 min), respectively. CONCLUSION: A three-sample breath test (baseline, 60/90 min and 120 min) has excellent sensitivity and specificity for lactase deficiency. Lactose H(2)-BT can be simplified but not shortened to <2 h.

MR defecography in patients with dyssynergic defecation: spectrum of imaging findings and diagnostic value.

OBJECTIVES: We describe the spectrum of findings and the diagnostic value of MR defecography in patients referred with suspicion of dyssynergic defecation. METHODS: 48 patients (34 females, 14 males; mean age 48 years) with constipation and clinically suspected dyssynergic defecation underwent MR defecography. Patients were divided into patients with dyssynergic defecation (n = 18) and constipated patients without dyssynergic defecation (control group, n = 30). MRIs were analysed for evacuation ability, time to initiate evacuation, time of evacuation, changes in the anorectal angle (ARA-change), presence of paradoxical sphincter contraction and presence of additional pelvic floor abnormalities. Sensitivity, specificity, positive and negative predictive values and accuracy for the diagnosis of dyssynergic defecation were calculated. RESULTS: The most frequent finding was impaired evacuation, which was seen in 100% of patients with dyssynergic defecation and in 83% of the control group, yielding a sensitivity for MR defecography for the diagnosis of dyssynergic defecation of 100% (95% confidence interval (CI) 97-100%), but a specificity of only 23% (95% CI 7-40%). A lower sensitivity (50%; 95% CI 24-76%) and a high specificity (97%; 95% CI 89-100%) were seen with abnormal ARA-change. The sensitivity of paradoxical sphincter contraction was relatively high (83%; 95% CI 63-100%). A combined analysis of abnormal ARA-change and paradoxical sphincter contraction allowed for the detection of 94% (95% CI 81-100%) of the patients with dyssynergic defecation. CONCLUSION: MR defecography detects functional and structural abnormal findings in patients with clinically suspected dyssynergic defecation. Impaired evacuation is seen in patients with functional constipation owing to other pelvic floor abnormalities than dyssynergic defecation.

Air suctioning during colon biopsy forceps removal reduces bacterial air contamination in the endoscopy suite.

BACKGROUND AND STUDY AIMS: Bacterial contamination of endoscopy suites is of concern; however studies evaluating bacterial aerosols are lacking. We aimed to determine the effectiveness of air suctioning during removal of biopsy forceps in reducing bacterial air contamination. PATIENTS AND METHODS: This was a prospective single-blinded trial involving 50 patients who were undergoing elective nontherapeutic colonoscopy. During colonoscopy, endoscopists removed the biopsy forceps first without and then with suctioning following contact with the sigmoid mucosa. A total of 50 L of air was collected continuously for 30 seconds at 30-cm distance from the biopsy channel valve of the colonoscope, with time starting at forceps removal. Airborne bacteria were collected by an impactor air sampler (MAS-100). Standard Petri dishes with CNA blood agar were used to culture Gram-positive bacteria. Main outcome measure was the bacterial load in endoscopy room air. RESULTS: At the beginning and end of the daily colonoscopy program, the median (and interquartile [IQR] range) bioaerosol burden was 4 colony forming units (CFU)/m (3) (IQR 3 - 6) and 16 CFU/m (3) (IQR 13 - 18), respectively. Air suctioning during removal of the biopsy forceps reduced the bioaerosol burden from a median of 14 CFU/m (3) (IQR 11 - 29) to a median of 7 CFU/m (3) (IQR 4 - 16) ( P = 0.0001). Predominantly enterococci were identified on the agar plates. CONCLUSION: The bacterial aerosol burden during handling of biopsy forceps can be reduced by applying air suction while removing the forceps. This simple method may reduce transmission of infectious agents during gastrointestinal endoscopies.

Characteristics of gastro-esophageal reflux episodes in Barrett's esophagus, erosive esophagitis and healthy volunteers.

BACKGROUND: Gastro-esophageal reflux is considered a major culprit in the pathogenesis of Barrett's esophagus (BE). Still, there is controversy on the role of weakly acidic and weakly alkaline reflux in BE. To compare characteristics of reflux episodes patients with BE, erosive esophagitis (EE), and healthy volunteers (HV). METHODS: One hundred consecutive patients with BE (75 short-segment BE, 25 long-segment BE), 50 with EE and 48 HV underwent multichannel intraluminal impedance-pH off-therapy. We quantified esophageal acid exposure, characteristics, and proximal extension of reflux episodes. KEY RESULTS: Total and acid reflux episodes gradually increased from HV [28 (17.5-43) and 18 (8-31)] to EE [73.5 (54-96) and 52 (39-68)], short-segment BE (SSBE) [83 (73.2-131) and 65 (43.3-95)] and long-segment BE (LSBE) [105 (102-187) and 77 (75-107)]. Weakly acidic reflux episodes were significantly higher (P < 0.05) in LSBE [36 (27.5-50.5)] and SSBE [34 (18.5-41)] compared to EE [21.5 (15-37)] and HV [19 (14-25)]. No differences in terms of proportion of acid, weakly acidic and weakly alkaline reflux were found [HV (49%-49%-2%) vs EE (68%-32%-1%) vs SSBE (65%-34%-1%) vs LSBE (69%-30%-1%); P = ns]. In LSBE, a higher percentage of reflux episodes (P < 0.05) reached the proximal esophagus (59%) compared with SSBE (43%). CONCLUSIONS & INFERENCES: Barrett esophagus patients have more severe reflux as shown by the number of acid and weakly acidic reflux episodes, re-reflux episodes and proximal migration. Given that PPI change only the pH of the refluxate, the role of weakly acidic reflux in Barrett's patients on acid suppressive therapy warrants further investigation.

Excellent agreement between genetic and hydrogen breath tests for lactase deficiency and the role of extended symptom assessment.

Clinical manifestations of lactase (LCT) deficiency include intestinal and extra-intestinal symptoms. Lactose hydrogen breath test (H2-BT) is considered the gold standard to evaluate LCT deficiency (LD). Recently, the single-nucleotide polymorphism C/T(-13910) has been associated with LD. The objectives of the present study were to evaluate the agreement between genetic testing of LCT C/T(-13910) and lactose H2-BT, and the diagnostic value of extended symptom assessment. Of the 201 patients included in the study, 194 (139 females; mean age 38, range 17-79 years, and 55 males, mean age 38, range 18-68 years) patients with clinical suspicion of LD underwent a 3-4 h H2-BT and genetic testing for LCT C/T(-13910). Patients rated five intestinal and four extra-intestinal symptoms during the H2-BT and then at home for the following 48 h. Declaring H2-BT as the gold standard, the CC(-13910) genotype had a sensitivity of 97% and a specificity of 95% with a κ of 0.9 in diagnosing LCT deficiency. Patients with LD had more intense intestinal symptoms 4 h following the lactose challenge included in the H2-BT. We found no difference in the intensity of extra-intestinal symptoms between patients with and without LD. Symptom assessment yielded differences for intestinal symptoms abdominal pain, bloating, borborygmi and diarrhoea between 120 min and 4 h after oral lactose challenge. Extra-intestinal symptoms (dizziness, headache and myalgia) and extension of symptom assessment up to 48 h did not consistently show different results. In conclusion, genetic testing has an excellent agreement with the standard lactose H2-BT, and it may replace breath testing for the diagnosis of LD. Extended symptom scores and assessment of extra-intestinal symptoms have limited diagnostic value in the evaluation of LD.

Functional heartburn has more in common with functional dyspepsia than with non-erosive reflux disease.

INTRODUCTION: Functional dyspepsia and non-erosive reflux disease (NERD) are prevalent gastrointestinal conditions with accumulating evidence regarding an overlap between the two. Still, patients with NERD represent a very heterogeneous group and limited data on dyspeptic symptoms in various subgroups of NERD are available. AIM: To evaluate the prevalence of dyspeptic symptoms in patients with NERD subclassified by using 24 h impedance-pH monitoring (MII-pH). METHODS: Patients with typical reflux symptoms and normal endoscopy underwent impedance-pH monitoring off proton pump inhibitor treatment. Oesophageal acid exposure time (AET), type of acid and non-acid reflux episodes, and symptom association probability (SAP) were calculated. A validated dyspepsia questionnaire was used to quantify dyspeptic symptoms prior to reflux monitoring. RESULTS: Of 200 patients with NERD (105 female; median age, 48 years), 81 (41%) had an abnormal oesophageal AET (NERD pH-POS), 65 (32%) had normal oesophageal AET and positive SAP for acid and/or non-acid reflux (hypersensitive oesophagus), and 54 (27%) had normal oesophageal AET and negative SAP (functional heartburn). Patients with functional heartburn had more frequent (p<0.01) postprandial fullness, bloating, early satiety and nausea compared to patients with NERD pH-POS and hypersensitive oesophagus. CONCLUSION: The increased prevalence of dyspeptic symptoms in patients with functional heartburn reinforces the concept that functional gastrointestinal disorders extend beyond the boundaries suggested by the anatomical location of symptoms. This should be regarded as a further argument to test patients with symptoms of gastro-oesophageal reflux disease in order to separate patients with functional heartburn from patients with NERD in whom symptoms are associated with gastro-oesophageal reflux.

Symptoms with acid and nonacid reflux may be produced by different mechanisms.

Twenty-four-hour multichannel intraluminal impedance and pH (MII-pH) esophageal monitoring detects both acid and nonacid gastroesophageal reflux episodes. The MII-pH catheter contains six impedance segments placed 3, 5, 7, 9, 15, and 17 cm above the lower esophageal sphincter (LES). A pH electrode at 5 cm above the LES identifies the type of reflux, i.e. acid or nonacid. Patients with acid and nonacid reflux exhibit typical and atypical symptoms often within 5 min following a reflux episode. The aim of this study is to compare the timing of symptoms after reflux episodes in patients with acid and nonacid reflux. Methods include a review of 70 MII-pH tracings (42 females, mean age 40, range 18-85 years) either on (50 points) or off (20 points) acid suppression therapy. Typical (heartburn, regurgitation) and atypical (cough) symptoms with acid or nonacid reflux episodes detected by impedance were analyzed. Symptoms were considered positive with acid reflux if there was a pH drop to <4, plus an MII detected a reflux episode and with nonacid reflux if pH remained >4 and MII detected a reflux episode. The timing of the symptom after each reflux episode was recorded. Symptom perception occurred significantly sooner after acid versus nonacid reflux (P < 0.05). Acid reflux episodes are more likely to be perceived in the first 2 min following the reflux episode. Patients with acid reflux are likely to perceive symptoms earlier, and symptoms with acid and nonacid reflux may be produced by different mechanisms.

Combined multichannel intraluminal impedance and manometry testing.

Oesophageal manometry has been considered the "gold standard" test for the evaluation of oesophageal motility. Oesophageal manometry allows physicians to assess peristalsis by using informations about the shape, amplitude and duration of the oesophageal contraction, but it does not offer direct information about bolus transit through the oesophagus. Recent studies demonstrate that combined impedance-manometry provides important additional information about oesophageal motility as compared to conventional manometry such as: (1) monitoring of bolus transport patterns without the use of radiation, (2) calculation of bolus transit parameters, (3) evaluation of bolus clearance and (4) investigation of the relationships between bolus transit and LES relaxation. These changes could potentially improve diagnostic accuracy of oesophageal motility testing, advancing both clinical and basic research. This review focuses on current aspects of the novel technology of combined impedance-manometry for oesophageal motility testing.