Beer effects on postprandial digestive symptoms and gastroesophagic physiology.

BACKGROUND: Beer has been related to gastroesophageal reflux (GER) and dyspepsia, based on its alcohol and gas content. The aim of this study is to evaluate the association between moderate consumption of traditional and alcohol-free beer and upper digestive symptoms, gastric accommodation and GER. METHODS: Healthy adults without frequent gastrointestinal symptoms and GER disease were included. The intervention involved administration of traditional beer to 10 subjects (substudy 1) and alcohol-free beer to 20 (substudy 2); control intervention entailed administration of water. Study duration was 2 weeks (control/intervention). Postprandial gastric accommodation was assessed through the maximum tolerated volume during a nutrient drink test after the ingestion of water (day 1) and beer (day 8), in which symptoms of dyspepsia were evaluated every 5 minutes. An impedance-pH monitoring assessed 24 hours and post-NDT GER (days 1 and 8). Symptoms were evaluated daily during the study. The defined variables were compared between visits and weeks using a nonparametric test for paired data. KEY RESULTS: Dyspepsia symptoms showed a progressive increase during the NDT for both interventions in the 2 substudies, though no significant differences were detected in the MTV analysis. No differences were detected in the sum of weekly symptoms. The analysis of impedance-pH monitoring did not show any differences between intervention and control visits for both interventions. CONCLUSIONS AND INFERENCES: Moderate consumption of traditional and alcohol-free beer does not increase dyspeptic symptoms or GER in healthy subjects, whether in a controlled-intake or real-life situation. Neither gastric accommodation nor reflux episodes are modified in this context.

Anxiety can significantly explain bolus perception in the context of hypotensive esophageal motility: Results of a large multicenter study in asymptomatic individuals.

BACKGROUND: Previous studies have not been able to correlate manometry findings with bolus perception. The aim of this study was to evaluate correlation of different variables, including traditional manometric variables (at diagnostic and extreme thresholds), esophageal shortening, bolus transit, automated impedance manometry (AIM) metrics and mood with bolus passage perception in a large cohort of asymptomatic individuals. METHODS: High resolution manometry (HRM) was performed in healthy individuals from nine centers. Perception was evaluated using a 5-point Likert scale. Anxiety was evaluated using Hospitalized Anxiety and Depression scale (HAD). Subgroup analysis was also performed classifying studies into normal, hypotensive, vigorous, and obstructive patterns. KEY RESULTS: One hundred fifteen studies were analyzed (69 using HRM and 46 using high resolution impedance manometry (HRIM); 3.5% swallows in 9.6% of volunteers were perceived. There was no correlation of any of the traditional HRM variables, esophageal shortening, AIM metrics nor bolus transit with perception scores. There was no HRM variable showing difference in perception when comparing normal vs extreme values (percentile 1 or 99). Anxiety but not depression was correlated with perception. Among hypotensive pattern, anxiety was a strong predictor of variance in perception (R2 up to .70). CONCLUSION AND INFERENCES: Bolus perception is less common than abnormal motility among healthy individuals. Neither esophageal motor function nor bolus dynamics evaluated with several techniques seems to explain differences in bolus perception. Different mechanisms seem to be relevant in different manometric patterns. Anxiety is a significant predictor of bolus perception in the context of hypotensive motility.

The Chicago Classification 3.0 Results in More Normal Findings and Fewer Hypotensive Findings With No Difference in Other Diagnoses.

OBJECTIVES: High-resolution manometry (HRM) is the preferred method for the evaluation of motility disorders. Recently, an update of the diagnostic criteria (Chicago 3.0) has been published. The aim of this study was to compare the performance criteria of Chicago version 2.0 (CC2.0) vs. 3.0 (CC3.0) in a cohort of healthy volunteers and symptomatic patients. METHODS: HRM studies of asymptomatic and symptomatic individuals from several centers of Spain and Latin America were analyzed using both CC2.0 and CC3.0. The final diagnosis was grouped into hierarchical categories: obstruction (achalasia and gastro-esophageal junction obstruction), major disorders (distal esophageal spasm, absent peristalsis, and jackhammer), minor disorders (failed frequent peristalsis, weak peristalsis with small or large defects, ineffective esophageal motility, fragmented peristalsis, rapid contractile with normal latency and hypertensive peristalsis) and normal. The results were compared using McNemar's and Kappa tests. RESULTS: HRM was analyzed in 107 healthy volunteers (53.3% female; 18-69 years) and 400 symptomatic patients (58.5% female; 18-90 years). In healthy volunteers, using CC2.0 and CC3.0, obstructive disorders were diagnosed in 7.5% and 5.6%, respectively, major disorders in 1% and 2.8%, respectively, minor disorders in 25.2% and 15%, respectively, and normal in 66.4% and 76.6%, respectively. In symptomatic individuals, using CC2.0 and CC3.0, obstructive disorders were diagnosed in 11% and 11.3%, respectively, major disorders in 14% and 14%, respectively, minor disorders in 33.3% and 24.5%, respectively, and normal in 41.8% and 50.3%, respectively. In both groups of individuals, only an increase in normal and a decrease in minor findings using CC3.0 were statistically significant using McNemar's test. DISCUSSIONS: CC3.0 increases the number of normal studies when compared with CC2.0, essentially at the expense of fewer minor disorders, with no significant differences in major or obstructive disorders. As the relevance of minor disorders is questionable, our data suggest that CC3.0 increases the relevance of abnormal results.

Normal values of esophageal pressure responses to a rapid drink challenge test in healthy subjects: results of a multicenter study.

BACKGROUND: Multiple water swallow is increasingly used as a complementary challenge test in patients undergoing high-resolution manometry (HRM). Our aim was to establish the range of normal pressure responses during the rapid drink challenge test in a large population of healthy subjects. METHODS: Pressure responses to a rapid drink challenge test (100 or 200 mL of water) were prospectively analyzed in 105 healthy subjects studied in nine different hospitals from different countries. Esophageal motility was assessed in all subjects by solid-state HRM. In 18 subjects, bolus transit was analyzed using concomitant intraluminal impedance monitoring. KEY RESULTS: A virtually complete inhibition of pressure activity was observed during multiple swallow: Esophageal body pressure was above 20 mm Hg during 1 (0-8) % and above 30 mm Hg during 1 (0-5) % of the swallow period, and the pressure gradient across the esophagogastric junction was low (-1 (-7 to 4) mm Hg). At the end of multiple swallow, a postswallow contraction was evidenced in only 50% of subjects, whereas the remaining 50% had non-transmitted contractions. Bolus clearance was completed after 7 (1-30) s after the last swallow, as evidenced by multichannel intraluminal impedance. CONCLUSIONS & INFERENCES: The range of normal pressure responses to a rapid drink challenge test in health has been established in a large multicenter study. Main responses are a virtually complete inhibition of esophageal pressures with a low-pressure gradient across esophagogastric junction. This data would allow the correct differentiation between normal and disease when using this test.

Clinical assessment and health-related quality of life in patients with non-cardiac chest pain.

INTRODUCTION: Non-cardiac chest pain (NCCP) is mainly related to oesophageal disease, and in spite of being a common condition in Mexico, information regarding it is scarce. AIM: To assess the clinical characteristics and health-related quality of life of patients with NCCP of presumed oesophageal origin. MATERIAL AND METHODS: Patients with NCCP of presumed oesophageal origin with no previous treatment were included in the study. Associated symptoms were assessed and upper gastrointestinal endoscopy and 24-hour oesophageal pH monitoring were performed to diagnose gastroesophageal reflux disease, while oesophageal manometry was used to determine oesophageal motility disorders. The SF-36 Health-Related Quality of Life (HR-QoL) questionnaire was completed and its results compared to a control group without oesophageal symptoms. RESULTS: The study included 33 patients, of which 61% were women, and the mean age was 46.1 (±11.6) years. Causes of NCCP were gastroesophageal reflux disease in 48%, achalasia in 34%, and functional chest pain in 18%. The average progression time for chest pain was 24 (2-240) months, with ≤ 3 events/week in 52% of the patients. The most frequent accompanying symptoms were: regurgitation (81%), dysphagia (72%) and heartburn (66%). Patients with NCCP show deterioration in HR-QoL compared to the control group (P=.01), regardless of chest pain aetiology. The most affected areas were general perception of health, emotional issues, and mental health sub-scale (P>0.05). CONCLUSIONS: In our population, patients with NCCP show deterioration in HR-QoL regardless of the aetiology, frequency, and accompanying symptoms.

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.

Normal values in ambulatory oesophageal pH monitoring at two levels in Spain.

AIM: Upper oesophageal pH monitoring may play a significant role in the study of extra-oesophageal GERD, but limited normal data are available to date. Our aim was to develop a large series of normal values of proximal oesophageal acidification. METHODS: 155 healthy volunteers (74 male) participated in a multi-centre national study including oesophageal manometry and 24 hours oesophageal pH monitoring using two electrodes individually located 5 cm above the LOS and 3 cm below the UOS. RESULTS: 130 participants with normal manometry completed all the study. Twelve of them were excluded for inadequate pH tests. Twenty-seven subjects had abnormal conventional pH. The remaining 91 subjects (37 M; 18-72 yrs age range) formed the reference group for normality. At the level of the upper oesophagus, the 95th percentile of the total number of reflux events was 30, after eliminating the meal periods 22, and after eliminating also the pseudo-reflux events 18. Duration of the longest episodes was 5, 4 and 4 min, respectively (3.5 min in upright and 0.5 min in supine). The upper limit for the percentage of acid exposure time was 1.35, 1.05 and 0.95%, respectively. No reflux events were recorded in the upper oesophagus in 8 cases. CONCLUSION: This is the largest series of normal values of proximal oesophageal reflux that confirm the existence of acid reflux at that level in healthy subjects, in small quantity and unrelated to age or gender. Our data support the convenience of excluding pseudo-reflux events and meal periods from analysis.

Videofluoroscopia y disfagia neurogénica / Videofluoroscopy and neurogenic dysphagia

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Recuperación de la peristalsis esofágica en paciente diagnosticada de achalasia / Restoration of peristalsis in the esop hagus of a patient diagnosed of achalasia

Presentamos una paciente con disfagia en la que se realizó un seguimiento clínico y manométrico. Inicialmente se observó un trastorno motor sugerente de espasmo difuso; en controles manométricos posteriores se observó progresión a achalasia vigorosa. La paciente fue tratada con dilatación neumática, obteniéndose una buena respuesta. En manometrías realizadas después del tratamiento se objetivo una recuperación de la peristalsis en cuerpo esofágico distal. El tratamiento precoz y la corta evolución de la enfermedad pueden facilitar la recuperación de la peristalsis en estos casos. Dicha recuperación plantea nuevas dudas acerca de la etiología de la achalasia (AU)

Restoration of peristalsis in the esophagus of a patient diagnosed of achalasia.

We report the case of a patient with dysphagia in whom a clinical and manometric follow-up was carried out. We initially observed a motor disorder of the esophageal spasm type. During manometric follow-up a progression to vigorous achalasia was observed. The patient was treated with pneumatic dilation, which obtained a good response to treatment. In manometries performed after treatment we observed a return of peristalsis in the distal esophageal body. Early treatment and short evolution of disease may allow peristalsis to recover in these cases. Peristalsis recovery casts new doubts on achalasia etiology.

Reproducibility of ambulatory cutaneous electrogastrography in healthy volunteers.

OBJECTIVE: Cutaneous electrogastrography (cEGG) is a technique used for recording gastric electrical activity through electrodes placed on the abdominal skin. Given its increasing use for different pathologies, we decided to study its reliability (or reproducibility), that had never been appropriately assessed before. METHODS: Ambulatory cutaneous electrogastrogram was recorded after US location of the gastric antrum in 26 healthy volunteers with ages ranging from 20 to 60 years. cEGG was recorded during 60 minutes in fasting state and 60 minutes after a standard meal and it was repeated in a different day but under the same conditions. RESULTS: ANOVA analysis showed significant individual differences regarding dominant frequency (DF) (p = 0.19) and power ratio (PR) (p = 0.11), and before and after the meal, except for DF (p = 0.12), dominant power (DP) (p = 0.59) and bradygastria (p = 0.09). No significant differences were found related to the day of the recording. The intra-observer agreement index showed a good agreement in the DF and the percentage of normogastria (0.91). CONCLUSIONS: Currently, DF and normogastria percentage are the most reliable variables for the non-invasive study of gastric electric activity.

Presence of a protective allele for achalasia on the central region of the major histocompatibility complex.

Idiopathic achalasia is a motility disorder of the esophagus whose etiology is unknown. An association between HLA genes and susceptibility to achalasia which suggests a possible immunogenetic mechanism has been reported recently. This study was designed to examine the HLA class II association in a large group of achalasia patients further and to investigate the distribution of TNFa and TNFb microsatellites in these patients. The study population, all Spanish, white and unrelated, consisted of 115 consecutive patients and 339 healthy controls. All of the patients had been diagnosed with primary achalasia of the esophagus with manometric, radiographic and endoscopic studies. All studies were performed on DNA samples after locus-specific amplification with the polymerase chain reaction: HLA-DRB1, DQA1 and DQB1 were typed by dot-blot hybridization and the size of the TNFa and TNFb microsatellites was measured using a semiautomatic method. The broad allele HLA-DQ1 was seen to be weakly associated with achalasia. The TNFa11 allele and the DRB1*1501-DQA1*0102-DQB1*0602 haplotype were reduced in achalasia patients but the stratified analyses showed that this was true only when both were present in the same individual. These results confirm the association between achalasia and HLA-DQ1 allele and suggest that TNFa11 is a marker for a protective allele for the disease, present on the B7-DRB1*1501 (7.1) ancestral haplotype in our population.

Diagnóstico de la hemocromatosis por resonancia magnética / Diagnosis of hemochromatosis by imaging resonance

La hemocromatosis se caracteriza por una sobrecarga parenquimatosa de hierro. El diagnóstico se basa en la clínica, hallazgos analíticos y en la concentración de hierro hepático. La resonancia magnética (RM) hepática muestra un descenso en la intensidad de señal. El valor aislado de este dato no ha sido aún claramente definido. Sin embargo, la razón entre las intensidades de señal hepática y del músculo paraespinal en densidad protónica (LD) muestra una excelente correlación con el hierro hepático. Un paciente con una cirrosis hepática de larga evolución, con datos sugerentes de hemocromatosis cuyo estudio de coagulación no permitía realizar la biopsia hepática fue diagnosticado con este método. Se realizó una RM hepática y se calculó la concentración de hierro mediante la ecuación: mg/g de hierro hepático = (-5174*LMPD)+9.932. La RM puede ser útil en la evaluación de pacientes con posible hemocromatosis que rechacen la biopsia hepática o tengan contraindicada su relización (AU)

[Diagnosis of hemochromatosis with magnetic resonance]. / Diagnóstico de la hemocromatosis por resonancia magnética.

Hemochromatosis is a disorder of parenchymal iron overload. The diagnosis is based upon clinical manifestations, laboratory findings and iron concentration in liver. Magnetic resonance imaging (MRI) shows a decrease in liver signal intensity. Its role has not been already defined. Nonetheless, ratio of liver to muscle proton density (LMPD) shows a significant correlation with hepatic iron. One patient with a long-standing cirrhosis with data of hemochromatosis whose coagulation study did not allow to perform a liver biopsy was diagnosed with this method. Hepatic iron concentration was calculated based upon: microgram/g of hepatic iron = (-5.174* LMPD) + 9.932. MRI can be useful in the evaluation of hemochromatosis among patients who refuse or have contraindication to liver biopsy.

Contribution of HLA class II genes to susceptibility in achalasia.

Achalasia is a motor disorder of the esophagus resulting in functional obstruction. The cause of the lesion is unknown although genetic and immunologic factors have been suggested. An association with serological HLA epitopes has been previously reported. In this study, we have further examined this HLA class II association with susceptibility to achalasia by DNA based methods. Achalasia patients (n=40) and healthy controls (n=275), all Caucasians and unrelated, were included in the analysis. The strongest associations were with HLA-DQA1*0101 and two HLA-DQ alphabeta heterodimers having their alpha chain encoded by this allele. Moreover, relative risk was significantly higher in DQA1*0101 homozygotes as compared to heterozygotes and results suggested that DQB1*02 may have a protective role.

Manometry and 24-hour ambulatory pH monitoring at two levels of the esophagus in patients with and without esophagitis.

OBJECTIVE: To define the relationship between esophageal dysmotility and severity of gastroesophageal reflux (GER) at the distal and proximal levels. METHODS: Two-level, 24-hour ambulatory pH monitoring and manometry of the esophagus were performed in 40 patients with abnormal distal acid exposure and in 20 healthy controls. Twenty patients with normal endoscopy or endoscopic evidence of grade I esophagitis were assigned to group 1 and 20 with grade II-III esophagitis were assigned to group 2. We used a dual-site pH probe with antimony electrodes spaced 15 cm apart. RESULTS: Patients had greater acid exposure than controls at both levels. The percentage of distal reflux episodes reaching proximal esophagus was significantly greater in group 1 than in the control group. The most marked reductions in the percentage of time of the pH remaining under 4 were detected in the patients with the most severe distal acid reflux and esophagitis (group 2). The mean lower esophageal sphincter pressure was significantly lower in group 2 than in group 1. The percentage of tertiary waves or nonperistaltic contractions was significantly higher in group 2 than in group 1 and the control group. Patients with milder distal reflux had significantly lower distal and middle esophageal wave amplitudes than controls. There were no significant differences between controls and patients with severe esophagitis in terms of the esophageal peristaltic wave amplitude in the middle third of the esophagus. CONCLUSIONS: No correlation was observed between episodes of distal reflux and proximal reflux in GER patients. Esophageal motor activity appears to be an important determinant of the severity and extension of GER in the proximal esophagus.

Simultaneous two-level esophageal 24-hour pH monitoring in patients with mild and severe esophagitis. Does probe position influence results of esophageal monitoring?

Simultaneous ambulatory esophageal pH monitoring was performed in 10 patients (group 1) with normal distal acid exposure and in 40 patients (group 2) with pathological distal reflux. The probes were placed 5 and 10 cm above the lower esophageal sphincter to quantify variations of pH values that can be due to a displacement of pH sensor. In group 1 the median percent time with pH < 4 for total and upright monitoring periods and composite score were significantly lower at the proximal than the distal level. In group 2 all pH data were significantly lower at the proximal than the distal level. The patients with pathological reflux were subdivided into two subgroups based on endoscopic findings (mild and severe esophagitis). The patients with severe esophagitis showed a proximal acid reduction higher than in patients with mild esophagitis. Nine patients with mild esophagitis showed normal values at 10 cm, but all patients with severe esophagitis had abnormal proximal acid exposure.

[Physiological reflux in proximal esophagus (assessment with simultaneous pH monitoring in proximal and distal esophagus in healthy subjects]. / Reflujo fisiológico en esófago proximal (valoración mediante pHmetría simultánea en esófago proximal y distal en sujetos sanos).

Two-level pH monitoring was performed for 24 hours in 20 healthy subjects to document the presence of reflux episodes and to obtain reference values for reflux studies. The pH probes were placed 5 and 20 centimetres above the LES by means of a manometric technique. Significant differences were found at these two levels. At the proximal esophageal level 18 of the 20 subjects had reflux episodes. Five centrimetres above the lower esphageal sphincter the total reflux time was 1.35%, 2.05% in the upright and 0.15% in the supine positions. At 20 centimetres level it was significantly lower: 0.5% the total percent time with pH below 4, 0.8% and 0% in the upright and supine positions respectively. The mean reflux time was about 40% of the distal value, but the same pattern of reflux was observed at two levels of the esophagus. This technique is useful in documenting the cephalad extend of GER and allows to identify normal GER patterns at different levels of the esophagus.