Distal oesophageal ph monitoring for gastro-oesophageal reflux

We investigated eight hour distal intra-oesophageal ph testing to see if this could replace the traditional 24 hour test period without significant loss of sensitivity in the diagnosis of gastro-oesophageal reflux (GOR) disease in symptomatic refluxers. Thirty-four patients were tested, all of whom had classical De Meester symptoms of GOR. All patients were admitted to hospital and commenced on 24 hour ambulant ph monitoring of the distal oesophagus. This was followed by a period of eight hour testing. The following variables were determined: (i) total reflux time, (ii) number of reflux episodes (total, upright and supine), (iii) longest episode of reflux, (iv) percent of time that ph was below four (total, upright and supine). All patients underwent endoscopic examination of the oesophagus subsequently. Twenty four hour monitoring resulted in a positive diagnosis of GOR in 26 of 34 patients, giving an overall sensitivity of 75%. Eight hour testing was positive in 23 patients (sensitivity of 68%, not significantly different). The best correlations were obtained when comparing total reflux episodes (r = 0.75, p less than 0.001), and the percent time ph less than 4 (total) (r = 0.69, p less than 0.001). Nineteen patients had evidence of oesophagitis on endoscopy, and in all such patients both eight and 24 hour testing were positive. We conclude therefore, that eight hour ph monitoring can be reliably used in the diagnosis of pathological GOR in patients symptomatic for acid reflux.     

A new optics-based gastroesophageal reflux probe.

This work was carried out with the purpose of developing a new method of gastroesophageal reflux (GOR) detection. It is based on the emission of a light beam to the inferior part of the oesophagus and on the detection and analysis of the corresponding reflected light intensity. The optical properties of the oesophageal lumen are then used to identify the GOR episodes, solving, in this way, the existing drawback of using pH probes that fail in the cases where GOR episodes are neutral or short duration acid. The necessary instrumentation for the application of this new technique, including the probe itself and its associated optics, was developed. The result is a low-cost portable instrument, based on the Microchip microcontroller PIC16C77, with enough flexibility to be used in other biomedical applications. This new simple apparatus only needs an adequate light source - diode laser - and an adequate photosensor - photodiode - to make the interface to the probe that guides the light to and from oesophagus. Our results show the capability of this new technique to make the identification of GOR episodes.     

Relationship between sleep and acid gastro-oesophageal reflux in neonates

The aim of the present study was to investigate the impact of gastro‐oesophageal acid reflux on sleep in neonates and, reciprocally, the influence of wakefulness (W) and sleep stages on the characteristics of the reflux (including the retrograde bolus migration of oesophageal acid contents). The pH and multichannel intraluminal impedance were measured during nocturnal polysomnography in 25 infants hospitalised for suspicion of gastro‐oesophageal reflux. Two groups were constituted according to whether or not the infants displayed gastro‐oesophageal reflux (i.e. a reflux group and a control group). There were no differences between the reflux and control groups in terms of sleep duration, sleep structure and sleep state change frequency. Vigilance states significantly influenced the gastro‐oesophageal reflux pattern: the occurrence of gastro‐oesophageal reflux episodes was greater during W (59 ± 32%) and active sleep (AS; 35 ± 30%) than during quiet sleep (QS; 6 ± 11%), whereas the mean duration of gastro‐oesophageal reflux episodes was higher in QS than in W and AS. The percentage of retrograde bolus migrations of distal oesophageal acid content was significantly higher in AS (62 ± 26%) than in W (42 ± 26%) and QS (4.5 ± 9%). In neonates, gastro‐oesophageal reflux occurred more frequently during W, whereas the physiological changes associated with sleep state increase the physiopathological impact of the gastro‐oesophageal reflux. The duration of oesophagus–acid contact was greater during sleep; AS facilitated the retrograde migration of oesophageal acid content, and QS was characterised by the risk of prolonged acid mucosal contact.     

Controversies of the cardiac mucosa and Barrett's oesophagus

Confusion regarding the diagnosis of Barrett's oesophagus exists because of a false dogma that cardiac mucosa is normally present in the gastro-oesophageal junctional region. Recent data indicate that the only normal epithelia in the oesophagus and proximal stomach are squamous epithelium and gastric oxyntic mucosa. When this fact is recognized, it becomes easy to develop precise histological definitions for the normal state (presence of only squamous and oxyntic mucosa), metaplastic oesophageal columnar epithelium (cardiac mucosa with and without intestinal metaplasia, and oxynto-cardiac mucosa), the gastro-oesophageal junction (the proximal limit of gastric oxyntic mucosa), the oesophagus (that part of the foregut lined by squamous and metaplastic columnar epithelium), reflux disease (the presence of metaplastic columnar epithelium), and Barrett's oesophagus (cardiac mucosa with intestinal metaplasia). It is also possible to assess accurately the severity of reflux which is directly proportional to the amount of metaplastic columnar epithelium, and the risk of adenocarcinoma which is related to the amount of dysplasia in intestinal metaplastic epithelium present within the columnar lined segment of the oesophagus. Histopathological precision cannot be matched by any other modality and can convert the confusion that exists regarding diagnosis of Barrett's oesophagus to complete lucidity in a manner that is simple, accurate, and reproducible.     

Cytokeratin 7 and 20 expression in intestinal metaplasia of the distal oesophagus: relationship to gastro-oesophageal reflux disease

AIMS: Intestinal metaplasia and gastro-oesophageal reflux disease typify classical Barrett's oesophagus. Cytokeratin (CK) 7 and 20 phenotypes differentiate intestinal metaplasia in long segment Barrett's oesophagus from gastric intestinal metaplasia. This study examines the relationship between CK7/20 phenotypes and reflux disease in intestinal metaplasia of the distal oesophagus. METHODS AND RESULTS: Eighty patients with oesophageal pH studies included 30 with long segment Barrett's, 16 with short segment Barrett's and 34 with intestinal meatplasia of the gastro-oesophageal junction. Representative biopsy specimens were immunostained for CK7 and CK20. All 30 long segment patients demonstrated a Barrett's CK7/20 phenotype. All nine short segment patients with gastro-oesophageal reflux had a Barrett's CK7/20 phenotype, while four of seven short segment patients without reflux had a gastric CK7/20 phenotype (P = 0.019). Of 14 patients with intestinal metaplasia of the gastro-oesophageal junction and reflux, 10 (71%) had a Barrett's CK7/20 phenotype, compared with 11 (55%) of the 20 non-reflux patients. CONCLUSIONS: CK7/20 immunoreactivity for patients with intestinal metaplasia of the distal oesophagus without long segment Barrett's oesophagus suggests a heterogeneous group, with an association between Barrett's CK7/20 pattern and gastro-oesophageal reflux disease in both short segment Barrett's and intestinal metaplasia of the gastro-oesophageal junction.     

Multichannel intra-luminal impedance signals variability during gastro-oesophageal activities

Multichannel intra-luminal impedance (MII) technique has been proven to be a successful diagnostic tool in detecting and displaying activities inside the oesophagus. It improves the diagnostic capability of oesophageal disorders since it gives accurate and more in-depth information about the activities inside the oesophagus, especially reflux episodes. A comparison is presented between normal and abnormal adults in terms of variability in MII signals during baselines and reflux episodes. A comparative study of episode duration for normal and abnormal subjects is presented. The characteristics of MII signals during gastro-oesophageal reflux episodes as well as during baselines are investigated. These characteristics show different responses between normal and abnormal individuals which help improving MII analysis capability in evaluating patients with gastro-oesophageal reflux disease and enhances the automatic detection of the oesophageal activities. Baselines from normal and abnormal samples were fitted to gamma distributions as a trial to distinguish between normal and abnormal samples.     

Clinicomorphological diagnosis and surgical treatment of complicated gastroesophageal reflux disease

Biopsy and surgery specimens taken from 224 patients with gastroesophageal reflux disease were clinically and morphologically analyzed. The morphological diagnosis of this condition is of more informative value than endoscopy and X-ray study. Malignization occurs in 25% of patients with Barrett oesophagus. One case of surgical treatment for gastroesophageal reflux disease yielding a good outcome is described.     

The efficacy of the upright position on gastro-esophageal reflux and reflux-related respiratory symptoms in infants with chronic respiratory symptoms

Purpose

Gastro-esophageal reflux (GER), particularly non-acid reflux, is common in infants and is a known cause of chronic respiratory symptoms in infancy. Recent guidelines recommended empirical acid suppression therapy and the head-up position in patients with suspected GER. However, the efficacy of the upright position in relieving GER and reflux-related respiratory symptoms in infants is unclear. We conducted this study to investigate the efficacy of the upright position on GER and reflux-related respiratory symptoms in infants with chronic respiratory symptoms.

Methods

Thirty-two infants (21 male; median age, 5 months; range, 0 to 19 months) with unexplained chronic respiratory symptoms underwent multi-channel intraluminal esophageal impedance and pH monitoring. We retrospectively compared the frequencies of GER and reflux-related symptoms according to body position.

Results

A mean of 3.30 episodes of reflux per hour was detected. Overall, refluxes were more frequent during the postprandial period than the emptying period (3.77 vs. 2.79 episodes/hour, respectively; P=0.01). Although there was no significant difference in the total refluxes per hour between the upright and recumbent positions (6.12 vs. 3.77 episodes, P=0.10), reflux-related respiratory symptoms per reflux were significantly fewer in infants kept in an upright position than in a recumbent position during the postprandial period (3.07% vs. 14.75%, P=0.016). Non-acid reflux was the predominant type of reflux in infants, regardless of body position or meal time.

Conclusions

The upright position may reduce reflux-related respiratory symptoms, rather than reflux frequency. Thus, it may be a useful non-pharmacological treatment for infantile GER disease resistant to acid suppressants.     

Gastroesophageal reflux and pulmonary disease

Gastroesophageal reflux (GER) is a functional entity which is defined as "the involuntary reflux of the gastric contents in the oesophagus, without vomiting and without the involvement of either the gastric, abdominal or diaphragmatic muscles". It is therefore a question of a syndrome which is independent of the anatomical abnormalities in the cardio-tuberositic region (i.e. hiatal hernia). It may also show itself through digestive symptoms, thoracic pains, ENT symptoms and breathing complications. The presence of the latter has been clearly established in certain circumstances: --in infants, GER can cause obstructive apneas, which are responsible for sudden inexplicable deaths (SID): GER and SID have very similar epidemiological characteristics; polygraphic recordings showed that a reflux may immediately precede the onset of obstructive apnea; the instillation of 0.1 N hydrochloric acid in the oesophagus of children with GER causes an apnea. Medical or surgical treatment of the reflux prevents the recurrence of these accidents; --in adults, and older children, GER is responsible for coughs, recurring bronchopneumopathies and asthma; long-term recordings of the oesophageal pH have proved that there is a time-relationship between the two events. Scintigraphic studies have shown the pulmonary contamination by a radioactive isotope placed in the stomach the previous evening. GER has been equally suspected for conditions such as lung abscess, bronchiectasis and hemoptysis, but here it is more difficult to prove. With certain pulmonary fibroses, histological lesions have been compared with those observed during inhalation bronchopneumopathies, but it is difficult to establish a link with a reflux; --functional respiratory studies have not produced a specific functional entity for patients with GER; --careful medical treatment or surgical correction of GER lead to the sedation of respiratory symptoms (RS) in the majority of cases; --the association frequency of a GER and of RS is difficult to establish because of the diversity of the means of diagnosis employed in the past and also because of the heterogeneity of the studied populations, but the frequency is nevertheless high, indeed significantly higher than the prevalence of GER in the general population. The mechanisms which link GER and RS are not well known: first of all, there is the failure of normal antireflux mechanisms and also certain hormonal, alimentary (coffee, alcohol, tobacco, etc.) and therapeutic (theophylline, betamimetics) factors, which facilitate the reflux.(ABSTRACT TRUNCATED AT 400 WORDS)     

Arousals induced by proximal esophageal reflux in infants.

We investigated whether acid reflux in the proximal esophagus can induce arousal from sleep in infants. Fifty normal infants with occasional regurgitations were studied at the age of 8 weeks (range 4-26 weeks). In each child a pH probe was placed in the proximal portion of the thoracic esophagus, in front of the third vertebra, under radiologic control. Polygraphic monitoring of state of alertness and of proximal esophageal pH changes was recorded continuously during one night. The data were analyzed blind. For 41 of the 50 infants, a total of 97 drops below pH 4 was computed. Reflux was more frequently associated with wakefulness (41% of the episodes), or rapid eye movement (REM) sleep (39%), than with nonREM (19%) or indeterminate sleep (1%). Comparing the fifth and the last minutes preceding the pH drops, a significant increase in the number of behavioral arousals was observed (p = 0.003). In comparison with the minute before the drop in esophageal pH, a further significant increase in the number of arousals occurred during the first minutes following the pH drop (p = 0.001). Although the first minutes following the 97 episodes of reflux represented only 0.4% of the total sleep time, 76% of all arousals (74 out of 97) took place during this time period (p = 0.001). Five minutes after the pH drops, the behavioral changes tended to return to prereflux values. It is concluded that in infants, during sleep, proximal gastroesophageal reflux can act as a strong arousal stimulus.     

Early adenocarcinoma of the oesophagus and oesophageal cyst

Aims : An increased risk of adenocarcinoma of the oesophagus has been demonstrated in patients with long segments of Barrett's mucosa. The risk of cancer associated with short segments of metaplasia of the oesophagogastric junction is not known. Methods and results : We report a case of early adenocarcinoma of the oesophagus arising on short tongues of Barrett's mucosa associated with an oesophageal cyst. The patient was a 68-year-old man with no previous clinical history of gastro-oesophageal reflux disease. The fortuitous discovery of an oesophageal cyst lead to the diagnosis of short tongues of Barrett's mucosa with high-grade dysplasia. On pathological examination of the resected specimen, an early adenocarcinoma had developed in Barrett's mucosa, localized just above the oesophageal cyst. Conclusions : As oesophageal cysts can cause symptoms suggestive of reflux, we hypothesize that this association may not be fortuitous.     

Cytometric bead array: a multiplexed assay platform with applications in various areas of biology

The introduction of flow cytometric bead-based technology has added a new approach for investigators to simultaneously measure multiple analytes in biological and environmental samples. This new technology allows for (1) evaluation of multiple analytes in a single sample; (2) utilization of minimal sample volumes to glean data; (3) reproducibility and results comparative with previous experiments; (4) direct comparison with existing assays; and (5) a more rapid evaluation of multiple samples in a single platform. The cytometric bead array (CBA) system enables simultaneous measurement of multiple analytes in sample volumes too small for traditional immunoassays. Results have been presented for the analysis of a variety of human cytokines. In addition, the technology allows for the design and creation of assays to measure a variety of analytes including inflammatory mediators, chemokines, immunoglobulin isotypes, intracellular signaling molecules, apoptotic mediators, adhesion molecules, and antibodies. New initiatives put forward by the Human Genome Project and the FDA require the development and use of assays for the rapid simultaneous quantitation of multiple analytes. The CBA technology provides the ability to quantify multiple proteins within a given sample, with precision and consistency.     

The effect of alginates on deoxycholic-acid-induced changes in oesophageal mucosal biology at pH 4

Long-standing gastro-oesophageal reflux disease (GORD) can give rise to Barrett's oesophagus (BM), a metaplastic condition and precursor to oesophageal adenocarcinoma (AC). Oesophageal cancer was once rare but is now the 5th biggest cancer killer in the U.K. Reflux of bile acids into the oesophagus is implicated in the progression to BM as bile acids at pH 4 have been shown to induce c-myc expression, an oncogene upregulated in BM and AC. In the present study we investigated the role of the biopolymer alginate on bile acid induced molecular changes in oesophageal cell lines. OE21, OE33 and TE-7 oesophageal cell lines were exposed to 100 microM deoxycholic acid at pH 4 in the presence or absence of alginates. Levels of c-myc, E-cadherin, beta-catenin and Tcf signalling were determined by Real-Time PCR, Western blotting, immunofluoresence and reporter assays. All alginates tested were able to prevent the induction of c-myc by acidified deoxycholic acid in vitro. The upstream effects of acidified deoxycholic acid on E-cadherin, beta-catenin and Tcf signalling were also suppressed by alginate. Therefore, we have demonstrated that reflux of bile acids into the oesophagus initiates a potentially damaging molecular cascade of events using an in vitro model and that a biopolymer, alginate, can protect against these effects.     

GOR抗体与HCV感染的相关性研究

用工合成的ＧＯＥ肽与ＢＳＡ交联后包被反应板，作为捕获抗原，建立了检测ＧＯＲ抗体的间接ＥＬＩＳＡ。共检测临床各类病人２７８例，正常供血员４８名。结果慢性丙肝患者抗ＧＯＲ阳性检出率为６０．０％（３６／６０），血透患者为４３．６％（１７／３９），白血病患者为５０．０％（６／１２），甲亢患者为４０．４％（１９／４７）。对抗ＧＯＲ抗体阳性的意义进行了分析。     

Naso-oesophageal probes decrease the frequency of sleep apnoeas in infants

The objective of the study was to determine whether a naso-oesophageal probe modifies sleep and cardiorespiratory patterns in infants with repeated obstructive apnoeas. Two polygraphic recording sessions were conducted in random order for 2 nights on 35 infants suspected to have repeated obstructive sleep apnoeas. One sleep study was performed with a pH probe inserted through the nasal passage down to the distal portion of the oesophagus. The other session was conducted without any naso-oesophageal probe (the baseline study). For the 25 infants who presented repeated obstructive apnoeas during baseline studies, the presence of the probe was associated with a small, but significant, decrease in the number of central apnoeas (median frequency of 18.5 apnoeas per hour without a probe; 16.1 per hour with the probe; P=0.040), and obstructive apnoeas (median of 1.9 apnoeas per hour without a probe; 0.6 per hour with the probe; P=0.016). The presence of the probe was also associated with a small increase in percentage non-rapid eye movement (NREM) sleep frequency. The changes were statistically significant only for infants who had no obstructive apnoea during baseline studies (29 vs. 31%). The presence of a naso-oesophageal probe significantly modifies the infants' respiratory characteristics during sleep. These findings should be considered when reporting and interpreting sleep studies in infants.     

The frequency of urinary tract infections in hospitalized infants

The authors present the frequency of urinary tract infections in hospitalised infants. A retrospective study of infants hospitalized during a five year period, from 1979-1983 was made. The average frequency for the mentioned period was 12%, all of which were bacterial infections. In 70.7% of patients we diagnosed cytopyelonephritis. Girls prevailed among the patients with urinary tract infections, even in the neonatal period. Vesicoureteric reflux was confirmed in 36.5% children. The results of this study show that the symptoms of urinary tract infections in infancy are not specific. As the frequency of cytopyelonephritis and vesicoureteric reflux was high it emphasizes the significance of early diagnosis. In every febrile child, diagnosis of urinary tract infections should be suspected.     

Combined pH and pressure measurement device for oesophageal investigations

A combined pH- and pressure-measurement device for oesophageal investigations has been designed using monocrystalline antimony pH electrodes and perfused polyvinyl catheters. The combined device facilitates pressure measurements simultaneously with pH recording, both distal and proximal to the pH electrode. The device is easier to pass through the nose to the oesophagus than the conventional glass pH electrode. pH and pressure measurements in the oesophagus are therefore simplified and valuable information about the function of the region of the lower oesophageal sphincter is added owing to the simultaneous recording of the two parameters.     

Eosinophil infiltration of the oesophageal mucosa in patients with pollen allergy during the season

BACKGROUND:The oesophagus is normally devoid of eosinophils. There are some disorders accompanying with eosinophil infiltration. Food allergy has been reported as a common reason, especially in children but some other studies have also indicated that aeroallergens might have a role in oesophageal eosinophil accumulation. OBJECTIVE:In this study we investigated whether there is any eosinophil recruitment in the oesophagus of pollen-allergic patients who had respiratory symptoms during the season. METHODS:Thirty-eight symptomatic patients (allergic rhinitis (AR) with or without asthma) who had sensitization to grass pollen were included in the study during the pollen season. Controls were composed of 25 healthy non-atopics and 24 patients diagnosed as having gastro-oesophageal reflux disease. Reflux was excluded in allergic and non-atopic groups, whereas the presence of allergy was eliminated in control groups. Gastrointestinal endoscopy was performed in all participants, and biopsy specimens were taken from both the proximal and the distal oesophagus to evaluate eosinophil accumulation. At the same time, blood eosinophil numbers were counted. Results Oesophageal eosinophil accumulation was found in 10 allergic patients (26%) and in five patients (21%) with gastro-oesophageal reflux disease but none of the healthy controls had eosinophils (0%) (P<0.05). Blood eosinophils were higher in these 10 patients than the rest of the 28 patients without infiltration. In this group, blood eosinophils were also correlated with the number of accumulated eosinophils in the oesophagus (P<0.001). There was more intense eosinophil infiltration at the distal part of the oesophagus in the reflux group when compared with the allergic group (mean 7.6+/-5.6 vs. 3.2+/-3.7). Nevertheless, eosinophils were found to be concentrated (mean 5.5+/-7.3) in the proximal oesophagus of allergic patients, although it was 1.7+/-1.5 in reflux patients (P>0.05). Conclusion Our results showed that eosinophil infiltration might be observed in oesophageal tissue of patients with respiratory tract allergy during the symptomatic period. This finding may possibly reflect the systemic and common mucosal aspects of allergic inflammation.     

Routinely diagnosed low-grade dysplasia in Barrett's oesophagus: a population-based study of natural history

Aims:  To examine the natural history of columnar-lined oesophagus with routinely diagnosed low-grade dysplasia and ascertain the risk of oesophageal adenocarcinoma development.
Methods and results:  A multicentre retrospective cohort study of 283 patients with low-grade dysplasia. Follow-up data were obtained from examination of hospital records. One hundred and forty-four patients had biopsies prior to low-grade dysplasia diagnosis and 217 had follow-up biopsies after index low-grade dysplasia diagnosis. In these patients the incidence of high-grade dysplasia and adenocarcinoma combined was 4.6% per annum and of adenocarcinoma alone was 2.7% per annum. At most recent follow-up, 43 (19.8%) had persistent low-grade dysplasia, 37 (17.1%) had changes indefinite for dysplasia and 108 (49.8%) had non-dysplastic columnar-lined oesophagus. When prevalent cases were excluded (those occurring within 1 year of index low-grade dysplasia diagnosis), the annual incidence of high-grade dysplasia and adenocarcinoma combined was 2.2% and of adenocarcinoma alone was 1.4%. The relative risk for adenocarcinoma development in low-grade dysplasia compared with non-dysplastic columnar-lined oesophagus was 2.871 ( P  = 0.002).
Conclusions:  Low-grade dysplasia has a threefold increased risk of progression to cancer compared with non-dysplastic epithelium, but in the majority of patients dysplasia is not subsequently detected.     

Loss of human leucocyte antigen class I and gain of class II expression are early events in carcinogenesis: clues from a study of Barrett's oesophagus

BACKGROUND: Human leucocyte antigen (HLA) expression is altered in oesophageal carcinomas compared with normal tissue. It is unclear, however, whether this phenotype precedes malignant transformation or results as a consequence of it. AIM: To investigate HLA class I and II expression in Barrett's oesophagus and normal squamous oesophageal tissue. METHODS: Asian patients with Barrett's oesophagus (n = 64) and a control group (n = 60) with a normal oesophagus but without reflux symptoms were recruited using endoscopic and histopathological criteria. Tissue samples were stained with monoclonal antibodies specific for HLA-ABC, HLA-DR alpha chain or HLA-DP/DQ/DR, and scored semiquantitatively. The results of immunohistochemical staining were correlated with clinical and histopathological characteristics of patients. RESULTS: Marked expression of HLA-ABC was observed in 50% of Barrett's oesophagus sections as compared with 68.3% of controls (p = 0.038). HLA-DR staining was seen in 51.6% of Barrett's oesophagus samples versus 11.7% of controls (p<0.001). Expression of HLA-DP/DQ/DR was evident in 73.4% of oesophageal intestinal metaplasia tissue as opposed to 18.3% of controls (p<0.001). Importantly, a total loss of HLA-ABC and a concomitant gain of HLA-DP/DQ/DR expression were seen in 37.5% of patients with Barrett's oesophagus but in none of the controls (p<0.001). Interestingly, this phenotype was associated positively with dysplasia (adjusted p, p* = 0.031) but negatively with non-steroidal anti-inflammatory drug use (p* = 0.004). CONCLUSIONS: HLA class I expression is down regulated and class II expression is up regulated in Barrett's oesophagus. As these changes predate malignant transformation, altered major histocompatibility complex expression may be a key event in disease progression, possibly in facilitating evasion from immune surveillance.