We have developed an artificial intelligence (AI)-based digital pathology model for the evaluation of histologic features related to eosinophilic esophagitis (EoE). In this study, we evaluated the performance of our AI model in a cohort of pediatric and adult patients for histologic features included in the Eosinophilic Esophagitis Histologic Scoring System (EoEHSS). We collected a total of 203 esophageal biopsy samples from patients with mucosal eosinophilia of any degree (91 adult and 112 pediatric patients) and 10 normal controls from a prospectively maintained database. All cases were assessed by a specialized gastrointestinal (GI) pathologist for features in the EoEHSS at the time of original diagnosis and rescored by a central GI pathologist (R.K.M.). We subsequently analyzed whole-slide image digital slides using a supervised AI model operating in a cloud-based, deep learning AI platform (Aiforia Technologies) for peak eosinophil count (PEC) and several histopathologic features in the EoEHSS. The correlation and interobserver agreement between the AI model and pathologists (Pearson correlation coefficient [rs] = 0.89 and intraclass correlation coefficient [ICC] = 0.87 vs original pathologist; rs = 0.91 and ICC = 0.83 vs central pathologist) were similar to the correlation and interobserver agreement between pathologists for PEC (rs = 0.88 and ICC = 0.91) and broadly similar to those for most other histologic features in the EoEHSS. The AI model also accurately identified PEC of >15 eosinophils/high-power field by the original pathologist (area under the curve [AUC] = 0.98) and central pathologist (AUC = 0.98) and had similar AUCs for the presence of EoE-related endoscopic features to pathologists' assessment. Average eosinophils per epithelial unit area had similar performance compared to AI high-power field-based analysis. Our newly developed AI model can accurately identify, quantify, and score several of the main histopathologic features in the EoE spectrum, with agreement regarding EoEHSS scoring which was similar to that seen among GI pathologists.

Experimental studies have suggested that sleep position plays a role in the occurrence of nocturnal gastroesophageal reflux and the left lateral decubitus position is most favorable. The aim of this study was to evaluate the effect of a novel electronic sleep positional therapy wearable device on sleep position and nocturnal reflux symptoms.

We performed a double-blind, randomized, sham-controlled trial in patients with nocturnal symptoms of gastroesophageal reflux. Patients were advised to sleep in the left lateral decubitus position and were assigned randomly (1:1) to an electronic sleep positional therapy wearable device, programmed to either produce a vibration when in the right lateral position (intervention) or only during the first 20 minutes (sham). The primary outcome was treatment success, defined as a 50% or more reduction in the nocturnal reflux score. Secondary outcomes included change in sleep position and reflux symptoms.

One hundred patients were randomized. In the intention-to-treat analysis, the rate of treatment success was 44% in the intervention group (22 of 50) vs 24% in the sham group (12 of 50) (risk difference, 20%; 95% CI, 1.8%-38.2%; P = .03). Treatment led to a significant avoidance of sleeping in the right lateral decubitus position (intervention 2.2% vs sham 23.5%; P = .000) and increased time sleeping in the left lateral decubitus position (intervention 60.9% vs sham 38.5%; P = .000). More reflux-free nights were observed in the intervention group (intervention 9 nights [interquartile range, 6-11 nights] vs sham 6 nights [interquartile range, 3-9 nights]; P = .01).

Sleep positional therapy using an electronic wearable device promotes sleeping in the left lateral decubitus position and effectively alleviates nocturnal reflux symptoms compared with sham treatment (https://www.trialregister.nl, NL8655).

To evaluate current diagnosis and treatment of patients with nocturnal gastroesophageal reflux (nGER).

This multicenter observational study was conducted in 44 hospitals in China from May 2017 to February 2018. Outpatients with nGER were recruited and their relevant data were collected using a questionnaire, including age, gender, body mass index, history of smoking and alcohol consumption, comorbid diseases, lifestyle, self-reported health status, medical history, nGER symptoms and severity, Hospital Anxiety Depression Scale, Pittsburgh Sleep Quality Index, diagnosis and treatment choices. The study was registered on the Chinese Clinical Trial Registry (no. ChiCTR1800017525).

The study included 4978 individuals, with valid questionnaires collected from 4448 patients (89.4%). The symptoms of heartburn and regurgitation were more severe at night than during the day (P < 0.05). Age and body mass index were positively correlated with reflux severity at night and during the day (P < 0.05). The severity of nGER was positively associated with lifestyle factors such as smoking, a high-fat diet, carbonated beverage consumption, late supper (later than 9 pm), and snoring (all P < 0.05). Night-time heartburn and regurgitation were related with sleep disorder.

Lifestyle factors are associated with nGER severity, and nGER affects sleep quality. It will be beneficial to popularize and strengthen the diagnosis and treatment of nGER.

Consideration of lung transplantation in patients with systemic sclerosis (SSc) remains guarded, often due to the concern for esophageal dysfunction and the associated potential for allograft injury and suboptimal post-lung transplantation outcomes.

The purpose of this study was to systematically report our single-center experience regarding lung transplantation in the setting of SSc, with a particular focus on esophageal dysfunction.

We retrospectively reviewed all lung transplants at our center from January 1, 2000 through August 31, 2012 (n = 562), comparing the SSc group (n = 35) to the following lung transplant diagnostic subsets: all non-SSc (n = 527), non-SSc diffuse fibrotic lung disease (n = 264), and a non-SSc matched group (n = 109). We evaluated post-lung transplant outcomes, including survival, primary graft dysfunction, acute rejection, bronchiolitis obliterans syndrome, and microbiology of respiratory isolates. In addition, we defined severe esophageal dysfunction using esophageal manometry and esophageal morphometry criteria on the basis of chest computed tomography images. For patients with SSc referred for lung transplant but subsequently denied (n = 36), we queried the reason(s) for denial with respect to the concern for esophageal dysfunction.

The 1-, 3-, and 5-year post-lung transplant survival for SSc was 94, 77, and 70%, respectively, and similar to the other groups. The remaining post-lung transplant outcomes evaluated were also similar between SSc and the other groups. Approximately 60% of the SSc group had severe esophageal dysfunction. Pre-lung transplant chest computed tomography imaging demonstrated significantly abnormal esophageal morphometry for SSc when compared with the matched group. Importantly, esophageal dysfunction was the sole reason for lung transplant denial in a single case.

Relative to other lung transplant indications, our SSc group experienced comparable survival, primary graft dysfunction, acute rejection, bronchiolitis obliterans syndrome, and microbiology of respiratory isolates, despite the high prevalence of severe esophageal dysfunction. Esophageal dysfunction rarely precluded active listing for lung transplantation.

Eosinophils are commonly detected in normal mucosal biopsies from all sites within the gastrointestinal tract where they are dispersed in the lamina propria and, to a lesser extent, in the epithelium. The distinction between the upper limit of normal and abnormally increased tissue eosinophils is not well defined. However, eosinophils that infiltrate the epithelium in more than occasional numbers, coalesce to form aggregates, or show extensive degranulation are always abnormal and raise a broad differential diagnosis. Although the differential diagnosis of purely eosinophilic inflammation is largely limited to hypersensitivity reactions and some infections, they are increased in several gastrointestinal conditions, including gastroesophageal reflux disease, autoimmune gastritis, infections, drug reactions, inflammatory bowel disease, radiation enteritis, and collagen vascular disease. These disorders feature eosinophils as one component of a mixed inflammatory infiltrate that can, in some instances, be prominent enough to cause diagnostic confusion. The purpose of this review is to discuss the normal distribution of eosinophils in the gastrointestinal tract and the differential diagnosis of inflammatory conditions that feature prominent eosinophilia.

Gastroesophageal reflux is commonly encountered in the infant population. Most children will outgrow their reflux but some develop pervasive disease and require medical or surgical treatment. Many tools exist for use in the workup of pediatric gastroesophageal reflux disease; however, the most effective method of diagnosis is not clear. Delineating which patients will benefit from more definitive therapy is a remarkable challenge in this group, often borrowing tools and principles from the adult patient population. Therefore, we reviewed the available literature to critically evaluate the merits and limitations of the current diagnostic modalities available for the evaluation of infantile gastroesophageal reflux.

Ambulatory 24 h esophageal pH monitoring enables quantification of esophageal acid exposure and assessment of the temporal relationship between symptoms and acid reflux events. Analysis of pH monitoring is currently divided into upright and recumbent periods based on the patient's body position. However, in this Review, we demonstrate that physiologic studies have shown that sleep, and not recumbency, has a greater impact on gastroesophageal reflux during night-time. The physiologic studies are further supported by clinical trials demonstrating that gastroesophageal reflux characteristics during the recumbent-awake period are similar to those in the upright rather than the recumbent-asleep period. The introduction of the integrated pH monitoring and actigraphy data analysis program offers better separation of the recumbent-awake and recumbent-asleep periods. The physiologic studies and clinical trials, as well as the availability of a better tool to measure pH during sleep, support a paradigm shift in the analysis of pH monitoring data from body position (upright or recumbent) to state of consciousness (awake or asleep).

Gastroesophageal reflux disease (GERD) is a common disease frequently encountered by surgical pathologists. Although the pathogenesis and clinical features of the disease have been studied for years, many unanswered questions remain. Typical clinical symptoms along with the endoscopic findings, pH monitoring, and biopsies, all support the diagnosis. However, these tests may yield conflicting findings, and at present there is no gold standard for the diagnosis of GERD. In patients with normal or nearly normal endoscopic findings (nonerosive reflux disease), the major diagnostic burden lies with the histology. The histologic diagnosis of GERD is based on a combination of findings, including basal cell hyperplasia, papilla elongation, inflammation, and dilatation of intercellular spaces. However, these features exhibit varying sensitivity and specificity, and minimal biopsy criteria for the diagnosis of reflux esophagitis have not been rigorously tested in well-characterized patient populations. However, given the high prevalence of GERD, pathologists face esophageal mucosal biopsies daily and must recognize the diagnostic strengths and limitations of histologic features of reflux esophagitis. Future studies and new techniques may improve the diagnostic strength of histology and establish meaningful minimal criteria for the diagnosis of reflux esophagitis.

More than half of patients with chronic gastroesophageal reflux (GERD) report nocturnal symptoms. We performed systematic literature review to define nocturnal heartburn and to determine potential causality between nocturnal reflux and extraesophageal manifestations.

We performed a search of literature published from 1974-2007. Each study was examined by 2 reviewers and rated on the basis of study type and outcome.

Screening of 445 trials identified 59 (13%) studies relevant for analysis. Twenty-two (5%) of the trials described potential changes in sleep parameters resulting from treatment of heartburn. In most studies, nocturnal reflux was defined as heartburn symptoms that impacted sleep quality and duration. On the basis of 5 large population studies, the mean +/- standard deviation prevalence of nocturnal heartburn was 54% +/- 22%. Consequences of nocturnal reflux included poor sleep quality, daytime fatigue, difficulty initiating sleep or arousals from sleep, and impaired work productivity. The strength of the association between the occurrence of nocturnal reflux and late evening meals was flawed as a result of the confounding effect of the evening meal content. There was no evidence supporting causality between nocturnal heartburn and asthma or obstructive sleep apnea. Subjective, but not objective, measures of sleep improved with antireflux therapy. Head of bed elevation, proton pump inhibitor therapy, H(2)-receptor antagonists, and Nissen fundoplication alleviated nocturnal heartburn and associated sleep disturbances.

Nocturnal GERD is common and is associated with adverse sleep parameters. It can be effectively managed with medical and surgical therapy.

The roles of intragastric pressure (IGP), intraesophageal pressure (IEP), gastroesophageal pressure gradient (GEPG), and body mass index (BMI) in the pathophysiology of gastroesophageal reflux disease (GERD) and hiatal hernia (HH) are only partly understood.

In total, 149 GERD patients underwent stationary esophageal manometry, 24-h pH-metry, and endoscopy.

One hundred three patients had HH. Linear regression analysis showed that each kilogram per square meter of BMI caused a 0.047-kPa increase in inspiratory IGP (95% confidence interval [CI] 0.026-0.067) and a 0.031-kPa increase in inspiratory GEPG (95% CI 0.007-0.055). Each kilogram per square meter of BMI caused expiratory IGP to increase with 0.043 kPa (95% CI 0.025-0.060) and expiratory IEP with 0.052 kPa (95% CI 0.027-0.077). Each added year of age caused inspiratory IEP to decrease by 0.008 kPa (95% CI -0.015-0.001) and inspiratory GEPG to increase by 0.008 kPa (95% CI 0.000-0.015). In binary logistic regression analysis, HH was predicted by inspiratory and expiratory IGP (odds ratio [OR] 2.93 and 2.62, respectively), inspiratory and expiratory GEPG (OR 3.19 and 2.68, respectively), and BMI (OR 1.72/5 kg/m(2)). In linear regression analysis, HH caused an average 5.09% increase in supine acid exposure (95% CI 0.96-9.22) and an average 3.46% increase in total acid exposure (95% CI 0.82-6.09). Each added year of age caused an average 0.10% increase in upright acid exposure and a 0.09% increase in total acid exposure (95% CI 0.00-0.20 and 0.00-0.18).

BMI predicts IGP, inspiratory GEPG, and expiratory IEP. Age predicts inspiratory IEP and GEPG. Presence of HH is predicted by IGP, GEPG, and BMI. GEPG is not associated with acid exposure.

Early gastric cancer (EGC) with 5-year survival rates exceeding 90% now accounts for nearly 50% of all gastric cancers treated at major institutions in Japan. D2 lymphadenectomy with resection of at least two-thirds of the stomach has been the mainstay of treatment for every stage of gastric cancer, including EGC. Post-gastrectomy syndrome is inevitable after surgery. Most of the symptoms resolve with time, though some patients suffer immensely for prolonged periods. Mucosal cancers rarely metastasize (3% or less). Surgeons have altered the traditional strategy for treatment which focused only on highly radical operations. The new strategy preserves patients' quality of life, while at the same time maintaining a high level of radicality, by employing a function-preserving operation which prevents post-gastrectomy syndrome. The Japanese gastric cancer treatment guidelines have standardized indications for the function-preserving surgery that is widely performed in Japan. There are various kinds of function-preserving operations, such as those reducing the extent of gastrectomy, and those providing nerve preservation, sphincter preservation, and formation of a new-stomach. Evaluation of preserved function is not satisfactory, because there is no gold standard for measuring gastrointestinal motor function and patients' quality of life.

We sought to determine the reliability of morphometric measurements on infant esophageal biopsies using a light microscope with eyepiece micrometer.

We measured epithelial thickness, basal layer thickness (B), papillary height (P) and epithelial lymphocyte and eosinophil numbers on approximately 500 existing esophageal suction biopsies from infants previously evaluated for reflux esophagitis. We tested these measurements for interobserver, test-retest and internal consistency reliability.

Infants ages 0.25 to 23.75 (median, 6.25) months provided 497 biopsies. Both investigators scoring the biopsies independently judged 93% of them scorable. Of the biopsies scored by both, the 2 readings were within 0.15 of each other for P in 97% and for B in 81%. In addition to these correlative measures of consistency, categoric measures demonstrated that 373 (89%) of the 420 scorable biopsies with visible papillae produced agreement as to P being abnormal (317, 85%) or normal (56, 15%). Similarly, 360 (78%) of the 463 scorable biopsies produced agreement as to B being abnormal (339, 94%) or normal (21, 6%). P values were 0.17 to 0.94 (median, 0.67), and B values were 0.13 to 0.91 (median, 0.34). Lymphocytes numbered 0 to 40 (median 5) per high-power field. Only 12% had any eosinophils; none of those with completely normal morphometrics had any eosinophils; and only 2% had >5 eosinophils per high-power field.

Simple quantitative esophageal histological morphometric parameters are reliably measurable on suction biopsies from infants using a light microscope fitted with an ocular micrometer, even by nonpathologists.

This review evaluates the current knowledge about the recognition of histologic esophageal mucosal changes in patients with nonerosive gastroesophageal reflux disease and analyzes the technical factors relevant to their interpretation. Studies investigating histologic changes in individuals with nonerosive reflux disease were identified by systematic Medline/PubMed searches from January 1966 to October 2005. Dilation of intercellular spaces was the most consistently reported histologic change in the esophageal mucosa of patients with nonerosive reflux disease, being observed in 41%-100% of patients and 0%-30% of controls. The mean intercellular space width was at least 2 times greater in patients than in controls, irrespective of esophageal acid exposure. Basal cell hyperplasia was observed in 9%-90% of patients compared with 10%-55% of controls. Papillary elongation was observed in 0%-85% of patients and 5%-20% of controls. Both of these features were more prevalent in reflux disease patients with abnormal esophageal acid exposure. All histologic changes responded to acid-suppressive therapy. Inflammatory cell infiltration was seldom observed or had a similar prevalence in patients and controls. Disparities in reported frequencies of change among studies were most likely caused by methodologic factors, most importantly the use of different methods for identifying patients and controls, for histologic sampling, and for biopsy scoring. The reviewed studies suggest that at least two thirds of patients with nonerosive reflux disease have histologic evidence of esophageal injury. Additional work is needed to assess the potential of these histologic changes for the diagnosis and assessment of reflux disease.

The purpose of this review was to explore issues relating to the nature of oesophageal injury in gastro-oesophageal reflux disease. Several structural and functional elements of the oesophageal epithelium provide for an inherent resistance against refluxed material. It is only when this defence is overcome that reflux-induced damage ensues. The light microscopic changes in reflux oesophagitis are manifold. Early changes are confined to the epithelium and consist of reactive changes and inflammatory cell infiltration. When the epithelial integrity can no longer be maintained, erosions and ulcers develop. Recently, dilatation of the intercellular spaces was described as a sensitive early marker for gastro-oesophageal reflux disease. This parameter was first identified by electron microscopy but can also be assessed by light microscopy in routinely stained tissue sections. Some of the changes occurring in early gastro-oesophageal reflux disease can be reproduced by incubating oesophageal mucosal biopsies in gastrointestinal fluids or their components. Activated pepsin, trypsin and conjugated bile acids at an acidic pH have been identified as probable causes of reflux-induced damage.

Although cases of reflux esophagitis (RE) developing after treatment to eradicate Helicobacter pylori have been discussed in some detail, no reports are available concerning the histologic examination of RE both before and after eradication therapy.

Sixty-one patients and 111 specimens were investigated using endoscopic and histologic techniques. The histologic findings including basal zone height, papillar height, Ki-67 labeling index, and COX-2 expression before and after treatment for H. pylori infection were compared with those in normal controls and patients with endoscopic RE.

Twelve months after eradication therapy, the incidence of newly developed endoscopic RE was 20% (5/25). Basal zone height and papillar height had increased at 1 month, but had returned to pretreatment levels after 12 months of eradication therapy. The Ki-67 labeling index was significantly increased 1 and 12 months after eradication therapy compared to values before treatment. COX-2 expression gradually increased after the treatment. The phenomena linked to esophagitis appeared after eradication therapy. However, the severity and extent of these signs were not so high after the treatment of H. pylori than those in patients with overt reflux esophagitis. Focusing on the patients with hiatal hernia, papillar height and Ki-67 labeling index increased significantly after eradication therapy, values being almost the same as those in the patients with endoscopic RE.

Hiatal hernia plays an important role in the possible occurrence of hidden RE after treatment for a H. pylori infection.

The relationship between gastroesophageal reflux disease and sliding hernia is controversial, especially following distal partial gastrectomy in patients with gastric cancer. The aim of this study was to examine the relationship between gastroesophageal reflux disease and sliding hernia of the esophagus after distal gastrectomy using the gastroesophageal scintigraphy and endoscopy.

Forty-five distal gastrectomy patients diagnosed with cancer of the stomach were studied. Twenty-five patients presented with reflux symptoms, such as heartburn and/or regurgitation and 20 patients exhibited no reflux symptoms. All of the patients were examined by gastroesophageal scintigraphy and their reflux indices were determined. Thirty-eight of the patients underwent upper endoscopy and both sliding hernias and reflux symptoms were classified as mild or severe.

Sliding hernias were diagnosed in all of the subjects and 65.8% of the patients exhibited reflux symptoms. Evidence of endoscopic esophagitis was noted in only 39.5% of the patients. The reflux indices for the mild and severe hernia groups were 5.03 +/- 2.2 and 10.3 +/- 6.4, respectively (P < 0.05). More severely symptomatic esophagitis was prevalent in the severe hernia group in comparison to the mild group (P < 0.05).

The results suggest that the onset of gastroesophageal reflux after distal gastrectomy is induced by the surgical procedures and that hiatal hernia may be an important factor in the etiology of reflux esophagitis.

To determine the natural history of infant gastroesophageal reflux disease (GERD) with esophagitis, we periodically analyzed symptoms and biopsies during 1 yr in 19 infants randomly assigned to placebo in a pharmacotherapy study.

One hundred infants who were referred during 1994-1999 for GERD, were unresponsive to 2-wk life-style measures, and manifested morphometric reflux esophagitis, were assigned at random to one of four treatment arms. This analysis examines the 19 (ages 2.8-6.0 months) assigned to placebo who returned for initial follow-up. SYMPTOMS and esophageal biopsy were assessed at baseline and 2, 4, 6, and 12 months. At any visit with both symptoms and biopsy unimproved, infants were "rescued" to open label active drug.

By 12 months, 10/19 completed without rescue; the 9 others withdrew (3) or required pharmacotherapy (6).

Among the 10 nonrescued completers, parents' global score rated 9 "completely well," and 1 "improved." Comparing 12-month symptoms to baseline symptoms in the 10 completers, fewer reported regurgitation >3/day, >1 Tbsp, or that was uncomfortable; crying >1 h/d, or during or after feeds; or arching spells or abnormal hiccups (p < 0.05, chi(2)). Biopsy: None of the 10 ever had normal biopsies (basal cell layer <25% and papillary height <53% of epithelial thickness). One had normal papillary height, but abnormal basal thickness. Five others had normal basal thickness, but all five of them had abnormal papillary height.

Although symptoms improved in more than half of the infants with reflux esophagitis followed longitudinally for 1 yr without pharmacotherapy, histology remained abnormal.

The histological changes that occur in the squamous epithelium in response to acute acid challenge was examined in healthy controls and proton pump inhibitor-treated gastroesophageal reflux disease (GERD) patients and related to the state of untreated erosive GERD in a saline-controlled, randomized perfusion study. In the basal state a stepwise significant increase in the thickness of the basal cell layer, papillary length, and dilatation of intercellular spaces (DIS) was seen when the three groups were compared. Acid perfusion induced a slight increase in the height of the basal cell layer mainly in healthy volunteers; this layer appears to be reactive to acute acid challenge as well as to acid suppressive therapy. DIS increases promptly in response to acute acid exposure in the healthy epithelium but no changes were seen in the lengths of the papillae or regarding DIS in the GERD patients. A protective effect of luminal nitric oxide on DIS development is suggested.

Gastro-oesophageal reflux disease (GERD) is among the most common gastrointestinal conditions in the USA. For most symptomatic patients, reflux events occur during both daytime and night-time hours. Whereas daytime reflux events tend to be frequent but brief, reflux events that occur during sleep are comparatively less frequent but significantly longer. Longer oesophageal acid-clearance and acid-mucosal contact times during sleep are at least partly due to several physiological changes associated with sleep, including dramatic declines in saliva production and frequency of swallowing, decreased conscious perception of heartburn and consequent arousal and clearance behaviours, and slower gastric emptying. Obstructive sleep apnea syndrome and obesity seem to predispose some patients to nocturnal GERD, and the presence of either of these conditions may help to identify patients with symptoms consistent with GERD. Recognition and treatment of night-time GERD are important because it can be associated with decreased quality of life (including sleep disruption) and increased risk of serious oesophageal and respiratory complications.

Children presenting with persistent symptoms attributed to gastroesophaeal reflux disease (GERD) that are unresponsive to both medical and surgical therapies are commonly submitted to esophageal biopsies, the results of which show an abnormal presence of eosinophils. In this setting, eosinophilic esophagitis may be the correct diagnosis. The purpose of this report is to clarify the importance of esophageal eosinophilic infiltration, regardless of whether associated with acid reflux, ie, as an independent symptomatic entity, when treating a patient with refractory GERD.

Two boys, aged 8 and 7 years, had the classic symptoms of GERD. They were treated with antacid without improvement of the esophagic lesions. Subsequent esophageal biopsy results showed marked eosinophilic infiltration. From this moment on, eosinophilic esophagitis started to be considered the main diagnosis.

Although eosinophilic infiltration caused by GERD is very frequently found in esophageal biopsy, in case of refractory drug treatment and microscopic findings of a great number of eosinophils and mast cells, eosinophilic esophagitis must be considered. This disease is better treated with corticoids instead of antacid drugs. It explains the reason some patients do not respond to antacid and surgical treatment and remain symptomatic with esophagic lesions.

In refractory cases of GERD, eosinophilic esophagitis must be considered before any surgical measure.

The incidence of gastroesophageal reflux disease (GERD) is increasing and if left untreated can lead to significant patient morbidity and even death. The disease results from the abnormal reflux of gastric contents into the distal esophagus causing symptoms in most and subsequent mucosal damage in some. Several investigations can be used to confirm the diagnosis, but most are dependent on the presence of sequelae and complications of the disease. The physiologic test of ambulatory 24-hour esophageal pH monitoring has proved to be the most sensitive and specific diagnostic investigation. It measures increased esophageal exposure to gastric juice by detecting the concentration of hydrogen ions (pH <4) in the distal esophagus. The technique measures gastric juice exposure at a point 5 cm above the manometrically determined upper border of the lower esophageal sphincter. The exposure is measured in components of frequency of reflux episodes, duration of reflux episodes, and accumulated exposure time. The components are integrated into a composite score, which is reproducible, gender and race independent, and correlates with the degree of esophageal epithelial damage determined histologically. The composite score has been shown to be the most reliable measurement of a therapeutic acid suppression regimen or an effective antireflux operation.

Gastro-oesophageal reflux disease (GERD) is a complex multifactorial disorder whose treatment is based on knowledge of its pathophysiology, natural history and evolution. Recently the relationship between the severest degrees of cardial incontinence and hiatus hernia has been emphasized, which causes the impairment of the mechanical properties of the gastro-oesophageal barrier and of oesophageal acid clearing. Among different types of hiatus hernia, those characterized by the permanent axial orad migration of the oesophago-gastric (EG) junction (nonreducible hiatus hernia) are correlated with severe GERD. Barium swallow may adequately differentiate hiatal insufficiency, concentric hiatus hernia and short oesophagus which are the steps of migration across or above the diaphragm. When associated with panmural oesophagitis and fibrosis of the oesophageal wall, these conditions may be the cause of recurrence of hiatus hernia and reflux after laparoscopic standard anti-reflux surgical procedures; in the presence of nonreducibility of the EG junction below the diaphragm without tension, dedicated surgical procedures are necessary. It is currently agreed that surgical therapy is indicated for patients affected by severe GERD who are not compliant with long-term medical therapy, require high dosages of drugs and are too young for lifetime medical treatment. While the existence of severe GERD correlated with an irreversible anatomical disorder represents an elective indication for surgery, warrants further investigation. Accurate identification of the functional and anatomical abnormalities underlying GERD is mandatory in order to decide whether medical or surgical therapy should be implemented, and to tailor the surgical technique, laparoscopic or open, to each patient.

Eosinophilic esophagitis (EoE), a disorder characterized by eosinophilic infiltration of the esophageal mucosa, has been defined in large part through published case reports and series leading to ambiguity in both diagnostic and treatment options. Corticosteroids, cromolyn, and elemental diet have all been reported as successful treatments for EoE. In this study, we sought to accurately define a population of patients with EoE and then assess their response to elemental diet.

A series of patients with chronic symptoms of gastroesophageal reflux disease and an isolated esophageal eosinophilia on esophagogastroduodenoscopy (EGD) were identified. Therapy with a proton pump inhibitor was instituted for 3 months, followed by repeat EGD when symptoms persisted. A 24-h pH probe study was performed, and those with significantly abnormal studies were excluded. The remaining patients were diagnosed with EoE and placed on an elemental diet for 1 month, followed by a repeat EGD.

Of 346 patients with chronic gastroesophageal reflux disease symptoms and eosinophils on esophageal biopsy, 51 (14.7%) were ultimately diagnosed with EoE. There was significant improvement in vomiting, abdominal pain, and dysphagia after the elemental diet. The median number of esophageal eosinophils per high-powered field (HPF) decreased from 33.7 before the diet to 1.0 after the diet (p <0.01). The average time to clinical improvement was 8.5 days.

Elemental diet resulted in striking improvement in both symptoms and histologic evidence of disease in children and adolescents with EoE, as identified by strict diagnostic criteria.

To determine the value of squamous mucosal histology in the assessment of patients with gastro-oesophageal reflux symptoms.

Sixty six patients with reflux symptoms underwent endoscopy with oesophageal biopsy, manometry, and 24 hour oesophageal pH testing. The following histological features were assessed in squamous mucosa: the degree of basal cell hyperplasia, the degree of papillary zone elongation, and the density of neutrophil and eosinophil infiltration. Comparisons were made between the histological findings and the oesophageal function tests.

The correlation between the traditionally accepted histological markers of gastro-oesophageal reflux disease in squamous mucosa and 24 hour pH testing was predominantly negative, with the exception of neutrophil inflammation in the squamous mucosa of patients with complicated reflux disease.

This study was unable to confirm the value of the Ismail-Beigi criteria as histological markers of acid reflux. By inference, biopsy of the oesophageal squamous mucosa is of limited value in the assessment of patients with reflux symptoms.

Patients with gastroesophageal reflux disease (GERD) accompanied by erosive reflux esophagitis (RE) exhibit an impairment within the esophageal pre-epithelial barrier protective components that may facilitate the development and/or progression of the mucosal injury. Little is known, however, whether such impairment is a general phenomenon affecting all patients with GERD or whether this is a characteristic feature only of patients with erosive RE. We therefore studied the rate of secretion of esophageal inorganic and organic protective factors in patients with endoscopically negative [E (-)] GERD and compared these results with the corresponding values in asymptomatic volunteers (CTRL).

The study was conducted on 33 white asymptomatic volunteers and 10 white patients with a long history of GERD confirmed by 24-h pH monitoring and a grossly negative upper endoscopy. Esophageal secretion was collected during mucosal exposure to NaCl, HCl, HC/pepsin and NaCl using the esophageal perfusion catheter. In collected samples all investigated parameters were measured.

The pH of esophageal secretion and its content of bicarbonate, EGF, and PGE2 in patients with E (-) GERD and asymptomatic volunteers were similar. Unexpectedly, the rate of esophageal glycoconjugate (predominantly mucin) secretion was significantly higher in patients with E (-) GERD than in controls during perfusion with HCl (p < 0.05). Furthermore, secretion of protein in patients with E (-) GERD was significantly higher than in the control group during the mucosal exposure to HCl/Pepsin (p < 0.05). The nonbicarbonate buffer secretion during perfusion with HCl and HCl/Pepsin as well as the rate of esophageal TGFalpha output during infusion of final saline in patients with E (-) GERD were significantly lower than in CTRL group (p < 0.05).

Our data indicate that patients with E (-) GERD have an esophageal secretory potential, in terms of glycoconjugate and protein, higher than that in asymptomatic controls. This phenomenon in patients with E (-) GERD may, by enhancing the quantity of the esophageal pre-epithelial barrier, help to prevent the development of erosive esophagitis. A significantly lower esophageal secretory response in patients with E (-) GERD in terms of nonbicarbonate buffers and TGFalpha may facilitate the development of GERD symptoms and histological changes of GERD, respectively.

As many as half of patients who have symptoms and objective evidence of gastroesophageal reflux disease (GERD) will have normal mucosa or only hyperemia at endoscopy. Because inflamed esophageal mucosa may appear normal endoscopically, and because hyperemia may or may not reflect histologic espophagitis, biopsy to document tissue injury in symptomatic patients with these minimal endoscopic findings may be helpful. Reflux may induce inflammation in the squamous mucosa of the esophagus, but in many patients only hyperplasia of the epithelium is seen. This hyperplasia is defined by a basal zone that exceeds 15% of the thickness of the mucosa and subepithelial papillae that exceed 67% of the thickness of the mucosa. Because these changes may be present normally in the distal 2.5 cm of the esophagus, and because they may be distributed over the distal 8 cm in a patchy fashion, multiple biopsies taken more than 2.5 cm above the esophagogastric junction are necessary to detect them reliably. Supraesophageal complications of GERD include posterior laryngitis, inflammatory polyp of the larynx (contact ulcer or laryngeal granuloma), subglottic stenosis and laryngeal squamous cell carcinoma.

Gastroesophageal reflux disease (GERD) is an extremely common disorder. Many patients require lifelong medical therapy for symptom control. In patients being considered for antireflux surgery, thorough evaluation is required. Laparoscopic antireflux surgery is a safe and effective method of treating patients who have severe, refractory, or complicated GERD. Excellent long-term results are obtained with minimal morbidity, freeing the patient from the burden of chronic medical therapy.

The aim of our study was to evaluate the success, complications, and morbidity following a modified Thal fundoplication in children with reflux-associated respiratory disease (RARD). We used a procedure consisting of retroesophageal hiatal plasty, wrapping the gastric fundus around the gastroesophageal junction 180 degrees, and fixation of the lesser curvature at the abdominal wall. Follow-up by questionnaire of 128 (77 male, 51 females) out of 196 antireflux procedures between 1992 and 1995 was achieved. Surgical therapy was considered justified whenever there was gastroesophageal reflux resulting in severe recurrent respiratory symptoms. Eleven percent of the children suffered from bronchiectasis. The diagnosis of RARD was based on a high index of suspicion, barium swallow with fluoroscopy, 24-hr two-level pH-monitoring, bronchoscopy, bronchoalveolar lavage and detection of lipid-laden alveolar macrophages, esophago-gastroscopy, and esophageal biopsy. Patients with bronchopulmonary diseases such as allergy, immunodeficiency, cystic fibrosis, primary ciliary dyskinesia, and malformation of the bronchial tree or vessels had been excluded. "Evident improvement" as a result of surgery was reported in 88%, "no change" in 10%, and a "change for the worse" in 2% of patients. Persistent mild difficulties in swallowing were observed in 11%. Paraesophageal hernia, gas-bloat syndrome, and dumping syndrome were not observed. Two children needed a second operation because of relapse. The use of emergency steroidal medication for acute respiratory distress decreased impressively (219 single doses/year before surgery vs. 30 single doses/year after surgery). The need for more than 4 times/year of antibiotic therapy before surgery was reduced from 52. 3% before to 14% after surgery. Most (90.6%) of the parents stated they would agree to have surgery done again if medically indicated. In conclusion, Thal fundoplication is sufficient, safe, and effective in the management of RARD. Complications of the procedure were minor and of little consequence to the patient.

Eosinophilic gastroenteritis (EG) was first described over 50 years ago. Despite its long history, it remains an ill-defined and poorly understood entity. EG can present in a number of ways, none of which are exclusive to the disorder. EG has features of allergy and immune dysregulation but does not clearly fit into the category of allergic or immune disorder. While EG has been reported to affect all locations and layers of the gastrointestinal tract, the vast majority of reported cases have demonstrated mucosal involvement of the gastric antrum and small intestine in addition to disease activity of other locations of the gastrointestinal tract. Recently, several reports have identified a disease consisting of an isolated esophageal eosinophilia. Eosinophilic esophagitis (EE), also known as primary eosinophilic esophagitis or idiopathic eosinophilic esophagitis, occurs in adults and in children and represents a subset of EG with an isolated severe esophageal eosinophilia. Patients with EE present with symptoms similar to those of gastroesophageal reflux but are unresponsive to antireflux medication. Reports have demonstrated that patients with EE respond to either dietary restriction or corticosteroids.

Nissen fundoplication gives lasting relief from symptoms of gastro-oesophageal reflux and cures endoscopic oesophagitis effectively. The histological effect on the oesophageal mucosa is less clear. We studied the long-term histological effect of Nissen fundoplication on refractory gastro-oesophageal disease with erosive oesophagitis or Barrett's metaplasia in 33 patients with biopsy both before and after antireflux surgery. The median postoperative interval to re-examination was 80 (range 37-110) months. Symptoms of reflux were greatly relieved; 31 (94%) of the 33 patients had none or, at the most, mild symptoms. Endoscopic oesophagitis was healed in 26 (79%) of the cases. The histological appearance of the oesophageal mucosa had been abnormal in all the patients preoperatively, but at follow-up it was normal in 22 cases (67%): in 89% of the patients without objectively observed recurrent reflux and in 45% of those with recurrence. Both the pre- and postoperative severity of the histological changes correlated significantly with the endoscopic grade of oesophagitis (r=0.42, P=0.017 and r=0.837, P=0.0001, respectively), but not with the clinical reflux score. In conclusion, Nissen fundoplication resulted in histological healing in the great majority of patients with oesophagitis.

Two studies were carried out in order to investigate the issue of meal-provoked nocturnal gastrooesophageal reflux.

In Experiment 1, 20 symptomatic reflux patients underwent both pH and polysomnographic monitoring on two nights. On one night, patients ate a non-provocative meal prior to 19.00 hours, while on the other night patients consumed a late evening meal (21.00 hours). In Experiment 2.17 symptomatic reflux patients were studied using pH and polysomnographic monitoring on two nights subsequent to a late evening provocative meal. On one night, patients received 75 mg of the H2-antagonist ranitidine, while on another night they received a placebo. The data from 12 of the 17 patients studied were used in the analysis.

For Experiment 1, no significant differences in the number or duration of reflux events, acid exposure (total %), or polysomnographic measures of per cent of sleep stages between the two nights were observed. The results of the second experiment demonstrated that when given ranitidine, patients experienced significant decrease in acid contact time (total %), and mean duration of reflux events. Subjective reports of discomfort and sleep disturbance were also significantly improved on the drug night. However, significant differences in polysomnographic measures were not observed.

Based on these results, we conclude that in some symptomatic reflux patients a late-night non-provocative meal may not increase the incidence of gastro-oesophageal reflux, and that a low dose of an H2-antagonist is effective in decreasing oesophageal acid contact time following a late evening provocative meal.

Because the collection of normative sleep data in the pediatric age group largely depends on technical issues, this article discusses various aspects of sleep recordings in infants and children. Polygraphic monitoring of sleep and waking behavior contributes to a better description of maturational stages in children, from the prenatal period to the end of adolescence. This article reviews the general characteristics of normal children's sleep and the environmental factors that influence these maturational processes. The use of polygraphic recordings to identify neurological deficits and to predict behavioral and neurological outcome in infants and children, however, does not hold great promise. The importance of polysomnographic evaluation is admitted for some major clinical conditions, such as risks for abnormal breathing or narcoleptic attacks.

Prolonged esophageal pH monitoring is the most accurate method for detecting abnormal gastroesophageal reflux (GER) in patients with gastroesophageal reflux disease (GERD). However, some investigators have found that short-duration postprandial pH monitoring in the upright position is also useful, while others have failed to find such results. Therefore, we have compared a 6-hr period of pH monitoring (3-hr postprandial period after daytime meal and 3-hr supine period) with a total 24-hr period in detecting abnormal gastroesophageal reflux. Sixty-five patients (44 men, mean age 41.3 years) with GERD and 16 healthy volunteers (11 men, mean age 34.3 years) underwent 24-hr pH monitoring according to a standard protocol. Various reflux parameters during 24-hr pH monitoring were compared with reflux parameters during the 6-hr period. Abnormal GER was detected in 56 patients presenting with typical symptoms of GERD (sensitivity 86.2%). These patients could be further divided into upright (N = 18), supine (N = 15), and combined (N = 23) refluxers, depending on the posture in which abnormal reflux occurred. Esophageal pH monitoring during the 3-hr postprandial upright period showed abnormal reflux in only 35 patients (sensitivity 53.8%; P < 0.00005, compared with the 24-hr pH monitoring period). Abnormal GER was identified in 13 of 18 upright, 19 of 23 combined, and only one of 15 supine refluxers, as well as in two of nine patients with normal 24-hr pH-metry. However, inclusion of the 3-hr supine monitoring period in the 3-hr postprandial upright period improved detection of abnormal GER to 78.5% (51 patients; P = NS compared with 24-hr pH monitoring period). This was related mainly to improved detection of abnormal GER in supine refluxers (11 of 15; 73.3%). Esophageal acid exposure time correlated significantly with severity of esophagitis only during the total and supine periods of both the 24- and 6-hr periods and not during the upright period. Esophageal acid clearance correlated significantly with increasing grades of esophagitis for the supine and total periods only. We conclude that 3-hr postprandial pH monitoring, as has been conventionally practiced, is not appropriate in the detection of abnormal GER; inclusion of a supine period in the short-duration pH monitoring schedule increases the detection of pathological reflux. We therefore recommend that a supine period should be included in short-duration pH monitoring schedules. We also found that supine reflex was the most important factor in the development of esophagitis.

The percentage of epithelial surface area covered by microridges (%MR) seen during scanning electron microscopy of oesophageal biopsy specimens has previously been shown to correlate with symptomatic reflux disease, a result < or = 35% being abnormal. The aim of this study was to compare %MR with endoscopy, light microscopy, and pH monitoring results.

Sixty-seven patients with heartburn were divided into oesophagitis or none on the basis of endoscopy and light microscopy findings and into those with and without abnormal acid reflux on the basis of pH monitoring.

The endoscopic and light microscopic oesophagitis groups had significantly greater degrees of acid reflux than those without oesophagitis (p < 0.05), even though neither the specific %MR nor the number of patients below the 35% cutoff showed any difference between those with and without endoscopic oesophagitis, light microscopic oesophagitis or those with normal and abnormal acid reflux on pH monitoring.

Despite the significant relationship between endoscopic and light microscopic oesophagitis and abnormal pH monitoring microridge analysis did not correlate with any of these variables

Histologic changes indicative of gastroesophageal reflux disease (GERD) are found on both sides of the squamocolumnar junction (Z-line). In the gastric cardia, inflammation is found as part of GERD in the absence of Helicobacter pylori or other causes of gastritis (carditis). The squamous mucosa is the location most likely to show inflammatory changes, such as neutrophils or eosinophils, close to the Z-line, whereas traditional reactive changes in the squamous mucosa are found only in biopsies taken at least 3 cm above the Z-line. Endoscopic criteria for GERD have a morphologic counterpart in capillary congestion and hemorrhage into the papillae, which have largely been ignored by pathologists as secondary to biopsy trauma. A biopsy protocol that maximizes the chances of detecting changes of GERD is suggested. The traditional definition of Barrett's esophagus as requiring 3 cm of glandular mucosa extending into the esophagus is no longer tenable. However, even the concept of short-segment Barrett's esophagus, in which less than 3 cm of intestinalized mucosa is present, often as tongues, is being challenged because random biopsies immediately distal to the Z-line may also show intestinal metaplasia when Barrett's esophagus is unsuspected endoscopically. Moreover, it is difficult or impossible to determine whether these changes indicate the earliest lesion of Barrett's esophagus or intestinal metaplasia in native cardiac mucosa. It is suggested that Barrett's esophagus be redefined as intestinal metaplasia in the lower esophagus. It is presently unclear whether patients with such minimal Barrett's epithelium are at increased risk for adenocarcinoma or require surveillance. Successful therapy for GERD results in healing of disease in squamous mucosa and may result in regression of Barrett's epithelium. In the stomach it may be associated with temporary regression of H. pylori and associated inflammation, migration of H. pylori into the oxyntic mucosa, hypertrophy and hyperplasia of parietal cells, and a variant of fundic gland polyps. Some patients may be at risk for accelerated atrophic gastritis if inflammation is present before therapy.

Treatment for gastroesophageal reflux may be ineffective in patients with an eosinophilic infiltration of the esophagus. The aim of this study was to investigate whether unremitting symptoms of gastroesophageal reflux and biopsy abnormalities of the esophagus may be associated with the ingestion of certain foods.

Ten children previously diagnosed with gastroesophageal reflux by standard testing with long-standing symptoms (median, 34.3 months; range, 6-78 months) despite standard antireflux therapies, including Nissen fundoplication in 6 patients, were fed the elemental formulas Neocate or Neocate-1-Plus (Scientific Hospital Supplies Inc., Gaithersburg, MD) for a minimum of 6 weeks. Each child had repeat endoscopy followed by open food challenges.

While receiving the formulas, patients had either resolution (n = 8) or improvement (n = 2) of symptoms. On follow-up esophageal biopsy, the maximal intraepithelial eosinophil counts decreased significantly before (median, 41; range, 15-100) to after (median, 0.5; range, 0-22) the formula trial (P = 0.005). Other reactive epithelial changes of the esophageal mucosa also improved significantly. All patients redeveloped their previous symptoms on open food challenges.

Chronic gastrointestinal symptoms and histological changes of the esophagus unresponsive to standard treatments for gastroesophageal reflux were improved by the use of elemental formulas. Symptoms recurred when specific dietary proteins were reintroduced during open food challenges. The mechanism of these observations is unknown.

Reactive oxygen species (ROS) produced by inflammatory cells can contribute to tissue destruction. ROS have been implicated in various gastrointestinal abnormalities, including the acid related peptic diseases. Although the development of oesophagitis and Barrett's columnar epithelium is associated with prolonged reflux of gastric acid, the exact mechanism by which tissue damage occurs is not known. To discover if ROS are involved in damage to the oesophageal mucosa, this study measured in vitro the mucosal ROS concentrations of biopsied mucosal samples taken from patients with reflux oesophagitis using luminol enhanced chemiluminescence (LECL). Mucosal biopsy specimens were taken from 83 patients: 19 with normal oesophageal mucosa (group I); 20 with macroscopic oesophagitis (group II); 20 with biopsy confirmed Barrett's epithelium without macroscopic oesophagitis (group III); and 24 with Barrett's epithelium with macroscopic oesophagitis (group IV). The mucosa from patients exhibited significantly higher LECL values than the mucosa from controls. But, there were no significant differences between groups II, III, and IV. Addition of the myeloperoxidase inhibitor, azide, or the hydrogen peroxide scavenger, catalase, to the tissue suspension caused a decrease in LECL values of 32% and 45%, respectively, suggesting that neutrophils--although important--are not the only source of mucosal LECL. These data are consistent with the proposal that ROS play an important part in the tissue injury associated with oesophagitis and Barrett's columnar epithelium.

Previous studies examining oesophageal acid clearance have employed a variety of techniques to induce or simulate acid reflux. Clearance abnormalities have been deduced from abnormal standard motility studies, barium radiology or from 24-h pH recordings. In this study a 24-h pH and oesophageal motility recording system was used to study naturally occurring acid reflux episodes in control subjects and in two groups of patients with severe acid reflux disease (erosive oesophagitis and oesophageal stricture). Acid clearance was compared between the subject groups. Patients with oesophageal stricture were found to have poor oesophageal peristaltic ability and particularly poor oesophageal acid clearance. Those with erosive oesophagitis had normal peristaltic swallowing but abnormal acid clearance. This study has characterized, for the first time, the abnormalities in acid clearance during naturally occurring acid reflux episodes in patients with severe reflux disease. A more complete understanding of these clearance abnormalities could influence future medical and surgical strategies in the management of severe gastro-oesophageal reflux disease.

Linxian, China, has one of the highest rates of esophageal cancer in the world. Other authors have described high prevalences of histologic esophagitis, atrophy, and dysplasia in Linxian and have suggested that these findings may represent precancerous lesions in this population. In 1987, a new endoscopic survey allowed the authors to make an independent study of esophageal histology in Linxian.

There were 1567 satisfactory squamous esophageal biopsies available from 754 patients. These biopsies were classified as normal, atrophy, acanthosis, esophagitis, squamous dysplasia, or squamous cancer.

Classified by their worst diagnosis, 56.5% of the 754 patients had normal mucosa, 0.0% atrophy, 11.5% acanthosis, 4.6% esophagitis, 22.7% squamous dysplasia, and 4.6% squamous cancer.

The results show a different distribution of esophageal squamous diagnoses than has been reported previously from this population. The authors believe that the major reason for this discrepancy was differences in histologic criteria. In this survey, seemingly small differences in criteria could cause large differences in apparent disease prevalence; this was especially true for esophagitis. By the criteria used in this study, histologic esophagitis and atrophy are uncommon findings in Linxian, raising questions about their significance as precursor lesions of esophageal cancer in this population.

Gastric acid suppression could improve heartburn by healing oesophagitis or by reduction of oesophageal sensitivity to acid. To independently assess changes in oesophageal sensitivity, it would be necessary to study patients with reflux disease but no oesophagitis. The aim of this study was to investigate the effect of acid suppression on oesophageal sensitivity and to assess the time course of any measured effect. Twenty seven patients were recruited, of whom 25 completed the study (14 men and 11 women, mean (SD) age 50 (15) years). All had classic symptoms of gastro-oesophageal reflux but normal results of upper gastrointestinal endoscopy and oesophageal mucosal histological tests. Each had abnormal 24 hour pH studies and a positive acid perfusion tests. Subjects were assigned double blind to placebo (n = 11) or famotidine 40 mg twice daily (n = 14) for four weeks. Acid perfusion tests were carried out at 0, 4, 5, and 8 weeks and time to heartburn recorded. Time to heartburn (mean (SEM)) was 124 (78) seconds in the famotidine and 187 (154) in the placebo group at week 0 (NS). Compared with baseline, significant increases in time to heartburn was found with famotidine at weeks 4 (383 (102), p < 0.01) and 5 (344 (92), p < 0.01) but not week 8 (336 (90) seconds). No significant effects were found with placebo (219 (41), 146 (23), and 144 (25) seconds for weeks 4, 5, and 8). Heartburn symptom score decreased significantly with famotidine (mean scores 3.6, 1.9, 2.1, and 2.6 at weeks 0, 4, 5, and 8 (p=0.001)) and showed a significant negative correlation with time to heartburn (r(s)=-0.60; p<0.0001). It is concluded that oesophageal sensitivity to acid is reduced by famotidine independent of and effect on oesophagitis; the effect wanes one to four weeks after the end of treatment and correlates with change in heartburn score.

Gastroesophageal reflux is a common disease that accounts for approximately 75% of esophageal pathology. Motility abnormalities of the esophagus and stomach, including an incompetent lower esophageal sphincter, are responsible for pathologic reflux in the majority of patients. Surgical treatment offers the only chance for long-term cure. Obtaining optimal results following surgery of the esophagus is one of the most challenging aspects of modern surgical therapy. Given a precise diagnosis, careful patient selection, critical attention to detail in the perioperative period, and the meticulous performance of the appropriate anti-reflux procedure, long-term success can be assured in more than 90% of patients.

This study was designed to assess the relationship between gastric acid output (GAO) and both pattern of gastroesophageal reflux (GER) and severity of esophageal lesions. Gastric acid secretory testing and 24-h intraesophageal pH-monitoring were performed in 31 patients with esophagitis and concomitant duodenal ulcer (E+DU) and compared with those of 72 patients with esophagitis (E). The second aim of this study was to evaluate the role of GAO and other potential pathogenetic factors in the development of esophagitis. The results of the study showed that GAO in patients with E+DU was significantly higher than in patients with E (p < 0.05). There was no significant difference between the two groups of patients with regard to endoscopic findings or GER variables (p < 0.05). Multiple regression analysis with stepwise deletion showed that the presence of hiatal hernia, GER in the upright position and age appear to correlate significantly with the presence of esophagitis. We conclude that no parallel relationship exists between GAO and severity of GER or esophageal lesions in patients with E+DU and that GAO is not a major pathogenetic factor in GER disease.

Scarce information is available on gastroesophageal reflux disease in elderly patients. In this study we investigated patterns of gastroesophageal reflux and esophageal lesions in 24 elderly patients with typical gastroesophageal reflux symptoms and a mean age of 69 years (range, 65-76 years), as compared with 147 symptomatic younger patients with a mean age of 45 years (range, 21-64 years). The results of 24-h pH-monitoring and endoscopy showed that the elderly patients had pathologic reflux and reflux esophagitis more frequently than the young patients. The percentage time with pH < 4 in elderly patients with reflux esophagitis was 32.5% in 24 h, as compared with 12.9% in the younger patients with reflux esophagitis (P < 0.05). The elderly patients with reflux esophagitis had more prolonged periods of acid reflux in both the upright and supine positions than the younger patients. Endoscopy showed that 20.8% of elderly patients had grade III/IV esophagitis, whereas only 3.4% of younger patients had grade III/IV esophagitis (p < 0.002). The percentages of grade I/II esophagitis in the two groups were 12.5% and 26.5%, respectively (p < 0.002). We concluded that, compared with younger subjects, elderly patients have more severe gastroesophageal reflux and esophageal lesions.