Recognizing atypical manifestations of GERD. Asthma, chest pain, and otolaryngologic disorders may be due to reflux

The presence of common symptoms, such as heartburn and regurgitation, usually make the diagnosis of gastroesophageal reflux disease (GERD) fairly straightforward. However, extraesophageal symptoms of GERD, such as asthma, noncardiac chest pain, and hoarseness, are often not recognized and therefore are poorly managed. This article sheds light on the atypical manifestations of GERD as well as current approaches to diagnosis and treatment.     

Gastroesophageal reflux in children

BACKGROUND: Gastroesophageal reflux is common in small children. It is important to recognise that its natural history and management differ from reflux in adults. OBJECTIVE: This article will summarise the clinical presentation, pathophysiology, appropriate investigations and therapy of reflux in small children. DISCUSSION: A small amount of regurgitation is common in infancy, and is only pathological if it results in harm. In children, reflux-induced injury can result from either acid exposure, nutrient loss or respiratory complications. Recognised presentations include heartburn, oesophagitis, infant irritability, dysphagia, haematemesis, stricture, growth failure, aspiration, apnoea and pneumonia. Excessive crying and irritable behaviour in infancy can be due to a variety of causes, but there is a fashionable tendency to assume that gastroesophageal reflux is a major factor. Regurgitation can be a symptom of other conditions such as infection or metabolic disturbance. It is important to carefully evaluate any infant with distressed behaviour to exclude a significant medical cause. Prolonged oesophageal pH monitoring is a very useful means of linking episodes of reflux with putative symptoms. The severity of gastroesophageal reflux tends to improve with age in infants and this should be considered when advising appropriate therapy, especially fundoplication.     

Evaluation of laparoscopic Toupet fundoplication as a primary repair for all patients with medically resistant gastroesophageal reflux

BACKGROUND: This prospective study assesses the outcome results in 100 consecutive patients with gastroesophageal reflux disease (GERD) treated with a laparoscopic Toupet fundoplication. METHODS: GERD was confirmed by 24-h pH study and/or esophagogastroduodenoscopy (EGD). Pre- and postoperative symptoms, operative times, and perioperative complications were recorded on standardized data forms. Early follow-up was at 3 months and late follow-up, including 24-h pH, manometry, and EGD was at 22 months. RESULTS: Preoperative symptoms included heartburn (92%), regurgitation (58%), water brash (39%), and dysphagia (39%). Mean operative time was 3.2 hours. There were no conversions to celiotomy and there were no mortalities. The perioperative complication rate was 14%; 6% (5/83) of patients reported heartburn at 3 months and 20% (15/74) at 22 months. Early and late dysphagia was 20% (17/83) and 9% (7/74), respectively; 24-h pH testing was abnormal in 90% of symptomatic patients (9/10), 39% of asymptomatic patients (12/31), and 51% overall. CONCLUSIONS: Despite early improvement in reflux symptoms following laparoscopic Toupet fundoplications, there is a high incidence of recurrent GERD. Symptomatic follow-up underestimates the true incidence of 24-h pH-documented reflux. Based on these results we cannot recommend the laparoscopic Toupet repair for GERD patients with normal esophageal motility.     

Effect of pneumatic dilation on gastroesophageal reflux in achalasia

The aims of this study were to assess the effect of pneumatic dilation on gastroesophageal reflux in achalasia, differentiate esophageal acid due to lactate from acid due to gastroesophageal reflux, and determine if chest pain and heartburn are reliable indicators of gastroesophageal reflux. Eight untreated achalasia patients underwent pre- and postdilation esophageal fluid/food residue lactate and pH analysis, esophageal manometry, 24-hr pH monitoring, and symptom assessment. All patients had a successful clinical outcome and a decrease in lower esophageal sphincter pressure from 29.1 +/- 12.7 to 14.7 +/- 3.8 mm Hg (mean +/- SD; P = 0.04). Abnormal acid exposure was present in two patients before and two patients after dilation. Postdilation acid exposure was mild. Lactate was detected before dilation in all patients. A lactate concentration >2 mmol/liter was associated with acidic residue and one abnormal 24-hr pH profile. There was no correlation between an abnormal 24-hr pH test and age, lower esophageal sphincter pressure, or duration of symptoms prior to treatment. Chest pain and heartburn were unrelated to drops in pH. Gastroesophageal reflux is rare in untreated achalasia and esophageal acidity may result from ingestion of acidic foods or production of lactate. Mild gastroesophageal reflux occurs after dilation but is of no clinical significance. Chest pain and heartburn are not indicators of acid reflux in achalasia.     

Pyloric muscle in asymptomatic infants: sonographic evaluation and discrimination from idiopathic hypertrophic pyloric stenosis

Nissen fundoplication is now the most common antireflux operation for gastroesophageal reflux disease. This study is a report on the laparoscopically performed floppy Nissen procedure. Two hundred consecutive patients were analyzed (84 women, 116 men, mean age 49 years, mean duration of symptoms 5 years) after laparoscopic Nissen fundoplication between 1992 and 1996. The main indications for surgery were daily heartburn, retrosternal pain, and regurgitation demanding continuous medical therapy. Eight patients (4%) had esophageal stricture, and 21 (11%) had Barrett's esophagus with intestinal metaplasia. All patients underwent upper gastrointestinal endoscopy, 24-h esophageal pH monitoring, and esophageal manometry before and 3 months after the operation. In addition, a questionnaire was completed an average of 2.2 years (range 1.0-4.6) after the operation. The results of the study were as follows: mortality was zero, and the morbidity rate was 5%. The mean hospital stay was 3.8 +/- 2.8 days, and sick leave was 14.3 +/- 10.4 days. Postoperatively, esophagitis was healed or significantly improved in all but 4 patients (98%), and 24-h pH and lower esophageal sphincter pressure were normal. After 2 years, 87% of the patients had Visick scores of I-II. It is concluded that laparoscopic floppy Nissen fundoplication provides an efficient and safe alternative for surgical treatment of gastroesophageal reflux disease.     

Complete-type DiGeorge syndrome treated by bone marrow transplantation

Since information concerning reflux oesophagitis in the elderly is limited, particularly in Japan, the severity and symptomatic profiles of reflux oesophagitis in elderly patients were investigated. One hundred and nineteen patients with reflux oesophagitis found among 2278 endoscopy cases between 1993 and 1996 were investigated in this study. The patients were divided into two groups, elderly and non-elderly. The severity of reflux oesophagitis was estimated by the Los Angeles classification. The presence or absence of typical symptoms (heartburn and regurgitation) was determined by interview. Reflux oesophagitis was not only more frequently found in the elderly group, but was more severe than in the non-elderly. Although the degree of manifestation of typical symptoms was similar between the elderly and the non-elderly with high-grade oesophagitis, the elderly patients with mild reflux oesophagitis were less symptomatic than the non-elderly. Mild reflux oesophagitis in the elderly may be missed due to its rarity of typical reflux symptoms and a substantial number of elderly persons might have subclinical reflux oesophagitis.     

Dormancy-associated gene expression in pea axillary buds. Cloning and expression of PsDRM1 and PsDRM2

OBJECTIVE: We evaluated the efficacy and safety of a twice-daily dosage regimen of cisapride 20 mg in relieving the symptoms of mild-moderate gastroesophageal reflux disease (GERD) in patients with moderate intensity heartburn and no history of erosive esophagitis. METHODS: After a 2-wk, single-blind, placebo run-in period, 398 patients who continued to experience moderate intensity heartburn were randomized to either placebo (n = 196) or cisapride 20 mg (n = 202) twice daily for 4 wk. RESULTS: Compared with placebo, cisapride significantly reduced scores for daytime and nighttime heartburn (p < 0.001), total regurgitation (p < 0.001), eructation (p = 0.04), and early satiety (p = 0.04). Cisapride 20 mg b.i.d. was also superior to placebo in reducing total use of rescue antacid medication (p < 0.001); reducing, in concordance analyses, daytime and nighttime heartburn with antacid usage (p < 0.001); increasing the percentage of heartburn-free days and antacid-free nights (p < 0.5); and increasing the percentage of patients self-rated as having minimal or better symptomatic improvement (p = 0.01). Cisapride 20 mg b.i.d. was well tolerated. The most common adverse event in the cisapride group was diarrhea, reported by 10% of patients, compared with an incidence of 4% in the placebo group. CONCLUSION: Cisapride 20 mg b.i.d. was shown to be effective and safe for the short-term treatment of daytime and nighttime heartburn and for other symptoms associated with mild-moderate GERD.     

Symptomatic gastroesophageal reflux: incidence and precipitating factors

The incidence and precipitating factors associated with symptomatic gastroesophageal reflux were evaluated by a questionnaire in 446 hospitalized and 558 nonhospitalized subjects. Of 385 control subjects 7% experienced heartburn daily, 14% noted heartburn weekly, and 15% experienced it once a month, giving a total of 36% of subjects having heartburn at least monthly. Daily heartburn occurred at a significantly greater (P less than 0.05) rate for 246 medical inpatients (14%) and for 121 patients seen in outpatient gastroenterological clinic (15%). Pregnant women seen in uncomplicated obstetrical clinic had symptoms of significantly greater (P less than 0.01) incidence: daily (25%) and at least once monthly (52%). Age, sex, or hospitalization did not significantly affect incidence. Fried foods, "spicy" foods, and alcohol were the most common precipitating factors.     

Gastroesophageal reflux disease: pathophysiology, diagnosis and drug therapy

The principal mechanism leading to gastro-oesophageal reflux is an increased frequency of transient lower oesophageal sphincter relaxations; other factors are oesophageal hypersensitivity to gastric juice, hiatus hernia, and possible duodenal reflux. Patients with classical symptoms such as heartburn and regurgitation may be treated pharmaceutically combined with life style counselling. If the symptoms have not improved after 6 to 12 weeks, endoscopical examination is performed and, if necessary, 24-hour pH monitoring, barium radiographing and manometry. In the case of atypical symptoms such as dysphagia, laryngitis, asthma and chest pain, there is more reason to pursue diagnostic testing. In patients with dysphagia endoscopy is indicated to exclude malignancy. Drug treatment can be subdivided into antacids, H2 receptor antagonists, cytoprotective agents, prokinetics and proton pump inhibitors. In general practice a step-up approach to treatment is preferable, while for specialist treatment a stepdown approach is more (cost-)effective. Drawbacks of medical treatment are considerable frequency of recurrence of oesophagitis, persistence of regurgitation in 'volume refluxers' and controversial data on the possible development of (pre)malignant lesions of oesophagus and stomach. Surgical treatment is a good alternative for patients with persistent severe regurgitation during medical therapy and for young patients who prefer surgery to lifelong medication. Patients with Barrett's oesophagus should undergo regular endoscopic biopsy surveillance.     

Variables influencing parental perception of inherited metabolic diseases before and after genetic counselling

BACKGROUND: Sixty percent of adults has typical symptoms of gastroesophageal reflux in Chile. AIM: To report the clinical and laboratory features of patients with gastroesophageal reflux. PATIENTS AND METHODS: Five hundred thirty-four patients (255 male) with gastroesophageal reflux were included in a prospective protocol that included clinical analysis, manometry and endoscopy in all patients, barium swallow in 427, scintigraphy in 195, acid reflux test in 359, 24 h pH in 175, and differential potential of gastroesophageal mucosa in 73 patients. RESULTS: There was no correlation between the severity of symptoms and the endoscopical severity. Patients with Barret esophagus were 12 years older, were male in a greater proportion and had a higher proportion of manometrically incompetent sphincters than patients with esophageal reflux but without esophagitis or with erosive esophagitis. Severity of acid reflux, measured with 24 h pH monitoring was proportional to the endoscopical damage of the mucosa. There was a close relationship between the mucosal change limit determined with differential potentials and with endoscopy. No short esophagi were found. CONCLUSIONS: Patients with symptoms of gastroesophageal reflux must be assessed using several objective measures to determine the severity of their pathological alterations.     

Gastroesophageal reflux disease--extraesophageal manifestations

Gastroesophageal reflux is often associated with symptoms of the respiratory tract. Chronic cough of unknown origin, laryngeal complaints and even non allergic asthma, resistant to steroid therapy, are suspicious of being reflux related. These extraesophageal manifestations can occur without typical reflux complaints, such as heartburn, and even without evident esophagitis. Therefore, prolonged pH-monitoring is essential to confirm the diagnosis. In some cases it will be adequate to start a therapeutic trial with proton pump inhibitors (PPI) to prove the causal connection between reflux and symptoms. The treatment of the extraesophageal manifestations of gastroesophageal reflux disease is identical with the management of reflux esophagitis. PPI are the treatment of choice. Sometimes higher doses of PPI are required. Fundoplication may be appropriate for selected patients.     

Gastroesophageal reflux disease versus Helicobacter pylori infection as the cause of gastric carditis

To explore the potential contributions of gastroesophageal reflux disease, as opposed to Helicobacter pylori infection, to the development of gastric carditis, we evaluated gastric carditis (using the criteria of the updated Sydney system for the classification of gastritis), clinical and morphologic features of esophagitis, and H. pylori infection (evaluation of Steiner stains) in biopsy specimens from the gastroesophageal squamocolumnar junction. We correlated clinical, endoscopic, and histologic features in an unselected group of 116 patients. Some degree of carditis was found in 107 (92%) of the patients. The mean age of the patients increased with increasing severity of carditis (P < .05). The various groups of patients with different degrees of carditis did not differ significantly in sex ratio, ethnic background, presence of obesity, percentage having symptoms of gastroesophageal reflux disease (such as heartburn, regurgitation, dysphagia, or odynophagia), endoscopic evidence of esophagitis and columnar epithelium in the distal esophagus, or histologic evidence of active esophagitis. The presence, however, of active gastritis and H. pylori infection in the distal stomach and/or in the cardia was significantly associated with carditis. In patients without carditis, H. pylori was not detected in any cardiac or distal gastric biopsy specimen. In contrast, H. pylori was demonstrated in gastric tissue samples (either from the cardia or distally) of patients with carditis, with the prevalence rate increasing with greater degrees of cardiac inflammation. The H. pylori prevalence rate was 12% in the group with mild carditis, 40% in those with moderate carditis, and 57% in patients with marked carditis (P = .0001). In summary, carditis is commonly found in patients with symptoms related to upper gastrointestinal diseases. From analysis of our study cohort, we concluded that carditis was significantly associated with H. pylori infection and active gastritis but not with symptoms or signs of gastroesophageal reflux disease. These findings suggest that carditis with histologic features similar to those of gastritis in the distal stomach was a sequel of H. pylori infection and represented a part of an H. pylori--associated gastric inflammation.     

Barrett's esophagus. Clinical review of 26 cases

Barrett's esophagus was diagnosed in 26 men in a five-year period by demonstrating esophageal specialized columnar epithelium in target biopsies obtained at endoscopy or in peroral suction biopsies of the esophageal mucosa. The clinical, radiologic and manometric features of these patients were reviewed retrospectively. Esophageal lesions associated with this epithelium included distal and midesophageal strictures and ulcers, alone or in combination, or simply esophagitis. One patient had an associated adenocarcinoma. Twenty of 26 (77%) had heartburn or regurgitation, 16 (62%) had easily elicited reflux of barium while supine and 16 of 17 tested had lower esophageal sphincter pressure in the incompetent range. Ninety-six percent had one or more of these parameters positive. This series demonstrates a wide spectrum of esophageal lesions in Barrett's esophagus, and supports the concept that this lesion occurs as a consequence of gastroesophageal reflux and erosive esophagitis. The case of adenocarcinoma in this series adds to the concern that the columnar lined lower esophagus may be a premalignant lesion.     

Recombinant erythropoietin and blood transfusions in cancer chemotherapy-induced anemia

BACKGROUND: We examined the relationship between religious attendance, religious affiliation, and use of acute hospital services by older medical patients. METHODS: Religious affiliation (n = 542) and church attendance (n = 455) were examined in a consecutive sample of medical patients aged 60 or older admitted to Duke University Medical Center. Information on use of acute hospital services during the year before admission and length of the current hospital stay was collected. Frequency of church attendance and religious affiliation were examined as predictors of hospital service use, controlling for age, sex, race, education, social support, depressive symptoms, physical functioning, and severity of medical illness as covariates using logistic regression. RESULTS: Patients who attended church weekly or more often were significantly less likely in the previous year to have been admitted to the hospital, had fewer hospital admissions, and spent fewer days in the hospital than those attending less often; these associations retained their significance after controlling for covariates. Patients unaffiliated with a religious community, while not using more acute hospital services in the year before admission, had significantly longer index hospital stays than those affiliated. Unaffiliated patients spent an average of 25 days in the hospital, compared with 11 days for affiliated patients; this association strengthened when physical health and other covariates were controlled. CONCLUSIONS: Participation in and affiliation with a religious community is associated with lower use of hospital services by medically ill older adults, a population of high users of health care services. Possible reasons for this association and its implications are discussed.     

Clinical investigations of gastro-oesophageal reflux: Part 1

Most people have at some time experienced the symptoms of heartburn associated with gastro-oesophageal reflux. Fortunately, these symptoms are usually short-lived and require no treatment, but in some patients severe and prolonged reflux of gastric juice into the mouth can cause dental erosion. This paper, the first in a two-part series, describes the aetiology of gastro-oesophageal reflux and associated problems that may be encountered.     

Deglutition disorders

Dysphagia is related to the impairment of food passage from the mouth to the stomach. Globus pharyngis implies the frequent and often painful sensation of a lump in the throat that usually does not interfere with swallowing and may even be relieved by food intake. The diagnosis is based upon a careful history, clinical examination, endoscopy, dynamic imaging (videofluoroscopy, cinematography, videosonography) and electrophysiologic procedures (including pharyngoesophageal manometry, electromyography and pH determinations). Structural lesions of the cervical spine such as diffuse idiopathic skeletal hyperostosis are rare causes of dysphagia. Dysphagia following anterior cervical fusion as well as globus and dysphonia due to dysfunction of the vertebral joints are more likely. Symptoms with swallowing fluids indicate a neurogenic origin. Dyscoordinated swallowing, nasal reflux, dysphonia or general weakness may also occur. Chronic aspiration with respiratory compromize is the main consequence in a variety of neurological disorders as well as in cases of postsurgical dysphagia. Relaxation of the upper esophageal sphincter indicates coordinated muscle movement between the pharynx and esophagus. Dysfunction of the pharyngoesophageal segment may lead to cricopharyngeal achalasia. A dyskinetic sphincter commonly represents an extrapharyngeal cause: i.e., disease associated with gastroesophageal reflux. Disorders of the esophageal phase of deglutition can produce retrosternal pain, heartburn, regurgitation and vomiting, as well as laryngeal and respiratory signs. Esophageal motility disorders include lower achalasia, tumors, peptic strictures, inflammatory diseases, drug-induced ulcers, rings and webs. Motility disorders present with aperistaltic, spontaneous contractions, diffuse esophagospasm, or a hypermotile esophagus. Gastroesophageal reflux with esophagitis must always be excluded, especially in patients with a globus sensation. The multiple features of the appearance of the symptoms of dysphagia and globus makes multidisciplinary approach necessary in order to establish a diagnosis and begin effective treatment.     

Systemic clotting activation by low-grade endotoxaemia in liver cirrhosis: a potential role for endothelial procoagulant activation

Laparoscopic fundoplication is technically feasible in treating gastroesophageal reflux disease (GERD). Although medication is the primary treatment for GERD, not all patients respond completely or are able to adhere to a medical regimen. In the present series, 59 patients were laparoscopically treated for GERD at three centers using a standardized technique. All patients had been medically treated prior to referral, although 84 per cent had heartburn and 2 per cent had laryngitis despite 20 to 40 mg/day of omeprazole. Fifteen per cent of patients were intolerant of or would no longer take omeprazole. Patients were evaluated by esophageal manometry (in 100%) and 24-hour pH studies (in 66%). Seventy-six per cent of patients had lower-esophageal sphincter pressure <15 mm Hg. Five patients had low esophageal body peristaltic pressures (<35 mm Hg). These patients underwent Toupet partial fundoplication, whereas 54 patients underwent Nissen fundoplication. Mean operative time was 158 +/- 7 minutes, and three patients (5%) were converted to an open procedure. Operative complications were minor and occurred in 13 per cent. In 45 patients evaluated 1 year after surgery, heartburn had resolved in 98 per cent. Thirty-nine of 56 patients (70%) had mild early (<1 month postoperatively) dysphagia, and 9 (19%) had severe early dysphagia, which improved in 7 after nonoperative dilatation. Two of these had continued mild dysphagia. Two patients had severe dysphagia and were laparoscopically converted from Nissen to Toupet fundoplications, which resulted in marked improvement. Early gas bloat symptoms occurred in 45 per cent and dropped to 5 per cent at 1 year. Laparoscopic treatment of GERD is safe and effective in preventing reflux symptoms. Although mild dysphagia occurs after the procedure, this is transient in most patients. Patients with severe dysphagia can be treated with nonoperative dilatation or laparoscopic partial fundoplication and maintain the antireflux characteristics of the wrap.     

Health-related quality of life outcomes of omeprazole versus ranitidine in poorly responsive symptomatic gastroesophageal reflux disease

OBJECTIVE: This study evaluated changes in health-related quality of life (HRQL) outcomes of once-daily omeprazole compared with ranitidine for the short-term treatment of patients with poorly responsive symptomatic gastroesophageal reflux disease (GERD). METHODS: A double-blind, randomized clinical trial, compared omeprazole versus ranitidine for the treatment of poorly responsive GERD. Eligible patients had a history of predominant heartburn symptoms with symptomatic heartburn after 6 weeks of ranitidine treatment. Patients were randomized to omeprazole 20 mg once daily (n = 156) or ranitidine 150 mg twice daily (n = 161) and followed for 8 weeks. Assessments were completed at baseline and after 8 weeks with physician-rated symptoms: Gastrointestinal Symptom Rating Scale (GSRS); Psychological General Well-Being (PGWB) Index; Sleep Scale; Impact on Daily Activities Scale, and Overall Treatment Effect. Primary HRQL endpoints were the GSRS reflux scale and PGWB total score. RESULTS: No differences between the 2 treatment groups were observed in baseline demographic, clinical or HRQL measures. After 8 weeks, omeprazole-treated patients had greater improvement in GSRS reflux scale scores (p<0.0001) and PGWB total scores (p = 0. 019) compared with ranitidine-treated patients. Significant between group differences favoring omeprazole were also observed in GSRS total scores (p<0.0001), abdominal pain scale scores (p = 0.003), and indigestion scale scores (p = 0.003), Impact on Daily Activities (p = 0.001), PGWB positive well-being (p = 0.015), anxiety (p = 0. 030), and general health scale scores (p = 0.010). Patient ratings of overall treatment effect demonstrated the significantly (p<0. 0001) greater benefits of omeprazole (mean = 5.26) compared with ranitidine treatment (mean = 3.83). CONCLUSIONS: Omeprazole treatment significantly reduced persistent reflux-related symptoms and normalized psychological well-being compared with ranitidine in poorly responsive symptomatic patients with GERD.     

Typical and atypical presentations of gastroesophageal reflux disease. The role of esophageal testing in diagnosis and management

Gastroesophageal reflux disease (GERD) is a common disease with many typical and atypical forms of presentation. In the classic presentations of GERD with heartburn and regurgitation, esophageal testing, except for endoscopy, is only required for poorly responding patients or prior to surgical therapy. The atypical presentations of GERD, including chest pain, asthma, and ear, nose, and throat complaints, frequently are not associated with heartburn or regurgitation. Esophageal testing, particularly 24-hour pH monitoring is key to making the diagnosis and ensuring adequate acid suppression.