Age and alarm symptoms do not predict endoscopic findings among patients with dyspepsia: a multicentre database study

INTRODUCTION: Symptoms of dyspepsia are common but most patients do not have major upper gastrointestinal pathology. Endoscopy is recommended for dyspeptic patients over the age of 45, or those with certain "alarm" symptoms. We have evaluated the effectiveness of age and "alarm" symptoms for predicting major endoscopic findings in six practising endoscopy centres. METHODS: Clinical variables of consecutive patients with dyspepsia symptoms undergoing upper endoscopy examinations were recorded using a common endoscopy database. Patients who had no previous upper endoscopy or barium radiography were included. Stepwise multivariate logistic regression was used to identify predictors of endoscopic findings. The accuracy of these for predicting endoscopic findings was evaluated with receiver operating characteristic analysis. The sensitivity and specificity of age thresholds from 30 to 70 years were evaluated. RESULTS: Major pathology (tumour, ulcer, or stricture) was found at endoscopy in 787/3815 (21%) patients with dyspepsia. Age, male sex, bleeding, and anaemia were found to be significant but weak independent predictors of endoscopic findings. A multivariate prediction rule based on these factors had poor predictive accuracy (c statistic=0.62). Using a simplified prediction rule of age > or =45 years or the presence of any "alarm" symptom, sensitivity was 87% and specificity was 26%. Increasing or decreasing the age cut off did not significantly improve the predictive accuracy. CONCLUSIONS: Age and the presence of "alarm" symptoms are not effective predictors of endoscopic findings among patients with dyspepsia. Better clinical prediction strategies are needed to identify patients with significant upper gastrointestinal pathology.     

Subtypes of functional dyspepsia

Functional dyspepsia is a common clinical condition characterised by chronic or recurrent upper abdominal pain or discomfort commonly associated with a variety of associated gastrointestinal symptoms and a normal endoscopy. To standardise research-based approaches, an initial categorisation of into sub groups was agreed to, based on clusters of symptoms. However the early expectation that these subgroups would be associated with distinct pathophysiologies amenable to specific therapy has not been realised. A classification based on the most troublesome symptom has been suggested but the utility of this is also unclear. More recent data suggest that some of the pathophysiologic dysfunctions may be associated with specific symptoms and so provide a better tool for grouping patients. But this approach remains incomplete as current insights into the pathogenesis are still too limited for this to be satisfactory. In conclusion, no classification provides for an adequate treatment-based approach to the syndrome of functional dyspepsia. As a consequence treatment remains largely empiric.     

Duodenal lymphocytosis in functional dyspepsia

Background and study aimsFunctional dyspepsia is an exclusion diagnosis requiring different tests, including endoscopy, often repeated over time. Duodenal biopsies are frequently resorted to, not rarely revealing duodenal microscopic inflammation. Aim of the study is to confirm a previously supposed role of antro-duodenal low-grade inflammation in functional dyspepsia, evaluating the frequency of duodenal lymphocytosis, H. pylori infection and their association in a group of patients with functional dyspepsia compared to asymptomatic control subjects.Patients and methodsA cross-sectional, observational study has been conducted screening all the patients who underwent duodenal biopsies during upper endoscopy, in a 30 months period. All the patients without endoscopic lesions were analysed. The study group consisted of patients compatible with the diagnosis of functional dyspepsia (Rome III criteria). The control group consisted of healthy asymptomatic subjects in the population subjected to endoscopy. The presence of duodenal lymphocytosis and of H. pylori infection in the two groups was evaluated.Results216 patients were enrolled: 161 in the functional dyspepsia group and 55 as asymptomatic control group. The frequency of duodenal lymphocytosis was similar between cases and control groups (25.47% vs 25.45%; p = 0.99), as well as H. pylori infection (26.71% vs 23.64%; p = 0.78). Duodenal lymphocytosis was significantly associated with functional dyspepsia only in H. pylori positive dyspeptic patients (p = 0.047). 94% of the subjects with both lymphocytosis and H. pylori infection suffer from dyspepsia. Duodenal intraepithelial lymphocytosis is significantly associated with bloating (p = 0.0082).ConclusionsIn our cohort of dyspeptic patients, duodenal lymphocytosis is significantly associated with bloating and the simultaneous presence of duodenal lymphocytosis and H. pylori infection is significantly more prevalent than in control subjects.     

Impact of functional dyspepsia on quality of life

Little information on functional status and well-being is available in patients with functional gastrointestinal disease. We aimed to evaluate whether quality of life is poorer in patients with functional dyspepsia. A consecutive sample of 73 patients with functional dyspepsia completed a validated questionnaire prior to endoscopy. Organic disease controls comprised 658 outpatients attending endoscopy. Quality of life was measured using the validated Medical Outcomes Survey (which assessed physical, role, and social functioning; mental health; health perception; and any bodily pain) and the Brief Symptom Inventory (for current anxiety and depression); additional specific gastrointestinal items were also included. A stepwise logistic regression analysis was used to assess the association between diagnostic group and the quality of life measures, adjusting for potential confounders. Patients who reported more interruptions in their daily activities due to abdominal pain and who had fewer limitations of physical functioning were more likely to have functional dyspepsia (vs other disease,P<0.01). Mental health, social functioning, and health perception also tended to be poorer in functional dyspepsia. We conclude that quality of life may be more impaired in patients with functional dyspepsia than in patients with other conditions, who present for upper endoscopy.This work was supported in part by grant AG09440 from the National Institutes of Health.     

Drug treatment of functional dyspepsia

Symptomatic improvement of patients with functional dyspepsia after drug therapy is often incomplete and obtained in not more than 60% of patients. This is likely because functional dyspepsia is a heterogeneous disease. Although great advance has been achieved with the consensus definitions of the Rome I and II criteria, there are still some aspects about the definition of functional dyspepsia that require clarification. The Rome criteria explicitly recognise that epigastric pain or discomfort must be the predominant complaint in patients labelled as suffering from functional dyspepsia. However, this strict definition can create problems in the daily primary care clinical practice, where the patient with functional dyspepsia presents with multiple symptoms. Before starting drug therapy it is recommended to provide the patient with an explanation of the disease process and reassurance. A thorough physical examination and judicious use of laboratory data and endoscopy are also indicated. In general, the approach to treat patients with functional dyspepsia based on their main symptom is practical and effective. Generally, patients should be treated with acid suppressive therapy using proton-pump inhibitors if the predominant symptoms are epigastric pain or gastroesophageal reflux symptoms. Although the role of Helicobacter pylori (H pylori) in functional dyspepsia continues to be a matter of debate, recent data indicate that there is modest but clear benefit of eradication of H pylori in patients with functional dyspepsia. In addition, H pylori is a gastric carcinogen and if found it should be eliminated. Although there are no specific diets for patients with FD, it may be helpful to guide the patients on healthy exercise and eating habits.     

Diagnostic approach to dyspepsia

The optimal diagnostic approach to the dyspeptic patient in primary care is still debated. Early endoscopy continues to be the diagnostic gold standard but competing non-invasive strategies challenge this. The most important approaches are empiric antisecretory treatment reserving endoscopy for unresponsive patients and patients with an early symptomatic relapse and helicobacter-based strategies reserving endoscopy for infected patients (test-and-scope) or for failures after eradication therapy (test-and-treat). Early endoscopy is recommended in patients with alarm features and should be considered in patients with new onset dyspepsia after age 50. In the remaining patients, early investigation can only be recommended in areas providing endoscopy at a low cost and with a short waiting list. The test-and-scope strategy may lead to a rise in the referral rates for endoscopy and cannot be recommended. The test-and-treat strategy is well documented in clinical trials as a safe and cost-effective approach. Helicobacter-based strategies are challenged by a decreasing prevalence of peptic ulcer disease and of the infection. In the near future, the empirical acid inhibition strategy will probably be cost-effective as gastro-oesophageal reflux becomes the predominant disorder in dyspeptic patients.     

Managing dyspepsia

The prevalence of dyspepsia in the general population is as high as 40%, and its management represents a considerable financial burden to the health care system. Causes of dyspepsia amenable to medical therapy include peptic ulcer and functional dyspepsia, and testing for Helicobacter pylori and treating positive individuals is beneficial in both conditions. Individuals presenting for the first time with uninvestigated dyspepsia, age greater than 50 years, or alarm features require upper gastrointestinal (GI) endoscopy to exclude gastroesophageal malignancy. Upper GI endoscopy for younger individuals without alarm features is not cost-effective compared with the “test and treat” approach. Test and treat and empirical acid-suppression using a proton pump inhibitor (PPI) have similar costs and effects. Recent evidence suggests that empirical acid suppression commencing with antacids is as effective as PPI. Screening and treatment of H. pylori in PPI users and the community may reduce the costs of managing dyspepsia.     

Role of Helicobacter pylori in functional dyspepsia

The aetiology of dyspepsia is unknown in the majority of patients. Helicobacter pylori (H pylori) is the cause in a subset of patients. A non invasive test to assess the presence of H pylori is recommended in the management of patients under the age of 50 presenting to a family practitioner with dyspepsia. A urea breath test or a stool antigen test are the most reliable non invasive tests. Eradication of H pylori will reduce the risk to the patient with dyspepsia of developing a peptic ulcer, reduce the complication rate if prescribed nonsteroid anti-inflammatory drugs and later reduce the risk of gastric cancer. The recommended treatment for non ulcer dyspepsia associated with a H pylori infection should be a 10-d course of treatment with a PPI and two antibiotics. Treatment efficacy should be assessed four weeks after completing treatment with a urea breath test or a stool antigen test.     

The value of alarm features in identifying organic causes of dyspepsia.

The unaided clinical diagnosis of dyspepsia is of limited value in separating functional dyspepsia from clinically relevant organic causes of dyspepsia (gastric and esophageal malignancies, peptic ulcer disease and complicated esophagitis). The identification of one or more alarm features, such as weight loss, dysphagia, signs of gastrointestinal bleeding, an abdominal mass or age over 45 years may help identify patients with a higher risk of organic disease. This review summarizes the frequency of alarm symptoms in dyspeptic patients in different settings (such as the community, primary care and specialist clinics). The prevalence of alarm features in patients diagnosed with upper gastrointestinal malignancy or peptic ulcer disease is described. The probability of diagnosing clinically relevant upper gastrointestinal disease in patients presenting with alarm features and other risk factors is discussed. Alarm features such as age, significant weight loss, use of nonsteroidal anti-inflammatory drugs, signs of bleeding and dysphagia may help stratify dyspeptic patients and help optimize the use of endoscopy resources.     

Sulpiride improves functional dyspepsia: A double-blind controlled study

A 4-week placebo-controlled trial was performed to study the efficacy of sulpiride, a hypothalamic non-sedative neuroleptic and dopamine antagonist, in the treatment of 100 patients with functional dyspepsia, defined as dyspeptic symptoms despite normal endoscopy and cholecystography. Two patients on sulpiride were withdrawn because of sleepiness; no other undue side effects were recorded. At the end of 4 weeks, significantly (P < 0.02) more patients on sulpiride had improvement of nausea and belching (78%, 54% respectively) than patients on placebo (45%, 17% respectively). Pain and vomiting disappeared in approximately 50% and 70% of patients, respectively. In the overall assessment, 72% and 39% of the patients on sulpiride and placebo respectively had satisfactory improvement or became symptom-free (P < 0.001). Response to treatment was not related to personal and environmental factors. It was concluded that sulpiride was effective in improving symptoms of dyspepsia, particularly nausea and belching.     

Functional dyspepsia: evaluation and treatment

Functional dyspepsia is one of the most common disorders seen in general practice and by gastroenterologists. New concepts regarding the pathophysiology and its role for the symptom pattern have emerged during the last few years. This is of importance for development of new treatment alternatives in the near future. At the moment, however, empirical treatment with acid-suppressive agents and prokinetics is the recommended therapeutic approach in the management of these patients, despite limited efficacy. Identification and treatment of H pylori infection has been recommended for uninvestigated dyspepsia, because it may cure underlying peptic ulcer disease, but is unlikely to provide symptomatic benefit to patients with functional dyspepsia. Refractory patients may respond to antidepressants or to psychologic treatments, but proof of efficacy is limited. New and more effective approaches are badly needed for functional dyspepsia.     

全国城市中、小学生功能性消化不良现况调查

目的 分析我国城市中、小学生功能性消化不良的临床特点.方法 采用多级整群随机抽样方法,于2005年5月至2006年1月按罗马Ⅱ标准诊断功能性消化不良对我国六个省及两个直辖市中51 956名中、小学生进行流行病学问卷调查.结果 51 956名学生中有10 174名符合罗马Ⅱ标准诊断功能性消化不良,占19.58%.烧心、打嗝即采用吞气来终止打嗝是青少年主要的功能性消化不良症状.上腹胀在男生中高于女生,上腹痛、纳差及失眠在女生中高于男生,但两者差异均无统计学意义(P＞0.05).嗳气、早饱、疲劳及心情焦虑烦躁在女生中高于男生,两者间差异有统计学意义(P＜0.05).结论 功能性消化不良是城市中、小学生.的常见病及多发病,在治疗中应着重加强认知教育及心理治疗.     

Gluten-sensitive enteropathy and functional dyspepsia

Gluten-sensitive enteropathy (GSE) is increasingly diagnosed in adults. The symptoms of this disease can overlap with those of functional dyspepsia. The prevalence of GSE in dyspepsia has been reported to be 1.2-6.2% and could be higher if the entire spectrum of lesions related to gluten sensitivity, including lymphocytic enteropathy, is considered. Patients with dyspepsia secondary to GSE could be mistakenly diagnosed with functional dyspepsia unless upper gastrointestinal endoscopy is completed with duodenal biopsy and immunostaining for intraepithelial lymphocytes. A missed diagnosis could have major consequences in terms of morbidity and mortality and quality of life. Consequently, endoscopic study of patients with dyspepsia should be completed by duodenal biopsy when there are symptoms suggestive of GSE.     

Epidemiology of functional dyspepsia: a global perspective

Dyspepsia refers to group of upper gastrointestinal symptoms that occur commonly in adults. Dyspepsia is known to result from organic causes, but the majority of patients suffer from non-ulcer or functional dyspepsia. Epidemiological data from population-based studies of various geographical locations have been reviewed, as they provide more realistic information. Population-based studies on true functional dyspepsia (FD) are few, due to the logistic difficulties of excluding structural disease in large numbers of people. Globally, the prevalence of uninvestigated dyspepsia (UD) varies between 7%-45%, depending on definition used and geographical location, whilst the prevalence of FD has been noted to vary between 11%-29.2%. Risk factors for FD have been shown to include females and underlying psychological disturbances, whilst environmental/ lifestyle habits such as poor socio-economic status, smoking, increased caffeine intake and ingestion of non-steroidal anti-inflammatory drugs appear to be more relevant to UD. It is clear that dyspepsia and FD in particular are common conditions globally, affecting most populations, regardless of location.     

1 Nomenclature of dyspepsia,dyspepsia subgroups and functional dyspepsia: Clarifying the concepts

There is international agreement that dyspepsia refers to pain or discomfort centred in the upper abdomen. However, the term ‘discomfort’ has been variably defined. While other symptoms may often be simultaneously present, gastro-oesophageal reflux disease can usually be clearly distinguished by the presence of predominant heartburn. Dyspepsia is a frequent reason for consultation in primary care and in gastrointestinal practice. With the widespread availability and utilization of endoscopy, it has become evident that a structural (or organic) explanation is found in only a minority of patients presenting with dyspepsia. Operationally, functional dyspepsia is defined as persistent or recurrent dyspepsia for 3 or more months in the absence of a clinically identifiable structural disease causing the symptoms. It has been proposed, based on symptoms, that functional dyspepsia be subdivided into symptom subgroups to promote patient homogeneity. The initially proposed ‘clustering’ of symptoms into ulcer-like and dysmotility-like functional dyspepsia has proved a dismal failure because of the considerable overlap observed, the lack of stability over time and the failure to identify robust pathophysiological abnormalities or responses to therapy. A subcategorization based upon the most bothersome symptom is theoretically more attractive but needs to be prospectively and rigorously tested.     

Central serotonergic and noradrenergic receptors in functional dyspepsia

Functional dyspepsia is a symptom complex characterised by upper abdominal discomfort or pain, early satiety, motor abnormalities, abdominal bloating and nausea in the absence of organic disease. The central nervous system plays an important role in the conducting and processing of visceral signals. Alterations in brain processing of pain, perception and affective responses may be key factors in the pathogenesis of functional dyspepsia. Central serotonergic and noradrenergic receptor systems are involved in the processing of motor, sensory and secretory activities of the gastrointestinal tract. Visceral hypersensitivity is currently regarded as the mechanism responsible for both motor alterations and abdominal pain in functional dyspepsia. Some studies suggest that there are alterations in central serotonergic and noradrenergic systems which may partially explain some of the symptoms of functional dyspepsia. Alterations in the autonomic nervous system may be implicated in the motor abnormalities and increases in visceral sensitivity in these patients. Noradrenaline is the main neurotransmitter in the sympathetic nervous system and again alterations in the functioning of this system may lead to changes in motor function. Functional dyspepsia causes considerable burden on the patient and society. The pathophysiology of functional dyspepsia is not fully understood but alterations in central processing by the serotonergic and noradrenergic systems may provide plausible explanations for at least some of the symptoms and offer possible treatment targets for the future.     

Current treatments in functional dyspepsia

Opinion statement By nature of the definition of functional dyspepsia (FD), organic causes have to be ruled out before therapy can be directed. However, in uninvestigated dyspepsia in the absence of alarm features, Helicobacter pylori “test and treat” or an empiric trial of acid suppression therapy for 4 to 8 weeks is reasonable. If alarm symptoms or signs are present, or if the dyspepsia symptoms first occur in those aged greater than 55 years, prompt esophagogastroduodenoscopy is mandatory to exclude serious disease and positively diagnose FD. Empiric acid suppression with H₂-receptor antagonists or proton-pump inhibitors is superior to placebo in treatment of FD, but those patients with meal-related symptoms are least likely to respond. Helicobacter pylori eradication in FD benefits a minority of cases but is worthwhile, as response may be maintained. There is increasing evidence that some prokinetics may be superior to placebo in treatment of FD, but probably only a minority respond; those with meal-related symptoms may have the best response. Antidepressant therapy may have a place in management of difficult cases, but adequate randomized controlled trials are unavailable.     

The optimal age threshold for screening upper endoscopy for uninvestigated dyspepsia in Taiwan, an area with a higher prevalence of gastric cancer in young adults

BACKGROUND: It is estimated that 1% to 2% of patients with dyspepsia are associated with gastric cancer. To avoid missing gastric cancer, most guidelines recommend that patients over 45 years old should undergo EGD for uninvestigated dyspepsia. In Taiwan, however, the prevalence of gastric cancer in younger patients is higher than that of Western countries. The optimal age threshold for endoscopy in patients with uninvestigated dyspepsia in Taiwan remains controversial. Therefore, we aimed to determine an optimal age threshold for screening endoscopy in patients with uninvestigated dyspepsia to avoid missing gastric cancer in Taiwan. METHODS: We reviewed the findings in all adult patients who underwent upper endoscopy because of uninvestigated dyspepsia at the National Taiwan University Hospital. In those patients with confirmed gastric cancer histology, further analysis was performed. Cumulative age frequency distributions for gastric cancer were calculated according to gender and to the presence or the absence of alarm features. The stages of gastric cancer also were analyzed according to the presence or the absence of alarm symptoms. RESULTS: During the 5-year period, a total of 17,894 patients received upper endoscopy caused by uninvestigated dyspepsia. Gastric cancer was found in 225 (12.6 cases per 1000 EGDs) patients who presented with uninvestigated dyspepsia, 135 men and 90 women. Thirty-one (13.7%) and 17 (7.6%) patients were aged less than 45 and 40 years old, respectively. Among these 225 patients with gastric cancer, 114 (50.7%) patients did not have alarm symptoms (simple dyspepsia), whereas 111 (49.3%) had alarm symptoms. About 5.3% (12/225) of gastric cancer cases would have been missed if endoscopy had been omitted in patients without alarm symptoms and aged less than 45 years. The cumulative age relative frequencies of patients with gastric cancer who presented with simple dyspepsia were 1.8 (12/6720), 1.02 (5/4920), and 0.59 (2/3411) cases per 1000 EGDs for uninvestigated dyspepsia in patients aged less than 45, 40, and 35 years, respectively. When the frequencies of gastric cancer were stratified by age and gender, we found a trend of male predominance in older patients but not in younger patients. The cutoff age was 60 years old ( p < 0.05). Early gastric cancer was detected in 9.9% (11/111) and 26.3% (30/114) of patients with and without alarm symptoms, respectively (p = 0.002). CONCLUSIONS: Gastric cancer is not uncommon in patients with dyspepsia aged less than 45 years in Taiwan. The age threshold of screening endoscopy for uninvestigated dyspepsia should be the same for both genders in view of comparable frequencies of gastric cancer in a young age population. Because more than 5% of gastric cancer cases would be missed in Taiwan if endoscopy was omitted in simple dyspeptic patients who were aged less than 45 years, we recommend that 40 years old might be an optimal age threshold for screening endoscopy for uninvestigated dyspepsia in Taiwan, in both men and women patients.     

Clinical presentation of Helicobacter pylori-positive and -negative functional dyspepsia

BACKGROUND: A questionnaire was used to record the clinical presentation of functional dyspepsia in relation to Helicobacter pylori infection in a consecutive series of patients sent for upper gastrointestinal endoscopy. Only patients without macroscopic abnormalities in their oesophagus, stomach and duodenum were included. METHODS: The study questionnaire included two questions related to daily life, and the calculation of a symptom score. Biopsy specimens were taken from all patients for histological and microbiological examination, and immunoglobulin G antibodies were also determined. RESULTS: Two hundred and twenty-two patients were H. pylori positive and 182 patients were H. pylori negative. Loss of weight was significantly more common in the H. pylori positive group (P<0.001). Patients with H. pylori infection had a significantly higher overall symptom score compared with H. pylori-negative subjects (P<0.05). In addition, the severity of epigastric and nocturnal pain, heartburn, retrosternal heartburn, and vomiting was significantly higher in H. pylori-positive functional dyspeptic patients, and the influence on daily life and activities was significantly worse. CONCLUSIONS: The combination of retrosternal pain, weight loss, food intolerance and the absence of halitosis signified a 64% accuracy in predicting H. pylori infection. It is not possible to differentiate between H. pylori-positive and H. pylori-negative functional dyspeptics on the basis of clinical presentation and the number of complaints. However, overall symptom score and severity of several symptoms was significantly higher in the H. pylori-positive group.     

Assessment of proximal gastric accommodation in patients with functional dyspepsia

Impaired gastric accommodation is one of the most important etiologic factors in the pathophysiology of functional dyspepsia.Ultrasound is a potential alternative method to study changes in gastric volume as a reflection of gastric accommodation.Ultrasound is suitable for patients because it is a non-invasive,easily repeated and non-radioactive procedure,and a previous study has demonstrated the feasibility of 3-dimensional ultrasound in examining functional dyspepsia.The brief article by Fan et al demonstrated that both the proximal gastric area and volume,measured by 2-and 3-dimensional ultrasound respectively,were significantly smaller in patients with functional dyspepsia than in healthy controls.These results are very interesting,but we raise the relevant point that it should have been mandatory to study both changes in gastric volume and their relationship with upper gastrointestinal symptoms in functional dyspepsia.In fact,the relationship between cardinal symptoms and several pathophysiologic mechanisms in functional dyspepsia remains a matter of debate.Moreover,further evaluation of distal gastric volume that has been previously implicated in the origin of functional dyspeptic symptoms is advisable.Therefore,impaired gastric accommodation does not serve as a clear marker of the cardinal symptoms experienced by patients with functional dyspepsia in daily life.