Evaluation and management of nonulcer dyspepsia

When no organic cause for dyspepsia is found, the condition generally is considered to be functional, or idiopathic. Nonulcer dyspepsia can cause a variety of symptoms, including abdominal pain, bloating, nausea, and vomiting. Many patients with nonulcer dyspepsia have multiple somatic complaints, as well as symptoms of anxiety and depression. Extensive diagnostic testing is not recommended, except in patients with serious risk factors such as dysphagia, protracted vomiting, anorexia, melena, anemia, or a palpable mass. In these patients, endoscopy should be considered to exclude gastroesophageal reflux disease, peptic or duodenal ulcer, and gastric cancer. In patients without risk factors, consideration should be given to empiric therapy with a prokinetic agent (e.g., metoclopramide), an acid suppressant (histamine-H2 receptor antagonist), or an antimicrobial agent with activity against Helicobacter pylori. Treatment of patients with H. pylori infection and nonulcer dyspepsia (rather than peptic ulcer) is controversial and should be undertaken only when the pathogen has been identified. Psychotropic agents should be used in patients with comorbid anxiety or depression. Treatment of nonulcer dyspepsia can be challenging because of the need to balance medical management strategies with treatments for psychologic or functional disease.     

Dyspepsia: challenges in diagnosis and selection of treatment

BACKGROUND: Despite considerable study, the pathophysiology of dyspepsia remains obscure. This and other factors have impeded development of precise and effective treatment strategies. OBJECTIVE: This paper provides a brief review of the clinical syndrome of dyspepsia and its pathophysiology, symptoms, diagnosis, and treatment. METHODS: To identify articles for inclusion in this review, a search of MEDLINE was conducted using the key word dyspepsia. Because the literature on this topic is voluminous and duplicative, the search was limited primarily to literature from the last decade and to articles concerning dyspepsia in adults. RESULTS: The symptoms of dyspepsia, which may include epigastric pain, heartburn. bloating, and early satiety, defy diagnosis in as many as 50% of patients, even after endoscopy and other appropriate studies. In the other half of patients, such causative disorders as gastroesophageal reflux disease (GERD), peptic ulcer disease, cholecystitis, pancreatitis, and gastric cancer may be diagnosed. Despite controversy regarding the selection of therapy, empiric treatment is common for apparent idiopathic dyspepsia. Histamine2-receptor antagonists, proton pump inhibitors (PPIs), promotility agents, and coating agents have all been used as empiric therapy for dyspeptic symptoms. With empiric treatment, subsequent management is directed by the therapeutic response. In the absence of a definitive diagnosis, treatment is usually selected on the basis of the type and severity of symptoms, a thorough history and physical examination, and factors such as age and the presence of Helicobacter pylori infection. Five PPIs are currently available--lansoprazole, omeprazole, rabeprazole, pantoprazole, and esomeprazole--all with established efficacy in GERD and other acid-mediated disorders. The PPIs can be expected to be useful in certain patients with dyspepsia, and may be prescribed for patients who are found to re- spond to potent antisecretory therapy. Patients' concern about their symptoms, practical considerations, and restrictions imposed by managed care organizations may all affect the choice between empiric therapy and early endoscopy in patients with dyspepsia. CONCLUSIONS: Despite the variety of therapeutic options available for the symptoms of dyspepsia, the many presentations of this condition and the uncertainty of the response to the currently available therapeutic options continue to pose a substantial clinical challenge.     

Management of Helicobacter pylori infection

Helicobacter pylori is the cause of most peptic ulcer disease and a primary risk factor for gastric cancer. Eradication of the organism results in ulcer healing and reduces the risk of ulcer recurrence and complications. Testing and treatment have no clear value in patients with documented nonulcer dyspepsia; however, a test-and-treat strategy is recommended but for patients with undifferentiated dyspepsia who have not undergone endoscopy. In the office setting, initial serology testing is practical and affordable, with endoscopy reserved for use in patients with alarm symptoms for ulcer complications or cancer, or those who do not respond to treatment. Treatment involves 10- to 14-day multidrug regimens including antibiotics and acid suppressants, combined with education about avoidance of other ulcer-causing factors and the need for close follow-up. Follow-up testing (i.e., urea breath or stool antigen test) is recommended for patients who do not respond to therapy or those with a history of ulcer complications or cancer.     

Test and treat Helicobacter pylori before endoscopy

BACKGROUND: Helicobacter pylori may have major implications for patients' wellbeing and future health. If a patient is found to be H. pylori positive it is important that the infection is eradicated because of the risk of associated peptic ulcers and gastric cancers. There are, however, great demands on NHS gastroenterology and endoscopy services and following the introduction of recent guidelines for dyspepsia some of these issues may be addressed. The literature suggests that a strategy of test and treat before endoscopy referral will benefit patients and be cost-effective. CONCLUSION: There is evidence that, over a period of time, it is more prudent to test and treat H. pylori first and then review the patient's condition before endoscopy is performed (if no other symptoms are identified).     

A trial of a test-and-treat strategy for Helicobacter pylori positive dyspeptic patients in general practice

Computer models of different strategies for the management of dyspepsia in primary care indicate that a 'test-and-treat' approach is likely to be associated with the lowest costs and acceptable clinical outcomes. We present information on computer modelling studies and report the findings of a randomised trial comparing a Helicobacter pylori test-and-treat strategy with referral to direct access endoscopy in the management of dyspepsia in general practice. We compared costs and clinical outcomes in patients managed for one year in study (test-and-treat) and control (endoscopy) practices in south London. Patients aged less than 45 years presenting with persistent dyspepsia without alarm symptoms (141 study patients, 91 control patients) were studied. In the one-year follow-up period there were 17 endoscopies in the study group: all the control patients underwent initial endoscopy and five further endoscopies were performed. None revealed peptic ulcer or cancer. Forty-three (30%) of the study patients compared with 16 (17%) of the controls were referred to hospital clinics (p < 0.025). The cost of management per patient for one year in the study group was 205.67 Pounds, compared with 404.31 Pounds in the control group (p < 0.0001). Clinical outcomes in both groups at one year were comparable. An H. pylori test-and-treat strategy for dyspeptic patients aged less than 45, employing office-based serology testing, appears to be associated with substantially lower costs than initial endoscopy and with similar clinical outcomes.     

Possible absence of Helicobacter pylori in the early stages of duodenal ulceration

BACKGROUND: Helicobacter pylori is thought to be a cause of duodenal ulceration, but there is some evidence that it is found less often in early than in later disease. AIM: To assess the presence of H. pylori in patients undergoing endoscopy for dyspepsia, with respect to their duration of symptoms. DESIGN: Retrospective case note review. METHODS: Patients were categorized as having a history greater or less than 6 months, and as H. pylori-positive or -negative, using biopsy rapid urease, culture and PCR tests. RESULTS: Thirty-two duodenal ulcer patients with a history >6 months were all H. pylori-positive according to the PCR test; the five with a shorter history were H. pylori-negative. No patient H. pylori-negative by PCR was positive by the other tests. DISCUSSION: H. pylori was (at least) less commonly present before 6 months. It is possible that H. pylori, although nearly always present after 6 months, is not present at the onset of the disease. Confirmation of this finding would imply that infection with the organism is not the cause of duodenal ulceration, but a factor producing recurrence and chronicity.     

根除幽门螺杆菌治疗功能性消化不良的临床证据

目的为临床实践提供有关功能性消化不良(FD)根除幽门螺杆菌(HP)治疗的循证医学证据。方法根据HP感染与FD的关系和HP根除治疗在治疗FD中的作用两个临床问题,检索VIP(1989～2005)、CBMdisc(1978～2005)、MEDLINE (1978～2006)以及Cochrane图书馆(2005年第4期)的系统评价,Meta分析,随机对照试验和临床指南,评价HP感染与FD的关系和HP根除治疗在治疗FD中的作用,为临床实践提供最佳的循证医学证据。结果共纳入2篇系统评价、1篇Meta分析和11篇随机对照试验。现有证据显示:FD患者HP感染率高于无症状者,但HP感染在FD发生中的作用还有待流行病学研究及病理生理研究的证据证实。HP根除治疗HP阳性FD,可以减缓部分消化不良患者的症状,但对改善患者生活质量无明显意义。HP根除治疗的成本-效益价值主要取决于患者希望明确诊断的愿望,还没有很好地证据显示需要对HP阳性FD都行HP根除治疗。结论基于目前的临床证据,我们认为对FD是否行HP根除治疗应根据患者的情况,做到个体化,对一些常规治疗差的患者可考虑采用HP根除治疗。     

Recognizing peptic ulcer disease. Keys to clinical and laboratory diagnosis

An algorithmic approach to evaluation of dyspepsia or abdominal discomfort begins with differentiation between peptic ulcer disease and gastroesophageal reflux disease as well as recognition of alarm signs and symptoms for gastric cancer, which are indications for early endoscopy. In the absence of alarm symptoms, most patients should undergo noninvasive testing for H pylori infection with a serologic, urea breath, or stool antigen test. Factors to consider in selection of appropriate testing include reliability, specificity, sensitivity, cost, and local access and expertise. As a general rule, physicians should choose a test that has the best accuracy for the level of testing expertise available. The basic principle underlying testing for H pylori is that patients should not undergo testing unless the physician is willing to treat on the basis of a positive test result. In patients who receive treatment, confirmation of cure is important for preventing further morbidity and reducing risk of transmission of infection.     

Ulcer and gastritis

The literature on peptic ulcer and gastritis in 2000 again focused on the topics of Helicobacter pylori, nonsteroidal anti-inflammatory drugs (NSAIDs), and gastric cancer. New diagnostic tests for H. pylori infection have been evaluated, and rescue therapies for failed H. pylori eradication have been tested. The causal relationship between H. pylori infection and nonulcer dyspepsia, gastric cancer, gastroesophageal reflux disease, and NSAID-related ulcers remained heated topics of debate. In 2000, landmark clinical trials and meta-analyses were published addressing these issues. The role of endoscopy in managing nonulcer dyspepsia was better defined. The role of H. pylori eradication in NSAID/aspirin users was reexamined in high-risk patients. Clinical benefit was finally confirmed for specific inhibitors of cyclooxygenase-2 (COX-2). The millennium year turned out to be a very important one in the advancement of knowledge in this field.     

Laboratory tests for the evaluation of Helicobacter pylori infections.

Helicobacter pylori is a highly motile bacterium with multiple unipolar flagella, and it produces the urease enzyme. The flagella and urease are the virulence factors of H. pylori. H. pylori often establishes a chronic infection in the stomach that may lead to gastric and duodenal ulcers, gastric cancers, gastric lymphomas, and other gastrointestinal diseases. There are several different invasive and noninvasive clinical laboratory tests for H. pylori. Laboratory testing is not indicated in asymptomatic patients and should be considered only if treatment of H. pylori infection is planned. Invasive tests for H. pylori, such as tissue histology, culture, and rapid urease tests, are used if an endoscopy is performed on the patient. The noninvasive tests for H. pylori, such as enzyme antibody and urea breath tests, are recommended in patients whose symptoms do not warrant endoscopy. The urea breath test is very useful and is recommended to evaluate effectiveness in the eradication and treatment of H. pylori infections. Nucleic acid tests can complement other diagnostic procedures, and are useful in evaluating fixed biopsy tissue, environmental samples, gastric juices, oral secretions, and stool samples.     

Multistate and multifactorial progression of gastric cancer: results from community-based mass screening for gastric cancer

Although multistate progression models for gastric cancer have been proposed, estimation of quantitative parameters of such models is yet to be done. The present study was conducted to elucidate risk factors for gastric cancer and its precursors, and to model the progression rates from superficial gastritis to gastric cancer. Data were derived from a community-based screening programme for gastric cancer in the Matzu region of Taiwan. A total of 2184 residents participated in a two-stage screening project. Subjects testing positive for Helicobacter pylori infection or pepsinogen (PGI or PII/PGII ratio) and immunoglobulin G (IgG), and subjects with a history of peptic ulcer or other upper gastrointestinal disease or with a family history of gastric cancer were referred to endoscopy. We identified 325 biopsy-proven precursors and gastric cancers, including 148 superficial gastritis (SG), 42 atrophic gastritis (AG), 117 intestinal metaplasia (IM) and two gastric cancers. Three further cancers were diagnosed on endoscopy alone and 14 were later diagnosed in those who did not comply with referral to endoscopy. A Markov process model was used to estimate the progression rates from superficial gastritis through to gastric cancer, with exponential regression to assess the effect of covariates on progression rates. The annual progression rate from SG to AG was 0.0670 (95% confidence interval [CI] 0.0446-0.0895). Annual progression rates from AG to IM and from IM to gastric cancer were 0.2775 (0.1665-0.3884) and 0.2265 (0.1315-0.3214), respectively. This gives average dwelling times in AG and IM of 3.60 years and 4.42 years, respectively. Progression from no disease to SG was significantly accelerated in those testing positive for H. pylori, those testing positive for PGI and in subjects with a family history of gastric cancer or a personal history of upper gastrointestinal disease. Further progression to AG and IM was significantly accelerated in those testing positive for PGI and in those with a history of upper gastrointestinal disease.     

High sensitivity and specificity of a laboratory-based serological test, pylori DTect ELISA, for detection of Helicobacter pylori infection

A number of commercial ELISA kits are now available for detection of Helicobacter pylori infection. Generally, whereas the manufacturers have claimed high sensitivity and specificity, independent studies have often failed to confirm the results. The aim of this study was to independently evaluate the pylori DTect ELISA, a commercial kit for detection of H. pylori infection, in Australian patients with dyspepsia and reflux symptoms. Two hundred and nine consecutive patients (102 males and 107 females, mean age 52.8 years) who were referred for endoscopy due to upper gastrointestinal symptoms, but had not received anti-H. pylori therapy were enrolled. A 10 mL blood sample was obtained from each subject and used to evaluate the kit. The absorbance index (AI) was calculated from the mean of two readings of optical density (OD) of each serum sample. Eight biopsies from the gastric antrum (x3), body (x2), fundus (x2), and incisura (x1) were obtained from each patient for CLO-testing (x1), culture (x3), and histological examination (x4) for H. pylori. Overall, 84 (40.2%) patients were infected with H. pylori as determined by the biopsy-based "gold standard." The AIs ranged from 0 to 1.86; 0.12 to 1.86 in H. pylori positive patients and 0 to 1.49 in negative patients. The pylori DTect ELISA obtained an accuracy of 94 to 95% under AI ranges between 0.20 to 0.40, with the highest accuracy being 95% under AIs of 0.25 and 0.35. An AI of 0.25 was recommended as the best cut-off AI, with a sensitivity of 96.4%, specificity of 93.6%, positive predictive value of 91% and negative predictive value of 97.5%. It is concluded that the pylori DTect ELISA is accurate for detecting H. pylori infection in patients with dyspepsia and reflux symptoms in Australia, when an AI of 0.25 is taken as the cut-off value.     

Ulcers and gastritis

Significant advances continue to be made in the area of gastritis and ulcer disease. Studies to identify the most appropriate use of capsule endoscopy have now confirmed that it is superior to other methods for identifying small-bowel mucosal pathology and sites of obscure gastrointestinal bleeding. It has increasingly been recognized that the complications of ulcer disease are secondary to the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and to interactions between NSAIDs and Helicobacter pylori. Effective prophylaxis for NSAID ulcers in H. pylori-negative individuals continues to be a challenge, as it has become clear that conclusions from studies focusing on "endoscopic ulcers" in patients whose H. pylori status was unknown provided a false sense of security. The concept of multifocal atrophic gastritis has been challenged. The precursor lesion to gastric cancer now appears to be a sheet of pseudopyloric metaplasia advancing into the gastric body with islands of intestinal metaplasia embedded within it. Multifactorial models such as those proposed for understanding periodontal disease, including the organism, environmental factors, and host factors, appear particularly applicable to understanding the pathogenesis of H. pylori-associated gastric cancer.     

慢性胃肠疾病的心身医学观

慢性胃炎是常见的消化系统疾病,其主要是由幽门螺旋杆菌感染引起的胃粘膜慢性炎症,虽然从18世纪已经有了慢性胃炎的诊断标准,但它仍旧存在许多临床上的困惑,缺乏客观的、容易执行的诊断标准。功能性胃肠病(FGIDs)是一组功能性胃肠疾病,功能性消化不良(FD)是FGIDs其中之一,与慢性胃炎从临床症状上不能鉴别。难治性慢性胃炎(CG)和FD因为医源性应激—过分夸大幽门螺旋杆菌感染引起癌变常常合并不同程度的情绪障碍(抑郁和焦虑),实际上都是心身疾病。对于难治性慢性胃炎和功能性消化不良用常规治疗是无效的,可以从生物-心理-社会医学模式(心身医学)观点看待CG和FD就可以得出不同结论和新的治疗方法,可以用这一新观点解决CG和FD诊断和治疗上的困惑,从临床实践证明抗抑郁/焦虑疗法是有效的。     

Quantification of Helicobacter pylori resistance in functional and organic dyspepsia

OBJECTIVE: To compare the efficacy of Helicobacter pylori eradication in patients with functional and organic dyspepsia. METHODS: The study included a cohort of 160 patients (115 with organic and 45 with functional dyspepsia) with dyspeptic symptoms and gastroscopically confirmed H. pylori infection. Triple therapy with omeprazole 20 mg, amoxicillin 1000 mg and metronidazole 400 mg (OAM) was administered twice a day for a week. Minimal inhibition concentration (MIC) was estimated on cultures from 41 patients with positive H. pylori for determination of antimicrobial sensitivity and primary resistance to amoxicillin and metronidazole. RESULTS: Endoscopic examination at least 6 weeks after therapy showed that 116 (72.5%) patients had H. pylori eradicated, whereas 44 (27.5%) were not. From the latter patients, 10 (23%) had functional dyspepsia and from 116 eradicated patients 35 (30%) had functional dyspepsia. Difference in efficacy of OAM therapy between patients with organic and functional dyspepsia was not significant (P > 0.5). Percentages of non-eradicated patients with organic and functional dyspepsia were 29.6 and 22.2%, respectively (ratio 1.3 : 1). MIC from 41 samples showed 18 (44%) in vitro resistant strains. There was no resistance to amoxicillin. CONCLUSIONS: There is no significant difference in H. pylori resistance to the same antibiotic between patients having functional or organic dyspepsia.     

Helicobacter pylori: why it still matters in 2005

Despite falling prevalence rates in the developed world, H pylori is still present in the United States and is particularly prevalent among racial minorities and recent immigrants. H pylori infection is clearly associated with an increased risk of peptic ulcer disease, gastric cancer, and MALT lymphoma, and it is associated with some cases of uninvestigated dyspepsia. Identification and eradication of H pylori improves outcomes in patients with peptic ulcer disease and causes tumor regression in patients with MALT lymphoma. It is uncertain whether H pylori eradication will improve outcomes in patients with gastric cancer. Decision analytic models suggest that a test-and-treat strategy for H pylori is rational and cost-effective for patients with uninvestigated dyspepsia.     

Relationship between the birth cohort pattern of Helicobacter pylori infection and the epidemiology of duodenal ulcer

BACKGROUND: Helicobacter-pylori-related duodenal ulcer (DU) is an important cause of dyspepsia. AIM: To determine the relationship between the pattern of H. pylori infection and the epidemiology of duodenal ulcer in a single population. DESIGN: Prospective two-part study of (i) patients with DU referred for endoscopy because of dyspepsia, and (ii) the incidence of H. pylori infection in the general population of the same area. METHODS: Details of 533 DU patients were recorded, and related to the pattern of H. pylori infection among 10 537 adults in the same community, determined by the (13)C-urea breath test. RESULTS: In patients with DU, birth year was more important than age in determining the rate of presentation for endoscopy (the 'birth cohort' effect). H. pylori infection showed a similar birth cohort effect, and the prevalence decreased steadily in those born in successive years, from 28.8% in the 1930s to 3.5% in the 1970s. The proportion of dyspeptic patients who had duodenal ulcers also fell progressively, from 22.2% in 1979 to 5.7% in 1998. H. pylori prevalence and duodenal ulcer incidence were closely correlated at all ages. DISCUSSION: Duodenal ulcer prevalence (as judged by the rate of referral of duodenal ulcer patients for endoscopy) is determined principally by the distribution of H. pylori infection in the local population. The birth cohort effect seen in adult duodenal ulcer patients reflects the acquisition of H. pylori in childhood. In Bristol, H. pylori prevalence and duodenal ulcer incidence are both declining to very low levels.     

小剂量阿司匹林肠溶片致上消化道出血危险因素分析

目的观察患者近期服用阿司匹林肠溶片(ASA)后致上消化道出血的危险因素。方法选择服用ASA在服药2月内出现呕血、黑便或大便隐血阳性的患者38例;对照组为30例服用相同制剂无消化道出血征象患者,比较两组患者血液流变学变化、药物致消化不良症状发生率、既往消化性溃疡病史及幽门螺杆菌(H.P)阳性率等指标。结果①出血组出血前PLT(25.4±6.8)×109/L、Fg(3.86±1.2)g/L、PT(10.2±1.6)s、APTT(28.5±5.9)s与对照组PLT、Fg、PT、APTT比较无统计学差异(P>0.05);②出血组出现ASA相关性消化不良症状,包括恶心、呕吐与对照组相比较发生率无统计学差异(P>0.05);③出血组年龄(66.3±8.7)岁较对照组(57.4±6.9)岁高(P<0.05)、出血组既往有消化性溃疡或出血发生率(26.3%)较对照组(5.7%)高(P<0.05)、出血组H.P阳性率(81.6%)较对照组(37.1%)高(P<0.05);④出血组中经胃镜检查发现以糜烂性胃炎者比例最多(44.7%)。结论老年人、既往有消化性溃疡史、H.P阳性者服用小剂量肠溶ASA有较高的上消化道出血风险,应加强伍用胃黏膜保护剂或抑酸剂及根除H.P治疗。     

幽门螺杆菌血清分型与上消化道疾病的关系

目的 探讨幽门螺杆菌(helicobacter pylori,Hp or H.pylori)分型与消化道不同疾病的关系。方法 入选198例Hp阳性的胃镜检查患者，采用免疫印迹法进行Hp的血清学分型，并取胃窦黏膜经HE染色观察胃窦黏膜病理组织学变化。结果 198例患者中检出HpI型菌株173例(87．4％)，Ⅱ型菌株25例(12．6％)。I型较II型Hp感染者胃镜下消化性溃疡、胃癌的比例更高，P=0.012；与胃炎组比较，十二指肠球部溃疡组、胃癌组的I型感染者更高（P值分别为0.026、0.048），而与胃溃疡组无显著差别(P=0.125)。病理组织学改变I型较II型Hp感染者的结果更为严重（P=0.038）。结论 临床上消化道疾病患者Hp感染以I型菌株最为多见。Hp感染的分型诊断有助于对胃、十二指肠疾病类型及病情的判断，I型菌株感染者需要更为积极的治疗。