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.     

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.     

Prevention of anti‐inflammatory drug‐induced gastrointestinal damage: Benefits and risks of therapeutic strategies

Patients who take non‐steroidal anti‐inflammatory drugs (NSAIDs) may develop serious gastrointestinal (GI) side effects in both the upper and lower GI tract. Those at risk should be considered for prevention with misoprostol, proton pump inhibitor (PPI) or COX‐2 selective inhibitor (coxib) therapy. A coxib or an NSAID+PPI combination is considered to have comparable GI safety profiles, but evidence from direct comparison is limited. PPIs are effective in the prevention of upper GI events in endoscopy trials and in a few, small, outcome trials in patients at risk. Coxibs have been evaluated in endoscopic ulcer studies and clinical outcome trials, and shown to significantly reduce the risk of upper GI ulcer and complications. Moreover, unlike PPIs, coxibs significantly reduce toxicity in the lower GI tract compared with NSAIDs. Coxibs and possibly some NSAIDs also increase the risk of developing serious cardiovascular events, an effect which may depend on the drug, dose and duration of therapy. It is not known whether concomitant low‐dose aspirin use, which occurs in more than 20% of patients, will reduce the incidence of cardiovascular events, although concomitant aspirin increases the risk of developing serious GI events in patients taking either an NSAID or a coxib. Such patients may require additional PPI co‐therapy. Current prevention strategies with an NSAID+PPI, misoprostol or a coxib must be considered in the individual patient with GI and cardiovascular risk factors. A PPI+coxib is indicated in those at highest risk (e.g. previous ulcer bleeding). PPI therapy must be considered for the treatment and prevention of NSAID‐induced dyspepsia.     

Prevention of anti-inflammatory drug-induced gastrointestinal damage: benefits and risks of therapeutic strategies

Patients who take non-steroidal anti-inflammatory drugs (NSAIDs) may develop serious gastrointestinal (GI) side effects in both the upper and lower GI tract. Those at risk should be considered for prevention with misoprostol, proton pump inhibitor (PPI) or COX-2 selective inhibitor (coxib) therapy. A coxib or an NSAID+PPI combination is considered to have comparable GI safety profiles, but evidence from direct comparison is limited. PPIs are effective in the prevention of upper GI events in endoscopy trials and in a few, small, outcome trials in patients at risk. Coxibs have been evaluated in endoscopic ulcer studies and clinical outcome trials, and shown to significantly reduce the risk of upper GI ulcer and complications. Moreover, unlike PPIs, coxibs significantly reduce toxicity in the lower GI tract compared with NSAIDs. Coxibs and possibly some NSAIDs also increase the risk of developing serious cardiovascular events, an effect which may depend on the drug, dose and duration of therapy. It is not known whether concomitant low-dose aspirin use, which occurs in more than 20% of patients, will reduce the incidence of cardiovascular events, although concomitant aspirin increases the risk of developing serious GI events in patients taking either an NSAID or a coxib. Such patients may require additional PPI co-therapy. Current prevention strategies with an NSAID+PPI, misoprostol or a coxib must be considered in the individual patient with GI and cardiovascular risk factors. A PPI+coxib is indicated in those at highest risk (e.g. previous ulcer bleeding). PPI therapy must be considered for the treatment and prevention of NSAID-induced dyspepsia.     

Ulcers and gastritis

This article reviews recently published reports on ulcers and gastritis. Helicobacter pylori is known to be an important pathogen involved in gastroduodenal inflammation and peptic ulcers. Conventional endoscopy is of limited usefulness in the evaluation of gastritis, but magnifying endoscopy is evidently helpful in the diagnosis of chronic atrophic gastritis, intestinal metaplasia, and H. pylori infection. A significant reduction in the incidence of refractory ulcers and the prevalence of H. pylori infection in patients with peptic ulcer disease followed the introduction of H. pylori eradication treatment. Chronic H. pylori infection is associated with gastric cancer, and the effect of H. pylori eradication on the prevention of gastric cancer is an important issue that is still a matter of controversy. Endoscopic hemostasis and intravenous proton-pump inhibitor (PPI) infusion represent a widely accepted approach to the treatment of peptic ulcer bleeding. In clinical practice, it is important to prevent recurrent bleeding and to treat patients who do not respond to endoscopic therapy or PPI treatment. Laparoscopic repair for peptic ulcer perforations, with postoperative eradication treatment, has gradually met with acceptance in patients with H. pylori infection. H. pylori infection and its treatment continue to be interesting problems in this field.     

Ulcers and gastritis

This article reviews recently published literature regarding ulcers and gastritis. Although endoscopy is the most useful procedure for diagnosis in the upper gastrointestinal tract, complications do occur, and procedure-related costs are significant. The appropriate indication for endoscopy has recently been debated. Helicobacter pylori is known to be an important pathogen involved in gastric and duodenal inflammation. Peptic ulcer disease and severe gastric mucosal injury are caused by virulent strains, and many reports have focused on CagA. Follow-up studies on surveillance endoscopy in patients with peptic ulcer or gastritis report that patients with atrophic gastritis and intestinal metaplasia are at significantly higher risk for gastric cancer. H. pylori eradication sometimes causes gastroduodenal erosion and reflux esophagitis, and the mechanisms involved have been revealed. Proton-pump inhibitors are useful in the treatment of ulcers caused by nonsteroidal anti-inflammatory drugs (NSAIDs), reflux esophagitis, and for preventing rebleeding after endoscopic hemostasis, but the effect of long-term acid suppression on the gastric mucosa is still a matter of debate. H. pylori infection and NSAID intake are both risk factors for peptic ulcer disease, and are important aspects in this field.     

Detection of gastric cancer by repeat endoscopy within a short time after negative examination

BACKGROUND AND STUDY AIMS: Although a large number of patients are examined using endoscopy in order to identify gastric cancer, it is unclear how individuals should be managed after they are not diagnosed as having gastric cancer at the time of their initial examinations. This study was conducted to identify the group at high risk for gastric cancer who should be examined by repeat endoscopy within a short time after obtaining negative results. PATIENTS AND METHODS: The study involved 3672 patients who were not diagnosed as having gastric cancer by endoscopy in 1993, but underwent re-examination by gastroscopy between January 1994 and December 1996. RESULTS: Among these participants, 32 patients (0.9%) were diagnosed as having gastric cancer. The incidence of gastric cancer was 2.0% in participants aged 60 to 69 and 2.7% in those with marked atrophy of the gastric mucosa. Multivariate analysis showed that the odds ratios (OR) for patients aged 60 to 69 and those with marked atrophy of the gastric mucosa were 3.092 and 3.255 (P < 0.01), respectively. Gastric cancer was detected in 17.2 % of patients who were previously diagnosed as having gastric adenoma and in 2.2% of those who were previously diagnosed as having gastric ulcer. The ORs for participants with these gastric lesions detected by the initial examination were 49.417 and 5.259 (P < 0.01), respectively. CONCLUSIONS: Groups at high risk for gastric cancer were identified by the initial endoscopy, when two findings (gastric lesions, atrophy) and age were combined. We emphasize the importance of repeat endoscopic examination for patients who are aged 60 to 69 or have marked atrophy of gastric mucosa, even if no lesions are detected on initial endoscopy. If gastric adenoma or ulcer are detected, endoscopic examination should be likewise repeated or these lesions should be treated by endoscopy or by other means.     

Guidelines for the management of Helicobacter pylori--Maastricht III-2005 and Japanese guidelines

The guidelines on the management of Helicobacter pylori were updated at the European Helicobacter study group third Maastricht consensus conference in March 2005. Especially, this conference emphasis on the management of non ulcer dyspepsia, GERD, and the patients who use non steroidal anti-inflammatory drug. Eradication of H. pylori is recommended in patients with peptic ulcer, low grade MALT lymphoma, atrophic gastritis, unexplained iron deficiency anemia, chronic idiopathic thrombocytopenic purpura and first degree relatives of patients with gastric cancer. H. pylori eradication is less effective than proton pomp inhibitor(PPI) treatment in preventing ulcer recurrence in long term NSAIDs users. This meeting also emphasized on the relationship between H. pylori and gastric cancer. The guideline concluded that H. pylori eradication has the potential to reduce the risk of gastric cancer development. Japanese guideline in 2003 does not mention the effect of eradication for prevention of gastric cancer. The H. pylori eradication and new strategy should be desirable for global strategy of gastric cancer prevention.     

Differences in the diagnostic yield of upper gastrointestinal endoscopy in dyspeptic patients receiving proton-pump inhibitors and H2-receptor antagonists

BACKGROUND AND STUDY AIMS: Patients attending for diagnostic oesophagogastroduodenoscopy (OGD) for dyspeptic symptoms are often receiving acid-suppression therapy that has not been discontinued prior to endoscopy, and this may reduce the diagnostic yield of endoscopy. The aim of this study was to compare the diagnostic yield of OGD in uncomplicated dyspepsia in patients receiving no medication, those receiving acid-suppression therapy, and those receiving nonsteroidal anti-inflammatory drugs (NSAIDs) at the time of endoscopy. PATIENTS AND METHODS: A total of 6825 diagnostic OGDs performed in our unit between 1993 and 2001 were analysed. Patients were excluded if they had sinister symptoms, were receiving NSAIDs, or were undergoing repeat or surveillance endoscopy. RESULTS: A total of 4233 OGDs (62 %) fulfilled the criteria for uncomplicated dyspepsia. Of the patients examined in these procedures, 1367 (32 %) were receiving acid-suppression therapy. A total of 724 patients (53 % of those on therapy) were receiving proton-pump inhibitors (PPIs), 393 of whom (54 %) had positive endoscopic findings (oesophagitis 31 %, gastritis 16 %, duodenal ulcer/duodenitis 16 %). A total of 643 (47 % of the patients on therapy) were receiving H 2 -receptor antagonists, 443 of whom (69 % of this group) had positive endoscopic findings (oesophagitis 30 %, gastritis 21 %, duodenal ulcer/duodenitis 31 %). A total of 2866 patients were not receiving acid-suppression therapy, 1805 of whom (63 %) had endoscopic findings (oesophagitis 37 %, gastritis 14 %, duodenal ulcer/duodenitis 24 %). The endoscopic yield was significantly lowest in the PPI group, except for the diagnosis of oesophagitis. Overall, 17 carcinomas were detected in patients referred with simple dyspepsia, and in five of these cases the patients were receiving acid suppression. CONCLUSIONS: The widespread use of acid suppression in the treatment of simple dyspepsia prior to endoscopy leads to a reduction in the endoscopic recognition of mucosal lesions caused by acid-peptic disease, but not to a high healing rate for these lesions, and it may mask malignancy.     

Ulcer recurrence in high-risk patients receiving nonsteroidalanti-inflammatory drugs plus low-dose aspirin: results of a post HOC subanalysis

BACKGROUND: Concomitant aspirin use is a risk factor for nonsteroidal anti-inflammatory drug (NSAID)-associated upper gastrointestinal toxicity. In high-risk individuals, such as those with a history of NSAID-related gastric ulcer bleeding, gastroprotective therapy with a proton pump inhibitor has been reported to reduce the risk of recurrent aspirin-associated gastroduodenal ulcer bleeding. OBJECTIVE: This analysis compared the efficacy of misoprostol, lansoprazole, and placebo in reducing the risk of gastric or duodenal ulcer recurrence in patients taking NSAIDs and low-dose aspirin. METHODS: This post hoc subanalysis was based on a previous multicenter, prospective, randomized, double-blind, placebo-controlled, 12-week study in patients who had a history of gastric ulcer, were Helicobacter pylori negative, required chronic NSAID therapy, and were free of gastric or duodenal ulcer on baseline endoscopy. The study treatments were misoprostol 200 microg QID or lansoprazole 15 or 30 mg OD. The subanalysis included data from patients in the intent-to-treat cohort who took aspirin at an amount 相似文献   

Low utility of endoscopy for suspected upper gastrointestinal bleeding occurring in hospitalized patients

OBJECTIVES: To determine the clinical utility of upper endoscopy in patients who have upper gastrointestinal bleeding after hospitalization. METHODS: Patients were studied who underwent upper endoscopy for an indication of suspected upper gastrointestinal bleeding that developed more than 48 hours after hospitalization. Demographic, clinical, and endoscopic data were extracted by chart review. Bleeding was characterized as clinically important (defined as overt bleeding in association with hemodynamic compromise or the need for blood transfusion) or non-clinically important. RESULTS: Eighty-six patients met inclusion criteria. Clinically important bleeding occurred in 17%. Peptic ulcer disease and gastritis were the most common sources of bleeding in the clinically important and non-clinically important groups, respectively. The bleeding source was not found in 24% of patients. Endoscopic therapy was required in 11% (all of whom had clinically important bleeding). Upper endoscopy prompted no treatment changes in the non-clinically important bleeding group. CONCLUSIONS: Endoscopic therapy was needed only in the few patients with clinically important bleeding. Nonendoscopic treatment can be recommended for upper gastrointestinal bleeding developing in hospitalized patients who do not meet established criteria for a clinically important bleed.     

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.     

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.     

Ulcerative colitis: diagnosis and treatment

Ulcerative colitis is a chronic disease with recurrent symptoms and significant morbidity. The precise etiology is still unknown. As many as 25 percent of patients with ulcerative colitis have extraintestinal manifestations. The diagnosis is made endoscopically. Tests such as perinuclear antineutrophilic cytoplasmic antibodies and anti-Saccharomyces cerevisiae antibodies are promising, but not yet recommended for routine use. Treatment is based on the extent and severity of the disease. Rectal therapy with 5-aminosalicylic acid compounds is used for proctitis. More extensive disease requires treatment with oral 5-aminosalicylic acid compounds and oral corticosteroids. The side effects of steroids limit their usefulness for chronic therapy. Patients who do not respond to treatment with oral corticosteroids require hospitalization and intravenous steroids. Refractory symptoms may be treated with azathioprine or infliximab. Surgical treatment of ulcerative colitis is reserved for patients who fail medical therapy or who develop severe hemorrhage, perforation, or cancer. Longstanding ulcerative colitis is associated with an increased risk of colon cancer. Patients should receive an initial screening colonoscopy eight years after the onset of pancolitis and 12 to 15 years after the onset of left-sided disease; follow-up colonoscopy should be repeated every two to three years.     

不同年龄段胃黏膜病变与胃癌相关因素的研究

目的 探讨不同年龄段胃黏膜病变与胃癌相关因素的关系。方法 从门诊或住院接受胃镜检查的4680名患者中，选择胃黏膜萎缩、肠上皮化生、异型增生、胃息肉、胃溃疡、幽门螺杆菌检测者3210例，按年龄大小分青年、中年和老年三组，定期胃镜检查，结合内镜、病理结果，分析与胃癌的相关性。结果 内镜诊断与病理结果相吻合，共可说明：胃黏膜病变中的萎缩、肠化生、异型增生及少数胃溃疡患者，随年龄的增长发病率及癌变率明显增高。结论随年龄增长上述胃黏膜相关因素与胃癌的发生密切相关，建议对与癌有密切相关的胃黏膜病变者，及时内镜和病理检查、治疗，避免癌症的发生。     

Peptic ulcer disease

Peptic ulcer disease usually occurs in the stomach and proximal duodenum. The predominant causes in the United States are infection with Helicobacter pylori and use of nonsteroidal anti-inflammatory drugs. Symptoms of peptic ulcer disease include epigastric discomfort (specifically, pain relieved by food intake or antacids and pain that causes awakening at night or that occurs between meals), loss of appetite, and weight loss. Older patients and patients with alarm symptoms indicating a complication or malignancy should have prompt endoscopy. Patients taking nonsteroidal anti-inflammatory drugs should discontinue their use. For younger patients with no alarm symptoms, a test-and-treat strategy based on the results of H. pylori testing is recommended. If H. pylori infection is diagnosed, the infection should be eradicated and antisecretory therapy (preferably with a proton pump inhibitor) given for four weeks. Patients with persistent symptoms should be referred for endoscopy. Surgery is indicated if complications develop or if the ulcer is unresponsive to medications. Bleeding is the most common indication for surgery. Administration of proton pump inhibitors and endoscopic therapy control most bleeds. Perforation and gastric outlet obstruction are rare but serious complications. Peritonitis is a surgical emergency requiring patient resuscitation; laparotomy and peritoneal toilet; omental patch placement; and, in selected patients, surgery for ulcer control.     

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.     

Gastroesophageal reflux disease and Barrett's esophagus

Gastroesophageal reflux disease (GERD) is a common clinical problem. Circumstantial evidence continues to suggest that infection with Helicobacter pylori may protect some patients from developing GERD and its complications. An empirical trial of a proton-pump inhibitor may now be a reasonable alternative to endoscopy or 24-hour pH testing for the diagnosis of GERD. Long-term follow-up data covering more than over a decade indicate that proton-pump inhibitors are effective and safe agents for the treatment of GERD. Furthermore, a strategy of proton-pump inhibitors first may be the most cost-effective approach to GERD. It remains unclear why some patients with GERD develop Barrett's esophagus, whereas others do not. Recent studies demonstrate the importance of pulses of acid or bile in increasing cell proliferation and cyclooxygenase-2 expression in Barrett's epithelium cell cultures. Short-segment Barrett's esophagus is now clearly associated with an increased risk of dysplasia or cancer compared to intestinal metaplasia of the cardia, and the cancer risk in this condition is similar to that with long-segment Barrett's esophagus. However, the overall cancer risk in patients with Barrett's esophagus is lower than previously estimated, at approximately 0.5% annually. Ablation techniques continue to show promise, but are not yet ready for routine clinical use. Endoscopic mucosal resection is a new treatment option for selected patients with high-grade dysplasia or superficial esophageal adenocarcinoma.     

Therapy of affective disorders

The key to the proper treatment of affective disorder is a correct diagnosis of the subtype of depressive illness. Thus, primary treatment recommendations include the TCAs for a depressive episode; ECT for a depressive episode with psychotic features; and MAOIs for dysthymic disorder and atypical depressive episodes. Nonresponding patients are treated with either lithium augmentation of TCA therapy, an MAOI, or ECT. Second-generation antidepressants are not usually indicated as initial treatments. They are recommended in situations in which their adverse-effect profiles offer significant advantages over TCAs in an individual patient. Second-generation antidepressants have not been extensively studied in patients who do not respond to TCAs. Maintenance antidepressant may be necessary to prevent recurrent depressive episodes. Lithium remains the mainstay of acute treatment of mania and for prophylaxis of subsequent affective episodes. In lithium-refractory or lithium-intolerant patients, carbamazepine is recommended. Valproic acid and verapamil have been useful, primarily in patients who do not respond to lithium and carbamazepine.     

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.