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1 : Approach to the patient with dyspepsia
2 : Dyspepsia defined as pain or discomfort centered in the upper abdomen. Discomfort is a negative feeling that the patient does not interpret as pain, which can be characterized by or associated with fullness, early satiety, bloating, or nausea. Dyspepsia can be intermittent or continuous, and may or may not be related to meals the American Gastroenterological Association (AGA) does not consider patients with reflux symptoms alone in their guidelines for the approach to the patient with dyspepsia. It occurs in approximately 25 % of the population but most affected people do not seek medical care . the most common cause of dyspepsia encountered in gastroenterology practice is functional dyspepsia,
3 : At least 12 weeks, which need not be consecutive, within the preceding 12 months of : 1- Persistent or recurrent dyspepsia 2- No evidence of organic disease that is likely to explain symptoms 3- No evidence that dyspepsia is relieved by defecation or associated with the onset of a change in stool frequency or stool form (ie, not IBS)
4 : differentiaal diagnosis of dyspepsia Peptic ulcer disease classic ulcer symptoms occur 2 to 5 hours after meals or on an empty stomach. Symptoms also occur at night, between 11 PM and 2 AM, The ability of alkali, food, and antisecretory agents to produce relief suggests the role of acid in this process. Although ulcer pain is often burning, gnawing, or hunger-like in quality, the discomfort may be vague or cramping. Symptomatic periods lasting a few weeks followed by symptom-free periods of weeks or months is a pattern characteristic of classic DU Gastroesophageal reflux The presence of GERD is important to identify since the treatment of this disorder often differs from the treatment of other causes of dyspepsia. The most common symptoms of GERD are heartburn and regurgitation. GERD should be suspected when these symptoms accompany dyspepsia and are the predominant complaints . Gastric malignancy Advanced gastroesophageal malignancy is an uncommon cause of chronic dyspepsia. However, the possibility of this disease influences testing, particularly in patients over 45 to 55 years of age
5 :   Alarm symptoms the following "alarm symptoms" raise the suspicion of gastric malignancy : - advanced age - Unintended weight loss - Persistent vomiting - Progressive dysphagia - Odynophagia - Anemia - Hematemesis - Palpable abdominal mass - lymphadenopathy - Unexplained iron deficiency - anemia - Jaundice - Previous gastric surgery - Family history of upper G I cancer
6 : Biliary pain characterized by episodic acute and severe upper abdominal pain, usually in the epigastrium or RUQ , that lasts for at least one hour. The pain may radiate to the back or scapula, and is often associated with sweating, or vomiting . Gallstones are sometimes implicated as the source of symptoms in patients with dyspepsia. However, gallstones may silently coexist in patients with dyspepsia, and other causes of dyspepsia are more common . cholecystectomy is usually not indicated in patients with gallstones who lack biliary pain or complications; thus, the incidental finding of gallstones in a patient with dyspepsia may lead to unnecessary cholecystectomy. Irritable bowel syndrome There is considerable overlap between IBS and functional dyspepsia. chronic abdominal pain and altered bowel habits remains the nonspecific yet primary characteristic of IBS . Abdominal wall pain Chronic pain emanating from the abdominal wall is frequently confused with visceral pain, often leading to extensive diagnostic testing before an accurate diagnosis is achieved. A response to treatment with an anesthetic agent can provide confirmation. Drug induced dyspepsia NSAID drugs ,calcium channel blockers, alendronate, orlistat, potassium supplements, acarbose , erythromycin and metronidazole
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8 : CLINICAL APPROACH History - Ulcer-like or acid dyspepsia (eg, burning, epigastric hunger pain with food, antacid, and antisecretory agent relief) - Dysmotility-like dyspepsia (with predominant nausea, bloating, and anorexia) - Unspecified dyspepsia However, these patterns overlap considerably, and clinical features alone have poor predictive value for the specific diagnosis found after endoscopy or distinguishing organic from functional dyspepsia Physical examination The physical examination is usually normal, except for epigastric tenderness, which should be evaluated with the Carnett test (increased local tenderness during muscle tensing) to assess for abdominal wall pain. A palpable mass usually indicates malignancy laboratory tests Routine blood counts and blood chemistry determinations are commonly obtained These tests help to identify patients with "alarm symptoms" (eg, anemia) who require endoscopy or other diagnostic testing. Noninvasive testing for H. pylori
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11 : Diagnostic strategies Several strategies for the management of new onset dyspepsia not caused by NSAIDs have been evaluated: 1- A trial of empiric antisecretory drug therap 2- Noninvasive testing for H. pylori infection followed by antibacterial treatment or endoscopy if the test is positive 3- Endoscopy in all patients 4- Barium radiography
12 : One of the most comprehensive systematic reviews included 17 controlled trials that involved comparison of 20 variations in the treatment strategies . The authors' main conclusions were that - initial endoscopy was associated with a small reduction in the risk of recurrent dyspeptic symptoms compared with a strategy of initial empiric treatment. - H. pylori testing (with endoscopy for a positive result) increased costs but did not improve symptoms. - H. pylori testing followed by eradication appeared to be as effective as initial endoscopy, but reduced costs by decreasing the proportion of patients that ultimately required an endoscopy. Empiric antisecretory therapy In 1985 the American College of Physicians recommended a trial of antisecretory therapy for patients without an obvious organic cause of dyspepsia who were under the age of 45, with endoscopy reserved for patients who had little or no response to therapy after 7 to 10 days or whose symptoms had not resolved after six to eight weeks this strategy may not be optimal based upon the following observations: 1- Peptic ulcer disease is responsible for a substantial number of cases of dyspepsia 2- H. pylori is the most common cause of peptic ulcers, and failure to eradicate H. pylori increases the risk of ulcer recurrence.
13 : Thus, treatment with empiric antisecretory drugs results in a delay of optimal therapy for a number of patients with dyspepsia. 3- A favorable symptomatic response to antisecretory therapy does not exclude a malignant gastric ulcer 4- Symptom recurrence is common following a trial of antisecretory therapy; 5- costs may not be reduced in the long run if substantial numbers of patients ultimately require further investigation. For example, a comparison of proton pump inhibitor (PPI) versus placebo for six weeks in 140 patients revealed a higher early response rate in the PPI group, but similar rates of dyspepsia recurrence one year later suggesting that empiric PPI treatment may have only delayed further investigation the limited data support the conclusion that antisecretory therapy compared with investigative strategies neither saves money nor improves quality of life in patients with dyspepsia.
14 : As an example, A study assigned 414 patients with dyspepsia to one of two strategies (373 of whom completed one year of follow-up ): group 1: treatment based on the results of prompt endoscopy group2 : empirical H2-blocker treatment with diagnostic endoscopy only in cases of therapeutic failure or symptomatic relapse within one year Organic disease was found at endoscopy in 33 % of group 1 patients. Endoscopy was ultimately performed in the majority 66 % of group 2 patients. After one year there were no differences in symptoms or quality of life measures between the two groups. The empiric treatment strategy was associated with higher costs, primarily because of a higher number of sick-leave days and medications costs
15 : Helicobacter pylori testing testing should be performed with a 13C-urea test or stool antigen test. Several studies have compared strategies involving H. pylori testing with endoscopy for the initial investigation in patients with dyspepsia . Differing assumptions have been made, resulting in various conclusions. Considered together, the results suggest that a strategy of noninvasive testing for H. pylori, followed by eradication treatment if present, may be the preferred strategy in young patients without alarm symptoms One of the largest trials to address this issue included 500 patients with dyspepsia who were assigned to a test-and-treat strategy or prompt endoscopy. After one year of follow-up there was no significant difference in symptoms, quality of life, number of sick-leave days, visits to general practitioners, or hospital admissions between the groups. Furthermore, 60 % fewer endoscopies were performed in the test-and-treat group. However, significantly more patients were dissatisfied with their management in the test-and-treat group compared with the endoscopy group Furthermore, a meta-analysis of individual patient data from five trials suggested that an endoscopy marginally decreased the likelihood of remaining symptomatic after one year compared with a test and treat approach
16 : Endoscopy Endoscopy provides a gold-standard for the diagnosis of PUD and gastroesophageal malignancy and can diagnose GERD in patients who have esophagitis or complications related to GERD, such as Barrett's esophagus. The diagnostic yield of endoscopy in patients with dyspepsia increases with age. The incidence of malignant disorders at endoscopy was analyzed for the years 1980 to 1986; of 707 cases identified, only 1.8 % occurred in patients under 45 years old, and all 13 had symptoms suggesting pathology more serious than simple dyspepsia These findings plus the known increasing incidence of gastric cancer with age provide the rationale for immediate endoscopy in patients with dyspepsia who are either over the age of 45 or who have alarm symptoms . In addition, some studies have found that initial evaluation with endoscopy in older dyspeptic patients increases the chance of finding a curable rather than incurable gastric cancer, Furthermore, a randomized trial of the test and treat strategy versus empirical PPI therapy in 219 patients less than 45 years of age revealed that a majority of patients in both groups underwent endoscopy within one year for symptom recurrence
17 : Barium radiography There is little role for barium radiography in the evaluation of patients with dyspepsia. Barium radiography is cheaper than endoscopy for the diagnosis of peptic ulcer disease, but is less accurate An inherent limitation of radiography is its inability to provide biopsies, including assessment for H. pylori. As a general rule, barium studies should be reserved for patients in whom an objective assessment of upper gastrointestinal tract is desirable but who (either because of preference or comorbidities) cannot tolerate endoscopy Other tests Many physicians obtain gallbladder sonography in patients with dyspepsia who lack typical biliary pain. However, as mentioned above, the discovery of gallstones in these cases can lead to unnecessary patient concern and surgery; Delayed gastric emptying has been found in 30 to 80 % of patients complaining of dyspeptic symptoms . However, therapy targeted at this disturbed physiology is of unproven benefit . Thus, the role of testing for gastric motor function in patients with dyspepsia is unclear. It can be considered in patients with risk factors for delayed gastric emptying, (diabetes mellitus)
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19 : RECOMMENDATIONS   American Gastroenterological Association - patients 55 years of age or younger without alarm features should receive a test and treat approach followed by acid suppression (preferably PPIs) Young patients who respond to H. pylori test and treat or PPI therapy can be managed without further investigation since endoscopy usually adds little even in those who continue to have upper gastrointestinal symptoms but do not have alarm features following such an approach. if symptoms remain. H. pylori testing should be performed using a 13C-urea breath test or stool antigen test.  - Those who are H. pylori negative should be given an empirical trial of a PPI for 4 to 8 weeks. American College of Gastroenterology an upper endoscopy is appropriate in patients with uninvestigated dyspepsia who are older than 55 or have alarm features . In those 55 and without alarm features, options include an empiric trial of acid suppression with a proton pump inhibitor or a test and treat strategy for H. pylori
20 : Functional dyspepsia The most common type of dyspepsia encountered in primary care and gastroenterology practice is functional (idiopathic) dyspepsia, also referred to as nonulcer dyspepsia. definition One or more of : Bothersome postprandial fullness, Early satiation ,Epigastric pain ,Epigastric burning AND No evidence of structural disease (including at upper endoscopy) that is likely to explain the symptoms These criteria should be fulfilled for the last three months with symptom onset at least six months before diagnosis PATHOPHYSIOLOGY Gastric motor function Abnormalities in Gastric motor function can lead to a delay in gastric emptying (gastroparesis), a disorder that is characterized by complaints of nausea, vomiting, early or easy satiety, bloating , and weight loss. Delayed gastric emptying has been found in 30 % of patients complaining of dyspepsia; however, Antral hypomotility has been found in a similar proportion of patients, Up to 10 % of patients have fast gastric emptying, which may also be associated with dyspepsia Gastric compliance is lower in patients with functional dyspepsia than in healthy controls .
21 : Visceral sensitivity Enhanced visceral sensitivity or visceral hyperalgesia refers to a lowered threshold for induction of pain by gastric distension in the presence of normal gastric compliance . Visceral hypersensitivity has been consistently demonstrated in patients with functional dyspepsia . Visceral hypersensitivity, which has also been proposed as an etiologic factor in irritable bowel syndrome, appears to occur independent of delayed gastric emptying . In contrast, somatic sensitivity is normal in these patients Helicobacter pylori infection H. pylori may cause altered smooth muscle dysfunction due to the induction of an inflammatory response or by the initiation of an antibody response multiple studies have evaluated the benefit of eradicating H. pylori in patients with functional dyspepsia, but results have been conflicting , although they suggest a small benefit. Postinfectious the onset of dyspepsia may be related to an infectious cause in a subset of patients A similar association has been described in patients with irritable bowel syndrome
22 : Psychosocial factors No unique personality profile has been found in patients with functional dyspepsia; however, anxiety, somatization, neurosis, and depression are increased in this group compared with healthy controls There is a link between self-reported childhood abuse and functional gastrointestinal disorders . It has been suggested that functional dyspepsia is best understood as the result of a complex interaction of psychosocial and physiological factors
23 : TREATMENT explanation, validation that the symptoms are not imaginary, evaluation and management of relevant psychosocial factors, and dietary advice. Medications that might contribute to symptoms (such as NSAIDs) should be substituted or discontinued One of the most comprehensive summaries focused on 57 trials comparing a variety of pharmacologic interventions . The following conclusions were reached H2 receptor antagonists Compared to placebo, were more likely to improve global symptoms and epigastric pain. Proton pump inhibitors A meta-analysis included six trials comparing PPIs with placebo A "good or excellent" outcome was significantly more likely with PPIs (60 versus 49 %). No significant differences between PPIs and H2RAs was detected. The benefit was greatest in those with ulcer-like or reflux-like symptoms; there was no significant benefit in patients with dysmotility-like symptoms.
24 : Prokinetic agents Global improvement was observed significantly more often with cisapride and domperidone compared with placebo. Metoclopramide also effective, but is associated with several side effects, particularly with long-term use Tegaserod (a partial 5-HT4 receptor agonist) improves gastric emptying is currently undergoing a phase III clinical trial for dyspepsia. Itopride is a dopamine D2 antagonist with acetylcholinesterase inhibitory activity that has prokinetic effects and probably effects on gastric accommodation Side effects ranging from 35 to 40 % Antidepressants Low-dose tricyclic antidepressant drugs or trazodone may improve commonly associated symptoms such as insomnia and fibromyalgia A therapeutic trial should begin with a low dose (eg, amitriptyline or desipramine 10 to 25 mg at night) If the patient responds in a few weeks, we usually continue the drug for a few months before stopping
25 : H. pylori therapy Trials of H. pylori eradication suggest that, at best, a small proportion of patients with functional dyspepsia improve following eradication Psychological therapy Psychological therapy (cognitive-behavioral therapy, hypnotherapy, or psychotherapy) has benefited selected patients Visceral analgesics such as the serotonin receptor antagonists, the somatostatin analogue octreotide, and the kappa receptor opioid agonist fedotozine, are undergoing evaluation in the management of functional digestive disorders such as functional dyspepsia and irritable bowel Complementary and alternative medicine A systematic review of studies involving herbal and natural products, acupuncture, and homeopathy suggested a benefit from peppermint oil
26 : AGA guideline American Gastroenterological Association MANAGEMENT OPTIONS FOR NEW-ONSET DYSPEPSIA (1) empirical H2-receptor antagonist therapy, (2) empirical proton pump inhibitor (PPI) therapy, (3) H pylori testing and treatment of positive cases followed by acid suppression if the patient remains symptomatic, (4) early endoscopy alone, (5) early endoscopy with biopsy for H pylori and treatment if positive, (6) acid suppression followed by endoscopy and biopsy if the patient remains symptomatic, (7) H pylori test and treat with endoscopy if the patient remains symptomatic
27 : Patients 55 years of age or younger without alarm features should receive H pylori test and treat followed by acid suppression (PPIs) if symptoms remain . Those who are H pylori negative should be prescribed an empirical trial of acid suppression with a PPI for four to eight weeks. Patients who respond to H pylori test and treat or PPI therapy can be managed without further investigation. Endoscopy usually adds little in young patients who continue to have upper gastrointestinal symptoms without alarm features despite H pylori test and treat and PPI therapy. There is a very low probability of finding relevant organic disease in this group of patients. Endoscopy may be appropriate for some young patients who continue to have dyspepsia, but this should be considered in the wider context of reevaluating the symptoms and the diagnosis.
28 : endoscopy is recommended for patients older than 55 years of age and younger patients with alarm features (eg, weight loss, progressive dysphagia, recurrent vomiting, evidence of gastrointestinal bleeding, or family history of cancer) presenting with new-onset dyspepsia. Biopsy specimens should be obtained for H pylori at the time of endoscopy and eradication therapy offered to those who are infected After endoscopy, and H pylori eradication therapy if positive, treatment should be targeted at the underlying diagnosis Patients of any age who continue to have symptoms despite appropriate investigations, therapy, and reassurance are a difficult group to manage . Symptoms should be reassessed and prokinetic agents, antidepressant therapy, or psychological treatments considered, although the benefits of these aproaches are not established
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