Bad Digestion

By Dr. Joel Doughten

A 22-year-old Caucasian woman presents with a complaint of vague abdominal discomfort. She uses her hand to rub over the upper

abdomen and has a look of discomfort on her face. The pain, described as burning, occurs at least twice weekly. Last year when she

was pregnant she had a similar but more severe pain. Which of the following statements is TRUE regarding this patient?

• A:She should undergo upper gastrointestinal endoscopy.

• B:She should be reassured that this is just heartburn and is nothing to be concerned about.

• C:She should be given a prescription for a proton pump inhibitor (PPI) because over-the-counter medications are unlikely to be effective.

• D:Measures such as elevation of the head of the bed, small meals and not reclining after eating are highly effective.

• E:Intermittent “on-demand” treatment with a PPI is a useful long-term treatment option.

Answer

• E:Intermittent “on-demand” treatment with a PPI is a useful long-term treatment option.

Dyspepsia•  Heartburn (dyspepsia) is the most common presenting symptom associated with gastroesophageal acid reflux (GERD). Forty percent of the U.S. population experience heartburn at

least monthly. Most people self-medicate with over-the-counter (OTC) antacids or histamine 2-receptor antagonists (H2RAs). A 2007 meta-analysis compared the placebo response, which ranged between 37 and 64 percent to common OTC agents; the relative benefit increase was up to 41 percent withH2RAs, 60 percent with alginate/antacid combinations (such asGaviscon®) and 11 percent with antacids alone.

•  • Proton pump inhibitors (PPIs) such as omeprazole/Prilosec OTC® provide greater GERD pain relief at 4 weeks compared to H2RAs. PPIs appear to have similar clinical

effectiveness when compared to one another for treating GERD (SOR A; Ref. 2). Also, PPIs andfundoplication surgery appear to be similarly effective in relieving symptoms and improving quality of life. Even if surgery is chosen, 10-65 percent of surgical patients still require medications 1 year later.

•  • Empiric therapy is recommended for new dyspepsia patients. Step-up therapy, beginning with a H2RA once or twice daily, then PPIs has historically been a useful and economical

choice. Others favor step-down therapy, beginning with twice-daily PPI for 2 weeks, then H2RA to maintain symptom-free state. On-demand PPI use in place of continuous daily maintenance therapy was recently shown effective in the long-term management of GERD. Modifications, such as avoiding spicy foods, elevating the head of the bed and avoiding foods before bedtime, may be helpful for some patients but have not been shown to significantly improve symptoms in all people.

•  Older patients (55 years of age or older) with new-onset dyspepsia should undergo upper gastrointestinal endoscopy. Other red-flag indications for endoscopy include anemia, melena,hematemesis, weight loss (>5 percent), persistent vomiting,dysphagia (difficulty swallowing) and odynophagia (painful swallowing) (SOR C; Ref. 5).  These patients have an elevated risk for gastric carcinoma, although even in this subgroup the prevalence is small. Poor correlation exists between severity of symptoms andendoscopic findings. Routine endoscopy is not recommended for patients with heartburn alone in the absence of red-flag or alarm symptoms, even if more than twice weekly. Endoscopy to screen for Barrett’s esophagus is indicated for patients requiring chronic continuous therapy with PPIs and those with chronic symptoms at risk for Barrett’s esophagus (i.e., duration of symptoms >5 years, white males, ≥50 years of age) (SOR C; Ref. 5).

•  Selected references:• 1. Agency for Healthcare Research and Quality (AHRQ). Comparative Effectiveness of Management Strategies for Gastroesophageal Reflux Disease.

http://effectivehealthcare.ahrq.gov/repFiles/GERD%20Final%20Report.pdf  Accessed March 2008• 2. Ebell M. All PPIs equivalent for treatment of GERD. http://www.aafp.org/afp/20060101/tips/3.html   Accessed March 2008• 3. Howden CW, Chey WD. Gastroesophageal reflux disease. J Fam Pract 2003; 52: 240-7. • 4. Klok RM, Postma MJ, van Hout BA, et al. Meta-analysis: comparing the efficacy of proton pump inhibitors in short-term use. Aliment Pharmacol Ther May 15, 2003; 17:1237-45.• 5. Medical Advisory Panel for the Pharmacy Benefits Management Strategic Healthcare Group. VHA/DoD clinical practice guideline for the management of adults

with gastroesophageal reflux disease in primary care practice. http://www.guideline.gov/summary/summary.aspx?ss=15&doc_id=5188&nbr=003570&string=GERD  Accessed March 2008

• 6. Pace F, Tonini M, Pallotta S, et al. Systematic review: maintenance treatment of gastro-oesophageal reflux disease with proton pump inhibitors taken 'on-demand.' Aliment Pharmacol Ther 2007; 26:195-204.

• 7. Tran T, Lowry AM, El-Serag HB. Meta-analysis: the efficacy of over-the-counter gastro-oesophageal reflux disease therapies. Aliment Pharmacol Ther 2007; 25:143-53.

True statement(s) about dyspepsia include(s) which of

the following?A) Upper abdominal pain not

related to colon functionB) Symptoms may include early satiety, fullness, bloating, and

nauseaC) Defined as predominant

epigastric pain present for ≥4 wk, with or without heartburn

D) All the above

Answer

• D) All the above

A 45-year-old man presents with complaints of heartburn often accompanied by a bitter taste in the back of his throat. These symptoms have been present for several months and seem to have gotten worse since starting a

high-stress job and gaining weight. You suspect that this patient has gastroesophageal reflux disease (GERD). All of the following factors can worsen symptoms of GERD

EXCEPT:• A:High protein intake

• B:Smoking

• C:Consumption of decaffeinated coffee

• D:Consumption of carbonated beverages

• E:Use of a phosphodiesterase inhibitor such as sildenafil (Viagra®) for erectile dysfunction

Answer

• A:High protein intake

Alarm features of GERD symptoms that should lead to endoscopic evaluation in from 1 to 10 days, depending upon the patient?s state of

illness, include all of the following EXCEPT:

• A:Anemia

• B:Acute onset dysphagia

• C:Melena

• D:Involuntary weight loss greater than 5 percent of baseline weight

• E:Age 50 years or older

Answer

• E:Age 50 years or older

Factors Associated with Decreased Lower Esophageal Sphincter Tone

•  Factor• Examples• Dietary supplements• ·         Arginine via the nitric oxide system• ·         Carminitive herbs such as peppermint (Mentha xpiperita), spearmint (Mentha spicat)a and other mint family (Lamiaceae) plants• ·         Essential oils (volatile, scented plant oils in high doses)• Foods/beverages• ·         Alcohol• ·         Chocolate (probably via themethylxanthines)• ·         Coffee (caffeinated more than decaffeinated)• ·         Cow’s milk• ·         Fat• ·         Orange juice & other citrus juices• ·         Spicy foods• ·         Tea• ·         Tomato juice• Lifestyle• ·         Smoking• ·         Stress• Medications• ·         Aminophylline (theophylline)• ·         Anticholinergics• ·         Beta-adrenergics• ·         Calcium channel blockers• ·         Nitrates• ·         Phosphodiesteraseinhibitors including sildenafil(Viagra®), vardenafil(Levitra®), tadalafil(Cialis®)• Physiologic, via stomach dilatation• ·         Post-prandial• ·         Gastric stasis• ·         Pyloric obstruction• Trauma/irritation/miscellaneous• ·         Acid hypersecretion• ·         Esophagitis• ·         Scleroderma-like diseases• ·         Surgical damage

Gastroesophageal Reflux Disease•  Gastroesophageal reflux disease (GERD) is caused by the reflux of acidic stomach contents (refluxate) passing into the esophagus, resulting in symptoms of heartburn, regurgitation and/or dysphagia. GERD is common. It is

estimated that 15 percent of people in the United Stateshave heartburn or regurgitation at least once a week and 7 percent of people suffer from symptoms daily. 

•  One of the main mechanisms that normally prevents refluxate from entering the esophagus is the lower esophageal sphincter (LES). The LES normally exists in a contracted state, but it will relax during the swallow sequence to let material into the stomach. The LES also relaxes to vent swallowed air and to allow retrograde expulsion of material from the stomach. Many substances decrease LES tone and can lead to the development of GERD or the exacerbation of preexisting GERD. These include dietary supplements, medications, trauma and smoking. (See Table.) The LES may relax with stomach distention, so some experts recommend not overeating or overconsuming fluids with meals to avoidGERD exacerbation via this mechanism.

• Research has been done to examine the specific effects of coffee and other beverages on GERD. For example, coffee (instant coffee, decaffeinated coffee, ground coffee) decreases LES for up to 90 minutes after ingestion. Caffeinated coffee seems to cause more gastric acid production, resulting in decreased LES tone with a more acidicrefluxate. Caffeine itself has some ability to decrease LES tone. High protein intake is not associated with GERD.

•  People report that stress worsens GERD symptoms, a fact that has supported in clinical trials. For example, stress increases GERD symptom reports, without necessarily being correlated to objective physiological changes such as increased esophageal acid exposure or duration of acid exposure in the esophagus. This phenomenon occurs especially in people with high levels of anxiety.

•  Elevating the head of the bed may help decrease GERD symptoms. This should be done by using 4- to 6-inch blocks under the bedposts at the head of the bed rather than using extra pillows. Extra pillows can compress the abdomen and increase intra-abdominal pressure, exacerbating GERD symptoms.

•  The mainstay of initial GERD treatment is pharmacologic with histamine type-2 receptor antagonists and proton pump inhibitors. Often, step-down therapy is recommended, so proton pump inhibitor therapy for 8 weeks is the first choice of treatment in many GERD guidelines. Starting doses include

•  Esomeprazole (Nexium®) – 40 mg daily

• Lansoprazole (Prevacid®) – 30 mg daily

• Omeprazole (generic, Prilosec®) – 20 mg daily

• Pantoprazole (Protonix) – 40 mg daily

• Rabeprazole (Aciphex®) – 20 mg daily

•  Patients with GERD should be tested for H. pylori infection and treated if positive. Patients who fail to respond to proton pump inhibitor therapy and those who are over the age of 50 years at the onset of symptoms should be referred for nonurgent endoscopic evaluation. Patients withGERD and alarm symptoms should be referred for endoscopicevaluation on a more urgent basis (SOR C; Ref. 6). Alarm symptoms and timeframes for endoscopy (in parentheses) are:

• Anemia (7-10 days)

• Acute onset dysphagia (within 1 day)

• Hematemesis (within 1 day if ill-appearing)

• Melena (within one day if ill-appearing)

• Persistent vomiting (7-10 days)

• Involuntary weight loss >5 percent (7-10 days)

•  Lifestyle modifications, such as smoking cessation and stress reduction, should be recommended, but there is little evidence that these interventions are helpful (SOR C; Ref. 8).

•  Selected references:

• 1. Behrman RE, Kliegman RM, Jenson HB. Nelson Textbook of Pediatrics. 17th ed.Philadelphia: WB Saunders Co., 2004.

• 2. Bradley LA, Richter JE, Pulliam TJ, et al. The relationship between stress and symptoms of gastroesophageal reflux: the influence of psychological factors. Am JGastroenterol 1993; 88:11-19.

• 3. Dennish GW, Castell DO. Caffeine and the lower esophageal sphincter. Am J DigDis 1972; 17:993-996.

• 4. Feldman M, Barnett C. Relationships between the acidity and osmolality of popular beverages and reported postprandial heartburn. Gastroenterol 1995; 108:125-131.

• 5. Goyal RK. Diseases of the esophagus. In: Kasper DL, Braunwald E, Fauci AS, et al., eds, Harrison’s Principles of Internal Medicine. New York: McGraw-Hill, 2005.

• 6. Institute for Clinical Systems Improvement (ICSI). Initial management of dyspepsia and GERD. http://www.guideline.gov/summary/summary.aspx?ss=15&doc_id=9658&nbr=005174&string=GERD   Accessed March 2008

• 7. MacDonald-Haile J, Bradley LA, Bailey MA, et al. Relaxation training reduces symptom reports and acid exposure in patients with gastroesophageal reflux disease. Gastroenterol 1994; 107:61-69.

• 8. University of Michigan Health System. Gastroesophageal reflux disease (GERD).http://www.guideline.gov/summary/summary.aspx?ss=15&doc_id=10631&nbr=005568&string=GERD   Accessed March 2008

A 30-year-old woman presents to your office with a complaint of intermittent abdominal discomfort and bloating as well as recurrent bouts of diarrhea. This has been going on for the last 6 months and more than 50 percent of days in a week. She states that the onset of

the pain is associated with the diarrhea and that she gets relief of the pain when she defecates. You consider the diagnosis of irritable bowel syndrome (IBS). Which of the following should be routinely ordered

or performed on patients in whom the diagnosis of irritable bowel syndrome is being entertained?

• A:Colonoscopy

• B:Complete blood count and fecal occult blood

• C:Stool cultures

• D:Sedimentation rate

• E:Serum chemistries

Answer

• B:Complete blood count and fecal occult blood

Which of the following statements is TRUE regarding the treatment of irritable bowel

syndrome?• A:Anxiolytic agents have been shown to be

helpful.• B:Alosetron (Lotronex®) is useful for

constipation-predominant IBS.• C:Lubiprostone (Amitiza®) is useful only in

women with constipation-predominant IBS.• D:Dietary changes are generally ineffective.• E:Interventions such as acupuncture and

psychotherapy are ineffective.

Answer

• C:Lubiprostone (Amitiza®) is useful only in women with constipation-predominant IBS.

Irritable Bowel Syndrome•  Irritable bowel syndrome (IBS) is the most common functional disorder of the gastrointestinal tract and affects 10-15 percent of the U.S.population. Although the exact pathophysiology of the disease is uncertain, various etiologies have been proposed. IBS has been shown to have a familial clustering, suggesting a genetic basis. Ten percent of patients with IBS have a flare-up after a gastrointestinal infection. Support for a neurologic basis comes from studies showing increase activation of pain signaling areas in the brain on magnetic resonance imaging (MRI) or positron emission tomography (PET). Other possible etiologies include gut hypersensitivity, small-bowel bacterial overgrowth, altered gastrointestinal motility, dietary intolerance, stress and other psychological factors. Although some patients with IBS may have an ongoing low-grade inflammatory state evidenced by an increase number of mast cells in the colon and an increase in the number of lymphocytes, an autoimmune component has not been proposed.

•  Traditionally, the diagnosis of IBS has been one of exclusion. The diagnosis is suggested in the absence of red-flag signs and symptoms that may suggest other serious processes. The American Gastroenterological Association states that a medical history and physical examination, and certain routine studies, are recommended to assess the presence of “alarm signs” or “red flags” (fever, weight loss, blood in stools, anemia, abnormal physical findings or blood studies, family history of inflammatorybowel disorders or cancer) that might require more extensive evaluation. For screening purposes, a stool Hemoccult and complete blood count are recommended (SOR C; Ref. 1). Other testing (e.g., sedimentation rate, stool cultures, serum chemistries) should be ordered based on symptom pattern. Colonoscopy is recommended for patients >50 years of age. Typical symptoms of IBS are abdominal bloating, abnormal stool frequency and form (diarrhea and/or constipation) and mucus in the stool.

•  • The revised Rome III criteria allow physicians to make a provisional diagnosis of IBS. The criteria include recurrent abdominal discomfort at least 3 days per month during the previous 3

months and 2 of the following 3 features: • ·         Abdominal discomfort is relieved with defecation.• ·         Onset of the discomfort is associated with a change in frequency of stool.• ·         Onset of the discomfort is associated with a change in form (appearance) of stool.•  • Treatment for IBS consists of dietary modifications and symptom-oriented medications. Conservative therapy is the goal for managing IBS, and unnecessary surgery should be avoided.

Patients should be reassured about this disorder and relaxation training and stress management considered. The American Gastroenterological Association states that cognitive-behavioral treatment, dynamic (interpersonal) psychotherapy, hypnosis and stress management/relaxation seem to be effective in reducing abdominal pain and diarrhea (but not constipation), and also reduce anxiety and other psychological symptoms (SOR C; Ref. 1).

•  • IBS is often classified based on the symptom complex – constipation-predominant, diarrhea-predominant and pain-predominant. Patients with predominantly constipation may benefit from

supplemental fiber in their diet. Patients should be encouraged not to put off the urge to defecate. Polyethylene glycol and lubiprostone (Amitiza®) may be used for persistent constipation. Patients with diarrhea-predominant IBS should try dietary changes such as elimination of lactose or caffeine and avoiding artificial sweeteners and high-fat foods. Lactose-intolerant patients may need to limit their milk consumption. Medications for diarrhea include loperamide, alosetron (Lotronex®) or a tricyclicantidepressant. Abdominal pain may be relieved with peppermint oil, antispasmodic medications, low-dose tricyclic antidepressants or selective serotonin reuptake inhibitors (SSRIs). Patients with abdominal bloating should avoid high-fiber diets because the fiber aggravates the gas. They should also eat more slowly, avoid chewing gum and avoid smoking to prevent excessive air swallowing. Probiotic therapy may decrease abdominal bloating. Medications that can be used for moderate to severe IBS are shown in the Table. Tegaserod (generic,Zelnorm®) was indicated for patients with constipation-predominant IBS but was removed from the market in April 2007 because of increased risk of serious cardiovascular events. Anxiolytics are generally not recommended unless the patient has a comorbid anxiety disorder.

•  

Pharmacologic Treatment of Irritable Bowel Syndrome

• Medication Type

• Medication

• Dose

• Comments

• Antispasmodics

• Dicyclomine(generic,Bentyl®)

• 20 mg 4 times daily

• Anticholinergicadverse effects

•  

• Hyoscyamine(generic,Levsin®)

• 0.125-0.25 mg every 4 hours or 0.375-0.75 mg sustained release twice daily

•  

• Antidiarrheal

• Loperamide(generic, Imodium®)

• 4-8 mg total daily dose

• Helps diarrhea but not other symptoms

• Antidepressants

• Tricyclics(e.g.,amitriptyline,nortriptyline,imipramine)

• Doses lower than those used for depression

• Anticholinergicadverse effects (current research investigating efficacy ofSSRIs)

• Chloride channel activator

• Lubiprostone(Amitiza®)

• 24 mcg taken twice daily with food

• For treatment of constipation; no drug interactions

• 5-hydroxytryptamine 3 receptor antagonist

• Alosetron(Lotronex®)

• 0.5-1 mg twice daily;

• available only through prescribing program

• Use in diarrhea-predominant IBS women; risk of ischemic colitis

The classic signs and symptoms of celiac disease include which

of the following? Iron-deficiency anemia

Diarrhea Weight loss

Abdominal pain

A) 1,3B) 2,4

C) 1,2,3D) 1,2,3,4

Answer

1. Iron-deficiency anemia 2. Diarrhea 3. Weight loss

In the patient with dyspepsia, alarm symptoms or factors

that warrant early referral to endoscopy include all the

following, except:A) Significant unanticipated

weight lossB) Difficulty swallowingC) Bleeding or anemia

D) Age <45 yr

Answer

• D) Age <45 yr

Which of the following drugs should the patient discontinue 2 wk before the stool

antigen test for Helicobacter pylori? Proton pump inhibitors

Antibiotics Bismuth

Nonsteroidal anti-inflammatory drugs

A) 1,3B) 2,4

C) 1,2,3D) 1,2,3,4

Answer

1. Proton pump inhibitors 2. Antibiotics 3. Bismuth

Dyspepsia that is bloating-like in character should be

treated with a(n)_______agent, while

dyspepsia that is ulcer-like should be treated with a(n)

_______ agent.A) Antisecretory; promotilityB) Promotility; antisecretory

Answer

• B) Promotility; antisecretory

According to the United States Preventive Services Task Force guidelines for CRC screening, routine colon cancer screening

_______ recommended for individuals 76 to 85 yr of

age.A) Is

B) Is not

Answer

• B) Is not

All the following statements about fecal immunochemical

testing are true, except:A) Less sensitive than fecal occult blood testing (FOBT)B) Detects human globinC) No dietary restrictions

requiredD) Less specific than FOBT

Answer

• A) Less sensitive than fecal occult blood testing (FOBT)

How common is celiac disease?What are the symptoms?

What tests must you order to make the diagnosis?

What is the final test before you put them on a gluten free diet for

the rest of their life?

Answer

• 1 in 125 people• One in 10 has all the classic symptoms,

anemia, diarrhea and weight loss• serum tissue transglutaminase

antibody and IgA level; 20% of individuals with celiac disease do not produce IgA and antiendomysial antibody

• Duodenal biopsies

Dyspepsia• “bad digestion”; definition—upper abdominal pain not

related to colon function• may include early satiety• fullness,• Bloating• nausea (component of many disorders, including• chronic headaches)• defined by Talley as predominant epigastric pain present for

4 wk, with or without heartburn• heartburn defined as chest burning with gross regurgitation

that can include dyspepsia; not 2 separate diseases, but consider more prominent symptom

• affects 26% to 41% of citizens in United States; • 5% of primary care visits

Uninvestigated dyspepsia• upper abdominal pain, as described, in which no investigation

(invasive or noninvasive) previously• Performed• causes—irritable bowel syndrome (IBS)• Nonulcer dyspepsia (NUD), or functional dyspepsia• ulcer disease• gastroesophageal reflux disease (GERD; often has dyspeptic

component);• carbohydrate malabsorption• gallstones (foregut organ)• chronic pancreatitis• malignancy (eg, pancreatic cancer);• Ischemia• systemic diseases (eg, amyloidosis, sarcoidosis)

Medications causing dyspepsia• top 2 aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs)• both most common cause of non-Helicobacter pylori, non-

aspirin/non-NSAID ulcers (due to nonreporting of medication use by patients);

• others include angiotensin- converting enzyme (ACE) inhibitors• Antibiotics• colchicine,• Estrogens• ethanol (causes diarrhea)• Gemfibrozil• steroids,• Iron• niacin

Gas producing foods• everyone has carbohydrate intolerance it

is the human condition.• (no human perfectly digests

carbohydrates), it keeps us humble• fructose with glucose (eg, apples)• fructans (eg, onions, leeks, watermelon)• breads and pasta• sorbitol (stone fruits eg. nectarines and

peaches)• raffinose (eg, legumes, cabbage)

Lactose deficiency• clinically common; low threshold• lactose in meal easier to absorb• diagnosis—lactose tolerance test or breath test; simpler test to

have patient drink 3 glasses of milk without food• treatment—lactose avoidance or lactase supplement• yogurt well-tolerated; most people, regardless of lactase state• tolerate one glass of milk daily without problems, no matter what is

the deficiency• People who produce lactase enzyme “genetic mutants” (normally

stop producing lactase at age of weaning)• Northern Europeans have no lactase deficiency • Asian-Americans are lactase-deficient• Lactaid dietary supplements contain the natural lactase enzyme

that is lacking. Take one tablet with the first bite of dairy and you can enjoy the food without worrying about discomfort. It comes in fast act chewables and caplets.

Celiac Disease• occurs in 1 in 125 people• >1 million Americans affected (>50% are women)• only 90,000 exhibit classic signs and symptoms,

including iron-deficiency anemia, diarrhea, and weight loss

• screening—serum tissue transglutaminase antibody and IgA level

• 20% of individuals with celiac disease do not produce IgA

• diagnosis—minimum of 6 biopsies from duodenum (>90% accurate)

• Can’t always diagnose with red flags• unable to distinguish celiac disease from IBS by history

Helicobacter pylori causes pathogenic changes to acid

production by inducing dysregulation of _______

production.(A) Gastrin (C) Tumor Necrosis

Factor (TNF)-(B) Somatostatin (D) CagA

protein

Answer

• (B) Somatostatin

In Western countries, which gastritis distribution is typically

associated with H pylori infection?

(A) Antral-predominant (B) Corpus-predominant (C)

Atrophic

Answer

• (A) Antral-predominant

Treating corpus-predominant gastritis patients for H pylori may

worsen or even induce gastroesophageal reflux

disease (GERD).(A) True (B) False

Answer

• (A) True

Which factor in a patient’s background is the most

significant predictor of H pylori infection?

(A) Age (C) Use of nonsteroidal anit-infammatory drugs

(B) GERD (D) Country of origin

Answer

• (D) Country of origin

Resistance to which of the following antibiotics is

associated with 90% failure rates when prescribing standard

“triple therapy” to eradicate H pylori?

(A) Metronidazole (B) Amoxicillin (C) Clarithromycin

(D) Tinidazole

Answer

• (C) Clarithromycin

Helicobacter pylori timeline:• H pylori prevalence currently decreasing

• in United States, with resulting dramatic changes in disease management

• 1982—first cultured accidentally

• Initial attempts to publish rejected by medical community because orthodoxy convinced ulcers acidogenic and bacteria

• could not survive stomach

• 1984—first paper published; Marshall ingested H pylori and successfully validated Koch’s postulates

• 1988—first randomized controlled trial treating ulcers as infectious

• 1994—National Institutes of Health (NIH) consensus conference concluded gastric ulcers share infectious etiology

• H pylori labeled class 1 carcinogen by World Health Organization (WHO)

• 1997—H pylori genome sequenced

Pathogenesis• does not invade tissue• incubates beneath gut mucosal layer• produces multiple enzymes and induces development of toxins• provokes strong immune response• systemic immune response allows serologic detection• local immune response affects acid secretion via dysregulation of D cell (produces somatostatin)• Western populations• typically experience antral-predominant gastritis with somatostatin down-regulation• gastrin upregulation,• increased acid secretion and risk for duodenal ulcer• reduced risk for gastric cancer• Eastern populations• typically develop corpus-predominant gastritis• Somatostatin up-regulation• acid suppression• decreased gastrin, and higher risk for gastric cancer• protected against duodenal ulcer and gastroesophageal reflux disease (GERD) • duodenal ulcers increasingly rare due to widespread use of proton pump inhibitors (PPIs) and antibiotics

Nonsteroidal anti-inflammatory drug (NSAID)–induced ulcers:

• until mid 1990s, most ulcers attributed to H pylori

• NSAIDs currently most common etiology

• virtually all complicated (bleeding) ulcers now NSAID-related

GERD and H pylori: distribution of gastritis determines treatment

• GERD symptom history critical; in patients with pre-existing GERD and typical Western antral-predominant gastritis

• treatment for H pylori results in reduced acid production and improvement of reflux in those without preexisting GERD

• new GERD unlikely to develop; in patients with Eastern corpus-predominant gastritis

• treatment for H pylori increases acid production• GERD may worsen or develop from latent form• controversies surrounding treatment of H pylori result from

geographic variations in distribution of gastritis

Functional dyspepsia: dyspepsia lacks singular etiology

• Functional nonulcer dyspepsia responds poorly to treatment of H pylori (only 1 in 15 patients improve

• testing dyspeptic individuals for H pylori recommended only in areas with established high demographic prevalence

• H pylori infection window ends after age 5 yr

• country of origin predicts risk forH pylori infection

H pylori and cancer• Correa cascade —H pylori induces atrophic gastritis, intestinal

metaplasia, dysplasia, and cancer• progression determined by genetics• alternative theory• suggests 1) bone marrow produces premalignant cells• 2) chronically inflamed tissues induce pluripotent cell migration• 3) premalignant cells generate tumors at site of inflammation• disrupting migration of premalignant cells may prevent H

pylori–related malignancies• possible concept can be extrapolated to other cancers

Genetics and gastric cancer• H pylori strains expressing cagA protein associated with increased risk for gastric cancers

• cagA-negative strains also induce malignancies

• Genetics determine cancer susceptibility, especially polymorphisms of inflammatory mediator genes

• eg, interleukin-1 (IL-1

• higher in cancer patients than in controls); some relatives of patients with gastric cancer produce less stomach acid

• These individuals susceptible to gastric cancer and express genetic polymorphisms affecting IL-1, IL-8, IL-10, and tumor necrosis factor (TNF)-alpha

• all associated with increased risk for gastric cancer

• distribution of gastritis also relevant

• Study data—found early treatment of H pylori may prevent development of gastric cancer

• however, preventive treatment ineffective

• once irreversible premalignant intestinal changes (eg, metaplasia, dysplasia) have occurred

• Mucosa-associated lymphoid tissue (MALT) lymphoma: B-cell lymphoma, but dependent on stimulation of T-cells by H pylori

• can be cured with antibiotics, but may require conventional lymphoma therapy when found outside gastric mucosa

Diagnosis of H pylori• serology unreliable for diagnosis, but negative predictive value good

• breath test has improved positive predictive value

• stool antigen testing effective

• Enzymelinked immunosorbent assay (ELISA) provides excellent sensitivity and specificity

• serology stays positive long after treatment

• PPI therapy alters intestinal microorganism populations, masking endoscopy results

• only multiple biopsies reliably detect H pylori in patients who use PPIs

• immunologic staining may improve detection

Treatment• no ideal treatment of H pylori• significant resistance rates exist among commonly used antibiotics• 10% to 11% resistance to clarithromycin• clarithromycin resistance associated with 90% failure rate in standard PPI-based triple therapy• 30% to 70% resistance to metronidazole; can overcome resistance to metronidazole by

increasing dose, but clarithromycin resistance absolute• Suggested treatment: includes PPI, amoxicillin, and clarithromycin for 14 days (increases

compliance)• metronidazole may be substituted for amoxicillin in penicillin-sensitive patients, but reduces

efficacy• bismuth, metronidazole, and tetracycline regimen also used• PPI, amoxicillin, and metronidazole least expensive regimen• useful for patients exhibiting macrolide resistance, but results poorer overall (50%-60%

success rate vs 70% average)• 25% to 30% of patients do not respond

Sequential therapy• involves amoxicillin and PPI twice daily for 5 days; followed by PPI,

clarithromycin, and tinidazole for 5 days

• regimen demonstrates 90% eradication, (>80% with clarithromycin resistance, vs 10%-15% with triple therapy)

• single-pill dosing with bismuth, metronidazole, and tetracycline (Pylera) increases compliance

• results comparable to triple therapy (circumvents clarithromycin resistance)

• Rescue therapies

• prescribed after patient fails 2 previous regimens

• frequently PPI, amoxicillin, and levofloxacin; rifabutin regimen costly and associated with hematologic side effects;

• furazolidone (uncommon in United States) available from compounding pharmacies

Guidelines for diagnosis and treatment of H pylori (American

College of Gastroenterology [ACG])• ulcer disease

• Past history of ulcer MALT lymphoma

• early gastric cancer

• Uninvestigated dyspepsia (some populations)

• Controversial indications—functional dyspepsia (endoscopy-negative)

• GERD

• NSAID use

• unexplained iron deficiency anemia

• Idiopathic thrombocytopenic purpura (ITP)

• populations at high risk for gastric cancer

Definition of dyspepsia• It consists predominantly of epigastiric pain, early satiation

and postprandial fullness, present for 1 month with or without heartburn (Rome III Committee)

• It is experienced regularly by 25% to 34% of Americans and accounts for over 5% of visits to a primary care provider.

• Patients may describe as indigestion or bloating, early satiety, nausea and vomiting

• Health care providers have also defined dyspepsia in different ways and as a result a multitude of esophageal, gastroduodenal, pancreatic, and hepatobiliary disorders could underlie the symptoms

Causes of dyspetic symptoms• Top 3 causes are ulcers, reflux disease and nonulcer dyspepsia

• Other causes include carbohydrate malabsorption, gallstones, chronic pancreatitis, malignancies, ischemic changes and other systemic diseases

• Consider celiac disease which affects 1 in 150 Americans

• Duodenogastric reflux, hypervigilance and somatic manifestation of psychiatric disease

• Medication intolerance, abdominal pain is a classic side effect of proton pump inhibitors and many other medication may cause dyspepsia. Review all medications with the patient, including nonprescription agents

• The most common cause of dyspepsia is functional (idiopathic) also referred to as nonulcer dyspepsia

Pathophysiology of nonulcer dyspepsia

• Impaired gastric accommodation

• Visceral hypersensitivity

• Delayed gastric emptying

• Helicobacter pylori infection

Refer for upper endoscopy if the following alarm symptoms are

present• Age greater than 45 years old

• Weight loss of greater than 10%

• Bleeding

• Increasing dysphagia

• Severe vomiting or early satiety

• History of ulcers or esphagogastric cancer

• Family history of GI cancer

• Abdominal mass of lymphadenopathy detected on physical examination

• Unexplained iron deficiency anemia

Drugs that can cause dyspepsia

• Calcium channel blockers

• Methylxanthines

• Alendronate

• Orlistat

• Potassium supplements

• Acarbose

• Erythromycin

• Metronidazole

Test and treat or treat then test?• Few randomized, controlled trails have compared strategies of empiric

antisecretory therapy versus immediate investigation. Nevertheless, 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. The empiric treatment strategy was associated with higher costs, primarily because of higher number of sick-leave days and medication costs.

• In young patients without alarm symptoms some studies have suggested that First perform a 13C urea breath test or a stool antigen test for H phlori infection, if positive, treat with H phlori eradication for 2 months, then reevaluate

• Alternatively, try PPI at least twice daily for 4 to 8 wk• PPI trail should be first choice if the community H Pylori prevalence is less

than 10%

Test and treat or treat then test?

• One of the largest trails to address this issue included 500 patients with dyspepsia with a median age of 45 years who were randomly assigned to a test and treat strategy or prompt endoscopy.

• After on 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 admission between the groups

• There were 60% fewer endoscopies performed in the test-and –treat group

• A higher number of patients were dissatisfied with their management in the test-and-treat group compared to endoscopy (12% versus 4%).

H Pylori as a cause of dyspepsia

• Results of 2 studies contradictory

• American College of Gastroenterology recommends H pylori testing for uninvestigated dyspepsia on a case-by-case basis

Testing for H phlori• The rate of H phlori infection is decreasing in western society• This decreases the effectiveness of tests, leading to more false negatives

and more false positives in low-prevalence areas such as the US• Antibodies persist, so serologic testing is not recommended in low-

prevalence areas.• Urea breath test has a high sensitivity and specificity, although it has a

high rate of false-negative results if the patient is already on acid suppression, on antibiotics for the past 2 months, or is taking PPIs or bismuth-based medication

• Stool antigen test has a sensitivity and specificity similar to those of the urea breath test and the drawbacks are similar

• Rapid test is now available with results in 5 minutes

Endoscopy

• It is the gold-standard

• The diagnostic yield of endoscopy increases with age

• Early endoscopy increases the chance of finding a curable rather than incurable gastric cancer

Major Society Recommendations• European Helicobacter Pylori Study Group consensus

statement regarding management of patients with dyspepsia as developed from a multinational European meeting in March 2005

• They recommended a test and treat strategy in adults less than 45 years of age who present with persistent dyspepsia

• They noted that the age cutoff may vary between countries, depending upon the prevalence of gastric cancer

• In areas of low H. Pylori prevalence (less than 20%), empirical PPI treatment or a test and treat strategy were considered to be equivalent

American Gastroenterological Association recommendations

• Patients 55 years of age or younger without alarm features should receive a test and treat approach followed by acid suppression.

• 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 four to eight weeks

• Empirical PPI therapy is the most cost-effective approach in populations with a prevalence of H. Pylori infection of 10% or less

• Young patients who respond to H. Pylori test and treat or PPR 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 symptoms

• The age of 55 years and older and those with alarm symptoms was based mainly on expert opinion due to the generally low risk of malignancy in most US populations

• The age cutoff of 45 to 50 years may be more appropriate for US patients of Asian, Hispanic, or Afro-Caribbean extraction.

Managing dyspepsia• Determine whether the pain is similar to ulcer pain or

mainly bloating sensation• Epigastric pain syndrome – ulcer like pain, discontinue

nonsteroidal anti-inflammatory drugs and try antisecretory agents like PPIs

• Other agents Metoclopramide which has a high likelihood of side effects including Parkinsons symptoms, Cisapride which is essentially unavailable and low-dose tricyclic antidepressants, selective serotonin reuptake inhibitors, psychotherapy and hypnosis

Dietary causes of bloating and dyspepsia

• Caffeine• Fatty foods in excess• Fruit• Sorbital• Fructose• Lactose• Beans• Raw cabbage• Broccoli• Cauliflower• Carbonated beverages• Some spices• Have a patient keep a dietary history for I week

Complementary remedies

• Peppermeint oil

• Caraway oil

• Artichoke leaf extract

• Capsaicin

• Celandine

• STW (lberogast) is a combination of 9 extracts, the company supported trails support use for functional dyspepsia

Diagnosis

• Comprehensive evaluations reveal no identifiable causes of dyspepsia in 30 to 60% of cases

• History alone is insufficient for distinguishing ulcer form nonulcer dyspepsia

• Animal studies suggest acidinduced gastric damage makes normal distention painful, even after lesions heal

• For humans this may result in dyspepsia• Some people genetically more susceptible to

unexplained functional dyspepsia

Which of the following conditions is not one of the top 3

causes of dyspepia?a. Ulcers

b. Gastroesophageal Reflux Disease

c. Psychosomatic Illness

d. Nonulcer dyspepsia

ANSWER

c. Psychosomatic illness

A patient complains of classic dyspeptic symptoms but has not undergone any test.

You decide to order an endoscopy when you learn that he:

a. Is 40 years of age

b. Has no personal or family history of gastrointestinal cancer

c. Drinks a six-pack of cola daily

d. Has lost more than 10% of his body weight within the last month

ANSWER

d. Has lost more than 10% of his body weight within the last month.

PPIs can cause Abdominal Pain?

a. True

b. False

ANSWER

a. True

Urea breath testing for Helicobacter Pylori is becoming less reliable in the western world

because?a. The overall prevalence of H Pylori

infection is decreasing

b. H Pylori is endemic in this region

c. The isotope used in the test is unstable

d. Newer strains of H Pylori use less urea than older strains

ANSWER

a. The overall prevalence of H Pylori infection is decreasing

In at least _____% of patients with dyspepsia, the cause is

never identifieda. 10%

b. 20%

c. 30%

d. 40%

ANSWER

c. 30%

The cause of dyspepsia is never identified in 30 to 60% of patients

WHEN TO TEST•  There are a number of clinical circumstances in which testing for H. pylori is considered.

Recommendations for diagnostic testing for H. pylori were first proposed by the National Institutes of Health (NIH) in 1994 [1]. More recent guidelines were published in 2006 by the European Helicobacter Study Group (EHSG) [2] and in 2007 by the American College of Gastroenterology (ACG) [3].

• ACG recommendations — The ACG guidelines made the following conclusions [3]:• Testing for H. pylori should be performed only if the clinician plans to offer treatment for positive

results.• Testing is indicated in patients with active peptic ulcer disease, a past history of documented peptic

ulcer or gastric MALT lymphoma.• The test-and-treat strategy for H. pylori (ie, test and treat if positive) is a proven management

strategy for patients with uninvestigated dyspepsia who are under the age of 55 years and have no "alarm features" (bleeding, anemia, early satiety, unexplained weight loss, progressive dysphagia, odynophagia, recurrent vomiting, family history of GI cancer, previous esophagogastric malignancy).

• Deciding which test to use in which situation relies heavily upon whether a patient requires evaluation with upper endoscopy and an understanding of the strengths, weaknesses, and costs of the individual test.

Uncomplicated duodenal ulcers and gastric ulcers• Uncomplicated duodenal ulcers — H. pylori is present in the majority of patients with uncomplicated

duodenal ulcers, especially if nonsteroidal antiinflammatory drugs are excluded [1]. As a result, it has been argued that no diagnostic method is cost-effective in such patients, and that treatment should be empiric [4]. However, H. pylori infection is absent in up to 27 percent of patients with endoscopically proven duodenal ulcers [3]. Such patients appear to have a significantly worse outcome, especially when treated empirically for infection [5]. (See "Helicobacter pylori-negative peptic ulcer disease").

• Thus, confirmation of infection should be obtained. The diagnosis can be established by a biopsy urease test if the patient is not taking a proton pump inhibitor or other medication that could interfere with the test (see "Biopsy urease testing" below).

• Uncomplicated gastric ulcer — H. pylori infection is present in the majority of uncomplicated gastric ulcers [6]. However, H. pylori negative gastric ulcers have been increasingly recognized. The surreptitious or unrecognized use of nonsteroidal antiinflammatory drugs may account for some of these cases. (See "Helicobacter pylori-negative peptic ulcer disease").

• Testing for H. pylori infection should be performed before antibiotic treatment. One approach is to obtain biopsies from the ulcer's edge and base to exclude gastric cancer plus at least two separate sites in the gastric mucosa distant from the ulcer to identify H. pylori organisms. Even if the biopsy does not indicate malignancy, confirmation of gastric ulcer healing is recommended in most instances within two to three months.

CONFIRMATION OF ERADICATION 

•  Confirmation of eradication should be strongly considered because of the availability of accurate, relatively inexpensive noninvasive tests (stool and breath tests). Confirmation of eradication has been recommended by a European consensus panel [2]. A 2007 guideline from the American College of Gastroenterology recommends confirming eradication in the following settings [3]:

• Any patient with an H. pylori-associated ulcer• Individuals with persistent dyspeptic symptoms despite the test-and-treat strategy• Those with H. pylori-associated MALT lymphoma• Individuals who have undergone resection of early gastric cancer• The above recommendations are based largely on expert consensus agreement.• Urea breath testing performed at least four weeks after treatment has been promoted as the test of choice to confirm

eradication of infection [2]. Stool antigen testing is a more widely available alternative, but it may be less accurate [57]. Until further data are available, the stool antigen test should not be performed sooner than four to six weeks after completion of treatment because of both false-positive and false-negative results in this time period [55,57].

• Recent antibiotics taken for reasons other than H. pylori eradication or recent treatment with bismuth or PPIs can affect test results. Antibiotics and bismuth should be discontinued for at least four weeks and PPIs at least one week if possible prior to testing done to confirm H. pylori cure (with urea breath test, stool antigen testing, or endoscopic testing) to reduce the chance of false-negative results.

• Endoscopy with biopsy for culture can be performed when antibiotic resistance is suspected. A biopsy obtained for histopathology only is appropriate if urea breath testing or stool antigen testing is not feasible or during follow-up of complicated ulcer disease. Serologic testing is not useful for follow-up since many patients continue to have antibodies for months or even years after eradication therapy [67].

Functional dyspepsia• DEFINITION — An international committee of clinical investigators developed the following

revised definition (Rome III criteria) of functional dyspepsia for research purposes, which can also be applied to clinical practice [1]:

• 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. Two subcategories (postprandial distress syndrome and epigastric pain syndrome) were also recognized but their main value lies currently in research.

• Dyspepsia has been classified according to the characteristics of symptoms that predominate. However, such classification systems do not reliably correlate with underlying pathophysiologic mechanisms 

PATHOPHYSIOLOGY —

•  The pathophysiology of functional dyspepsia is unclear. Research has focused upon the following factors:

• Gastric motor function

• Visceral sensitivity

• Helicobacter pylori infection

• Psychosocial factors

Gastric motor function • Gastric motor function — Normal gastrointestinal motor function is a complex series of events that requires

coordination of the sympathetic and parasympathetic nervous systems, neurons within the stomach and intestine, and the smooth muscle cells of the gut. Abnormalities of this process 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. (See "Etiology and diagnosis of delayed gastric emptying").

• Delayed gastric emptying has been found in approximately 30 percent of patients complaining of dyspepsia [4-6]; however, there is generally a poor correlation between these entities. Antral hypomotility has been found in a similar proportion of patients, but its relationship to symptoms is also uncertain. Up to 10 percent of patients have fast gastric emptying, which may also be associated with dyspepsia.

• The relationship between gastric motor function and gastric volumes may be important. A study of 57 adults suggested that symptoms were associated with low fasting gastric volume and faster gastric emptying [7].

• Gastric compliance is lower in patients with functional dyspepsia than in healthy controls [8,9]. In one study, for example, postprandial gastric accommodation was evaluated in 40 patients with functional dyspepsia and 35 healthy controls [9]. Impaired gastric accommodation was found in 40 percent of patients with functional dyspepsia (compared to the lower range observed in controls), and was associated with early satiety and weight loss. Treatment with sumatriptan (a 5-hydroxytryptamine agonist that causes fundus relaxation) restored gastric accommodation and improved meal-induced satiety.

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 [10-12]. In a representative study, for example, the sensorial responses (on a 0 to 10 perception score) and the gastric tone responses (by electronic barostat) to either gastric accommodation or to cold stress were measured in 20 patients with functional dyspepsia and 20 healthy controls [10]. The mechanical accommodation of the stomach to gastric distention (compliance) was similar in patients and controls (52 versus 57 mL/mmHg). However, isobaric gastric distention elicited more upper abdominal discomfort in the patients with dyspepsia (perception scores 4.7 versus 1.1). Similar findings were noted in another report in which reduced perceptual thresholds or altered pain referral were found in 20 of 23 patients (87 percent) with functional dyspepsia compared to only 2 of 10 patients (20 percent) with organic causes of dyspepsia [11]. Patients with dyspepsia are also more sensitive to acid infusion into the duodenal bulb (which produced nausea and fewer duodenal pressure waves) compared to controls [12].

• Visceral hypersensitivity, which has also been proposed as an etiologic factor in irritable bowel syndrome, appears to occur independent of delayed gastric emptying [13]. (See "Pathophysiology of irritable bowel syndrome"). In contrast, somatic sensitivity (as measured by transcutaneous electrical stimulation of the hand) is normal in these patients [14].

• Both mechanoreceptor dysfunction (peripheral mechanism) and aberrant processing of afferent input in the spinal cord or brain (central mechanism) may play a role in the pathophysiology of visceral hypersensitivity. The latter mechanism is supported by the observation that sympathetic autonomic activity enhances the perception of gut distension in normal subjects

Helicobacter pylori infection —• Helicobacter pylori infection — Although a possible role for H. pylori infection in functional dyspepsia is suggested by several potential pathogenic

mechanisms, a clear association among these factors, H. pylori, and functional dyspepsia has not been established.• H. pylori is a well known cause of chronic active gastritis. However, gastritis is probably not the cause of symptoms in most patients with functional

dyspepsia. A consistent link between findings on endoscopy and dyspepsia has not been found [16].• H. pylori may cause altered smooth muscle dysfunction due to the induction of an inflammatory response or by the initiation of an antibody response [17]. (

See "Pathophysiology of and immune response to Helicobacter pylori infection"). However, most studies have not found an association between H. pylori and abnormal gastric motor function in patients with functional dyspepsia. In one report, for example, the gastric function of 27 patients with functional dyspepsia and H. pylori infection was compared to that of 38 uninfected patients with functional dyspepsia [18]. The gastric emptying time was similar in both groups.

• The inflammatory response induced by H. pylori may lower the discomfort threshold to gastric distension by causing alterations in the enteric or central nervous system [17]. However, visceral hypersensitivity did not appear to be important in at least one study which found that H. pylori positive and negative patients with functional dyspepsia had no difference in the perception of mechanically-induced gastric distension [19].

• In addition to these rather unconvincing findings, most studies have not been able to establish a temporal relationship between H. pylori infection and chronic dyspepsia, nor has a specific symptom complex been linked to H. pylori [17]. Furthermore, multiple studies have evaluated the benefit of eradicating H. pylori in patients with functional dyspepsia, but results have been conflicting [20], although in aggregate they suggest a small significant benefit [21]. The results of three trials illustrate the controversy:

• In one study, 318 patients with dyspepsia who were H. pylori positive were randomly assigned to antibiotic therapy aimed at eradicating the infection or to omeprazole without antibiotics for the same duration [22]. After one year of follow-up, dyspepsia resolved significantly more frequently in patients who received antibiotic therapy (21 versus 7 percent). Resolution was more common in patients who had had symptoms for five years or less (27 versus 12 percent).

• Two similarly designed studies involving 328 and 170 patients, respectively, reached the opposite conclusion [23,24]. At the end of one year of follow-up, no significant differences in dyspepsia or quality of life were detected between the two groups.

• Despite the similar study design, differences in inclusion criteria and outcome measures may have accounted for the discordant results [25]. A meta-analysis concluded that there was evidence for a small benefit [21]. Thus, at best, only a minority of patients with functional dyspepsia will benefit from H. pylori eradication. This conclusion was supported by a systematic review of 21 randomized controlled trials, which found that 14 patients needed to be treated to cure one case [26].

• Nevertheless, guidelines issued by the American Gastroenterological Association and the American College of Gastroenterology recommend H. pylori eradication in patients with functional dyspepsia emphasizing a possible short-term benefit (number needed to treat around 17) and a possible long-term benefit for prevention of gastric cancer 

Psychosocial factors • No unique personality profile has been found in patients with functional

dyspepsia; however, anxiety, somatization, neuroticism, and depression are increased in this group compared with healthy controls [4,34]. Higher levels of psychopathology have also been found in patients with functional dyspepsia compared to those with duodenal ulcer; the most important factor was multiple somatic complaints [35]. However, the psychological profile and health care seeking behavior in patients with dyspepsia may vary among different cultures. In a study of Australian patients with dyspepsia, for example, health care seeking was related more to symptom severity and duration than to psychological factors [36].

• There is a link between self-reported childhood abuse and functional gastrointestinal disorders [37,38]. It has been suggested that functional dyspepsia is best understood as the result of a complex interaction of psychosocial and physiological factors 

TREATMENT • Treatment of patients with functional dyspepsia is controversial and often disappointing, a sharp contrast to the therapy of

peptic ulcer disease [40]. The goal is to help patients accept, diminish, and cope with symptoms rather then eliminate them [40].

• Similar to patients with irritable bowel syndrome, the most important aspects of the therapy of functional dyspepsia include 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 whenever possible. (See "Patient information: Abdominal pain (functional dyspepsia) in adults").

• Drug therapy, which is based upon the putative pathogenetic mechanisms described above, may help some patients. Several systematic reviews have summarized treatment trials of pharmacologic therapy for nonulcer dyspepsia [41-46]. One of the most comprehensive summaries focused on 57 trials comparing a variety of pharmacologic interventions [42]. The following conclusions were reached:

• Prokinetic agents were more effective than placebo (relative risk reduction (RRR) of 50 percent, 95% CI 30 to 65 percent).

• H2 receptor antagonists were more effective than placebo (RRR of 30 percent, 95% CI 4 to 48 percent).• Proton pump inhibitors and bismuth salts were more effective than placebo, but the benefits were of marginal statistical

significance.• There was no statistically significant benefit from antacids, bismuth, or sucralfate.• A limitation of virtually all the treatment trials was their short duration, calling for caution in accepting the benefits in a

disorder characterized by chronicity. Interpretation of drug trials is also complicated by the heterogeneous nature of the syndrome, the possible dissimilarity of statistical and clinical significance [47], the possible inclusion of patients with gastroesophageal reflux, which could respond to prokinetic agents or acid suppression, and the uncertainty that the study patients are representative of those cared for by primary care physicians (by far the largest group).

ABDOMINAL PAIN DIAGNOSIS •  There are a number of reasons why you can develop symptoms of dyspepsia. Organic (non-functional) dyspepsia can cause

symptoms that are similar to those of functional dyspepsia, or the symptoms may be slightly different. A healthcare provider will perform a medical history and physical examination to narrow the possible list of causes, with special attention to the following:

• Is the pain "gnawing" or worsened by hunger?• Is the pain worsened by certain movements or pressure on certain areas of the abdomen?• Do you take medications for pain, such as aspirin, ibuprofen (Advil, Motrin) or naproxen (Aleve)? Do you have a history of

ulcers?• Do you have heartburn in addition to upper abdominal discomfort?• Do you have intense pain in the upper right or middle of the abdomen? Does the pain extend to the back or between the

shoulder blades? Does this happen periodically, along with vomiting, sweating, or feeling restless?• Have there been changes in your bowel habits (eg, constipation or diarrhea)?• Have you recently unintentionally lost weight, vomited repeatedly, or had difficulty swallowing?• Testing recommendations — The best way to diagnose functional dyspepsia is not clear. The American Gastroenterological

Association suggests the following:• People who are older than 55 or with serious symptoms, such as repeated vomiting, weight loss, difficulty swallowing, or a

low blood count, should have an upper endoscopy procedure. (See "Patient information: Upper endoscopy").• People who are younger than 55 and who do not have serious symptoms are generally offered noninvasive testing to detect

infection with H. pylori (eg, stool or breath testing). (See "Patient information: Helicobacter pylori infection and treatment").• If symptoms fail to improve within four to eight weeks or if more serious symptoms develop, further testing, including upper

endoscopy, is usually recommended. Other diagnostic tests may be recommended in selected cases.

ABDOMINAL PAIN TREATMENT• Understanding the condition — Being diagnosed with functional dyspepsia may be a relief to some people and a frustration to others. It is important to

understand that symptoms are not imaginary. One or more treatments may be recommended, often in combination; having realistic expectations of the benefits of treatment may help to reduce frustration. If there are mood problems, such as anxiety or depression, an evaluation with a mental health specialist (eg, social worker, psychologist, counselor) may be recommended.

• Lifestyle changes — Some people benefit from avoiding fatty foods (which can slow the emptying of the stomach), and eating small frequent meals. Foods that aggravate symptoms should be avoided, if possible, although eliminating entire food groups is not recommended. If you have questions about which foods should be avoided, discuss this with a healthcare provider and/or dietitian.

• Medications — Certain medications may help to reduce the symptoms of functional dyspepsia.

• Acid reducing medications — Some people benefit from treatment with medications that inhibit or reduce the production of stomach acid (eg, H2 blockers such as Zantac®, Axid®, or Pepcid® or proton pump inhibitors such as Prilosec®, Nexium®, Prevacid® AcipHex®, or Protonix®).

• H. pylori therapy — Treatment of H. pylori is recommended if an ulcer is diagnosed. (See "Patient information: Helicobacter pylori infection and treatment").

• This treatment may be considered for people who have H. pylori, but who are not known to have an ulcer. However, the benefit of treating H. pylori in this situation is unclear. At best, a small proportion of people with functional dyspepsia improve following treatment of H. pylori.

• Visceral analgesics — As mentioned previously, some people with dyspepsia are sensitive to enlargement (distension) of the stomach. Medications that relieve visceral pain are being studied, but are not yet available.

• Pain medications — Low doses of an antidepressant medication may be recommended to reduce pain, even if the patient is not depressed. The dose of TCAs is typically much lower than that used for treating depression. It is believed that these drugs reduce pain perception when used in low doses, but the exact mechanism of their benefit is unknown.

• TCAs commonly used for pain management include amitriptyline,desipramine, and nortriptyline. In the beginning, many people who take TCAs experience fatigue; this is not always an undesirable side effect since it can help improve sleep when TCAs are taken in the evening. TCAs are generally started in low doses and increased gradually. Their full effect may not be seen for weeks to months.

• Narcotic pain medications, such as codeine, hydrocodone, oroxycodone, are not usually recommended for long-term relief of functional dyspepsia because of the risk of side effects (eg, constipation) and the potential risk of becoming addicted.

• Complementary and alternative medicine — Several complementary and alternative medicine approaches to functional dyspepsia have been described. Studies involving herbal and natural products, acupuncture, and homeopathy suggested a benefit frompeppermint oil and STW5 (a European multi-herbal preparation that includes peppermint and caraway, also known as Iberogast). However, the quality of the evidence supporting these treatments is generally poor.

• More research is needed before these approaches can be routinely recommended.

ABDOMINAL PAIN PROGNOSIS — Dyspepsia is

typically a relapsing condition. In studies, 60 to 90 percent of people

continue to have symptoms of varying degree two to three years after being diagnosed. However, most people feel better once their condition has been diagnosed, and

many will respond to the treatments discussed above.