Bad Digestion

1
Bad Digestion

• By Dr. Joel Doughten

2
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?

• AShe should undergo upper gastrointestinal
  endoscopy.
• BShe should be reassured that this is just
  heartburn and is nothing to be concerned about.
• CShe should be given a prescription for a proton
  pump inhibitor (PPI) because over-the-counter
  medications are unlikely to be effective.
• DMeasures such as elevation of the head of the
  bed, small meals and not reclining after eating
  are highly effective.
• EIntermittent on-demand treatment with a PPI
  is a useful long-term treatment option.

3
Answer

• EIntermittent on-demand treatment with a PPI
  is a useful long-term treatment option.

4
Dyspepsia

•  Heartburn (dyspepsia) is the most common
  presenting symptom associated with gastroesophagea
  l 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 andfundo
  plication 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 (gt5
  percent), persistent vomiting,dysphagia (difficult
  y 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 Barretts
  esophagus is indicated for patients requiring
  chronic continuous therapy with PPIs and those
  with chronic symptoms at risk for Barretts
  esophagus (i.e., duration of symptoms gt5 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/repFil
  es/GERD20Final20Report.pdf  Accessed March 2008
• 2. Ebell M. All PPIs equivalent for treatment
  of GERD. http//www.aafp.org/afp/20060101/tips/3.h
  tml   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 171237-45.
• 5. Medical Advisory Panel for the Pharmacy
  Benefits Management Strategic Healthcare
  Group. VHA/DoD clinical practice guideline for
  the management of adults with gastroesophageal ref
  lux disease in primary care practice. http//www.g
  uideline.gov/summary/summary.aspx?ss15doc_id518
  8nbr003570stringGERD  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 26195-204.
• 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 25143-53.

5
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 heartburnD)
All the above
6
Answer

• D) All the above

7
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

• AHigh protein intake
• BSmoking
• CConsumption of decaffeinated coffee
• DConsumption of carbonated beverages
• EUse of a phosphodiesterase inhibitor such as
  sildenafil (Viagra) for erectile dysfunction

8
Answer

• AHigh protein intake

9
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

• AAnemia
• BAcute onset dysphagia
• CMelena
• DInvoluntary weight loss greater than 5 percent
  of baseline weight
• EAge 50 years or older

10
Answer

• EAge 50 years or older

11
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)
•          Cows milk
•          Fat
•          Orange juice other citrus juices
•          Spicy foods
•          Tea
•          Tomato juice
• Lifestyle
•          Smoking
•          Stress

12
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. Pati
  ents 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 gt5 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).

13
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?

• AColonoscopy
• BComplete blood count and fecal occult blood
• CStool cultures
• DSedimentation rate
• ESerum chemistries

14
Answer

• BComplete blood count and fecal occult blood

15
Which of the following statements is TRUE
regarding the treatment of irritable bowel
syndrome?

• AAnxiolytic agents have been shown to be
  helpful.
• BAlosetron (Lotronex) is useful for
  constipation-predominant IBS.
• CLubiprostone (Amitiza) is useful only in women
  with constipation-predominant IBS.
• DDietary changes are generally ineffective.
• EInterventions such as acupuncture and
  psychotherapy are ineffective.

16
Answer

• CLubiprostone (Amitiza) is useful only in women
  with constipation-predominant IBS.

17
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 disor
  ders 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
  gt50 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 (Lotron
  ex) or a tricyclicantidepressant. Abdominal pain
  may be relieved with peppermint oil,
  antispasmodic medications, low-dose tricyclic anti
  depressants 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.
•  

18
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,imipra
  mine)
• Doses lower than those used for depression

19
The classic signs and symptoms of celiac disease
include which of the following? Iron-deficiency
anemia Diarrhea Weight loss Abdominal painA)
1,3B) 2,4C) 1,2,3D) 1,2,3,4
20
Answer

• Iron-deficiency anemia
• Diarrhea
• Weight loss

21
In the patient with dyspepsia, alarm symptoms or
factors that warrant early referral to endoscopy
include all the following, exceptA) Significant
unanticipated weight lossB) Difficulty
swallowingC) Bleeding or anemiaD) Age lt45 yr
22
Answer

• D) Age lt45 yr

23
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 drugsA) 1,3B) 2,4C)
1,2,3D) 1,2,3,4
24
Answer

• Proton pump inhibitors
• Antibiotics
• Bismuth

25
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
26
Answer

• B) Promotility antisecretory

27
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) IsB) Is not
28
Answer

• B) Is not

29
All the following statements about fecal
immunochemical testing are true, exceptA) Less
sensitive than fecal occult blood testing
(FOBT)B) Detects human globinC) No dietary
restrictions requiredD) Less specific than FOBT
30
Answer

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

31
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?
32
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

33
Dyspepsia

• bad digestion definitionupper 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

34
Uninvestigated dyspepsia

• upper abdominal pain, as described, in which no
  investigation (invasive or noninvasive)
  previously
• Performed
• causesirritable 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)

35
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

36
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)

37
Lactose deficiency

• clinically common low threshold
• lactose in meal easier to absorb
• diagnosislactose tolerance test or breath test
  simpler test to have patient drink 3 glasses of
  milk without food
• treatmentlactose 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.

38
Celiac Disease

• occurs in 1 in 125 people
• gt1 million Americans affected (gt50 are women)
• only 90,000 exhibit classic signs and symptoms,
  including iron-deficiency anemia, diarrhea, and
  weight loss
• screeningserum tissue transglutaminase antibody
  and IgA level
• 20 of individuals with celiac disease do not
  produce IgA
• diagnosisminimum of 6 biopsies from duodenum
  (gt90 accurate)
• Cant always diagnose with red flags
• unable to distinguish celiac disease from IBS by
  history

39
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
40
Answer

• (B) Somatostatin

41
In Western countries, which gastritis
distribution is typically associated with H
pylori infection?(A) Antral-predominant (B)
Corpus-predominant (C) Atrophic
42
Answer

• (A) Antral-predominant

43
Treating corpus-predominant gastritis patients
for H pylori may worsen or even induce
gastroesophageal refluxdisease (GERD).(A) True
(B) False
44
Answer

• (A) True

45
Which factor in a patients 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
46
Answer

• (D) Country of origin

47
Resistance to which of the following antibiotics
is associated with 90 failure rates when
prescribing standardtriple therapy to
eradicate H pylori?(A) Metronidazole (B)
Amoxicillin (C) Clarithromycin (D) Tinidazole
48
Answer

• (C) Clarithromycin

49
Helicobacter pylori timeline

• H pylori prevalence currently decreasing
• in United States, with resulting dramatic changes
  in disease management
• 1982first cultured accidentally
• Initial attempts to publish rejected by medical
  community because orthodoxy convinced ulcers
  acidogenic and bacteria
• could not survive stomach
• 1984first paper published Marshall ingested H
  pylori and successfully validated Kochs
  postulates
• 1988first randomized controlled trial treating
  ulcers as infectious
• 1994National Institutes of Health (NIH)
  consensus conference concluded gastric ulcers
  share infectious etiology
• H pylori labeled class 1 carcinogen by World
  Health Organization (WHO)
• 1997H pylori genome sequenced

50
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

51
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

52
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

53
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

54
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 pylorirelated malignancies
• possible concept can be extrapolated to other
  cancers

55
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 datafound 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

56
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

57
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

58
Sequential therapy

• involves amoxicillin and PPI twice daily for 5
  days followed by PPI, clarithromycin, and
  tinidazole for 5 days
• regimen demonstrates 90 eradication, (gt80 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

59
Guidelines for diagnosis and treatment of H
pylori (AmericanCollege of Gastroenterology
ACG)

• ulcer disease
• Past history of ulcer MALT lymphoma
• early gastric cancer
• Uninvestigated dyspepsia (some populations)
• Controversial indicationsfunctional dyspepsia
  (endoscopy-negative)
• GERD
• NSAID use
• unexplained iron deficiency anemia
• Idiopathic thrombocytopenic purpura (ITP)
• populations at high risk for gastric cancer

60
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

61
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

62
Pathophysiology of nonulcer dyspepsia

• Impaired gastric accommodation
• Visceral hypersensitivity
• Delayed gastric emptying
• Helicobacter pylori infection

63
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

64
Drugs that can cause dyspepsia

• Calcium channel blockers
• Methylxanthines
• Alendronate
• Orlistat
• Potassium supplements
• Acarbose
• Erythromycin
• Metronidazole

65
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

66
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).

67
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

68
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

69
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

70
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

71
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.

72
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

73
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

74
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

75
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

76
Which of the following conditions is not one of
the top 3 causes of dyspepia?

1. Ulcers
2. Gastroesophageal Reflux Disease
3. Psychosomatic Illness
4. Nonulcer dyspepsia

77
ANSWER

• c. Psychosomatic illness

78
A patient complains of classic dyspeptic symptoms
but has not undergone any test. You decide to
order an endoscopy when you learn that he

1. Is 40 years of age
2. Has no personal or family history of
   gastrointestinal cancer
3. Drinks a six-pack of cola daily
4. Has lost more than 10 of his body weight within
   the last month

79
ANSWER

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

80
PPIs can cause Abdominal Pain?

1. True
2. False

81
ANSWER

• a. True

82
Urea breath testing for Helicobacter Pylori is
becoming less reliable in the western world
because?

1. The overall prevalence of H Pylori infection is
   decreasing
2. H Pylori is endemic in this region
3. The isotope used in the test is unstable
4. Newer strains of H Pylori use less urea than
   older strains

83
ANSWER

• a. The overall prevalence of H Pylori infection
  is decreasing

84
In at least _____ of patients with dyspepsia,
the cause is never identified

1. 10
2. 20
3. 30
4. 40

85
ANSWER

• c. 30
• The cause of dyspepsia is never identified in 30
  to 60 of patients

86
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.

87
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.

88
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.

89
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 

90
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

91
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.

92
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

93
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 

94
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 

95
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 trial