Gut Reactions: Concepts in Gastroenterology

Educational Objectives

The goal of this program is to improve management of common gastrointestinal (GI) disorders. After hearing and as­similating this program, the clinician will be better able to:

1.   List distinguishing characteristics of irritable bowel syndrome (IBS), dyspepsia, and gastroparesis.

2.   Counsel patients about empiric therapy for IBS.

3.   Discuss the role of Helicobacter pylori in dyspepsia.

4.   Identify patients with dyspeptic symptoms who may require endoscopy.

5.   Select appropriate medication for patients with gastroparesis.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the plan­ning committee to disclose relevant financial relationships within the past 12 months that might create any personal con­flicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the following has been disclosed: Dr. Schei­man is a consultant for AstraZeneca, Bayer, NicOx, Novartis, Pfizer, Pozen, and Takeda Pharmaceuticals North America. He has also received speaker’s honoraria from Takeda Pharmaceuticals North America. Drs. Lawson and Al-Juburi and the planning committee reported nothing to disclose. In his lecture, Dr. Scheiman presents information related to the off-label or investigatonal use of a therapy, product, or device.

Acknowledgements

Drs. Lawson and Al-Juburi spoke in Napa, CA, at 2009 Update in Gastroenterology and Hepatology for the Primary Care Practitioner, presented July 11-12, 2009, by the University of California, Davis, Health System. Dr. Scheiman was recorded in Bellaire, MI, at the 45th Annual Northern Michigan Summer Conference: Update on Common Clinical Concerns in Pri­mary Care, presented June 22-26, 2009, by the University of Michigan Medical School. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.

Irritable Bowel Syndrome

Michael J. Lawson, MD, Clinical Professor of Medicine, Department of Gastroenterology, University of Cali­fornia, Davis, School of Medicine, Sacramento

Characteristics of irritable bowel syndrome (IBS): chronic lower abdominal pain; disturbed defecation; bloating; feeling of incomplete evacuation; no biochemical or structural abnormality; visceral hypersensitivity (eg, lower threshold for pain)

Etiologies: postinfectious IBS  —  accounts for »30% of cases; chance for IBS 5 times greater after clearance of acute infection (with, eg, Campylobacter or Salmonella), and 7 times greater chance for nonulcer dyspepsia; patients who developed functional complaints had significant life event (eg, bereavement, divorce) and greater population of mast cells and enterochromaffin cells that secrete cytokines in lamina propia; data about broad-spectrum antibiotics based on unreliable breath testing; cultures obtained from small intestine show no evidence of increased bacterial overgrowth in IBS patients; genetics  —  transporter proteins (eg, serotonin transporter protein) genetically different in some IBS patients; concordance rate among monozygotic twins, »20%; twin studies show that mothers with IBS have twins with IBS; motility disturbance  —variable; magnetic resonance imaging (MRI) studies show IBS pa­tients often have greater diameter of transverse colon (supports possibility of simultaneous contractions; enteric-coated peppermint oil may be helpful); environment  —  “the more the mom catastrophizes, the more likely the child is to have IBS”; depression in parents likely to increase risk for functional complaints in child; physical or mental abuse likely to result in chronic pain syndromes

Pain gate: protective; controlled by activity in prefrontal cortex; stress  —  increases gastrointestinal (GI) tract sensitiv­ity due to increased activity in prefrontal cortex; stress management (eg, cognitive behavioral therapy [CBT]) effec­tive; sleep  —  most patients with IBS do not sleep well and complain of fatigue; patients may have fibromyalgia, temporomandibular joint (TMJ) disorder, and migraine headaches; tricyclic antidepressants (TCAs; eg, nortripty­line [associated with fewest side effects]) may be effective (start low [eg, 10 mg 2 hr before bed] and gradually in­crease dose [to eg, 20-30 mg]); exercise  —endorphin-sensitive receptors in pain gate can be blocked by exercising; patients with IBS who exercised vigorously did better than those who exercised moderately, who did better than those who did not exercise at all

Nonulcer dyspepsia: part of spectrum of IBS; causes belching, feeling of fullness after meals, early satiety, and bloating; caused by poor accommodation by fundus of stomach

Reasons patients seek care: somatoform disorders; pain caused by comorbidities (eg, fibromyalgia, TMJ, migraine headaches); comorbidities reliable sign of IBS

Management: in young patients, diagnosis based on history reasonable; prescribe empiric therapy (ie, address stress, sleep, and exercise); educate patient about stress management; explain pain gate and validate symptoms; ask about comorbidities; IBS diagnosed correctly 97% of time (consider celiac sprue or Crohn’s disease in young patients and ovarian or colon cancer in older patients); empiric therapy effective after »2 wk; fecal leukocyte testing and qualitative fecal fat testing good for patients with diarrhea; sigmoidoscopy recommended for patients >50 yr of age; evaluate patients with presence of bright red GI bleeding; patients often present with skepticism (due to eg, failure to improve after treatment for Helicobacter pylori)

Treatment: dietary fiber may cause bloating due to gas (patients subconsciously push diaphragm down and contort abdominal muscles to compensate for poor accommodation); recommend fiber cautiously; increasing intake of liq­uids not beneficial; lactulose can exacerbate symptoms; over-the-counter emulsified mineral oil (eg, Kondremul) and polyethylene glycol (Miralax) effective; lubiprostone may be effective; psychologic treatment shown effective; drugs  —  many side effects; placebo response high (£90%); loperamide (eg, Imodium) effective for diarrhea; treat nonulcer dyspepsia by addressing stress, sleep, and exercise; new drugs  —  centrally acting corticotropin agents; corticotropin releasing factor antagonists; opioid antagonists; synthetic endorphins; many side effects

Speaker’s approach to IBS: focus on health rather than illness; group therapy reduces number of consultations; pa­rental concerns important, especially in adolescents with recurrent abdominal pain; program comprised of 2 90-min sessions of yoga, pilates, exercise with stability ball, and CBT effective in reducing physician visits and improving abdominal complaints in adolescents; involve parents in education and discussion

Dyspepsia

James M. Scheiman, MD, Professor of Medicine, Division of Gastroenterology, University of Michigan Medi­cal School, Ann Arbor

Dyspepsia: intermittent or continuous upper abdominal pain or discomfort; distinct from gastroesophageal reflux dis­ease (GERD) and heartburn; additional symptoms (eg, bloating, fullness, nausea, early satiety) may or may not be present

Causes: H pylori (especially when associated with peptic ulcer disease); environmental factors (eg, food); gut hyper­sensitivity; psychosocial factors; nonulcer dyspepsia (“upper GI version of IBS”); acid secretion and dysmotility play limited role

Uninvestigated dyspepsia and nonulcer dyspepsia: uninvestigated dyspepsia  —  patient complains of upper abdom­inal pain or discomfort, but has not undergone evaluation; nonulcer dyspepsia  —  patient has undergone diagnostic evaluation (eg, endoscopy); consider cardiac or biliary disease; imaging study required to rule out ulcer

Functional GI disorder: persistent or recurrent abdominal pain or discomfort (without evidence of recurrent dis­ease) lasting >12 wk within preceding year; not associated with defecation; no changes in stool frequency or form; many patients with upper abdominal pain have IBS (patient history important); symptoms do not correlate well with imaging studies; patients have impaired quality of life

Differential diagnosis: for uninvestigated dyspepsia, consider nonulcer dyspepsia (most common); GERD; peptic ul­cer disease; rule out malignancy with imaging studies and endoscopy; pancreatitis; cardiovascular disease

Management: assess character of symptoms and degree of patient's distress; patients with alarm features (eg, weight loss, anemia, GI bleeding) mandate immediate assessment for organic illness

Organic dyspepsia: abnormality (eg, reflux disease [esophagitis], gastroparesis [typically in diabetic patients], or ul­cer disease) identified; cancer rare; ulcer disease occurs in £1 in 5; rate of esophagitis, 10% to 25%; rate of func­tional dyspepsia, ³33%; 33% to 50% have no upper endoscopic findings

H pylori: »50% prevalence in nonulcer dyspepsia population; in patients with clearly defined ulcer disease, eradica­tion standard of care; role of H pylori in absence of ulcer disease minimal (treatment controversial); test-and-treat strategy less effective in low-prevalence populations; approach  —  if patient >50 yr of age or at increased risk for gastric cancer (eg, positive family history, or from country with high H pylori and gastric cancer prevalence), per­form endoscopy (if positive, treat; if negative, consider testing for H pylori [if positive, treat with antibiotics]); ben­efits of treating nonulcer dyspepsia with H pylori eradication modest

H pylori, functional dyspepsia, and GERD: no significant role of H pylori in functional dyspepsia; inflammation does not correlate with pain, symptoms, or functional measurements; H pylori eradication  —  trials show no benefit; does not alter natural history of GERD, and may increase acid secretion in some patients; may have minor long-term benefits (eg, reduction in risk for gastric cancer) in patients with predominantly heartburn symptoms, but no effect on symptoms; no evidence that eradication causes GERD; H pylori may improve GERD because chronic in­flammation in stomach suppresses acid; acid suppression with proton pump inhibitor (PPI) often better in patients positive for H pylori

Initial management of new-onset dyspepsia: 1) test-and-treat strategy; treat patients who test positive for H pylori; patients treated for H pylori who have ulcer disease improve in £2 wk; outcomes similar to those of early endos­copy; initially inexpensive; may avoid endoscopy, but only in small group of patients; curing H pylori improves symptoms in <50% of patients; antibiotic therapy leads to increased resistance; useful for young patients who have no alarm symptoms and low risk for gastric cancer; 2) empiric antisecretory therapy; 3) endoscopy; antibody test­ing in 300 patients with dyspepsia  —study found only 1 in 5 positive for H pylori; 81% of test-and-treat patients did not undergo endoscopy; outcomes similar in both arms; usual care vs test-and-treat  —  speaker’s prospective ran­domized trial; no difference in GI referrals, endoscopy, or primary care visits; H pylori eradication resulted in re­duction in repeat treatment with antisecretory medications; symptomatic status at 1 yr similar; other studies show test-and-treat not significantly more cost-effective, and outcomes similar

Algorithm for suspected peptic ulcer disease: determine whether ulcer complications (eg, bleeding) suspected; dis­continue nonsteroidal anti-inflammatory drugs (NSAIDs); if patient has dyspepsia (rather than GERD), and has not been previously treated for H pylori, perform noninvasive H pylori testing (if positive, treat); if symptoms persist 1 to 2 wk after treatment, refer for evaluation

Does H pylori eradication treat nonulcer dyspepsia? “expect 9 out of 10 won't get better”

H pylori testing: antibody testing  —  for patients not previously treated; quantitative and qualitative; office-based qualitative tests not highly accurate; sensitivity and specificity of enzyme-linked immunosorbent assay (ELISA) antibody test, 79% to 85%; active testing  —  urea breath test; urea blood test; fecal antigen test; if prevalence of H pylori £50%, use active testing (more accurate)

Empiric therapy: over-the-counter products (ie, antacids, H₂-blockers, and PPIs); concerns about masking serious disease (eg, cancer); important to stop long-term therapy to check whether symptoms have resolved; PPIs may be more effective than H₂-blockers because many dyspeptic patients have GERD

Endoscopy: rules out cancer; if positive, give PPI for esophagitis; if findings negative, begin trial of PPI; risk for complications low; essential in older patients, patients with alarm symptoms, and nonresponders to test-and-treat; perform in patients with recent onset or change in symptoms, painful or difficult swallowing, or worsening symp­toms

Empiric therapy vs test-and-treat: test-and-treat addresses only peptic ulcer disease; decision based on background prevalence of ulcer disease, H pylori, and percentage of ulcers attributable to H pylori (if low, empiric antisecretory therapy “not of much value”); management of patients who fail therapy  —  reevaluate diagnosis; consider physical and sexual abuse and depression; consider antidepressants to treat visceral sensitivity

Gastroparesis

Amar Al-Juburi, MD, Assistant Clinical Professor, Division of Gastroenterology and Hepatology, University of California, Davis, School of Medicine, Sacramento

Gastroparesis: delayed gastric emptying in absence of mechanical obstruction; chronic disease leading to many symptoms (eg, nausea, vomiting, abdominal pain, regurgitation, early satiety, fullness, bloating); may be associated with malnutrition and poor nutritional status; causes  —  idiopathic; diabetes; postsurgical; central nervous system (CNS) disease (eg, Parkinson disease); infections; medications; mortality rate in 2003 43% for diabetic gastropare­sis (13% for idiopathic)

Differential diagnosis: gastroparesis-like syndrome (GLS)  —symptoms of gastroparesis with no delayed emptying; cyclic vomiting syndrome  —  episodic; patients feel well between episodes; gastric emptying normal or slightly rapid; rumination  —  requires behavioral therapy; early regurgitation; gastric emptying normal; eating disorders  —  electrolyte abnormalities may affect gastric emptying

History and physical examination: ask patients to keep journal to record food intake, symptoms, events, and stress; evaluate gastric emptying; evaluation of motor function and mild electrical activities of stomach of little clinical significance; evaluate autonomic nervous system; review medications; assess comorbidities, metabolic states, and CNS; look for obstruction

Evaluation of gastric emptying: gastric emptying scintigraphy  —gold standard; 4-hr test recommended over 90-min test; upper GI series with barium  —  helps rule out obstructive processes; ¹³C-breath testing  —  office-based test

Management: multidisciplinary approach required for symptom management, nutritional status, and psychosocial rehabilitation; diet modification  —  encourage liquids supplemented by multivitamins and minerals (liquid emptying not affected); avoid or minimize insoluble fiber, saturated fat, alcohol, and tobacco smoking

Medications: prokinetic agents to increase motility; metoclopramide (eg, Reglan)  —  effective prokinetic agent; anti­emetic; not tolerated by ³30% of patients; crosses blood-brain barrier; side effects include insomnia, nervousness, anxiety, and depression; recent blackbox warning for tardive dyskinesia (document that patients informed about side effects; informed consent recommended; monitor closely for involuntary movement disorders); domperidone  —  acts on dopamine receptor; similar to metoclopramide, but does not cross blood-brain barrier; diffi­cult to obtain because not approved by Food and Drug Administration (written request and signed patient consent required); associated with increased risk for arrhythmia (perform electrocardiography and rule out prolonged QT interval]); erythromycin  —  only intravenous (IV) form effective and only for few days; recommended for severe ex­acerbation in hospital; antinausea agents  —  metoclopramide as long-term agent; TCAs used in evening beneficial; scopolamine; dronabinol (Marinol; appetite stimulant); promethazine (Phenergan), prochlorperazine (eg, Compa­zine), and ondansetron (Zofran) good for breakthrough symptoms; step-down approach for refractory gastroparesis  —  start aggressively with combination therapy (eg, antinausea and 2 prokinetic agents), and slowly remove medications as acute exacerbation resolves; patients can be discharged on subcutaneous metoclopramide (give 2-mg test dose before prescribing)

Other therapies: alternative therapies (eg, acupuncture, hypnosis) may be effective; small studies look at efficacy of injection of botulinum toxin type A (eg, Botox) into pylorus; gastrostomy and jejunostomy tubes helpful for nutri­tion, but do not improve quality of life; many side effects (eg, 10%-20% rate of infection, liver problems) and high costs associated with total parenteral nutrition; little data about gastric bypass surgery for treatment of gastropare­sis; gastric electrical stimulation  —  poorly stimulated nerves cause symptoms; in 1963, postsurgical ileus mini­mized by placement of electrode through nasogastric tube to stimulate antrum, resulting in quicker discharge; over time, procedure translated into gastric stimulation therapy

Suggested Reading

Anaparthy R et al: Gastroparesis and gastroparesis-like syndrome: response to therapy and its predictors. Dig Dis Sci 54:1003, 2009; Bortolotti M: Treatment of gastric emptying delay. Minerva Gastroenterol Dietol 55:345, 2009; Ford AC et al: Should we step-up or step-down in the treatment of new-onset dyspepsia in primary care? Pol Arch Med Wewn 119:391, 2009; Jung IS et al: The clinical course of postinfectious irritable bowel syndrome: a five-year follow-up study. J Clin Gastroenterol 43:534, 2009; Khoo J et al: Pathophysiology and management of gastroparesis. Expert Rev Gastroen­terol Hepatol 3:167, 2009; Lee KJ et al: The alteration of enterochromaffin cell, mast cell, and lamina propria T lympho­cyte numbers in irritable bowel syndrome and its relationship with psychological factors. J Gastroenterol Hepatol 23:1689, 2008; Mayer EA et al: Differences in brain responses to visceral pain between patients with irritable bowel syndrome and ulcerative colitis. Pain 115:398, 2005; Peura DA et al: Helicobacter pylori-negative Gastritis in Erosive Esophagitis, Nonerosive Reflux Disease or Functional Dyspepsia Patients. J Clin Gastroenterol Aug 14. [Epub ahead of print] 2009; Rao AS et al: Review article: metoclopramide and tardive dyskinesia. Aliment Pharmacol Ther Nov 3. [Epub ahead of print] 2009; Reddymasu SC et al: Severe gastroparesis: Medical therapy or gastric electrical stimulation. Clin Gastroen­terol Hepatol Sep 16. [Epub ahead of print] 2009; Summers A et al: Managing dyspepsia in primary care. Practitioner 253:23, 2009.