GASTROINTESTINAL PROBLEMS
From the 31st Semi-Annual Family Practice Review, sponsored by the Temple University School of Medicine
| CLOSTRIDIUM DIFFICILE INFECTIONS —Benjamin Krevsky, MD, MPH, Professor of Medicine, and Director of Gastrointestinal
Endoscopy, Temple University School of Medicine, Philadelphia, PA
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| Clostridium difficile and pseudomembranous colitis: also known as C difficile diarrhea, C difficile colitis, and C
difficile-associated diarrhea (CDAD; most commonly used); incidence and severity increasing; resistant strains becoming
more common; C difficile—causes 10% to 15% of antibiotic-associated diarrhea; commonly found in normal
healthy infants, 5% of healthy adults, and 10% of hospitalized patients; pseudomembranous colitis—toxin-mediated;
noninvasive; toxin A (enterotoxin); toxin B (cytotoxin) 10 times more potent than toxin A; causes necrotizing enterocolitis;
pseudomembranes grossly or microscopically visible (may be plaques or nodules, sometimes coalesce; entire mucosa
white and may appear ischemic)
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| Risk factors: surgery; spinal fracture; intestinal obstruction; colon cancer; burns; transplantation; nasogastric tubes;
antibiotics—clindamycin; lincomycin; ampicillin; amoxicillin; fluoroquinolones; cephalosporins; penicillins; erythromycin
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| Endoscopic findings: pseudomembranes (fibrin and inflammatory cells); rare in small bowel (usually pancolonic); definitive
diagnosis based on optical appearance; endoscopy may skip areas; at splenic flexure with sigmoidoscopy,
pseudomembranes visible (if present)
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| Clinical course: fatal if untreated; features—diarrhea most common symptom; abdominal pain; tenderness; fever; leukocytosis;
onset highly variable; may occur 4 to 6 wk after discontinuing antibiotic that caused diarrhea; inquire about
antibiotic use in last 1 to 2 mo
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| Diagnosis: stool—fecal leukocytes may or may not be present; x-ray—nonspecific; edema; may appear as ischemic
colitis; endoscopy—flexible sigmoidoscopy or colonoscopy; biopsy or aspirate for laboratory confirmation; cytopathogenic
effect (CPE)—gold standard; stool applied to fibroblasts in cell culture; takes 4 to 5 days; highly sensitive for
toxin B; enzyme-linked immunosorbent assay (ELISA)—detects only toxin A; latex agglutination—used in emergency
department; slide test; detects glutamate dehydrogenase, but agglutination may be caused by other bacteria; enzyme
immunoassay (EIA)—most commonly performed; detects toxins A and B; not as sensitive or specific as CPE, but
“very good”; culture usually not obtained; diagnostic approach—suspect in patients with diarrhea who were exposed to
antibiotics or who have risk factors (eg, hospitalization after surgery); if single stool-specimen testing negative and diarrhea
persists, send more specimens (EIA dependent on volume); endoscopy used when rapid diagnosis needed or when
laboratory testing delayed
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| Treatment: stop antibiotic; correct fluid and electrolyte balance; avoid antiperistaltics (eg, loperamide, opioids); practice
infection control and prevention (eg, wash hands; note, alcohol-based gel hand sanitizers do not kill spores of C difficile
); indications for antibiotic treatment—evidence of colitis; persistent diarrhea despite cessation of offending antibiotic;
underlying infection (eg, osteomyelitis); metronidazole—preferred antibiotic; 250 mg qid or 500 mg tid for 10 to
14 days; inexpensive; oral or intravenous (IV); effective in most patients; warn patients to abstain from alcohol until 1 to
2 days after finishing; vancomycin—125 mg po qid; IV use ineffective; expensive (>$600 for 10-day course); treat for
10 to 14 days; if patient has serious infection, prolong use for 1 wk longer than other antibiotics on board; if patient improves,
no need to repeat stool study; pregnancy—pregnancy category B (not absorbed); oral vancomycin safe during
lactation; treatment failure—suspect noncompliance; consider additional cause of diarrhea; escalate treatment by initiating
vancomycin 125 mg qid; if patient already on vancomycin, increase to 500 mg qid; consider IV immunoglobulin or
surgery
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| Indications for surgery: peritoneal signs; bacteremia; patient unresponsive to antibiotics; progressive fever; rigors;
pericolonic inflammation with fat stranding in mesentery on computed tomography (CT; patients need colectomy)
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| Recurrent CDAD: seen in 10% to 25% of patients; repeat course of original antibiotic; consider adding tapered or
pulsed antibiotics (ie, after 14-day treatment, taper to bid dosing, then to qd dosing, then to every other day for 1-2 mo);
consider adding cholestyramine; Saccharomyces boulardii changes gut immunogenicity and attacks bacteria; vaccination
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| Prevention: meta-analysis showed S boulardii prevented CDAD; enhanced infection control; pay attention when patients
on enteric precautions; early diagnosis; formal management teams; informatics tools to analyze outbreaks within hospital;
targeted antibiotic restriction
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| PEPTIC ULCERS AND HELICOBACTER PYLORI —Robert S. Fisher, MD, Stanley Lorber Professor of Medicine, and
Chief of Gastroenterology Section, Temple University School of Medicine, Philadelphia
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| Sites of ulceration: duodenal bulb most common site, followed by stomach (usually lesser curvature of stomach); distal
esophagus (usually with Barrett’s esophagus); consider hypersecretory state (eg, gastrinoma) with postbulbar or multiple
ulcers; consider Meckel’s diverticulum with ulcers near terminal ileum or right lower quadrant pain; pathogenesis multifactorial
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| Development of ulcers: due to imbalance between aggressive factors (eg, acid, peptic proteolysis, bile salts) and defensive
factors (eg, mucus coating that protects mucosa from luminal content); defensive factors mediated by endogenous
prostaglandins (depletion of endogenous prostaglandins with nonsteroidal anti-inflammatory drugs [NSAIDs] or aspirin
can cause damage); Helicobacter pylori; ischemic (stress) ulcers in setting of intensive care unit (ICU); hypersecretion
(can be associated with gastrinoma [Zollinger-Ellison syndrome] or massive small bowel resection); contributing factors
include tobacco smoking (>10 cigarettes daily), psychologic stress, genetics (eg, type O blood and duodenal cancer); rule
out gastroparesis in women with ulcer who do not respond to routine therapy and who complain about nausea, vomiting,
and abdominal pain (consider stasis-induced ulcer; be hesitant to operate)
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| Acid secretion: proton pump inhibitors (PPIs) and H2 -receptor antagonists inhibit acid secretion; no good drugs that inhibit
cholinergic receptor or gastrin receptor; prostaglandins decrease acid secretion; somatostatin receptor potent inhibitor
of acid secretion
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| H pylori: transmission—oral-oral; fecal-oral; infected instruments; prevalence—decreasing; higher in young people and
in developing countries; 50% to 60% of patients with duodenal ulcer positive for Helicobacter
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| Important associations with H pylori: chronic active gastritis—1) involvement of antrum; reversible with eradication;
2) diffuse; may involve antrum and body of stomach; reversible; decreases acid secretion; 3) atrophic gastritis; substrate
for gastric cancer; duodenal ulcer; gastric ulcer; adenocarcinoma—due to class I carcinogens; cytotoxic-
associated gene (cagA) genotype of H pylori associated with more prevalent atrophic gastritis in stomach and diffuse reversible
gastritis; mucosa-associated lymphoid tissue (MALT) lymphoma
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| Possible associations with H pylori: nonulcer dyspepsia—abdominal pain or discomfort; early satiety; nausea with or
without vomiting; bloating with or without distention; normal endoscopy and x-ray; H pylori not important factor; in populations
of uninvestigated dyspepsia, 15% to 20% may have ulcer (important to test and treat for H pylori); H pylori may be
protective against erosive esophagitis, Barrett’s esophagitis, and esophageal adenocarcinoma; NSAIDs—may damage mucosa
of upper gastrointestinal (GI) tract in acute setting; some studies suggest H pylori may be protective in long-term users;
unresolved; virulence factors—urease; cagA phenotype
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| Testing: indications—presence or history of duodenal or gastric ulcer; MALT lymphoma; gastric adenocarcinoma; dyspepsia
(determine prevalence of H pylori in local population; not cost-effective to test and treat if <25%); before initiating
acute treatment with NSAIDs or PPIs (controversial); in presence of H pylori, PPIs increase likelihood of atrophic
gastritis; tests available—serology (cannot be used to establish eradication, but can be used for diagnosis); rapid urease
(in presence of urea, H pylori makes ammonia and CO2 ); endoscopy; biopsy; staining; culture difficult; fecal antigen
testing inexpensive and effective and can be used for diagnosis and establishing eradication (performed by few centers);
urea breath test (depends on normal duodenal, portal, hepatic, and pulmonary function); when performing rapid urease
testing in patient on acid suppression, sample antrum and more proximally because organisms migrate in setting of treatment
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| Treatment: triple therapy (PPI and 2 antibiotics) twice daily; clarithromycin (5% resistance) and amoxicillin (no resistance)
most common combination; metronidazole (30% resistance); tetracycline rarely used; recent articles about levofloxacin (eg,
Levaquin); quadruple therapy—add bismuth subsalicylate (eg, Pepto-Bismol; 1 g qid); 2-wk or 10-day course; 7-day
course with rapid PPI (eg, rabeprazole); recurrence rate 60%, with failure to eradicate H pylori in patients with duodenal or
gastric ulcer
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| COLON CANCER —Dr. Krevsky
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| Classification: TNM staging system and Dukes classification comparable; involve depth of invasion (eg, through muscularis
propria or serosa, metastatic disease [Dukes D or TNM stage IV]); 5-yr survival rates—90% if detected in stage
I or Dukes A; 70% in stage II; 50% in stage III; 5% in stage IV
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| Fecal occult blood testing (FOBT): pros—effective; noninvasive; no bowel preparation required; readily performed;
cost-effective; cons—effectiveness limited (“misses a lot of colon cancers”); requires annual testing; patient resistance
to handling stool; dietary restrictions; false-positive results
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| Sigmoidoscopy: rigid—59% reduction in risk for death from colorectal cancers in reach of sigmoidoscope; (reaches half
of colon that causes cancer); flexible—office-based procedure; more effective than FOBT; does not require sedation; easier
preparation; lack of sedation leads to patient discomfort; less effective than colonoscopy; preparation and expertise of practitioner
can limit insertion depth; risk for perforation 1 in 10,000
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| Double-contrast barium enema: pros—inexpensive ($75); full colon evaluation; low risk; cons—poor sensitivity
compared to endoscopy; false-positive results; poor patient tolerance; optimal screening interval unknown; radiologist expertise
declining
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| Colonoscopy: gold standard; pros—most accurate test for detection of polyps; 90% to 95% sensitivity for polyps ≥1
cm; diagnostic and therapeutic capabilities; longest protective interval; reduced colorectal cancer mortality (indirect evidence);
better patient satisfaction than with sigmoidoscopy; cons—≤1% risk for perforation if polyp removed (risk
lower when polyp removal not required); highest upfront cost; compliance issues with bowel preparation; detection limitations;
high-definition endoscopy—high-definition cameras on endoscopes allow improved narrow-band imaging; after
5.9-yr follow-up, studies saw significant reduction in incidence of cancer by performing colonoscopy and
polypectomy
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| New screening techniques: virtual colonography or colonoscopy—sensitivity 94% in one study, 55% in another
study; learning curve for interpretation by radiologists; risk for perforation low; lack of sedation results in patient discomfort
from air insufflation; bowel preparation similar to that of colonoscopy; most expensive diagnosis-only strategy; high
rate of false-positive results; DNA testing—detects cells shed by adenoma or carcinoma in stool; blood testing tells genetic
background of patient and helps stratify risk; capsule endoscopy —new; patient swallows capsule comprised of
camera and radiotransmitter; capsule obtains image every 1 sec for 2 days; sensitivity 85% to 90%; bowel preparation required
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| High-risk factors: personal history of colorectal cancer or adenoma; positive family history in first-degree relative; genetic
syndromes (eg, familial adenomatous polyposis [FAP] syndrome, hereditary nonpolyposis colorectal cancer
[HNPCC; Lynch syndrome]); inflammatory bowel disease; 1 in 4 risk of developing colorectal cancer (risk 100% in patients
with FAP)
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| Recommended screening strategies: options beginning at age 50 yr in patients at average risk—annual FOBT
and/or flexible sigmoidoscopy every 5 yr; double-contrast barium enema every 5 yr or colonoscopy every 10 yr; digital
rectal examination with or without FOBT not appropriate; black patients—higher incidence of colorectal cancer; younger
mean age at diagnosis; increased proximal distribution (more on right side than left side of colon); begin screening at age
45 yr; patients at increased risk—if patient has positive family history for polyps or colorectal cancer, start screening at
age 40 yr or 10 yr younger than index case (whichever lower); in patients with positive genome for FAP, start screening
with flexible sigmoidoscopy at age 10 yr (colectomy indicated when polyps appear); in patients with HNPCC, colonoscopy
every 2 yr, starting at age 25 yr or 5 yr below age of onset of index case; annual screening after age 40 yr; in patients
with personal history of colorectal cancer, perform colonoscopy after clearance at time of resection; colonoscopy every 3
yr thereafter (sometimes also at first year); in patients with prior adenoma, colonoscopy 3 to 6 yr after colon clearance; in
patients with ulcerative colitis or Crohn’s colitis, incidence begins rising 8 yr after diagnosis (perform colonoscopy every 1
to 3 yr, with systematic random biopsies [ie, 4 biopsies every 10 cm to look for dysplasia; dysplasia indication for colectomy]);
cost-effective
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| Polypectomy intervals: 5 yr, if patient had 1 to 2 tubular adenomas <1 cm; 3 yr, if patient had ≥3 adenomas (high-grade
dysplasia), polyp >1 cm, or villous polyp; 5 yr, if patient has history of polyp but most recent colonoscopy negative; 3 to 6 mo,
if patient had large sessile polyp (>2 cm; check for residual tissue)
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| Primary prevention: exercise; low-fat diet rich in fruits and vegetables (high-fiber diets ineffective); NSAIDs (eg, celecoxib
[Celebrex]) shown to slow rate of polyp development and progression of polyps, especially in patients with polyposis
syndromes; do not use aspirin for colorectal cancer prophylaxis; calcium, estrogen, folate, and selenium shown beneficial
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| Diagnosis and staging: symptoms—fatigue; anemia; weight loss; obstruction; 5% of patients have synchronous lesions,
30% have synchronous polyps; adenoma on sigmoidoscopy prompting colonoscopy and polyp removal may lead
to identification of colon cancer in cecum; imaging studies for staging—CT; magnetic resonance imaging (MRI);
positron emission tomography (PET); intraoperative ultrasonography; tumor size not as important as depth of invasion
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| Hemicolectomy: can be performed laparoscopically; faster discharge (2-3 days vs 10-15 days) with fewer complications;
long learning curve
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| Surveillance: risk for recurrence low (<5%) after 5-yr survival; aggressive therapy beneficial; 35% of recurrent disease
curable; examination every 3 mo for 2 yr; carcinoembryonic antigen (CEA) and liver function tests (LFTs) every 3 mo;
colonoscopy at 1 yr and every 3 to 5 yr thereafter if normal; CT every 3 to 4 mo for first 1 to 2 yr
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| Adjuvant therapy: 50% to 60% of newly diagnosed patients have postoperative micrometastatic disease; chemotherapy
(5-fluorouracil [5-FU] and leucovorin standard; can increase 5-yr survival by 16%) given to reduce micrometastatic disease;
recommended for 6 mo
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| Management of metastases: surgical resection; 5-FU and leucovorin standard; consider adding combinations of irinotecan
and oxaliplatin; myriad investigational protocols; radiation therapy; local palliation; stent placement to temporarily decompress
colon and reduce likelihood of postoperative colostomy
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| New agents: bevacizumab (Avastin)—monoclonal antibody against vascular endothelial growth factor; improves median
survival; approved by Food and Drug Administration (FDA); cetuximab (Erbitux)—monoclonal antibody against
epidermal growth factor; response rates high; time to treatment failure longer; does not improve median survival
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Suggested Reading
[No authors]: Guidelines for colorectal cancer screening and surveillance. Gastrointest Endosc 51:777, 2000;
Agrawal S et al: Colorectal cancer in African Americans. Am J Gastroenterol 100:515, 2005; Anderson J et al: H
pylori infection. Review of the guideline for diagnosis and treatment. Geriatrics 55:44, 2000; Cappell MS: The pathophysiology,
clinical presentation, and diagnosis of colon cancer and adenomatous polyps. Med Clin North Am 89:1,
2005; Fekety R: Guidelines for the diagnosis and management of Clostridium difficile-associated diarrhea and colitis.
American College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol 92:739, 1997; Howden
CW et al: Practice patterns for managing Helicobacter pylori infection and upper gastrointestinal symptoms. Am J
Manag Care 13:37, 2007; Hurley BW et al: The spectrum of pseudomembranous enterocolitis and antibiotic-associated
diarrhea. Arch Intern Med 162:2177, 2002; Kopanski Z et al: Serological diagnosis of infection by Helicobacter
pylori in chronic ulcer disease. Mater Med Pol 25:81, 1993; McFarland LV: Meta-analysis of probiotics for the prevention
of antibiotic associated diarrhea and the treatment of Clostridium difficile disease. Am J Gastroenterol 101:812,
2006; Moayyedi P: Review: Eradication therapy supplemented by probiotics increased eradication rates and reduced
side effects in H. pylori infection. ACP J Club 146:63, 2007; Schroeder MS: Clostridium difficile--associated diarrhea.
Am Fam Physician 71:921, 2005.
Cultural and Linguistic Resources
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For more information about CME courses from Temple University School of Medicine, and for access to two online
courses from Temple University, go to the Education Contributor page on our website: www.audiodigest.org.
Educational Objectives
| The goal of this program is to improve management of common gastrointestinal (GI) problems by reviewing risk factors
and management strategies. After hearing and assimilating this program, the clinician will be better able to:
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 | 1. Use appropriate screening tests to diagnose Clostridium difficile-associated diarrhea.
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| 2. Select safe and effective antibiotics to treat pseudomembranous colitis.
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| 3. Describe conditions associated with Helicobacter pylori, such as nonulcer dyspepsia.
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| 4. Choose the most effective screening tool for colorectal cancer.
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| 5. Initiate a screening regimen for colorectal cancer based on patient history and risk factors.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty members 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. Krevsky is on the Speakers’ Bureaus for Novartis Pharmaceuticals
Corp. and Takeda Pharmaceuticals America, Inc., is a consultant for Boston Scientific, and is a stockholder in
Schering-Plough Corp.
Acknowledgements
Drs. Krevsky and Fisher spoke in Lancaster, PA, at the 31st Semi-Annual Family Practice Review, presented March 25-30,
2007, by Temple University School of Medicine and Lancaster General Hospital. The Audio-Digest Foundation thanks the
speakers and the sponsors for their cooperation in the production of this program.
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