GASTROINTESTINAL (GI) DILEMMAS
From the spring Family Practice Review, sponsored by the Temple University School of Medicine, Philadelphia, PA
| GI COMPLICATIONS OF DIABETES —Robert S. Fisher, MD, Professor of Medicine and Chief, Gastroenterology Section
and Digestive Disease Center, Temple University School of Medicine, Philadelphia, PA
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| Diabetes mellitus: refers to disorders with hyperglycemia common denominator; associated with GI complications
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| Studies about GI problems in diabetes: most involved type 1 diabetes; most common GI complaints involved disorders
relating to bowel action (eg, constipation, diarrhea, abdominal pain, nausea and vomiting, dysphagia, heartburn); up
to 76% of type 1 diabetics and up to 71% of type 2 diabetics have ≥1 GI symptoms
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 | German study: found that patients with poor glycemic control more likely to have major GI symptoms; concluded that if
blood glucose (BG) well controlled, GI symptoms will likely disappear
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| GI manifestations of diabetes: esophagus (symptoms include dysphagia and heartburn); small intestine (bacterial
overgrowth, bloating, distention, and abnormalities in frequency of bowel habits); colon (constipation major problem);
anal sphincter complex (decreased anal sphincter pressure, leading to fecal incontinence); pancreas, liver, and gallbladder
(enlarged gallbladder volume and decreased cholecystokinin [CCK] release in response to meals); stomach (main
site for GI problems due to diabetes)
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| Mechanisms involved in these disorders: multifactorial
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| Diabetic gastropathy: includes disorders of gastric electrical and motor activity; gastroparesis (delayed gastric emptying
in absence of mechanical obstruction) one manifestation; also manifested as abdominal pain or discomfort, early
satiety, postprandial fullness or bloating, nausea, vomiting, heartburn, and regurgitation; patients may develop anorexia
or sitophobia, leading to weight loss; pathophysiologic mechanisms (impaired fundic relaxation; abnormalities in
gastric pacemaker; abnormalities of electromechanical coupling; abnormalities in antroduodenal coordination)
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| Impact of poor glycemic control on smooth muscle function: induction of gastric dysrhythmias and abnormal proximal
stomach relaxation; decreased amplitude of antral contractions; pylorospasm; hyperglycemia causes delayed stomach
emptying of solids and liquids
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| Prevalence: 30% to 60% in type 1 diabetics and 10% to 30% in type 2 diabetics; incidence higher in women
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| Risk factors: duration of diabetes; poor glycemic control; presence of autonomic neuropathy (evidence weak)
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| Diagnostic work-up: history—review medications; causative drugs include anticholinergics, tricyclic antidepressants, and
opioid analgesics; routine screens—check for calcium, potassium, and magnesium imbalances; look for anemia; probe
for possible tumor obstructing stomach; perform thyroid function tests; evaluation of stomach emptying—upper GI series;
endoscopy; gastric emptying scintigraphy (remains gold standard for diabetic gastropathy); breath test, utilizing 13 C
octanoate; normal emptying 50% by 2 hr and 90% by 4 hr
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| Treatment: glycemic control—important; dietary and nutrition recommendations—5 to 6 small meals daily; avoid
high amounts of fat and fiber; supplement diet with protein; emphasize liquids (eg, bouillion, Gatorade); jejunal feedings
preferred to total parenteral nutrition (TPN)
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| Antiemetics: nausea and vomiting controlled in medulla; phenothiazines—antagonize dopamine-2 (D2 ) receptors in medulla
without having effects on motility; antihistamines—act on histamine-1 (H1 ) receptors; meclizine most commonly
used agent; promethazine (Phenergan) and diphenhydramine (Benadryl); anticholinergics—scopolamine and dicyclomine;
generally poor antiemetics; D2 antagonists with prokinetic effects—metoclopramide and domperidone; 5-hydroxytryptamine
3 (HT3 ) antagonists—expensive; save for “last resort”; substance P neurokinin-1 antagonist—
aprepitant just introduced; cannabinoids—appear to decrease nausea and vomiting; can give dronabinol (Marinol) if
nothing else works
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| Prokinetic agents: D2 antagonists—metoclopramide (Reglan) associated with many side effects (tardive dyskinesia
most feared one); domperidone not available in United States; motilin receptor antagonists—erythromycin accelerates
stomach emptying (often given parenterally; watch for tachyphylaxis); 5-HT4 agonists—tegaserod only available
agent (evidence weak that it treats dyspeptic symptoms); cisapride withdrawn
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| Pyloric relaxants: sildenafil (Viagra)—antiemetic effects disappointing; botulinum toxin type A (Botox)—appears effective
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| Gastric electrical stimulator: appears to decrease symptoms; approved by Food and Drug Administration (FDA) as “humanitarian
device”; implanted via mini-laparotomy or laparoscopy into anterior wall of abdomen
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| Embryonic stem cell implants: experiments done in mice; restores nitric oxide and gastric emptying
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| COLORECTAL CANCER (CRC)—Benjamin Krevsky, MD, Professor of Medicine and Director of Gastrointestinal Endoscopy,
Temple University School of Medicine, Philadelphia, PA
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| Epidemiology: 145,000 new cases diagnosed yearly; lifetime risk ≈5%; expensive cancer to treat, but eminently treatable
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| Natural history: ≈10 yr required for polyp to convert to tumor
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| Classification: tumor, node, metastasis (TNM) staging based on depth of invasion; 5-yr survival (using old Duke’s staging
system) for stage 1 lesion 90%, for stage 2, 70%, and for stage 4, only ≈5%
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| Testing and screening modalities: fecal occult blood test (FOBT)—has best evidence for screening; cost-effective;
drawbacks include that it misses some lesions, requires annual testing, some patients reluctant to adhere to preparatory
diet restrictions, and false-positives sometimes occur; rigid sigmoidoscopy—uncomfortable; reduces risk for colorectal
cancer by 59% in areas within reach; preparation much easier than for colonoscopy but less effective; no sedation required;
perforation rate 1 in 10,000; double-contrast barium enema—rarely done; low risk and inexpensive; has poor
sensitivity, compared to colonoscopy; optimal screening interval unclear (may be every 5 yr); radiologic expertise in performing
test disappearing; same-day colonoscopy not possible
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| Colonoscopy: pros—most accurate test for detecting polyps; diagnostic and therapeutic; has longest protective interval;
reduces CRC mortality; has better patient satisfaction than sigmoidoscopy; cons—risk for perforation 0.6% for diagnostic
procedures and ≈0.75% for therapeutic procedures; highest up-front cost; many patients fearful of test or its
preparation; may miss interval polyps and lesions obscured by suboptimal bowel preparation; comment—
polypectomy reduces cancer risk by 95% over 6 to 10 yr
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| Virtual colonoscopy (virtual colonography or computed tomography [CT] colonography): sensitivity and specificity same as
or worse than colonoscopy; same-day colonoscopy possible; can detect extracolonic lesions; drawbacks—cost not covered
by insurance companies; still requires bowel preparation; most expensive diagnostic-only strategy; high false-positive
rate; radiation exposure; acceptability of results variable
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| Stool-based DNA screening: new test on horizon; noninvasive; not as sensitive or specific as colonoscopy
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| Risk factors: average risk—asymptomatic people >50 yr of age with no high-risk factors; high risk—personal or family
history of CRC or adenomas; certain genetic syndromes (eg, familial adenomatous polyposis, hereditary nonpolyposis
CRC); inflammatory bowel disease
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| Screening procedures: average-risk individuals (excluding blacks)—begin screening at 50 yr of age with annual
FOBT, flexible sigmoidoscopy every 5 yr, combination of annual FOBT and flexible sigmoidoscopy every 5 yr, double-
contrast barium enema every 5 yr, or colonoscopy every 10 yr; digital rectal examination (DRE) not helpful; average-risk
blacks—begin screening at 45 yr of age with colonoscopy; patients with family history of polyps or CRC—begin
screening at 40 yr of age or 10 yr younger than index case; perform colonoscopy every 5 yr; patients with adenomatous
polyposis—begin flexible sigmoidoscopy at 10 yr of age; colonoscopy when first polyp detected; patients with history
of hereditary nonpolyposis CRC—perform colonoscopy every 2 yr, starting at 25 yr of age or 5 yr younger than index
case; personal history of CRC—clear remainder of colon around time of resection, then colonoscopy 1 yr after surgery;
personal history of adenoma—after colon cleared with colonoscopy, then every 3 to 6 yr, depending on size and number
of polyps; presence of ulcerative colitis (UC) or Crohn’s disease (CD)—colonoscopy every 1 to 3 yr with systematic
biopsies for dysplasia, starting 8 yr after onset of UC or CD
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| Cost factors: CRC screening fairly inexpensive, considering number of lives saved
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| Primary prevention modalities: exercise; low-fat diet; use of nonsteroidal anti-inflammatory drugs (NSAIDs, eg,
celecoxib [Celebrex]), calcium, folate, selenium, and possibly estrogen; remark—fiber discredited
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| Observations: symptoms associated with CRC include anemia, fatigue, weight loss, and obstruction; staging procedures
for patients with CRC include CT, magnetic resonance imaging (MRI), positron emission tomography (PET), and intraoperative
ultrasonography; tumor size not as important as depth of invasion and nodal status; surgery curative, but ascertain if
nodes positive; check for evidence of involvement of adjacent organs; laparoscopic colorectal surgery associated with early
recovery and fewer complications, but involves long learning curve
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| Postsurgical surveillance: <5% of recurrences occur after 5 yr; recurrent disease often resectable; patients need to see
physician or oncologist every 3 mo for first 2 yr after surgery; carcinoembryonic antigen (CEA) levels and liver function
tests (LFTs) should be done frequently, colonoscopy should be done 1 yr after surgery and every 3 to 5 yr thereafter if
first one normal, and CT should be done every 3 to 4 mo, especially during first year
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| Adjuvant chemotherapy: indicated for patients with stage 2 CRC or higher (associated risk for micrometastatic disease
50% to 60%); standard therapy involves 5-fluorouracil (5-FU) and leucovorin
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| Other modalities for managing metastases: surgical resection; more intensive chemotherapy (eg, combination of
irinotecan and oxaliplatin); local radiation therapy; tumor bulk reduction using endoscopic laser; use of plastic or metal
stents; monoclonal antibodies (looks promising)
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| GASTROESOPHAGEAL REFLUX DISEASE (GERD)—Dr. Fisher
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| Many faces of GERD: cardinal symptoms—heartburn; regurgitation; dysphagia, with or without erosive esophagitis;
variant symptoms—noncardiac chest pain; hoarseness; sore throat; coughing; wheezing; hiccups; abnormal dentition
and gingivitis (sometimes); complications—erosive esophagitis; ulcers; Schatzki’s ring; Barrett’s esophagus; adenocarcinoma
(related to Barrett’s esophagus)
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| Pathogenesis: GERD is motility disorder, not hypersecretory disorder; sites of dysmotility at gastroesophageal (GE)
junction, body of esophagus, and stomach; in some patients, abnormality in tissue resistance, allowing back diffusion of
hydrogen ions and pepsin into lining of esophagus; comment—some GERD patients have salivary deficiencies with decreased
bicarbonate (endogenous buffer of esophagus)
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| Diagnostic tests: therapeutic challenge with proton pump inhibitors (PPIs); upper endoscopy (test of choice); upper GI
barium studies; esophageal pH monitoring
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| Indications for endoscopy: presence of red flags or alarm symptoms; cancerophobic patients; detection of Barrett’s
esophagus; need to obtain biopsy; detection of infectious esophagitis; comments—Swedish study concluded that any patient
with heartburn should have at least “once in a lifetime” endoscopy; Texas study found that majority of heartburn patients
have nonerosive esophagitis
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| Nonerosive esophagitis: less severe form of GERD; <25% of untreated patients progress to erosive form
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| pH monitoring: provides insight into pathogenesis; involves placing electrode 5 cm above proximal border of esophagus
and measuring pH for 24 hr; comments—normal people have some reflux after eating but very little at night; nighttime
reflux more deleterious than daytime reflux; 95% of people with erosive esophagitis have abnormal pH test
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| Treatment: stage 1—includes lifestyle changes (eg, diet, head elevation, avoidance of eating within 2 to 3 hr of bedtime)
and over-the-counter (OTC) antacids, histamine-2 (H2 ) blockers, and omeprazole; stage 2 (those with continuing
symptoms)—use of acid suppressants, H2 blockers bid, or once-daily PPI; if patient fails to respond to one PPI, try another;
stage 3 (nonresponders)—perform endoscopy, then consider PPI bid; if symptoms persist, add nighttime H2
blocker; stage 4 (medically refractory patients)—perform pH monitoring and consider possible invasive procedure
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| Red flags in GERD patients: anorexia; weight loss; dysphagia; odynophagia; blood in stool; long-standing heartburn;
intractable symptoms; heartburn in people >50 yr of age
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| Erosive esophagitis: Canadian meta-analysis concluded that PPIs superior to H2 blockers in healing esophagitis
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| Surgery: laparoscopic fundoplication generally done today; endoscopic procedures to bolster GE junction investigational;
indications for surgery—intractable reflux; severe esophageal bleeding; nonhealing ulcers; need for long-term or high-
dose PPIs; comments—patients who do not respond to PPIs may not do very well with surgery; surgery does not reverse
Barrett’s esophagus
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| Maintenance PPI therapy: supported by several studies, while others suggest acceptable to try to wean patients off
and try other agents (H2 blockers, prokinetic agents)
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| Possible strategies: 1) maintain patient on H2 blocker bid or once-daily PPI; 2) antireflux surgery; 3) “on demand” therapy
(patient takes PPIs when symptomatic)
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| Complications of GERD: erosive esophagitis; benign strictures; Barrett’s esophagus (predisposes to cancer); unexplained
chest pain; cough; wheezing; sore throat; hoarseness
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| Therapeutic PPI trial: patient should respond within 2 wk if case uncomplicated; up to 3 mo use may be required to
relieve wheezing and coughing due to GERD; >3-mo use may be needed to relieve hoarseness and sore throat due to
GERD
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Educational Objectives
| The goal of this program is to educate the listener about gastrointestinal (GI) complications of diabetes mellitus, colorectal
cancer (CRC), and gastroesophageal reflux disease (GERD). After hearing and assimilating this program, the clinician will
be better able to:
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| 1. Diagnose and treat the various GI complications for diabetes.
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| 2. Recognize that glycemic control is the key to treating GI problems due to diabetes.
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| 3. Screen patients for adenomatous polyps and CRC.
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| 4. Provide postsurgical care for patients with CRC.
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| 5. Manage patients with GERD.
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Discussed on This Program
Aprepitant [Emend]
Botulinum toxin type A [Botox, Botox Cosmetic]
Calcium (several preparations and trade names)
Celecoxib [Celebrex]
Cisapride [Propulsid]
Dicyclomine HCl (several trade names)
Diphenhydramine [Benadryl, others]
Domperidone [Motilium] (investigational)
Dronabinol [Marinol]
Erythromycin (several trade names)
Estrogen (several preparations and trade names)
Fluorouracil (5-fluorouracil, 5-FU) [Adrucil, Carac, Efudex, Fluoroplex]
Folic acid (folacin; pteroylglutamic acid; folate) [Folvite]
Irinotecan HCl [Camptosar]
Leucovorin calcium (folinic acid; citrovorum factor) [Wellcovorin]
Loxiglumide (investigational)
Meclizine (several trade names)
Metoclopramide [Reglan, others]
Omeprazole [Prilosec, Prilosec OTC, Rapinex]
Oxaliplatin [Eloxatin]
Promethazine HCl [Phenadoz, Phenergan]
Scopolamine HBr (hyoscine HBr) [Isopto Hyoscine, Scopace]
Selenium [Sele-Pak, Selepen]
Sildenafil citrate [Revatio, Viagra]
Tegaserod maleate [Zelnorm]
YM443 (investigational)
Suggested Reading
Abir F et al: The management of rectal cancer in the elderly. Surg Oncol 13:2234, 2004; Anwar S et al: Systemic review
of genetic influences on the prognosis of colorectal cancer. Br J Surg 91:1275, 2004; Bergman JJ: Gastroesophageal
reflux disease and Barrett’s esophagus. Endoscopy 37:8, 2005; Bytzer P et al: GI symptoms in diabetes mellitus are
associated with poor glycemic control and diabetic complications. Am J Gastroenterol 97:11, 2002; Chandran M et al:
Gastrointestinal disturbances in diabetes. Curr Diab Rep 3:43, 2003; De Csepel J et al: Overcoming diabetic gastroparesis
en route to kidney transplant. Clin Transplant 20:258, 2006; DeVault VR, Castell DO: Current diagnosis and treatment
of gastroesophageal reflux disease. Mayo Clin Proc 679:867, 1994; Heidelbach JJ et al: Management of
gastroesophageal reflux disease. Am Fam Physician 68:1311, 2003; Iqbal A et al: Endoscopic therapies for gastroesophageal
reflux disease. World J Gastroenterol 12:2641, 2006; Irwin RS: Chronic cough due to gastroesophageal reflux disease:
ACCP evidence-based clinical practice guidelines. Chest 129(1 Suppl):80S, 2006; Jung AD: Gastroesophageal
reflux in infants and children. Am Fam Physician 64:1853, 2001; Kale-Pradham PB et al: Esomeprazole for acid peptic
disorders. Ann Pharmacother 36:655, 2002; Lee TJ, Kahrilas PJ: Medical management of Barrett’s esophagus.
Gastrointestinal Endosc Clin N Am 13:405, 2003; McMahon PM, Gazelle GS: Colorectal cancer screening issues: a
role for CT colonography? Abdom Imaging 27:124, 2002; Mjornheim AC et al: Gastrointestinal symptoms in type 1
diabetic patients, as compared to a general population. A questionnaire-based study. Digestion 68:102, 2003; Mulhall BP
et al: Metaanalysis: computed tomographic colonography. Ann Intern Med 142:635, 2005; Palmer RC, Schneider
EC: Social disparities across the continuum of colorectal cancer: a systematic review. Cancer Causes Control 16:55,
2005; Park MI, Camilleri M: Gastroparesis: clinical update. Am J Gastroenterol 101:1129, 2006; Pettit M: Treatment
of gastroesophageal reflux disease. Pharm World Sci 27:432, 2005; Provenzole D, Gray RN: Colorectal cancer
screening and treatment: review of outcome research. J Natl Cancer Inst Monogr (33):44, 2004; Shalauta MD, Saad
R: Barrett’s esophagus. Am Fam Physician 69:2113; 2004; Shelton BK: Introduction to colorectal cancer. Semin Oncol
Nurs 18(2 Suppl 2):2, 2002; Talley NJ et al: Predictors of turnover of lower gastrointestinal symptoms in diabetes mellitus.
Am J Gastroenterol 97:3087, 2002; Talley NJ: Diabetic gastropathy and prokinetics. Am J Gastroenterol 98:264,
2003; Walsh JM, Terdiman JP: Colorectal cancer screening: scientific review. JAMA 289:1299. 2003; Weaver
EM: Association between gastroesophageal reflux and sinusitis, otitis media, and laryngeal malignancy: a systematic review
of the evidence. Am J Med 115(Suppl 3):81S, 2003; Zimmerman AE et al: A review of omeprazole use in the treatment
of acid-related disorders in children. Clin Ther 23:660, 2001; Zuber TJ: Flexible sigmoidoscopy. Am Fam Physician
63:1375, 2001.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial
relationship with the manufacturer or provider of any commercial product or service discussed. The following has been disclosed:
Dr. Fisher is a lecturer for Novartis Pharmaceuticals, Janssen Limited, and Santarus Incorporated.
Drs. Fisher and Krevsky were recorded March 27, 2006, at the annual spring Family Practice Review, sponsored by
the Temple University School of Medicine, and held in Lancaster, PA. The Audio-Digest Foundation thanks the
speakers and Temple University School of Medicine for making this program possible.
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