COLONIC ISSUES
| COLON PREP UPDATE —Jack DiPalma, MD, Professor of Medicine, Director, Division of Gastroenterology, and Director,
USA Digestive Health Center, University of South Alabama, College of Medicine, Mobile
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| Preparation for colonoscopy: evolved from barium enema; American College of Gastroenterology—recommends
colonoscopy every 10 yr as preferred screening strategy for colon cancer; family history and inflammatory bowel disease
(IBD) special circumstances that warrant screening at other intervals; 30% to 35% compliance; primary care providers
most important factor as to whether patient gets screened for colon cancer
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| Diet and cathartic methods: ideal cleansing method—rapid, safe, thorough, with minimal patient discomfort; past
cleansing method—involved 3 days of clear liquids, magnesium citrate or extract of senna fruit (X-Prep Liquid) or castor oil,
with additional cathartics, eg, bisacodyl (oral or suppository), and enemas until clear on night before procedure; diet designed
to leave minimal colonic fecal residue as effective as clear liquids for 3 days
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| Gut lavage: solution must be electrolyte balanced, osmotically balanced, and noncombustible, with no net fluid and electrolyte
shifts; compared to balanced electrolyte solutions, osmotically- and electrolyte-balanced gut lavage solution had less
flux (less net absorption and secretion of water, sodium, and electrolytes); study—compared 4 preparations, including 3
days of clear liquids, 3-day minimum-residue diet, 1-day minimum-residue diet, and polyethylene glycol-electrolyte lavage
solution (PEG-ELS [GoLYTELY]); found that less aggressive diet resulted in better preparation than clear liquids, and gut
lavage solution even better (preferred by patients); when used for radiologic procedures, air-contrast barium enemas, and
intravenous pyelography (IVP), PEG-ELS adequately removed feces but inadequate for mucosal coating (corrected with
addition of bisacodyl as drying agent); study by speaker—randomized 60 patients undergoing elective colorectal surgery;
found that PEG-ELS-based solutions even better than clear liquids, with less weight loss and more tolerability; also studied
adjuncts with metoclopramide, cisapride, and bisacodyl after 4-L lavage and found no significant change; sulfate-free (SF)-
ELS—GoLYTELY formula has sodium sulfate and PEG; has electrochemical and osmotic gradient; sodium sulfate causes
“rotten egg” smell; without sulfate, osmotic balance altered (increased PEG in solution); basis for NuLytely (generic equivalent
TriLyte); solutions enhanced (eg, split-dose, flavored); flavored solutions—study showed they did not produce combustible
gas; also found that if bisacodyl or magnesium citrate given as adjunct, can use reduced volume (basis of bisacodyl
and PEG-3350 [HalfLytely]); others also using PEG-based preparations (MiraLax, GlycoLax); study—looking at 4-L
preparation with SF-ELS (NuLytely) vs 2-L preparation with 20 mg of bisacodyl; found that reduced-volume preparation
had no difference in cleansing efficacy, no adverse experiences, no laboratory differences, and one half of volume-related
side effects (eg, fullness, nausea, vomiting, overall discomfort); gut lavage solutions also used for preparation of laboratory
animals, drug overdose, cystic fibrosis, fecal impaction, and constipation in pediatric patients (off-label uses); speaker
warns about use of gut lavage solutions for constipation; when small regular doses of PEG-ELS or SF-ELS given, salts all
absorbed; PEG 3350 (MiraLax, GlycoLax) has no salt absorption (preferred agent for constipation but not for bowel preparation);
sugar-containing preparations—addition of sugar-containing solutions (eg, Gatorade, ginger ale) to preparations
not recommended; sodium absorption linked to glucose; fermentable gases induced by sugars; recent publication about
MiraLax-Gatorade preparation reports patient suffered seizures and hyponatremia; MiraLax-based prepations not electrolyte
balanced, not osmotically balanced, and contain sugar that affects salt absorption; PEG, electrolytes, sodium sulfate,
and ascorbic acid (MoviPrep)—ascorbic acid added to improve taste, induce diarrhea, and inhibit gas generation and bacterial
reproduction; split-dose administration; Food and Drug Administration (FDA) approved in August 2006; little clinical
data published
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| Sodium phosphate preparations: Fleet phospho-soda, Visicol, and OsmoPrep; speaker concerned about elemental
phosphorus load of oral sodium phosphate; study by speaker—7 volunteers given Fleet phospho-soda according to directions
12 hr apart and blood, urine, and vital signs monitored (every 2-3 hr for 36 hr); found hypophosphatemia, hypocalcemia,
low ionized calcium, and elevated serum parathyroid hormone (PTH) and urinary cyclic adenosine
monophosphate, indicating true biologic event; raised concern about using phosphates in patients with renal, cardiac, or
hepatic insufficiency; nephrocalcinosis—deposits of calcium and phosphate in kidneys in presence of phosphate load;
30% of ingested phosphate absorbed; predisposing factors include older age, female sex, hypertension, and drugs, eg, angiotensin-receptor
blockers (ARBs), that exacerbate volume depletion; study looking at renal biopsies for nephrocalcinosis
found that 21 of 31 patients with these predisposing factors had nephrocalcinosis and renal failure after phosphate
bowel preparation; 4 of 21 patients eventually on hemodialysis, and 17 have chronic renal failure; as result, FDA issued
warning on phosphate products; adverse effects include significant fluid shifts, electrolyte abnormalities, seizures, and
cardiac arrhythmias; to avoid these, FDA advises encouraging fluid intake and performing laboratory tests before and after
phosphate preparations; industry-sponsored advisory panel—concluded that phosphate products should not be used
in megacolon, gastrointestinal (GI) obstruction, ascites, heart failure, kidney disease, and children <5 yr of age; should be
used with caution in renal failure, heart disease, acute myocardial infarction, unstable angina, preexisting or increased
risk for electrolyte disturbances, debilitated or elderly patients, or with medications known to prolong QT interval; can
cause mucosal ulcerations (can be confused with aphthous lesions of IBD) and deposition of microcrystalline cellulose;
OsmoPrep—same active ingredients as Visicol but form changed to avoid microcrystalline deposits; tablet form; requires
hydration; improved tolerance and less mucosal debris, but produces similar increases in phosphorus, and requires
same cautions and restrictions as other phosphates
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| Cleansing advice: avoid nasogastric administration of preparation (if used, ensure gastric position of tube to avoid aspiration);
to avoid hypothermia, preparations should not be refrigerated; bisacodyl can cause preparation abnormalities, neurologic
problems (due to magnesium), and ischemic colitis; no preparation ideal; studies showing phosphates better than gut
lavage, better tolerated, contraindicated in some conditions, and used with caution in many others; careful instructions and
handouts to patients, and common sense important; do not use lavage in gastroparesis or suspected obstruction; solution can
be chilled to improve palatability; speaker uses bottled water because of chlorine content of tap water; no literature on what
to do if preparation inadequate or poor
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| WIRELESS CAPSULE ENDOSCOPY: IS THERE A ROLE IN IBD?—Arthur Asher Kornbluth, MD, Associate Clinical
Professor of Medicine, Division of Gastroenterology, Mount Sinai School of Medicine, New York, NY
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| Retrospective series for capsule endoscopy vs small-bowel radiography: patients who had stricture on small-
bowel series eliminated from capsule study; overall yield 66% for positive finding on capsule endoscopy compared to
small-bowel radiography; looked at computed tomography (CT) enterography and found that capsule endoscopy picked up
more mucosal lesions; incremental yield of capsule endoscopy compared to all other studies; differences present based on
sensitivity and specificity in suspected Crohn’s disease (CD) subgroup undergoing capsule endoscopy, compared to patients
where capsule endoscopy performed for known reasons; test less useful in suspected CD than in established CD;
capsule endoscopy detects more proximal disease (35% in proximal and middle ileum) than CT enterography (10%) in patients
with known CD; no difference in total ileum; capsule endoscopy may pick up background noise in proximal small
bowel (probably random mucosal breaks); CD may be more panenteric disease than previously thought; need prospective
studies with hard end points for defining CD and which lesions considered significant; in study, capsule endoscopy highly
sensitive but not specific, ie, picked up many lesions not due to CD
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| Proposed diagnostic algorithm for CD: if CD suspected, perform ileal colonoscopy; if positive and has typical appearance
of CD, can make diagnosis; speaker believes small-bowel follow-through will be replaced in future by CT enterography
(if positive for typical CD, can make diagnosis); if CD suspected despite negative radiographic imaging and negative ileal
colonoscopy, and patient has no obstructive symptoms, perform capsule endoscopy (might pick up classic CD lesions); if patient
has obstructive symptoms, perform other more sensitive tests, eg, enteroclysis, magnetic resonance imaging (MRI), patency
capsule test
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| Patency capsule: already approved in Europe; has radiofrequency device (12 mm x 2 mm) in middle of capsule; capsule
has barium and lactose coating designed to dissolve; radiofrequency detected by handheld scanner over patient’s abdomen
(“PillCam”; prevents repeated x-rays or searching for device in stool); capsule retention—incidence varied, depending
on study; inform patient of 1 in 10 to 1 in 20 chance of capsule becoming stuck and requiring surgery
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| Capsule endoscopy in IBD: in patients with suspected CD, want to know specificity; nonsteroidal anti-inflammatory
drugs (NSAIDs)—lesions can be indistinguishable from most severe CD lesions; ask patient about NSAID use; study by
Pfizer—normal volunteers given naproxen and omeprazole vs celecoxib vs placebo; 2-wk study; all volunteers had not
taken NSAIDs for previous 2 wk; 14% had mucosal breaks at start of study; over next 2 wk, 6% developed new mucosal
breaks; mucosal breaks not specific for CD; study—looked at capsule studies in Veterans Affairs population; mean age 50
yr; patients typically had osteoarthritis; 50% of patients taking NSAIDs had small-bowel lesions; of those taking only acetaminophen,
17% had mucosal breaks; consensus—need standardized scoring index; need threshold index to distinguinsh
normal from abnormal; need to determine how capsule index score relates to clinical disease activity score; limited data
from colonoscopy on how CD endoscopic severity score correlates with CD activity score; no matter what scoring index indicates
about severity of lesions, it does not indicate whether lesion from CD or from NSAIDs
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| Consensus report from International Conference on Capsule Endoscopy: capsule endoscopy can identify
small-bowel mucosal lesions not seen with other imaging modalities and might be of value in evaluation of indeterminate
colitis; has value in evaluation of patients with unexplained symptoms; can find strictures in patients with pain (makes
difference in outcome); of specific value in patients with obscure bleeding
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| Future roles for capsule endoscopy: may have role in assessing mucosal healing after medical therapy, in assessing
early postoperative recurrence, and in guiding therapy; may serve as subclinical marker in asymptomatic family members
and contribute to understanding of natural history of IBD
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| COLONOSCOPIC SURVEILLANCE IN IBD: WHAT WE BELIEVE —Wilfred M. Weinstein, MD, Professor of Medicine,
David Geffen School of Medicine at the University of California, Los Angeles
|
| Colonoscopic surveillance: necessary; cancer rate overrated; should start surveillance at 8 yr of disease for pancolitis
and later for left-sided colitis; speaker believes should start surveillance at 8 yr in all cases; idea of left-sided colitis having
lower risk originated from radiologic data (recent data from Lahey Clinic show not much difference); experts recommend
multiple biopsies, large-cup forceps, and expert tissue processing (not realistic); false belief that patient can be cured if
found with high-grade or low-grade dysplasia; almost half of patients with high-grade dysplasia have cancer, and half of
those cancers Duke C classification or worse (about 20% low-grade dysplasia); accepted by most that low-grade dysplasia
indication for colectomy; known that in Barrett’s esophagus and gastric dysplasia, reading of “indefinite” by expert means
minor problem (low end of low-grade dysplasia); must get pathologists to stop using term “moderate dysplasia” because
no action plan in literature for moderate dysplasia (pathologists must use terms for which published action plan present);
biopsy—up to descending colon, use anatomic landmarks; from descending colon down, can perform measured withdrawals;
speaker focuses more on left side because of data suggesting that about two thirds of cancers occur in left colon;
to perform quickly, patient needs to be slightly oversedated and preparation must be immaculate; survey data from United
Kingdom— ≈50% of colonoscopies for surveillance sampled 5 to 10 biopsies per colon and in one third, 11 to 15 biopsies
per colon; data from United States—50% of endoscopists sampling ≥5 sites and other 50% sampling <5 sites in ulcerative
colitis surveillance; jumbo forceps—not used by endoscopists because it requires large-channel scope, and procedure
done every 3 yr up to 20 yr; not just for biopsy; when scoping patient for bleeding, should have large-channel scope available;
<10% of scopes in country large-channel scopes; when using large-cup forceps, biopsy size such that it can be oriented
by histotechnologist, and pathologist sees oriented material (main advantage); putting all biopsies into one bottle
affects ability of pathologist to diagnose; “twofer” phenomenon—2 biopsies taken before forceps pulled out; works well
in colon and small intestine with large-cup forceps; maximum number 4 to 6 biopsies per bottle so biopsies interpretable
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| Distinguishing sporadic adenomas from dome lesions: most endoscopists can make distinction; term “dome”
means raised lesion that requires removal; grade of dysplasia does not matter; must take 4 biopsies within 1 cm of lesion to
ensure no dysplasia away from it; colectomy for low-grade dysplasia—find cancer in 20% to 25%; chromoendoscopy—
detects more dysplasia but too time-consuming; speaker believes should not be routinely used but has 2 indications for use
(one indication left-sided colitis with indefinite dysplasia); highlighter gives good topographic view; indigo carmine preferred
for suspicious lesions; speaker’s recommendations—should do surveillance as recommended (2 yr consecutively
every 3 yr for 20 yr, then yearly); official American Society for Gastrointestinal Endoscopy (ASGE) guidelines recommend
every 2 yr after 2 negative results and more frequently with family history of colon neoplasia; biopsy should be sent to specialized
laboratory; if pseudopolyps found, consider polypectomy
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Educational Objectives
| The goal of this program is to educate the listener about colon cleansing preparations, the role of wireless capsule endoscopy
in inflammatory bowel disease (IBD), and colonoscopic surveillance in IBD. After hearing and assimilating this program,
the clinician will be better able to:
|
 | 1. Select the ideal colon cleansing preparation.
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| 2. Describe the adverse effects of some colon cleansing preparations.
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| 3. Employ a diagnostic algorithm for Crohn’s disease.
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| 4. Summarize the role of wireless capsule endoscopy in IBD.
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| 5. Explain the importance of colonoscopic surveillance in IBD.
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www.audiodigest.org
To locate lectures of related interest, or to see a complete listing of Audio-Digest CME Programs, including written
summaries.
Suggested Reading
Apostolopoulos P et al: The role of wireless capsule endoscopy in investigating unexplained iron deficiency anemia after
negative endoscopic evaluation of the upper and lower gastrointestinal tract. Endoscopy 38:1127, 2006; Chilton AP et
al: A blinded, randomized comparison of a novel, low-dose, triple regimen with fleet phospho-soda: a study of colon cleanliness,
speed and success of colonoscopy. Endoscopy 32:37, 2000; Delegge M et al: Efficacy of bowel preparation with
the use of a prepackaged, low fibre diet with a low sodium, magnesium citrate cathartic vs. a clear liquid diet with a standard
sodium phosphate cathartic. Aliment Pharmacol Ther 21:1491, 2005; DiPalma JA et al: Colon cleansing: acceptance by
older patients. Am J Gastroenterol 81:652, 1986; Ell C et al: A randomized, blinded, prospective trial to compare the
safety and efficacy of three bowel-cleansing solutions for colonoscopy (HSG-01*). Endoscopy 35:300, 2003; Farraye FA
et al: Chromoendoscopy: a new vision for colonoscopic surveillance in IBD. Gastroenterology 131:323, 2006; Hamilton
D et al: Sodium picosulphate compared with polyethylene glycol solution for large bowel lavage: a prospective randomised
trial. Br J Clin Pract 50:73, 1996; Hangartner PJ et al: Comparison of three colon cleansing methods: evaluation of a
randomized clinical trial with 300 ambulatory patients. Endoscopy 21:272, 1989; Hawkins S et al: Barium enema preparation:
a study of low-residue diet, "Picolax' and 'Kleen-Prep'. Australas Radiol 40:235, 1996; Hayes A et al: Bowel preparation
comparison: flavored versus unflavored colyte. Gastroenterol Nurs 26:106, 2003; Hookey LC et al: A
prospective randomized trial comparing low-dose oral sodium phosphate plus stimulant laxatives with large volume polyethylene
glycol solution for colon cleansing. Am J Gastroenterol 99:2217, 2004; Lee JT: The bowel prep conundrum. Infect
Control Hosp Epidemiol 23:224, 2002; Moum B et al: Ulcerative colitis, colorectal cancer and colonoscopic surveillance.
Scand J Gastroenterol 40:881, 2005; O'Donovan AN et al: A prospective blinded randomized trial comparing oral sodium
phosphate and polyethylene glycol solutions for bowel preparation prior to barium enema. Clin Radiol 52:791, 1997;
Pelargonio G et al: Use of video capsule endoscopy in a patient with an implantable cardiac defibrillator. Europace
8:1062, 2006; Pockros PJ et al: Golytely lavage versus a standard colonoscopy preparation. Effect on normal colonic
mucosal histology. Gastroenterology 88:545, 1985; Selvasekar CR et al: Capsule endoscopy: A note of caution. Surgery
141:123, 2007; Sidhu R et al: Capsule endoscopy for the evaluation of nonsteroidal anti-inflammatory drug-induced
enteropathy: United Kingdom pilot data. Gastrointest Endosc 64:1035, 2006; Sjoqvist U: Dysplasia in ulcerative colitis--
clinical consequences? Langenbecks Arch Surg 389:354, 2004; Sloots CE et al: Effect of bowel cleansing on colonic
transit in constipation due to slow transit or evacuation disorder. Neurogastroenterol Motil 14:55, 2002; Thomas T et al:
Management of low and high-grade dysplasia in inflammatory bowel disease: the gastroenterologists' perspective and current
practice in the United Kingdom. Eur J Gastroenterol Hepatol 17:1317, 2005; Tsianos EV: Risk of cancer in inflammatory
bowel disease (IBD). Eur J Intern Med 11:75, 2000; Tuttobene SA: A bowel prep that's easy to swallow. RN 47:52, 1984;
Ullman TA: Cancer in Inflammatory Bowel Disease. Curr Treat Options Gastroenterol 5:163, 2002
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. For this issue, Dr. DiPalma
reported that he is a consultant for Braintree Laboratories, Inc. Dr. Weinstein reported that he received a research grant from
Wyeth Ayerst Research. Dr. Kornbluth reported that he has received grant or research support from Procter & Gamble,
Salix Pharmaceuticals, Synta Pharmaceuticals, Centocor, Inc., Given Imaging, Prometheus Laboratories, and NPS Pharmaceuticals.
He is also a consultant/scientific advisor for Procter & Gamble, Salix Pharmaceuticals, Centocor, Inc., Given Imaging,
Prometheus Laboratories, Berlex Inc., and Union Chimique Belge and is on the Speakers’ Bureaus of and receives
honoraria from Procter & Gamble, Salix Pharmaceuticals, Prometheus Laboratories, Abbott Laboratories, and Centocor,
Inc.
Dr. DiPalma was recorded at the 31st Annual Texas Program, held September 15-17, 2006, in San Antonio, TX, and
sponsored by the Texas Society for Gastroenterology and Endoscopy and the American College of Gastroenterology.
Dr. Kornbluth was recorded at State-of-the-Art Diagnosis and Treatment of IBD, held April 1, 2006, in Long Beach,
CA, and sponsored by the Cedars-Sinai Medical Center and the Crohn’s and Colitis Foundation of America, Greater
Los Angeles and Orange County Chapters. Dr. Weinstein was recorded at the 3rd Annual UCLA Gastroenterology
Symposium, held February 18-19, 2006, in Beverly Hills, CA, and sponsored by the Division of Digestive Diseases
and the Office of Continuing Medical Education, David Geffen School of Medicine at the University of California,
Los Angeles. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production
of this program.
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