Endoscopy Review

Educational Objectives

The goal of this program is to improve the efficacy of colonoscopy and endoscopy in various clinical settings. After hearing and assimilating this program, the clinician will be better able to:

1.   Recognize factors that affect the efficacy of colonoscopy in colorectal cancer screening.

2.   Discuss the relationship between the use of a new colon preparation regimen and the incidence of ischemic colitis.

3.   Use techniques to manage or minimize bleeding secondary to endoscopic procedures in patients on anticoagu­lation.

4.   Explain the differences between new antiplatelet agents and clopidogrel.

5.   Evaluate the effects of proton pump inhibitors on cardiovascular risk in patients on clopidogrel.

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. Elta is a consultant for Avantis Medical Systems. Dr. Smalley and the planning committee reported nothing to disclose. In his lec­ture, Dr. Smalley presents information related to the off-label or investigational use of a therapy, product, or device.

Acknowledgments

Dr. Elta was recorded at Digestive Disease Week Wrap-Up 2009, held July 17-19, 2009, in Mackinac Island, MI, and spon­sored by the Division of Gastroenterology, University of Michigan Medical School, Ann Arbor. Dr. Smalley was recorded at Gastroenterology and Hepatology Update 2009, held September 11-12, 2009, in Nashville, TN, and sponsored by the Vanderbilt Digestive Disease Center. The Audio-Digest Foundation thanks the speakers and the sponsors for their coopera­tion in the production of this program.

Abstract Review from Digestive Disease Week Wrap-up 2009

Grace H. Elta, MD, Professor of Medicine, University of Michigan Medical School, Ann Arbor

Efficacy of colonoscopy in colorectal cancer (CRC) screening: large Canadian database reported that colonoscopy not protective for right-sided CRC and only 70% protective for left-sided CRC; attributed to poor cecal intubation rates and low adenoma detection rates; study  —  looked at Medicare data (2005-2006); >1500 patients >69 yr of age with previous surgery for CRC and colonoscopy 6 to 36 mo before surgery; found miss rate of 5.7%; risk factors for missed CRC included diverticulosis, no polypectomy, and in-office procedures (12%-15% of all colonosco­pies); 10% to 12% of all colonoscopies performed by family practitioners and general internists; quality of colonos­copy key; excellent preparation important; other key operator skill; even with same withdrawal times, difference in adenoma detection rate between operators seen

Effect of sedation type: Clinical Outcomes Research Initiative (CORI) database  —  looked at moderate vs deep seda­tion; in United States, deep sedation almost always anesthesia provider-delivered propofol; »100,000 patients re­ceived standard moderate sedation and »3500 received deep sedation for screening colonoscopies; controlled for age, race, sex, and preparation quality; showed that more large polyps (³10 mm) found in those with deep sedation (7.2% vs 6%; clinically significant); results require confirmation; no improvement in number of medium-sized pol­yps (6-9 mm) found with deep sedation

Removal of small polyps: current practice  —  avoid electrocautery; hot biopsy associated with more postpolypec­tomy bleeding; cold biopsy technique considered adequate (ie, not necessary to burn base of polyp); study  —  to as­sess adequacy of resection, looked at 29 small polyps (<6 -7 mm) resected with cold biopsy and washed; same site lifted with saline, snared off, and specimens examined to determine whether residual adenoma present; 50% of time, residual adenoma tissue present at base

Colon preparations: polyethylene glycol (eg, Miralax) and electrolyte replacement sports drink (Gatorade) preparation  —increasingly popular, but no safety data; well tolerated; only over-the-counter preparation available; hyperosmolar mixture; before drinking preparation, 2 or 4 bisacodyl tablets taken; should avoid in patients with re­nal disease or significant liver or cardiac disease; large gastroenterology (GI) practice  —reported complaints of cramping and some cases of ischemic colitis in patients undergoing colonoscopy for screening or polyp surveil­lance; determined that 4 bisacodyl tablets used in these cases; in cases where preparation not used, chance of ran­dom discovery of ischemic colitis 0.07% (0.48% in those receiving combination preparation); possibly not problem if only 2 bisacodyl tablets used

Topical treatment for GI bleeding: granular material  —nanopowder used by military in battlefield for open arterial wounds; applied directly to wound to temporize before soldier receives medical care; study  —  animal model devel­oped with 1-cm gastrotomy, with gastroepiploic vessels pushed through lumen and closed; heparin given few days later; vessel then cut open to create arterial bleeding in stomach; animals randomized to spraying vessel with nanopowder via catheter vs no endoscopic therapy; found no bleeding in animals sprayed with nanopowder and persistent bleeding in those who did not receive treatment (died within 6 hr); endoscopy at 7 days showed no bleed­ing in sprayed animals; subsequent necropsy showed healed gastrotomy with no evidence of embolization; no re­port of embolization in battlefield

Endotherapy for diverticular bleeding: limited long-term efficacy data; multicenter study  —  250 patients with lower GI bleeding underwent colonoscopy after rapid purge; found 28 patients with diverticular stigmata and 36 patients with no clear stigmata, but with suspected diverticular source; in general, chance of positive findings with endoscopy for upper GI bleeding 90% (20% chance for lower GI bleeding); in this study, efficacy of endoscopic therapy 93% (25 of 28 achieved hemostasis), with no rebleeding at <30 days; of 25 who achieved hemostasis, late rebleeding seen in 24% (6 patients) at mean of 44 mo; of late rebleeding, most self-limited, some required repeat endotherapy, 2 required interventional radiology, and 1 required surgery; concluded that endotherapy efficacious, with late rebleeding in only 25% of patients; confirms validity of lower GI bleeding algorithms using colonoscopy after rapid purge as first-line therapy

Endoscopic sedation: anesthesia providers for routine endoscopy  —increasing in use (26% annual increase from 2003-2007; »30% projected for 2009); significant geographic variation noted in database, with largest anesthesia provider use seen in Northeast (least in West); doubles cost of routine procedures; when using anesthesia providers, almost al­ways deep sedation; advantages include fewer support personnel required and deep sedation preferred by patients; in randomized controlled trials (RCTs), no difference in safety or tolerance found between deep sedation by anes­thesia providers and standard or moderate sedation by gastroenterologists (preferred by gastroenterologists due to ease and efficiency); propofol without anesthesia providers  —  gastroenterologist directed or nurse administered; RCT evaluated balanced propofol sedation (BPS; propofol given with low doses of midazolam and fentanyl for moderate level of sedation) vs standard agents for upper endoscopy in 81 patients; looked at patient satisfaction scores and recovery time; with BPS, patient satisfaction scores higher (99 on 0-to-100 scale, vs 88) and recovery times faster; no difference in number of transient deep sedation episodes; supports addition of propofol to standard agents; survey found that propofol sedation preferred by gastroenterologists; American Society of Anesthesiolo­gists guidelines not updated; joint position statement made by 3 GI societies deemed propofol safe for use by gas­troenterologists

Biodegradable stents: not yet on market; for refractory benign esophageal strictures; plastic stents no longer accept­able (frequently migrate and cause complications; efficacy low); trial  —  12 patients with refractory strictures (nu­merous dilations before stenting); endoscopies at 1, 2, 3, and 6 mo after stenting; at 3 mo, 6 stents not visible, 6 partially visible or still visible; stents appear to last »3 mo; 2 of 12 stents migrated; excellent outcomes (10 of 12 dysphagia-free at 22 wk)

Capsule endoscopy: 2 studies (1 in dogs and other in 2 individuals) looked at ways to navigate capsules in stomach; technical problems seen in both studies; found 9 of 10 objects placed in various locations in dog’s stomach; mag­netic navigator used in both systems; no need for sedation or placement of scope

Endoscopic ultrasonography-fine needle injection (EUS-FNI): primarily diagnostic; study  —  20 of 29 patients with unresectable pancreatic cancer treated with injected adenovector (TNFerade) plus standard of care vs 9 pa­tients treated with standard of care only; TNFerade is adenovector carrying trans-gene encoding for human tumor necrosis factor (TNF)-a; 5 weekly sessions of therapy adminstered; median survival 14.7 mo in standard of care plus therapy group, vs 11 mo in group that received standard of care only; multicenter phase III trial ongoing, with target enrollment of 330 patients; well tolerated by patients

EUS-celiac plexus neurolysis: for treatment of pancreatic cancer pain; study  —  sham-controlled RCT; patients with pancreatic cancer pain randomized to sham neurolysis vs true neurolysis; 98 patients over 2.5 yr; both groups re­ceived conventional pain control; standard neurolysis therapy consisted of bilateral injections of bupivacaine and ethanol; age, sex, and survival similar in both groups; at 3 mo, lower pain scores in neurolysis group (0.6 vs 2.4); quality of life (QOL) scores and narcotic use equivalent; results borderline favorable

Endoscopy in the Setting of Anticoagulation

Walter Smalley, MD, Associate Professor of Medicine, Department of Preventive Medicine and Surgery, Van­derbilt University School of Medicine, Nashville, TN

Introduction: anticoagulation  —  traditional indications include deep venous thrombosis (DVT), aortic valve replace­ment, and pulmonary embolism (PE); current indications include atrial fibrillation (AF), peripheral vascular dis­ease, and patients with coronary artery disease after percutaneous intervention; polypectomy one of most common causes of bleeding; disadvantages  —  involves older patient population, usually on nonaspirin nonsteroidal anti-in­flammatory drugs (NSAIDs) and at increased risk for peptic ulcer disease (PUD); disorganized system for informa­tion and barriers to communication; lack of clear evidence on which to base guidelines (few RCTs); competing priorities of convenience and compulsiveness; constantly balancing risks and benefits of endoscopy; in some cases, risk for thrombosis increased if anticoagulation withheld; factors include efficacy of anticoagulation for condition and underlying thrombotic disease

Risk for stroke: 3 large trials  —  patients with AF with no previous stroke given warfarin to prevent stroke; rate of stroke »3% per year in these patients and decreased to 1% per year with warfarin; RCT of patients with PE fol­lowed for 3 mo and found that if not treated, 50% develop recurrent PE; if treated with warfarin, only 2% had stroke at 3 mo; Mayo Clinic study  —  no strokes seen in patients who underwent endoscopy but did not have antico­agulation scheme changed; tended to manipulate anticoagulation by withholding warfarin for 3 to 4 days; 12 strokes in 987 cases (1.22% rate); varied according to underlying condition (0.38% in nonvalvular AF); previous stroke greatest risk factor for another stroke; older age and hypertension also important risk factors

Risk of bleeding: present whenever procedure performed; high-risk procedures (1% risk of bleeding de novo without anticoagulation) include polypectomy and sphincterotomy; low-risk procedures include diagnostic endoscopy and biopsy; Stanford study  —  found 1% bleeding rate when polyps <1 cm removed using standard practice of placing clips and withholding warfarin for 36 hr; Kaiser study  —  retrospective; bleeding rate of 2.6% in 425 patients on warfarin (0.2% for those not on warfarin)

Management of bleeding: if patient actively bleeding, withhold or even reverse antithrombosis therapy until hemo­stasis obtained; once hemostasis obtained, start intravenous (IV) heparin to protect patient from risk for stroke or thrombosis and reverse if technology ineffective (controversial); broad consensus that mechanical devices prefera­ble (eg, endoclips, banding); use of fresh frozen plasma (FFP; works in minutes to hours and lasts minutes to hours) ideal way of reversing warfarin emergently; vitamin K effective for hours to days; for heparin and enoxaparin (Lo­venox), protamine used; for antiplatelet drugs, emergent platelet transfusion necessary to achieve hemostasis; sev­eral retrospective studies suggest that therapies employed when patient not on anticoagulation just as effective in setting of anticoagulation when anticoagulation withheld or partially reversed; treat bleeding lesions aggressively if reversal of anticoagulation already started

Aspirin: evidence suggests that risk of bleeding with endoscopic procedures minimal in patient on aspirin or NSAIDs; guidelines consistent in policy of not recommending withholding of aspirin before procedure; case 1  —  patient on warfarin for primary prophylaxis for AF requires esophagogastroduodenoscopy to evaluate dyspepsia (low risk); 2005 American Society for Gastrointestinal Endoscopy guidelines recommend continued anticoagula­tion if within therapeutic range; case 2  —patient with dysphagia and lesion requiring dilation (high-risk procedure); guidelines recommend discontinuation of warfarin 3 to 4 days before high-risk procedure in patient with high risk for thrombosis; case 3  —  man, 55 yr of age, with drug-eluting stent placed 1 mo before and symptomatic choledo­cholithiasis requiring endoscopic retrograde cholangiopancreatography; guidelines recommend discontinuation of clopidogrel; worrisome to stop clopidogrel in this patient, and guideline questioned; drug-eluting stent  —more prone to thrombosis than bare-metal stent; German study  —  drug-eluting stent occlusion rate at 9 mo 1.2% overall; 30% in those off dual therapy at 9 mo (»1% per week), with 50% mortality; extremely high mortality seen with thrombosis in drug-eluting stent; new high-risk conditions  —include bare-metal stent and drug-eluting stent; should rarely, if ever, withhold aspirin, and should consider adding aspirin if withholding clopidogrel in patient not on dual therapy (standard of care); should consider time required for antithrombotic therapy in elective procedures; in ab­sence of clear guidelines, communication among various specialists essential when patient on high-level antiplate­let agents; no clear consensus as to when to restart anticoagulation therapy

New antiplatelet agents: prasugrel  —  compared to clopidogrel, has benefit of reducing cardiac events; more effec­tive; should not be used, unless certain that cardiac surgery not necessary (rate of bleeding extremely high [40% higher than clopidogrel]); need to balance risks and benefits; Clopidogrel for High Arterothrombotic Risk and Isch­emic Stabilization, Management, and Avoidance (CHARISMA) trial  —  5 cardiac events prevented for every 7 GI events; in some studies, GI events much lower than cardiac events; in one study, 30 cardiac events prevented at cost of »23 major GI bleeding events; <3 g/dL drop in hemoglobin considered minor GI bleeding; ticagrelor  —  causes more cardiac events than clopidogrel

Proton pump inhibitors (PPIs) and clopidogrel: new guidelines for high-risk patients; patient with previous PUD requires PPI; if risk factors present for PUD (eg, older age, corticosteroid use), PPI required; study  —  showed 50% increase in risk for cardiac events among clopidogrel users receiving PPI; explicitly recommended switch from PPI to histamine type-2 receptor antagonist (H₂RA); H₂RAs not reliably effective in treatment of gastroesophageal re­flux disease or to prevent NSAID-related damage, especially to duodenum; clopidogrel  —  prodrug; must be metab­olized in liver for efficacy; in vitro studies showed omeprazole affected bioavailability; ability to inhibit platelets clearly decreased by omeprazole; Veterans Affairs study also found 25% increased risk in patients on clopidogrel who received PPI; subanalysis of observational study found that effect not seen in pantoprazole users (in vitro stud­ies showed pantoprazole safer drug); another study found no effect on cardiovascular risk with PPI use among pa­tients followed up from large trials; same results in speaker’s study, but also found 50% decrease in GI events and number needed to treat 50

Suggested Reading

Bassett M et al: Propofol for endoscopy sedation. Gastroenterology 124:1162, 2003; Blacker DJ et al: Stroke risk in anti­coagulated patients with atrial fibrillation undergoing endoscopy. Neurology 61:964, 2003; Bressler B: Rates of new or missed colorectal cancers after colonoscopy and their risk factors: a population-based analysis. Gastroenterology 132:96, 2007; Bretthauer M: The capsule and colorectal-cancer screening--the crux of the matter. N Engl J Med 361:300, 2009; Chang KJ et al: Phase I clinical trial of allogeneic mixed lymphocyte culture (cytoimplant) delivered by endoscopic ultra­sound-guided fine-needle injection in patients with advanced pancreatic carcinoma. Cancer 88:1325, 2000; Hayes S: Ad­verse outcomes associated with use of proton pump inhibitors and clopidogrel. JAMA 302:30, 2009; Lewis JD: Urgent endoscopy with endoscopic therapy for acute diverticular bleeding. Gastroenterology 118:978, 2000; Padmanabhan U et al: Early cognitive impairment after sedation for colonoscopy: the effect of adding midazolam and/or fentanyl to propofol. Anesth Analg 109:1448, 2009; Saito Y et al: Novel biodegradable stents for benign esophageal strictures following endo­scopic submucosal dissection. Dig Dis Sci 53:330, 2008; Saw J et al: Lack of evidence of a clopidogrel-statin interaction in the CHARISMA trial. J Am Coll Cardiol 50:291, 2007; Sreenarasimhaiah J: Interventional endoscopic ultrasound: the next frontier in gastrointestinal endoscopy. Am J Med Sci 338:319, 2009 Wijns W: Late stent thrombosis after drug-eluting stent: seeing is understanding. Circulation 120:364, 2009.