Digestive Diseases Wrap-Up

From DDW Wrap-Up, sponsored by the University of Michigan Medical School, Division of Gastroenterology,
Department of Internal Medicine

Educational Objectives

The goal of this program is to improve the management of upper gastrointestinal tract disease. After hearing and as­similating this program, the clinician will be better able to:

   Discuss the various colonoscopy techniques (eg, warm water immersion,  conventional, cap-assisted), and the importance of the quality of preparation.

   Compare the advantages and disadvantages of the 2 major types of image-enhanced endoscopy.

   Review the mechanisms involved in the pathophysiology of gastroesophageal reflux disease (GERD).

   Describe new technologies used in the management of GERD.

   Discuss the management of eosinophilic esophagitis and Barrett’s esophagus.

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, Olympus Medical Systems, MGI Pharma, Inc, and Ethicon, Inc. Dr. Nostrant and the planning committee reported nothing to disclose.

Acknowledgements

Drs. Elta and Nostrant were recorded at DDW Wrap-Up, held July 18-20, 2008, in Bay Harbor, MI, and sponsored by the University of Michigan Medical School, Ann Arbor, Division of Gastroenterology, Department of Internal Medicine. The Audio-Digest Foundation thanks the speakers and the University of Michigan Medical School for their cooperation in the production of this program.

Endoscopy and Emerging Therapies: Abstract Review

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

Colonoscopy technique: insertion of colonoscope difficult part for patient and operator; generous lubrication recom­mended; study  —  compared lubrication with oil  or warm water to standard lubricants; found oil or warm water su­perior for patient comfort, amount of medication used, and physician’s assessment of facility of inserting scope; study  —  looked at water immersion vs conventional colonoscopy; procedures performed by fellows and attending physicians; for water immersion colonoscopy, cecal intubation time for fellows, 11 min (24 min with standard lu­bricant); no time difference with faculty physicians; statistically significant difference in amount of sedation re­quired; no difference in patient satisfaction

Cap-assisted colonoscopy: reported to decrease pain at colonoscopy, increase adenoma detection rates (ADR), im­prove cecal intubation rates, and allow cecal intubation in previously failed patients; definition  —  plastic cap placed at end of endoscope; most studies use standard endoscopic mucosal resection (EMR) cap; retractable cap also used; Asian study  —  cap-assisted vs conventional colonoscopy; experienced endoscopists; found no difference in polyp detection rate, cecal intubation rate, and patient pain score; cap-assisted colonoscopy had statistically significant better cecal intubation time and total colonoscopy time; cap preferred by majority of endoscopists

Adenoma detection rates: slow withdrawal times correlate better with ADR; even with same withdrawal time, ADR varies with endoscopist; study  —  retrospective review of 309 screening or surveillance colonoscopies (126 per­formed by faculty alone and 183 by fellow alone); more poor preparations seen in fellow patients; fellows found more adenomas (37% ADR vs 23% for faculty) and more small and flat adenomas; speaker’s opinion that fellows perform better on withdrawal and careful inspection

Colonoscopy quality: quality of preparation single most important factor; current preparation choices include so­dium phosphate (over-the-counter liquid or OsmoPrep tablets), 4  L polyethylene glycol (PEG)-based preparations, 2  L PEG-based preparations with citrate or stimulant laxative, and various “home-grown alternatives” (eg, polyeth­ylene glycol [MiraLax]/Gatorade); studies show split dosing (one-half dose at night and other half in morning) bet­ter; study  —  looked at timing of last dose of preparation; found that preparations with quality of 0 to 1 (excellent) had statistically significant shorter interval to last dose of preparation; another study found that colonoscopies per­formed in afternoon associated with poor preparation

Image-enhanced endoscopy: 2 major types chromoendoscopy and scope-based image enhancement (eg, narrow band imaging [NBI] for Olympus scopes and optimal band imaging [OBI] or Fuji Intelligent Color Enhancement [FICE] for Fuji scopes); both scopes highlight certain color bands and tend to highlight vascular structures and to­pography; chromoendoscopy uses absorptive and surface stains and gives better views of surface of mucosa; in pol­yps, Barrett’s esophagus (BE), and early gastric cancer, controversial benefit for chromoendoscopy or scope-based imaging over high-definition (HD) white light with careful inspection; study  —  NBI vs conventional colonoscopy for colorectal cancer screening; found no difference in ADR, total number of adenomas, number of flat adenomas, and withdrawal times; German study  —  compared OBI (FICE) to colonoscopy with targeted chromoendoscopy; found no difference in ADR and procedural time and that FICE system equally accurate for determining type of polyp (92% vs 90%); future of endoscopic image enhancement  —  whether recognition of polyp histology and dys­plasia or cancer better still in question; difficult for randomized controlled trials (RCTs) to show that any of image enhancements superior to standard HD white light endoscopy

Third eye retroscope: based on computed tomographic colonography (CTC) data that suggest missed polyps on colonoscopy present on back of haustral folds (seen through retroflex view); open-label study  —  third eye increased polyp detection rate by 17% and ADR by 12%; question whether third eye scope worth cost and effort for increase in polyp detection rate; average size of additional polyps detected, 4 mm; technical problems

Saving on cost of colonoscopy: based on premise that 80% of polyps removed <6 mm and that in polyps £5 mm, risk for cancer or high-grade dysplasia (HGD) rare (0.5%); histology used mainly to determine surveillance intervals; careful endoscopic inspection 90% accurate in determining whether hyperplasia or adenoma

Endoscopic sedation: 40% of routine endoscopies have anesthesia-provider-delivered propofol; payors starting to deny, except for special patients or procedures; gastroenterologist-directed nurse-delivered propofol  —  rarely per­formed (only 1%-2% of endoscopies), due to restrictive label of propofol and rules of state nursing boards; fospro­pofol (Aquavan)  —prodrug for propofol; longer half-life; approval pending; possible restrictive label; computer-assisted personal sedation (CAPS)  —  device delivers propofol according to patient’s response; for use by gastroen­terologists and nurses; not yet approved; pooled experience with gastroenterologist-directed propofol  —  complications include requirement for mask ventilation in 0.08%; twice as common for upper endoscopy than for colonoscopy; endotracheal intubation or death extremely rare; extremely safe; alternative to cost-prohibitive anes­thesia provider-delivered sedation; delivers moderate sedation

Importance of experience in capsule endoscopy reading: credentialing guideline states endoscopist must 1) be skilled in routine endoscopy, 2) have taken short course (2 days), and 3) have review of first 10 cases; study  —  found major disagreement with capsule reading in 38% and minor disagreement in 31%, suggesting that misinter­pretation common and that original credentialing requirements possibly inadequate

Colon capsule: study  —  compared to colonoscopy for polyp detection; results divided according to polyp size (>6 mm and >10 mm); sensitivity for polyps »60%, regardless of size; capsule not necessarily better for larger polyps; specificity better for larger polyps; 60% detection rate inadequate

Esophageal Disease: Abstract Review

Timothy T. Nostrant, MD, Professor of Medicine, University of Michigan Medical School, Ann Arbor

Pathophysiology of gastroesophageal reflux disease (GERD): several mechanisms for developing GERD; most common is inappropriate relaxation of lower esophageal sphincter (LES) several times during day (way of venting air); in GERD, large amounts of acid brought up when individual vents air; 80% of normal reflux of acid occurs during day; other aspect of reflux salivary secretion and salivary neutralization (seen more commonly, as more head and neck irradiation performed and as more medications given that dry up saliva); moderation of changes in weight  (strain reflux)  —  probably real mechanism by which esophagitis develops; large volumes of acid required for long period; 1-in increase in waist circumference >40 in increases pressure in abdomen by »10 mm Hg; diaphragm ma­jor component for preventing reflux; gastric sling, comprised of muscles at gastroesophageal (GE) junction, also involved; acid pockets  —  one found in gastric fundus and another between gastric fundus and LES; possibly more important and more difficult to monitor; acid component most important with diaphragmatic sling; how sphincter responds also important; swallowing decreases sphincter pressure into stomach, so food boluses pass through; pro­tein meal increases sphincter pressure; should recommend to patient to have protein meal 30 min after taking pro­ton pump inhibitor (PPI) to increase efficacy of PPI; fatty meals decrease sphincter pressure; increased abdominal pressure causes increase in gastric and sphincter pressures, due to increased diaphragmatic and gastric sling pres­sures; gastric distention associated with both

New technologies for GERD

Endoscopic therapies: based on principle that gastric pressure monitoring complex can be changed without affect­ing swallowing mechanism; no problems with swallowing mechanism with any of endoscopic techniques, but they have had no effect on GE junction parameters; compared to open surgery, laparoscopic surgery associated with better effect on GE junction, but also associated with swallowing dysfunction

Augmentor: miniature magnetic bracelet with titanium laparoscopically placed around LES; precise forces allow LES complex to come together; possibly associated with better swallowing function; feasibility study  —  found no perioperative complications; 86% of patients taken off medical therapy and symptomatically improved; quality of life and acid reduction scores remarkable; all patients able to belch, with no gas bloat; only one patient re­quired removal

Gastric bypass: all patients have significant change in reflux over time; likely produces change in reflux related (predominantly) to augmentation of LES in general; patient should have no previous reflux; if patient had previ­ous significant reflux, possible to have reflux postoperatively; upright and recumbent reflux reduced and progres­sively improved; detected reflux episodes also improved (»50%); acid and nonacid reflux decreased over time, although nonacid reflux appeared to increase at »6 mo; desired response obtained, with no postoperative compli­cations

PPI use and risk for esophageal carcinoma (CA): believed that acid reduction lowers risk for esophageal CA, but no data; study  —  found that odds ratio for developing CA good in those taking PPIs; no duration response; hista­mine (H)₂ blockers not associated with substantial improvement in risk

Extent and duration of medications: based on large prescription database for patients taking PPIs who had BE or non-Barrett’s GERD, PPI use quite small; duration 158 days (135 days in non-Barrett’s GERD); only two-thirds of patients take medications for long periods

Natural history of GERD: substantial improvement and change over time seen with nonerosive reflux disease (NERD); looking at cohort, 75% do not change, but substantial number develop Los Angeles (LA) Class A or B mild esophagitis; only small percentage develop severe esophagitis; study  —  found that in follow-up endoscopy 4 yr after initial evaluation, most patients followed for long period; of 294 participants, 128 still had troublesome GERD, and 47% had reflux esophagitis; BE seen in 24 patients; more reason to consider long-term therapy

Eosinophilic esophagitis (EE): eosinophils infiltrate squamous mucosa, producing change in cytokine production, with fibrous and inflammatory changes; commonly seen in adults 30 to 50 yr of age; affects men more than women; long history of dysphagia for solid foods; often present with food impaction; prospective study  —  patients with noncardiac chest pain sent for endoscopy; chest pain common presentation; 2 of 58 participants had signifi­cantly increased eosinophils; significant number had diagnostic criteria for EE; previously thought that endoscopy usually not useful in patients who present with chest pain (14% have endoscopic findings; 86% normal endoscopy); fluticasone  —standard treatment drug; some patients do not respond; in patients with allergic response vs nonaller­gic response, efficacy greater in nonallergic group (likely related to predominance and severity of eosinophilia, rather than nonresponse of patients); montelukast  —  response seen in many patients, but does not necessarily lead to major changes in eosinophilic infiltration in distal esophagus; nevertheless, significant improvement seen; trial  —  budesonide (eg, Pulmicort) respules 1 mg bid vs placebo; criteria for remission <5 eosinophils per high power field; 62% of patients on budesonide had remission (vs 5.7% with placebo); clinical response substantially im­proved, but not as much as previously thought; reintroduction and elimination diets in treatment of EE  —  23 partic­ipants underwent 6-food elimination diet after skin testing for air and food allergens; aeroallergens seen in 72% (food allergens in 55%); most had histologic and endoscopic improvement; one-third had complete response; symptom scores decreased in most, but all had recurrence with food reintroduction; wheat and milk intolerance most common (not true allergy)

Synergy of GERD and obesity: looking at body mass index (BMI) in patients with reflux, substantial increase in ad­enocarcinoma seen in those with higher BMI; also seen as BMI increases over time; in combined groups, risk in­creases 16-fold

Survey of screening patterns for BE: 98% of gastroenterologists would screen men 55 yr of age with 20 yr of GERD, 75% would screen  35-yr-old with 20 yr of GERD; »50% would screen women 55 yr of age with 2-yr his­tory of GERD, 16% would screen 35-yr-old women with 2 yr of GERD; relatively young patients with short dura­tion of disease should not undergo screening; as patient grows older or as GERD worsens, screening appropriate; problem of not obtaining biopsy when BE not seen visually; study  —  6200 participants with NERD and erosive esophagitis; found 171 participants without endoscopic suspicion of BE had histologic evidence of BE (defined as microscopic BE [MBE]); looking at progression to endoscopic BE 2 to 5 yr later, 2.4% had no MBE and 22.9% had MBE; necessary to perform biopsy when “tongue” of tissue seen or circumferential disease present (but not if irreg­ular Z-line seen); previously, biopsy performed in all patients with BE but no longer done because 21% of patients with normal endoscopy had Barrett’s change, and meaning unclear; current thinking that many of these patients will have significant disease 5 yr after endoscopy

Treatment of BE: techniques  —  mechanical EMR, thermal therapy, and photochemical therapy; EMR useful for raised lesions and focal areas of dysplasia; study  —  found that nodular specimens had higher incidence of CA, and 6% of flat lesions had CA in areas removed by EMR; major usefulness of EMR detection of cancer; photodynamic therapy (PDT)  —advantage of having tracking balloons in esophagus; complications include photosensitivity, stric­ture, and subsquamous BE; study showed incidence of HGD and CA significantly decreased with PDT; in study comparing treatment with EMR and/or PDT to surgery, cumulative mortality equivalent in both 2 groups; radiofre­quency ablation (RFA)  —  used Barrx system (related to Stretta procedure); delivers radiofrequency energy to esophagus at shallow depth by system of concentric balloons; wattage relatively low (no deep damage); fewer treat­ments needed; most of mucosa removed

Ablation of Intestinal Metaplasia Containing Dysplasia (AIM) trial: compared RFA to sham; participants strati­fied by low-grade dysplasia (LGD) or HGD; both groups had EMR of nodules and high-dose PPI therapy; treat­ment with RFA in HGD group led to 80% to 90% improvement, while sham-treated participants had only 10% change; in LGD cohort, sham group had better response (in sham group, tendency for LGD to return to normal), with significant improvement with use of Barrx; 75% had complete removal of all Barrett’s tissue (none in sham treatment); problem of strictures seen in 6% of patients, but all resolved with few dilations; serious adverse events  —  seen in 3 of 84 participants; RFA group had relatively little progression (4%; 15%-20% in sham group); buried BE  —seen in 20% of HGD group (30% in LGD group); 12-mo prevalence  —  6% in RFA cohort (60% in sham)

Suggested Reading

Anandasabapathy S et al: Clinical and endoscopic factors predict higher pathologic grades of Barrett dysplasia. Cancer 109:668, 2007; Bampton PA et al: Improving surveillance for Barrett's esophagus. BMJ 332:1320, 2006; Barclay RL et al: Colonoscopic withdrawal times and adenoma detection during screening colonoscopy. N Engl J Med 355:2533, 2006; Barriga J et al: Sedation for upper endoscopy: comparison of midazolam versus fentanyl plus midazolam. South Med J 101:362, 2008; Basson MD: Choosing sedation for upper endoscopy. South Med J 101:345, 2008; Curvers W et al: Chromoendoscopy and narrow-band imaging compared with high-resolution magnification endoscopy in Barrett's esophagus. Gastroenterology 134:670, 2008; Eldaif SM et al: Radiofrequency ablation of Barrett's esophagus: short-term results. Ann Thorac Surg 87:405, 2009; Kaltenbach T et al: A randomised tandem colonoscopy trial of narrow band imaging versus white light examination to compare neoplasia miss rates. Gut 57:1406, 2008; Kaltenbach T et al: American Gastroenterological Association (AGA) In­stitute technology assessment on image-enhanced endoscopy. Gastroenterology 134:327, 2008; Lieberman D et al: Polyp size and advanced histology in patients undergoing colonoscopy screening: implications for CT colonography. Gastroenterology 135:1100, 2008; Pandolfino JE et al: Transient lower esophageal sphincter relaxations and reflux: mechanistic analysis using concurrent fluoroscopy and high-resolution manometry. Gastroenterology 131:1725, 2006; Rex DK et al: High yields of small and flat adenomas with high-definition colonoscopes using either white light or narrow band imaging. Gastroenterology 133:42, 2007; Swoger JM et al: Eosinophilic esophagitis: is it all allergies? Mayo Clin Proc 82:1541, 2007; Wu JC et al: Obesity is associated with increased transient lower esophageal sphincter relaxation. Gastroenterology 132:883, 2007.