MANAGEMENT OF BARRETT'S ESOPHAGUS - CME Conferences

3 rd Annual Essentials in Primary CareSummer Conference: Session 1Thursday, July 26, 2012MANAGEMENT OF BARRETT’SESOPHAGUSScreening, surveillance and treatmentDonald O. Castell M.D.Professor of MedicineDirector, Esophageal Disorders ProgramMedical University of South CarolinaDonald Castell, MDManagement of Barrett’s Esophagus

3 rd Annual Essentials in Primary CareSummer Conference: Session 1Thursday, July 26, 2012DIAGNOSIS OF BARRETT’S ESOPHAGUS• Suspected by endoscopy• Confirmed by biopsyBARRETT’S EPITHELIUMH&EArrows = goblet cellsMUCINDonald Castell, MDManagement of Barrett’s Esophagus

3 rd Annual Essentials in Primary CareSummer Conference: Session 1Thursday, July 26, 2012BARRETT’S ESOPHAGUS“Short segment”• Definition: Intestinal metaplasia present within 3cm or less of distal esophagus• 142 patients for elective endoscopy– Biopsies from distal 3 cm of esophagus,including squamocolumnar junction– 26 (18%) showed intestinal metaplasia(Spechler SJ, et al: Lancet 344:1533, 1994)HEARTBURN AND ESOPHAGEAL CANCERSymptomatic gastroesophageal reflux as a riskfactor for esophageal adenocarcinoma.(Lagergren J, et al: N Engl J Med 1999; 340:825)Donald Castell, MDManagement of Barrett’s Esophagus

3 rd Annual Essentials in Primary CareSummer Conference: Session 1Thursday, July 26, 2012INCIDENCE OF ESOPHAGEALCANCER IN U.S.WHITE MALESCase per 100,000 person-years5432101970 1975 1980 1985 1990 1995AdenoSquamous(Devesa S, et at: Cancer 83:2049,1998)BARRETT’S ESOPHAGUS RISK FACTORS• Caucasian male• Older age: >40 yrs; >50 yrs ?• Duration of GERD: >5 yrs; >10 yrs ?• Visceral fat: waist size ?• Family history• H. pylori freeDonald Castell, MDManagement of Barrett’s Esophagus

3 rd Annual Essentials in Primary CareSummer Conference: Session 1Thursday, July 26, 2012GASTRIC ACID CONTROL IN BEIs symptom relief a reliable index?DECREASED ACID SENSITIVITY IN BARRETT’SPositive Bernstein (%)100508642Time to Sx (min)0RE BE RE BE(Johnson D, et al: J Clin Gastroenterol 9:23, 1987)Donald Castell, MDManagement of Barrett’s Esophagus

3 rd Annual Essentials in Primary CareSummer Conference: Session 1Thursday, July 26, 2012GERNABRECUMBENT REFLUX INASYMPTOMATIC BARRETT’S42 patients on lansoprazole (15-60 mg/d)403018/42 abnormal2010024/42 normal(Ouatu-Lascar, et al: Gastroenterology 117:327, 1999)Donald Castell, MDManagement of Barrett’s Esophagus

3 rd Annual Essentials in Primary CareSummer Conference: Session 1Thursday, July 26, 2012NOCTURNAL ACID BREAKTHROUGH INBARRETT’S ESOPHAGUS10080% of patients6040200NABNAB & GER(Katz PO, et al: Aliment Pharmacol Ther 12:1231, 1998)Donald Castell, MDManagement of Barrett’s Esophagus

3 rd Annual Essentials in Primary CareSummer Conference: Session 1Thursday, July 26, 2012GASTRIC ACID CONTROL IN BARRETT’SDoes acid control affect length of metaplasticepithelium?BARRETT’S ESOPHAGUSMaximal acid control (titrate with pH monitor)• 9 patients (8 male; age 44-72yrs)• Follow up 13-118 months (median 37)• Rx:PPI BID (2)PPI BID + ranitidine (7)• Linear regression: 9/9 (1-3 cm)• Squamous islands: 5/9(Srinivasan R, et al: Aliment Pharmacol Ther 15:519, 2001)Donald Castell, MDManagement of Barrett’s Esophagus

3 rd Annual Essentials in Primary CareSummer Conference: Session 1Thursday, July 26, 2012REGRESSION OF BARRETT’S WITHOMEPRAZOLE• 53 patients with BE randomized prospectively.27: ranitidine 150 mg bid26: omeprazole 40 mg bid• Symptoms controlled for 24 months• 24 hr pH at 3 months (mean and 95% CI)ranitidine: 9.4 (6.2 - 13.0)%omeprazole: 0.1 (0-1.2)%(Peters et al: Gut 45:489, 1999)RELATIVE CHANGES IN LENGTH ANDSURFACE AREA OF BARRETT’S ESOPHAGUS421-1OmeprazoleRanitidine% change (length)0-2-4% change (area)-3-5-6-7-83 9 15 24Time (months)-93 9 15 24Time (months)Peters, et al: Gut 1999;45:489-494Donald Castell, MDManagement of Barrett’s Esophagus

3 rd Annual Essentials in Primary CareSummer Conference: Session 1Thursday, July 26, 2012PRIOR ACID SUPPRESSION THERAPYRELATED TO SHORTER BARRETT’S• Retrospective analysis of 340 BE patients– Diagnosis made between 1981-2000• Mean length of BE at initial Dx: 4.4 cm (range: 0.5-16)– 201(59%) no prior Rx: 4.8 cm– 63(19%) H2RA only: 4.6 cm p=0.55– 35(10%) PPI only: 3.4 cm p=0.0013– 41(12%) both PPI & H2RA: 3.1 cm p=0.002• Conclusions:– Provides a rationale for aggressive therapy of GERD– Counters the concept that antisecretory therapyincreases risk of esophageal adenocarcinoma(El-Serag et al(Sampliner): Aliment Pharmacol Ther 2004; 19: 1255)NORMALIZATION OF INTESTINALMETAPLASIA WITH ACID CONTROLN = 101; average FU = 4 yrsDysplasia or cancer: 13% LSBE; 3% SSBE; 0% EGJSIM(Horwhat et al: Am J Gastroenterol 2007; 102: 497)Donald Castell, MDManagement of Barrett’s Esophagus

3 rd Annual Essentials in Primary CareSummer Conference: Session 1Thursday, July 26, 2012MAXIMAL ACID CONTROL FORBARRETT’S ESOPHAGUS• Not achieved in prior studies• pH monitoring required (i.e. can not rely on Sx)• May produce endoscopic regression• Does it affect progression to dysplasia or cancer?PPI DELAYS DEVELOPMENT OFDYSPLASIA IN BARRETT’S• BE surveillence program from 1981-2001• PPI began in 1989• 350 patients with Barrett’s (intestinal metaplasia)– 1422 surveillance endoscopies– Median FU = 4.7 years• Delayed PPI use(>2 yrs) compared to PPI in 1 st year– 5.6X greater risk of LGD– 20.9X greater risk of HGD or adenocarcinoma• Conclusion: “PPI therapy appeared beneficial in theprevention of dysplasia & adenocarcinoma. Wesuggest that all patients with this condition, eventhose with no esophagitis or symptoms, should beencouraged to continue long term PPI therapy”.(Hillman AC et al: Med J Australia 180: 387, 2004)Donald Castell, MDManagement of Barrett’s Esophagus

3 rd Annual Essentials in Primary CareSummer Conference: Session 1Thursday, July 26, 2012HIGH GRADE DYSPLASIA IN BE• Diffuse HGD: 67 patients• Focal HGD: 33 patientsAssociated with > risk of AdenoCA Relative riskExtent of HGD 5.63Nodule on endoscopy 3.98Lack of acid suppression 2.48( Buttar et al, Gastroenterology 120:1639, 2001)PPIs REDUCE INCIDENCE OF DYSPLASIA IN BE• Retrospective review of 236 VA pts with BE over20 yrs.– 56 pts developed dysplasia (4.7%/yr)• Incidence of dysplasia lower (p

3 rd Annual Essentials in Primary CareSummer Conference: Session 1Thursday, July 26, 2012HOW A COMMON HEALTH PROBLEM IS QUIETLYBECOMING AN UNSUSPECTED KILLERTara Parker-PopeThe Wall Street JournalOctober 10, 2005“Chronic heartburn can turn deadly, leading to anaggressive esophageal cancer that few survive”“Use of acid-suppressing drugs may play a rolein the rise of esophageal cancer”“An alternate to drug treatment is surgery”ANTI-REFLUX SURGERY DOES NOT REMOVERISK OF ESOPHAGEAL CANCER IN GERDsurgery no surgeryMales with GERD: 6,406 35,274AdenoCa risk:* 14.1 (CI,8-23) 6.3 (CI,4.5-8.7)“The risk of developing adenocarcinoma of theesophagus remains increased after antirefluxsurgery”* Excluded 1 st year FU(Ye, Chow, Lagergren et al: Gastroenterology 121:1296, 2001)Donald Castell, MDManagement of Barrett’s Esophagus

3 rd Annual Essentials in Primary CareSummer Conference: Session 1Thursday, July 26, 2012FUNDOPLICATION DOES NOT DECREASE THERISK OF ESOPHAGEAL CANCER IN GERD• Review of VA data base from 1986-199097.5% men; mean age 55 yrsFollow-up > 10 yrs for all• GERD with fundo: 946 (8 cancer) (risk ratio=1.9)• GERD without fundo: 1,892 (8 cancer)• No GERD: 5,676 (0 cancer)• Conclusion: “GERD is a risk factor foresophageal cancer, but there is insufficientevidence that fundoplication reduces that risk”(Tran et al: Am J Gastro 2005; 100: 1002)MEDICAL VS SURGICALTREATMENT?“When you come to a fork in the road,TAKE IT”Yogi BerraDonald Castell, MDManagement of Barrett’s Esophagus

3 rd Annual Essentials in Primary CareSummer Conference: Session 1Thursday, July 26, 2012BARRETT’S SURVEILLANCE GUIDELINESACG 2008–The grade of dysplasia determines thesurveillance interval– No dysplasia in 2 consecutive samples: every 3 years– LGD: every year until no dysplasia– HGD: intensive surveillance (q 3 months) orintervention; particularly for mucosal irregularity ormulti-focal (>5 crypts)MANAGEMENT OF HGD IN BARRETT’S• Intensive surveillance• Surgery• Endoscopic–Ablation–Mucosectomy/dissectionDonald Castell, MDManagement of Barrett’s Esophagus

3 rd Annual Essentials in Primary CareSummer Conference: Session 1Thursday, July 26, 2012MANAGEMENT OF HGD IN BE• Intensive surveillance (flat mucosa)–Repeat biopsies q3months for 1 year(i.e. “the hunt”)–Then, yearly if no cancer–Intervene when adenocarcinoma arises»Incidence @ 16% at 10 years(Sontag et al: Loyola)MANAGEMENT OF HGD IN BE• Esophagectomy–Operative mortality varies by center»8.1% if high volume (>19/year)»23% if low volume (50%Birkmeye. N Engl J Med 2002;346:1128-37Donald Castell, MDManagement of Barrett’s Esophagus

3 rd Annual Essentials in Primary CareSummer Conference: Session 1Thursday, July 26, 2012GERD TREATMENTGod put the esophagus in theback of the chest to keep itaway from surgeons.MANAGEMENT OF HGD IN BEEndoscopic Ablation of Barrett’s epitheliumSuppress Acid reflux (medical or surgical)Healing with squamous epitheliumDonald Castell, MDManagement of Barrett’s Esophagus

3 rd Annual Essentials in Primary CareSummer Conference: Session 1Thursday, July 26, 2012ENDOSCOPIC ABLATION OF BE: PDTPDT + OM(n=138)OM alone(n=70)HGD eliminated(p < .0001)Progression tocancer(p = .027)77% 39%15% 29%(Overholt et al: GIE 2007; 66: 460ENDOSCOPIC ABLATION OF BE: PDT• Complications:–Stricture 39%»up to 50% in other reports–Sunburn 46%–Nausea 33%–Chest pain 32%–Fever 21%Donald Castell, MDManagement of Barrett’s Esophagus

3 rd Annual Essentials in Primary CareSummer Conference: Session 1Thursday, July 26, 2012RFA: COMPLETE DYSPLASIA RESPONSEOne year follow-up% of patients1009080706050403020100N=37N=22RFAShamN=17N=17HGDLGDAll patients on esomeprazole 40mg bid(Shaheen et al:DDW, 2008)ENDOSCOPIC ABLATION OF BE: RFA• Complication:–Stricture (rare)–Throat pain–Odynphagia–DysphagiaSelf limited(Ganz, et al: GIE, 2007; 65: AB147)Donald Castell, MDManagement of Barrett’s Esophagus

3 rd Annual Essentials in Primary CareSummer Conference: Session 1Thursday, July 26, 2012THE BEST TREATMENT FOR BARRETT’SALTERNATIVES TO EVIDENCEBASED MEDICINEEminence-based medicineVehemence-based medicineEloquence-based medicineProvidence-based medicineConfidence-based medicineExperience; white hairEmphasis; volumeVerbal; sartorial“God only knows”Restricted to surgeons(Isaacs D, Fitzgerald D: The Oncologist 2001; 6: 390)Donald Castell, MDManagement of Barrett’s Esophagus